Female Pelvic Health and Reconstructive Surgery (Drugs and the Pharmaceutical Sciences)

Female Pelvic Health and Reconstructive Surgery edited by

Bruce I. Carlin Washington University School of Medicine St. Louis, Missouri, U.S.A.

Fah Che Leong St. Louis University School of Medicine St. Louis, Missouri, U.S.A.

Marcel Dekker, Inc.

New York • Basel

TM

Copyright © 2002 by Marcel Dekker, Inc. All Rights Reserved.

ISBN: 0-8247-0822-9 This book is printed on acid-free paper. Headquarters Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016 tel: 212-696-9000; fax: 212-685-4540 Eastern Hemisphere Distribution Marcel Dekker AG Hutgasse 4, Postfach 812, CH-4001 Basel, Switzerland tel: 41-61-260-6300; fax: 41-61-260-6333 World Wide Web http:/ /www.dekker.com The publisher offers discounts on this book when ordered in bulk quantities. For more information, write to Special Sales/Professional Marketing at the headquarters address above. Copyright  2003 by Marcel Dekker, Inc. All Rights Reserved. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher. Current printing (last digit): 10 9 8 7 6 5 4 3 2 1 PRINTED IN THE UNITED STATES OF AMERICA

Preface

In the year 2000, the American Board of Urology and the American Board of Obstetrics and Gynecology established a combined subspecialty entitled Female Pelvic Health and Reconstructive Surgery. The motivation for this decision was to emphasize and promote collaborative efforts between the specialties to further our understanding of pelvic floor disorders. As such, we embarked on this effort to establish this volume as a representation of those collaborative efforts. This volume provides comprehensive, authoritative coverage of female pelvic health and reconstructive surgery. It is a compilation of contributions from many experts who specialize in the treatment of pelvic floor disorders. It will serve as an invaluable resource for investigators in the field and practitioners who treat pelvic floor disorders. Likewise, it will be an effective educational tool for both residents and medical students. We have enjoyed this effort greatly. As the two fields develop this area of interest further, we hope that this type of collaboration and cooperation continues. Bruce I. Carlin Fah Che Leong

iii

Contents

Preface Contributors

1. The Epidemiology and Etiology of Incontinence and Voiding Dysfunction Scott L. Brown and Kathleen C. Kobashi

iii ix

1

2. Diagnostic Evaluation of the Female Patient Joseph M. Carbone

11

3. Bladder Physiology and Neurophysiological Evaluation J. Thomas Benson

27

4. Diagnosis and Assessment of Female Voiding Function J. Thomas Benson

43

5. Radiological Evaluation Huy Q. Tran, Vamsidhar R. Narra, and Cary Lynn Siegel

51

6. Urodynamic Evaluation of Pelvic Floor Dysfunction Sumana Koduri and Peter K. Sand

77

7. Injectable Agents for the Treatment of Stress Urinary Incontinence in Females Natania Y. Piper and R. Duane Cespedes

107

8. Transabdominal Procedures for the Treatment of Stress Urinary Incontinence Alan D. Garely and Leah Kaufman

121 v

vi

9.

10.

11.

Contents

Transvaginal Surgery for Stress Urinary Incontinence Tracey S. Wilson and Gary E. Lemack

137

Laparoscopic Approaches to Female Incontinence, Voiding Dysfunction, and Prolapse Jaime Landman and Elspeth M. McDougall

161

Diagnosis and Management of Obstruction Following AntiIncontinence Surgery Michael Volpe, Mohamed A. Ghafar, and Alexis E. Te

179

12.

Pediatric Dysfunctional Voiding in Females Paul F. Austin and Yves L. Homsy

195

13.

Nonsurgical Treatment of Urinary Incontinence Fah Che Leong

215

14.

Sacral Nerve Root Neuromodulation/Electrical Stimulation Steven W. Siegel and Jyothi B. Kesha

225

15.

Musculoskeletal Evaluation for Pelvic Pain Heidi Prather

241

16.

Diagnosis and Management of Interstitial Cystitis Tomas L. Griebling

263

17.

Abdominal Approach to Apical Prolapse Jenny Jo and Cheryl B. Iglesia

281

18.

Vaginal Prolapse: Types and Choice of Operation for Repair Dionysios K. Veronikis

291

19.

Colpocleisis for the Treatment of Vaginal Vault Prolapse Kenneth H. Ferguson and R. Duane Cespedes

311

20.

Technique of Vaginal Hysterectomy Mary T. McLennan

329

21.

Urethral Diverticulum Sam Bhyani and Bruce I. Carlin

351

22.

Evaluation and Management of Urinary Fistulas Elizabeth A. Miller and George D. Webster

363

23.

Iatrogenic Urological Trauma Steven B. Brandes

381

Contents

24. Surgical Treatment of Rectovaginal Fistulas and Complex Perineal Defects Dionysios K. Veronikis

vii

397

25. Pessaries Kim Kenton

407

26. Menopause and Hormone Replacement Therapy Sangeeta T. Mahajan, Anil B. Pinto, and Daniel B. Williams

417

27. Diagnosis of Female Sexual Dysfunction Cathy K. Naughton

475

Index

495

Contributors

Paul F. Austin, M.D. Associate Professor of Surgery, Department of Urology, Washington University School of Medicine, and St. Louis Children’s Hospital, St. Louis, Missouri J. Thomas Benson, M.D. Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana Sam Bhyani, M.D. Chief Resident, Division of Urology, Washington University School of Medicine, St. Louis, Missouri Steven B. Brandes, M.D. Assistant Professor, Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri Scott L. Brown, M.D. Department of Urology, San Diego Urology, La Mesa, California Joseph M. Carbone, M.D. Director, Piedmont Institute for Continence, Danville Urologic Clinic, Danville, Virginia Bruce I. Carlin, M.D. Assistant Professor of Surgery, Division of Urology, Washington University School of Medicine, St. Louis, Missouri R. Duane Cespedes, M.D. Director, Female Urology and Urodynamics, Department of Urology, Wilford Hall Medical Center, San Antonio, Texas Kenneth H. Ferguson, M.D. Chief Resident, Department of Urology, Wilford Hall Medical Center, San Antonio, Texas Alan D. Garely, M.D. Chief, Division of Urogynecology and Pelvic Reconstructive Surgery, Department of Obstetrics and Gynecology, Winthrop University Hospital, Mineola, New York ix

x

Contributors

Mohamed A. Ghafar, M.D. Department of Urology, College of Physicians and Surgeons, Columbia University, New York, New York Tomas L. Griebling, M.D. Assistant Professor of Urology and Assistant Scientist, Center on Aging, University of Kansas, Kansas City, Kansas Yves L. Homsy, M.D. Clinical Professor of Urological Surgery, University of South Florida School of Medicine and Children’s Urology Group, Tampa, Florida Cheryl B. Iglesia, M.D. Department Obstetrics and Gynecology, Washington Hospital Center, Washington, D.C. Jenny Jo, M.D. Department Obstetrics and Gynecology, Washington Hospital Center, Washington, D.C. Leah Kaufman, M.D. Associate Residency Director, Department of Obstetrics and Gynecology, Long Island Jewish Medical Center, New Hyde Park, New York Kim Kenton, M.D. Department of Obstetrics and Gynecology and Department of Urology, Loyola University Medical Center, Maywood, Illinois Jyothi B. Kesha, M.D.

Metro Urology, St. Paul, Minnesota

Kathleen C. Kobashi, M.D. Co-Director, Continence Center, Department of Urology and Renal Transplantation, Virginia Mason Medical Center, Seattle, Washington Sumana Koduri, M.D. Assistant Professor, Division of Urogynecology, Department of Obstetrics and Gynecology, University of Wisconsin–Milwaukee Clinical Campus, Milwaukee, Wisconsin Jaime Landman, Division of Urologic Surgery, Department of Surgery, Washington University, St. Louis, Missouri Gary E. Lemack, M.D. Assistant Professor and Director of Neurourology, Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas Fah Che Leong, M.D. Assistant Professor, Department of Obstetrics and Gynecology, St. Louis University School of Medicine, St. Louis, Missouri Sangeeta T. Mahajan, M.D. Resident Physician, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri Elspeth M. McDougall Department of Urology, Vanderbilt University, Nashville, Tennessee

Contributors

xi

Mary T. McLennan, M.D. Assistant Professor, Department of Obstetrics and Gynecology, St. Louis University, St. Louis, Missouri Elizabeth A. Miller, M.D. Assistant Professor, Department of Urology, University of Washington, Seattle, Washington Vamsidhar R. Narra, M.D. Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri Cathy K. Naughton, M.D. Assistant Professor, Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri Anil B. Pinto, M.D. Fellow, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri Natania Y. Piper, D.O. Chief Resident, Department of Urology, Wilford Hall Medical Center, San Antonio, Texas Heidi Prather, D.O. Assistant Professor, Physical Medicine and Rehabilitation, Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, Missouri Peter K. Sand, M.D. Professor, Department of Obstetrics and Gynecology; Director, Evanston Continence Center; and Director, Division of Urogynecology, Evanston Northwestern Healthcare, Northwestern University Medical School, Evanston, Illinois Cary Lynn Siegel, M.D. Assistant Professor of Radiology, and Chief, Genitourinary Radiology, Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri Steven W. Siegel, M.D. Metro Urology, St. Paul, Minnesota Alexis E. Te, M.D. Associate Professor, Department of Urology, Weill Medical College of Cornell University, New York, New York Huy Q. Tran, M.D. Thoracic Imaging Fellow, Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri Dionysios K. Veronikis, M.D. Chief of Gynecology, Department Obstetrics and Gynecology, St. John’s Mercy Medical Center, St. Louis, Missouri Michael Volpe, M.D. Department of Urology, College of Physicians and Surgeons, Columbia University, New York, New York

xii

Contributors

George D. Webster, M.D. Professor, Department of Urology, Duke University Medical Center, Durham, North Carolina Daniel B. Williams, M.D. Assistant Professor, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri Tracey S. Wilson, M.D. Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas

1 The Epidemiology and Etiology of Incontinence and Voiding Dysfunction SCOTT L. BROWN San Diego Urology La Mesa, California, U.S.A. KATHLEEN C. KOBASHI Virginia Mason Medical Center Seattle, Washington, U.S.A.

I.

INTRODUCTION

Urinary incontinence among women is a prevalent condition with a significant influence on well-being. Approximately one third of all women have involuntary leakage of urine; 10% have incontinence at least weekly, and 5% have incontinence daily [1–3]. Incontinence is so common in elderly patients that it is often mistakenly viewed as a consequence of aging and an inevitable problem with which women must contend. Incontinence, however, is also a problem among younger women in the community and in those younger women with particular medical problems [4,5]. Many factors, such as age, childbirth, parity, bowel dysfunction, obstetric complications, obesity, pelvic surgery, medications, functional impairment, chronic diseases, menstrual cycle, race, and family history, are associated with urinary incontinence [2,6–11]. It has been suggested that the prevalence of urinary incontinence increases at the time of menopause [12]. However, it remains uncertain whether this is due to the hormonal changes associated with menopause or is just part of the aging process [13]. This chapter focuses on the epidemiology and etiology of urinary incontinence and includes associated risk factors for incontinence. II. PREVALENCE AND INCIDENCE The prevalence of urinary incontinence in women varies widely. This is probably due to differences in populations studied, in data collection methods, and in defi1

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nitions of incontinence. The tendency for patients to underreport incontinence due to embarrassment further exacerbates this problem. Therefore, estimates from the literature should be accepted with some caution. Urinary incontinence is estimated to affect 30% to 40% of older American women [14–17]. It has long been felt that the prevalence of any urinary incontinence increases with age, but contrary to popular belief, the few studies that have assessed incontinence across an age spectrum have shown only minimal increases in prevalence with age [2] or a higher prevalence in younger age groups [14]. The severity and type of urinary incontinence, however, may increase with aging. The way in which incontinence is defined is particularly important. Estimates of the prevalence of urinary incontinence in women vary widely depending on the epidemiological methods used and the population studied. Hampel et al. observed that the epidemiological data are difficult to compare because of differences in definitions of incontinence, populations sampled, and study designs [18]. Using the definition of Diokno et al. of “any incontinence in the prior year” [17], the average prevalence estimate was 40.5%; using the definition of Thomas et al. of “more than two incontinent episodes per month” [2], the prevalence estimate was 14%; using the International Continence Society (ICS) definition of “social or hygienic problem and objectively demonstrable” [19], the prevalence estimate was 23.5%. Further, the overall average prevalence using a variety of miscellaneous definitions was 28.3% [14]. Studies that evaluated incontinence objectively had lower prevalence estimates (23.5%) [19] than those that depended only on the results of an interview (29.5%) [18]. Epidemiological studies conducted in the United States rarely confirm urinary incontinence objectively and have higher estimates of prevalence (37%) than do European (26%) and British (29%) series [18]. The prevalence of urinary incontinence has been shown to range from 26% to 57% depending on the definition used [20]. The tremendous range of prevalence data reported for incontinence in most studies is probably related to the differences in study populations and sampling procedures, the differences in methodologies used, and the differences in the definition of incontinence used by each investigator [21]. Another problem that affects the accuracy of prevalence studies of urinary incontinence is underreporting by patients. The incontinent woman is often embarrassed to report the condition to a health care professional and sometimes even attributes the incontinence to normal aging. As a result, incontinent patients often choose to manage their incontinence on their own by using undergarments or protective pads or by altering their voiding behaviors [22,23]. Due to a lack of knowledge of urinary incontinence and because their patients often do not report this problem, many health care professionals also underreport incontinence. Incidence of urinary incontinence is defined as the probability of becoming incontinent during a defined interval of time, presuming incontinence at the beginning of the time interval. As few long-term longitudinal studies have been performed, there is little information available regarding the incidence of urinary incontinence. Studies of elderly patients have shown that about 10% of originally continent adults developed urinary incontinence over a 3-year period [24]. Therefore, in reviewing studies that address the prevalence and incidence of urinary incontinence, several issues should be kept in mind: (1) the definition

Incontinence and Voiding Dysfunction

3

of urinary incontinence used in the study; (2) the methods of sampling used; (3) the setting studied; (4) the sample or population demographics; (5) the reliability and validity of the study; (6) the methods of data collection and procedures; and (7) the response rate of study participants [21]. III. RISK FACTORS FOR URINARY INCONTINENCE A. Sex Incontinence is two to three times more common in women than men [24]. Differences in sex are most pronounced among adults under 60 years of age, which is most likely related to the very low prevalence of incontinence among younger men. In patients over 60 years of age, one study showed uncontrolled urine loss was reported in 18% of men and 38% of women [24]. These differences appear to be consistent among men and women no matter what the definition of urinary incontinence. Stress incontinence is relatively uncommon in men and far more common in women. Voiding problems, in general, are more common in elderly men [24]. B. Age The prevalence of urinary incontinence appears to increase with age. Thomas et al. found that the percentage of British women reporting urinary leakage at least two times per month steadily increased from 4% of women aged 15 to 24 years to 16% of women over 75 years old [2]. Type of incontinence was shown to vary with age as well. Stress urinary incontinence was more common in women less than 65 years of age. Urge incontinence and mixed incontinence were more common after age 65. Yarnell and St. Leger found an increase in the reporting of incontinence by women across different age groups, with 28% of women 17 to 34 years of age reporting incontinence, and 59% of women over 75 years old reporting some degree of incontinence [25]. However, the prevalence rates did not differ by decades after 35 years of age [25]. The reasons for differences in the prevalence of incontinence with aging are unknown. With normal aging, there is a decline in the reserve capacity of all organ systems. Bladder capacity, voluntary restriction of micturition, bladder compliance, and urinary flow rate probably decrease with increasing age in both men and women. Postvoid residual urine volumes and the occurrence of uninhibited bladder contractions increase with aging. These changes in bladder function, along with changes in urethral function, appear to be directly related to the aging process. Sier et al. reported that over one third of elderly patients admitted to the medical and surgical wards of a major teaching hospital experienced urinary incontinence at some time during their hospital stay [26]. The study also found that, in persons over 75 years of age, urinary incontinence was associated with other functional disabilities, such as difficulties with ambulation and cognitive impairment. The authors found that the urinary incontinence persisted and was not just a transient problem associated with the hospitalization. Among residents of nursing homes, the prevalence of urinary incontinence varies from 40% to 70% depending on the proportion of functionally impaired

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residents [27,28]. A substantial proportion of nursing home residents are already incontinent at the time of admission. When compared to ambulatory, communitydwelling elderly persons, nursing home residents suffer from urinary incontinence that is more severe and is more commonly associated with fecal incontinence. Incontinent nursing home residents generally have multiple episodes of urinary incontinence throughout the day and night [29]. C.

Race

There is little information available regarding racial differences in urinary incontinence. In Chinese, Eskimo, and black women, pelvic prolapse, enterocele, and stress incontinence are uncommon [24]. Studies have been done to look at the general anatomic relationship of the levator ani musculature and urethra among different racial groups, and although certain differences were identified, the work was uncontrolled and subjective and should therefore not be considered a definitive explanation [24]. D.

Childbirth

An association between urinary incontinence and parity has been shown [2]. Nulliparous women report incontinence less often than parous women regardless of age. However, no difference in rate of incontinence was noted for women who had three or fewer births. Women who had at least four births were most likely to report incontinence. The increase in prevalence of incontinence with parity is primarily due to an increase of stress and mixed urinary incontinence. There is little or no association between urge incontinence and parity [24]. Injury to pelvic support muscles resulting from childbirth has been implicated as a major etiological factor in stress urinary incontinence. In addition to vaginal delivery directly damaging the pelvic support muscles, there may be partial denervation of the pelvic floor and urethral muscles during childbirth [24]. Most of the muscle injury that occurs with childbirth is recoverable with exercise. Women who have delivered via cesarean section demonstrate increased pelvic muscle strength during and after the postpartum period compared to women who have delivered vaginally [24]. History of abortion was inversely related to the prevalence of daytime urinary frequency, but was positively associated with the sensation of an empty bladder [6]. Obstetrical complications, such as with episiotomies, anal sphincter lesions, deliveries of a large fetus, and prolonged delivery times, might predispose women to postpregnancy urinary incontinence [7]. These data suggest that childbirth adversely affects the function of the lower urinary tract and may even explain some cases of genuine stress urinary incontinence, but further research is needed to understand fully the roles of pregnancy and childbirth in the etiology of pelvic muscle dysfunction and urinary incontinence. E.

Menopause

There is little epidemiological evidence to support the association between menopause and urinary incontinence. Normal urethral function in the female is affected

Incontinence and Voiding Dysfunction

5

by age and estrogen status. Maximum urethral pressure and urethral length increase from birth until 25 years of age and then decrease [24]. A further decrease in functional urethral length occurs after menopause, possibly due to estrogen deprivation. Continence is normally maintained by a complex interaction of urethral smooth muscle, urethral wall elasticity and vascularity, and periurethral striated muscle [24]. Decreased urethral vascularity and abnormal smooth and skeletal muscle function result in low resting urethral pressure and an abnormal stress response, which may explain a relationship between menopause and incontinence. Burgio et al. [16] in the United States and Jolleys [30] in the United Kingdom reported significantly lower prevalence rates of incontinence in postmenopausal women compared with premenopausal women, whereas studies in Sweden, Denmark, and the Netherlands demonstrated no significant differences between these two groups [8,31,32]. Although Rekers et al. [32] noted no differences in premenopausal and postmenopausal prevalence rates, they noted that most postmenopausal women who were incontinent stated that their incontinence began at menopause. F.

Smoking

A significant relationship between cigarette smoking and the development of all forms of urinary incontinence has been shown [33]. Smoking was associated with a two- to threefold increase in relative risk of urinary incontinence [24,33]. This information may encourage women to avoid smoking or to stop smoking if they have already begun. G.

Obesity

Obesity is well established as a risk factor for urinary incontinence [34,35]. Moller et al. described a positive and almost linear association between obesity and urinary incontinence, and there was a similar association between other lower urinary tract symptoms and obesity [6]. Dwyer et al. defined obesity as a weight greater than 120% of the average for height and age and found that obesity was significantly more common in women with genuine stress incontinence and detrusor instability than in the normal population [36]. Obesity was related to age, prior incontinence operations, and parity, but there were no significant differences for any of the urodynamic variables measured between obese and nonobese incontinent women [24]. Therefore, it is not known whether obesity is an independent risk factor in the development of urinary incontinence. In another study, however, Wingate et al. demonstrated obesity to be a significant risk factor for urinary incontinence independent of obstetric history, surgery, smoking, and family history [37]. Several other epidemiological studies have shown obesity and increased body mass index to be a significant and independent risk factor for urinary incontinence [16,34,38]. Subjective resolution of stress and urge urinary incontinence and objective resolution of detrusor instability, genuine stress incontinence, and the combination of the two conditions have been documented in a group of morbidly obese women who underwent bariatric surgery with resultant massive weight loss [10].

6

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Brown and Kobashi

Constipation

Chronic constipation with repeated prolonged straining efforts to defecate has been shown to contribute to progressive neuropathy and dysfunction of the pudendal nerve, thereby resulting in various degrees of urinary incontinence [39,40]. Older women with urinary incontinence are much more likely to have both constipation and fecal incontinence than are women without urinary incontinence [41]. I.

Recreational Stresses

Despite the fact that recreational activities that result in excessive and repetitive increase in abdominal pressure would seem to contribute to the development of pelvic floor dysfunction and lower urinary tract symptoms, few studies have investigated the potentially causative mechanism. Studies have demonstrated that urinary incontinence is not uncommon among young nulliparous athletes, is more common in those women who exercise than in those women who do not, and increases in severity with higher impact activities [14,42,43]. J. Surgery The thought that hysterectomy causes de novo bladder and urethral dysfunction in previously normal women may not be entirely correct. Most of the studies mentioned to support this conviction are anecdotal or retrospective, do not have appropriate control groups, or are based on subjective parameters [14]. Studies that have included preoperative and postoperative urodynamic parameters have demonstrated variable and inconsequential changes in bladder function related to hysterectomy [44–46]. K.

Medications

Medications can act directly by affecting the partially decompensated lower urinary tract and precipitate or worsen the severity of urinary incontinence (e.g., αadrenergic receptor blockers, caffeine, and diuretics) [47,48]. Other medications can indirectly affect the development of urinary incontinence by promoting such other risk factors as severe constipation (e.g., nonsteroidal anti-inflammatory agents, antacids, and iron) or causing a severe nonproductive cough (e.g., some angiotensin-converting enzyme inhibitors) [49,50]. IV. SUMMARY Urinary incontinence is a prevalent, disruptive, and complex problem that affects a large number of adults and thereby presents a significant burden to health and economic resources. A relatively small number of patients with urinary incontinence volunteer their symptoms. Urinary incontinence is not a normal consequence of aging and is curable, if not manageable, in most instances. However, many individuals with this condition are not seriously evaluated and managed by health care professionals. Risk factor identification and the development of proper strategies for prevention should be priorities for future research. Defining the relative importance

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of various risk factors for the development of urinary incontinence is paramount to prevention. REFERENCES 1. Samuelsson EC, Victor FTA, Svarsudd KF. Five-year incidence and remission rates of female urinary incontinence in a Swedish population less than 65 years old. Am J Obstet Gynecol 2000; 183:568–574. 2. Thomas TM, Plymat KR, Blannin J, Meade TW. Prevalence of urinary incontinence. BMJ 1980; 281:1243–1245. 3. Holst K, Wilson PD. The prevalence of female urinary incontinence and reasons for not seeking treatment. N Z Med J 1988; 101:756–758. 4. Campbell AJ, Reinken J, McCosh L. Incontinence in the elderly: prevalence and prognosis. Age Aging 1985; 14:65. 5. Herzog AR, Fultz NH. Prevalence and incidence of urinary incontinence in community-dwelling populations. J Am Geriatr Soc 1990; 38:273. 6. Moller LA, Lose G, Jorgensen T. Risk factors for lower urinary tract symptoms in women 40 to 60 years of age. Obstet Gynecol 2000; 96:446–451. 7. Viktrup L, Lose G, Rolff M, Barfoed K. The symptom of stress incontinence caused by pregnancy or delivery in primiparas. Obstet Gynecol 1992; 79:945–949. 8. Milsom I, Ekelund P, Molander U, Arvidsson L, Areskoug B. The influence of age, parity, oral contraception, hysterectomy and menopause on the prevalence of urinary incontinence in women. J Urol 1993; 149:1459–1462. 9. Spence-Jones C, Kamm MA, Henry MM, Hudson CN. Bowel dysfunction: a pathogenic factor in uterovaginal prolapse and urinary stress incontinence. Br J Obstet Gynaecol 1994; 101:147–152. 10. Bump RC, Sugerman HJ, Fantyl JA, McClish DK. Obesity and lower urinary tract function in women: effect of surgically induced weight loss. Am J Obstet Gynecol 1992; 167:392–397. 11. Mommsen S, Foldspang A. Body mass index and adult female urinary incontinence. World J Urol 1994; 12:319–322. 12. Iosif S, Henriksson L, Ulmsten U. The frequency of disorders of the lower urinary tract, urinary incontinence in particular, as evaluated by a questionnaire survey in a gynecological health control population. Acta Obstet Gynecol Scand 1981; 60:71. 13. Cardozo L. Role of estrogens in the treatment of female urinary incontinence. J Am Geriatr Soc 1990; 38:326. 14. Bump RC, Norton PA. Epidemiology and natural history of pelvic floor dysfunction. Obstet Gynecol Clin North Am 1998; 25(4):723. 15. Teasdale TA, Taffet GE, Luchi RJ, et al. Urinary incontinence in a community-residing elderly population. J Am Geriatr Soc 1988; 36:600–606. 16. Burgio KL, Matthews KA, Engel BT. Prevalence, incidence and correlates of urinary incontinence in healthy, middle-aged women. J Urol 1991; 146:1255–1259. 17. Diokno AC, Brock BM, Brown MB, et al. Prevalence of urinary incontinence and other urological symptoms in the noninstitutionalized elderly. J Urol 1986; 136:1022–1025. 18. Hampel C, Wienhold D, Benken N, et al. Definition of overactive bladder and epidemiology of urinary incontinence. Urology 1997; 50S:4–14. 19. Abrams P, Blaivas JG, Stanton SL, et al. The International Continence Society Committee on Standardization of Terminology: the standardization of terminology of lower urinary tract function. Scand J Urol Nephrol 1988; 1145:5–19. 20. Mailet VT, Fenner DE, Kuchibhalta M, et al. Defining UI for population prevalence studies. 18th Annual Scientific Meeting of the American Urogynecologic Society, Tucson, AZ, Sept 25–28, 1997.

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21. Locher JL, Burgio KL. Epidemiology of incontinence. In: Ostergard DR, Bent AE, eds. Urogynecology and Urodynamics Theory and Practice. 4th ed. Baltimore, MD: Williams & Wilkins; 1996. 22. Brink CA. Absorbent pads, garments, and management strategies. J Am Geriatr Soc 1990; 38:368–373. 23. Fultz NH, Herzog AR. Measuring urinary incontinence in surveys. Gerontologist 1993; 33:708–713. 24. Walters MD. Epidemiology and social impact of urinary incontinence. In: Walters MD, Karram MM, eds. Clinical Urogynecology. St. Louis, MO: Mosby; 1993. 25. Yarnell JWG, St. Leger AL. The prevalence, severity, and factors associated with urinary incontinence in a random sample of the elderly. Age Aging 1979; 8:81. 26. Sier H, Ouslander JG, Orzeck S. Urinary incontinence among geriatric patients in an acute-care hospital. JAMA 1987; 257:1767–1771. 27. Ouslander JG. Urinary incontinence in nursing homes. J Am Geriatr Soc 1990; 38:289– 291. 28. Ouslander JG, Schnelle JF. Incontinence in the nursing home. Ann Intern Med 1995; 122:438–449. 29. Ouslander JG, Morishita L, Blaustein J, Orzeck S, Dunn S, Syre J. Clinical, functional, and psychosocial characteristics of an incontinent nursing home population. J Gerontol 1987; 42:631–637. 30. Jolleys JV. Reported prevalence of urinary incontinence in women in a general practice. BMJ 1988; 296:1300–1302. 31. Hording U, Pedersen KH, Sidenius K, et al. Urinary incontinence in 45-year-old women. Scand J Urol Nephrol 1986; 20:183–186. 32. Rekers H, Drogendijk AC, Valkenburg H, et al. The menopause, urinary incontinence and other symptoms of the genito-urinary tract. Maturitas 1992; 15:101–111. 33. Bump RC, McClish DK. Cigarette smoking and urinary incontinence in women. Am J Obstet Gynecol 1992; 167:1213. 34. Mommsen S, Foldspang A. Body mass index and adult female urinary incontinence. World J Urol 1994; 12:319–322. 35. Brown JS, Grady D, Ouslander JG, Herzog AR, Varner RE, Posner SF. Prevalence of urinary incontinence and associated risk factors in postmenopausal women. Heart and Estrogen/Progestin Replacement Study (HERS) Research Group. Obstet Gynecol 1999; 94:66–70. 36. Dwyer PL, Lee ETC, Hay DM. Obesity and urinary incontinence in women. Br J Obstet Gynaecol 1988; 95:91. 37. Wingate L, Wingate MB, Hassanein R. The relation between overweight and urinary incontinence in postmenopausal women: a case control study. J North Am Menopause Soc 1994; 1:199–203. 38. Brown JS, Seeley DG, Fong J, et al. Urinary incontinence in older women: who is at risk? Obstet Gynecol 1996; 87:715–721. 39. Jones PN, Lubowski DZ, Swash M, et al. Relation between perineal descent and pudendal nerve damage in idiopathic fecal incontinence. Int J Colorectal Dis 1987; 2:93– 95. 40. Lubowski DZ, Swash M, Nichols J, et al. Increases in pudendal nerve terminal motor latency with defecation straining. Br J Surg 1988; 75:1095–1097. 41. Diokno AC, Brock BM, Herzog AR, et al. Medical correlates of urinary incontinence in the elderly. Urology 1990; 36:129–138. 42. Nygaard IE, Thompson FL, Svengalis S, et al. Urinary incontinence in elite nulliparous athletes. Obstet Gynecol 1994; 84:183–187. 43. Nygaard IE, DeLancey JOL, Arnsdorf L, et al. Exercise and incontinence. Obstet Gynecol 1990; 75:848–851.

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44. Lalos O, Bjerle P. Early and late effects of subtotal and total hysterectomy on bladder function. Arch Gynecol 1985; 237:140. 45. Parys BT, Haylen BT, Hutton JL, et al. The effects of simple hysterectomy on vesicourethral function. 1989; 64:594–599. 46. Wake CR. The immediate effect of abdominal hysterectomy on intravesical pressure and detrusor activity. Br J Obstet Gynecol 1980; 87:901–902. 47. Dwyer PL, Teele JS. Prazosin: a neglected cause of genuine stress incontinence. Obstet Gynecol 1992; 79:117–121. 48. Creighton SM, Stanton SL. Caffeine: does it affect your bladder? Br J Urol 1990; 66: 613–614. 49. Romero Y, Evans JM, Fleming KC, et al. Constipation and fecal incontinence in the elderly population. Mayo Clin Proc 1996; 71:81–92. 50. Overlack A. ACE inhibitor-induced cough and bronchospasm: incidence, mechanisms, and management. Drug Safety 1996; 15:72–78.

2 Diagnostic Evaluation of the Female Patient JOSEPH M. CARBONE Danville Urologic Clinic Danville, Virginia, U.S.A.

I.

INTRODUCTION

The diagnostic evaluation of the female patient requires the art of focused interviewing and active listening. It is a process of taking what may appear to be myriad seemingly unrelated complaints and focusing on one or two problems from which all complaints seem to stem. It is not an easy process. It requires patience, understanding, empathy, and time. The process begins in the office with a detailed history and physical examination. Preliminary information is derived from the patient’s history as obtained from the initial interview. Further data are obtained from voiding diaries, pad tests, and self-administered questionnaires. Physical examination includes a thorough survey as well as provocative testing. Objective data are obtained by laboratory tests, radiologic studies, ultrasound studies, urodynamic studies, and cystoscopy. This process is ongoing and should continue during and after treatment to assess outcomes. The goal of this chapter is to discuss the process of focusing the initial office visit to identify specific categories of complaints that help in planning therapeutic interventions. The particulars regarding further investigation with multichannel urodynamics and/or radiological studies are beyond the scope of this discussion and are addressed separately.

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II. FEMALE PELVIC DYSFUNCTION Female pelvic dysfunction often presents as problems related to urinary incontinence; pelvic floor prolapse; frequency and urgency in the need to void and nocturia; pelvic pain; and sexual dysfunction. These categories are closely related and often occur together. A.

Urinary Incontinence

Urinary incontinence is defined as the accidental or involuntary loss of urine that is socially embarrassing or creates a problem with hygiene [1]. Blavias describes incontinence on the basis of a symptom, a condition, and a cause (Table 1) [2]. Several other classification systems exist to categorize different types of incontinence, but generally speaking, incontinence can be categorized according to the circumstances precipitating the loss of urine. Table 1 Symptoms, Conditions, and Causes of Urinary Incontinence Symptom

Condition

Urge incontinence

Detrusor overactivity

Stress incontinence

Sphincter hypermobility Intrinsic sphincter deficiency

Unaware incontinence

Detrusor overactivity Sphincter abnormality Extraurethral incompetence

Continuous leakage

Sphincter abnormality Impaired contractility Extraurethral incontinence

Nocturnal enuresis

Sphincter abnormality Detrusor overactivity

Postvoid dribble

Postsphincteric collection of urine Vesico- and urethrovaginal fistula Ectopic ureter

Extraurethral incontinence

Source: Ref. 2.

Medical/surgical causes Idiopathic Neurogenic Urinary tract infection Bladder cancer Outlet obstruction Pelvic floor relaxation Prior urethral, bladder, or pelvic surgery Neurogenic Idiopathic Neurogenic Prior urethral, bladder, or pelvic surgery Vesico-, uretero-, or urethrovaginal fistula Ectopic ureter Neurogenic Prior urethral, bladder, or pelvic surgery Ectopic ureter Urinary/vaginal fistula Idiopathic Neurogenic Outlet obstruction Idiopathic Urethral diverticulum Trauma (surgical, obstetrical, other) Congenital

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Stress incontinence is the loss of urine coincident with an activity that increases the intra-abdominal pressure (e.g., coughing, sneezing, bending, or lifting). Urge incontinence is the inability to delay voiding after perceiving that the bladder is full. Overflow incontinence is the loss of urine with a full bladder due to obstruction or a poorly contracting bladder. Extraurethral incontinence is the continuous loss of urine due to a lower urinary tract abnormality (e.g., ectopic ureter or fistula). Functional incontinence is the loss of urine secondary to factors extrinsic to the urinary tract (e.g., decreased mobility, changes in medication, or cognitive disorders). Both bladder and sphincter abnormalities can cause urinary incontinence. Detrussor hyperreflexia denotes involuntary bladder contractions that are due to underlying neurological conditions. Detrusor instability denotes involuntary bladder contractions that are not due to neurological disorders. Low compliance denotes an abnormally decreased volume/pressure relationship in the bladder during filling. Urethral hypermobility denotes a sphincter abnormality caused by a weak pelvic floor that results in urinary incontinence. Urethral hypermobility is often present in women who are not incontinent. Thus, the mere presence of urethral hypermobility is not sufficient to make a diagnosis of a sphincter abnormality unless incontinence is concomitantly demonstrated. Intrinsic sphincter deficiency denotes an intrinsic malfunction of the urethral sphincter itself, resulting in incontinence. Often, more than one type of incontinence and more than one etiologic factor are present. A good diagnostic evaluation of the female patient is therefore critical to the proper classification of urinary incontinence. B. Pelvic Floor Prolapse Prolapse refers to the protrusion of the pelvic organs beyond their normal anatomical location. This can involve the urethra (urethrocele), bladder (cystocele), uterus (uterine prolapse), intestine (enterocele), or rectum (rectocele). Physical findings of pelvic floor prolapse do not necessarily correlate with symptoms. Traditional classification systems have categorized pelvic prolapse on a scale of 1 to 4 based on the lowest extent of protrusion in the standing position [3]. These categories are defined as follows: grade 1, mobility with straining confined within the vagina; grade 2, mobility with straining reaching the introitus; grade 3, mobility with straining beyond the introitus; grade 4, mobility at rest beyond the introitus. While simple, this traditional grading system has been criticized with respect to both its reproducibility and the clinical significance of different grades [4]. In 1995, a standardization document was introduced for the description, quantification, and staging of female pelvic organ prolapse and pelvic floor dysfunction [4]. Briefly, the pelvic organ prolapse-quantitation (POP-Q) system is measured with respect to the hymen as the fixed point of reference. There are six other defined points (two on the anterior vaginal wall, two in the superior vagina, and two on the posterior vaginal wall) (Fig. 1) that are measured with reference to the plane of the hymen. The anatomic position of these six defined points for measurement is centimeters above or proximal to the hymen (negative number)

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Figure 1 Six sites (points Aa, Ba, C, D, Bp, and Ap), genital hiatus (gh), perineal body (PB), and total vaginal length (TVL) used for pelvic organ support quantitation in the POPQ system. (From Ref. 3.)

or centimeters below or distal to the hymen (positive number) with the plane of the hymen being defined as zero. Total vaginal length (TVL) is the greatest depth of the vagina in centimeters when all prolapse is reduced to its fullest extent. Pelvic organ prolapse is then staged on a scale of 0 to 4 based on the lowest extent of protrusion in the standing and straining position. These stages are defined as follows: stage 0, no prolapse demonstrated with all points at ⫺3 cm and the two superior vaginal points at ⫺[TVL-2] cm; stage 1, the most distal portion of the prolapse does not extend beyond ⫺1 cm; stage 2, the most distal portion of the prolapse is greater than ⫺1 cm but less than ⫹1 cm; stage 3, the most distal portion of the prolapse is greater than ⫹1 cm but less than ⫹[TVL-2] cm; stage 4, complete eversion with the most distal portion of the prolapse greater than ⫹[TVL-2] cm. In addition, the POP-Q system considers the descriptive terms such as cystocele, rectocele, enterocele, and urethrocele obsolete since these terms imply an unrealistic certainty as to the structure on the other side of the vaginal bulge, particularly in women who have had previous prolapse surgery [5]. Descriptions are limited to prolapse only with respect to anterior vaginal wall, superior vagina, or posterior vaginal wall. Clearly, a good diagnostic evaluation of the female patient with a thorough physical exam is critical to the proper grading or staging of pelvic floor prolapse. C.

Frequency, Urgency, Nocturia

Women with refractory complaints of daytime urinary frequency and urgency and/or nocturia without incontinence represent a considerable number of pa-

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tients presenting for diagnostic evaluation. Once objective etiologies such as infection, neoplasm, stones, urethral diverticulum, foreign bodies in the bladder, or untreated medical conditions are ruled out, the underlying cause of this condition is often quite elusive. The common denominator seems to be an overactive bladder without neurological dysfunction [6]. There is no simple classification of these disorders. Often, the diagnosis is based on treatment response. Initially, behavior modification is attempted with some combination of fluid management, pelvic floor exercises, timed voiding, and anticholinergic medications. This may be supplemented with biofeedback and/or electrical stimulation to teach the patient to relax the bladder. For the most refractory patients, bladder neuromodulation with sacral nerve stimulation may be warranted. D. Pelvic Pain Closely related to the problems of frequency, urgency, and nocturia is the complaint of pelvic pain. This complex problem has been given many monikers, including “painful bladder syndrome,” “urethral syndrome,” and “interstitial cystitis.” Much has been written regarding possible etiologies for these conditions; however, they continue to remain diagnoses of exclusion. Objective causes of pelvic pain must initially be investigated, including refractory urinary tract infections; sexually transmitted diseases; tumors; stones; neurological disorders; collagen diseases; severe pelvic, vaginal, or lower abdominal trauma; radiation therapy; exposure to toxins; and endometriosis. The typical patient is a young to middle-aged woman with chronic irritative voiding symptoms, sterile and cytologically negative urine, and an unremarkable physical examination. Cystoscopy or slow-fill cystometry are also unremarkable except for worsening bladder pain with filling; the pain is relieved after drainage. Cystoscopic findings of “Hunner’s ulcer,” glomerulations, and bleeding under anesthesia may be present. The cornerstone of this diagnosis is individualized therapy. Since no universal etiology has been discovered, treatment must be patterned to the individual patient response. Treatment options are presented elsewhere in the text. E.

Sexual Dysfunction

Until recently, investigation of the causes and treatment of female sexual dysfunction has lagged far behind that of male dysfunction. In 1998, an international multidisciplinary consensus development conference on female sexual dysfunction was convened to begin to address the shortcomings and problems associated with previous classifications of female sexual dysfunction. The final classification system, published in 2000 [7], followed the same general structure as the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and International Classification of Diseases, 10th Revision (ICD-10), classification systems, but expanded definitions to include physical as well as psychological causes of female sexual dysfunction. Briefly, the consensus system groups female sexual dysfunction into four major categories:

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Sexual desire disorder: Hypoactive sexual desire disorder is the persistent or recurrent deficiency (or absence) of sexual fantasies/thoughts and/or desire for or receptivity to sexual activity, which causes personal distress. Sexual aversion disorder is the persistence or recurrent phobic aversion to and avoidance of sexual contact with a sexual partner, which causes personal distress. Sexual arousal disorder: Persistent or recurrent inability to attain or maintain sufficient sexual excitement, causing personal distress, which may be expressed as a lack of subjective excitement, lack of genital (lubrication/ swelling), or other somatic responses. Sexual orgasmic disorder: Persistent or recurrent difficulty, delay in, or absence of attaining orgasm following sufficient sexual stimulation and arousal, which causes personal distress. Sexual pain disorders: Dyspareunia is the recurrent or persistent genital pain associated with sexual intercourse. Vaginismus is the recurrent or persistent involuntary spasm of the musculature of the outer third of the vagina that interferes with vaginal penetration, which causes personal distress. Noncoital sexual pain disorder is recurrent or persistent genital pain induced by noncoital sexual stimulation. An essential element of the new diagnostic system is the inclusion of a personal distress criterion for most of the diagnostic categories. Currently, there are no validated instruments available for immediate use in clinical assessment specific for sexual distress. A thorough, yet focused, clinical interview is therefore still critical to the proper classification and treatment of female sexual dysfunction. III. DIAGNOSTIC EVALUATION A.

History

The history begins with a detailed description of the patient’s symptoms. This includes information as to the duration, severity, quality, and modifying factors affecting the patient’s complaints. Did the problem develop slowly over months to years? Was there recent worsening of symptoms? Are there any events that precipitated an exacerbation of the complaint, such as childbirth, pelvic trauma, surgery, or onset of menopause? The severity of the symptoms should be subjectively graded. Are incontinence pads used for protection against urinary leakage? How often are they changed? Are slim panty liners adequate or does the leakage require superabsorbant pads? On a subjective scale of 1 to 10, how does she rate the severity of her problem? Have any lifestyle changes been adopted because of the presenting complaint? Identifying the quality of the problem is also important. How often does she urinate during the day? If she has daytime urinary frequency, is it associated with a sense that her bladder is full, or is it associated with keeping the bladder empty to prevent incontinence? Does she leak because she cannot make it to the bathroom in time? Does she leak with activity or abdominal straining? If so, is the leakage associated with only high-impact exercise such as jogging and aerobics or with minimal activity such as walking or rising from a chair? If she leaks with

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stress, is the urine lost only for an instant during the strain, or does the stress lead to a precipitous void? Does she wake up at night to urinate? If so, is she awoken by the urge to urinate, or does she awaken for an unrelated reason and then go to the bathroom out of habit? Are there problems with hesitancy or straining to begin the urinary stream? When voiding is complete, is there a persistent sense that the bladder is full? Does she notice a bulge or fullness in the vagina when she sits? If pain is the complaint, does the act of voiding relieve or exacerbate the symptoms? Finally, asking about modifying factors can prove helpful is considering possible interventions for the complaint. What is the average fluid intake for the patient on a daily basis? Do the symptoms improve with decreased fluid intake? Are the symptoms exacerbated by the nature of the drink, such as coffee, tea, or soda? Does the patient make it a habit to drink just before bedtime? Are there foods that must be avoided to prevent painful bladder symptoms such as spicy foods, citrus fruits or bananas? Does the severity of symptoms vary in relation to the menstrual cycle? Many women find incontinence or pelvic pain exacerbated premenstrually and may be dry or pain free during the early part of their cycle. Specific associated symptoms must also be addressed. Does the patient have any chronic bowel complaints? What measures are necessary, if any, to prevent constipation? Does the patient complain of associated bouts of diarrhea? Does she have chronic lower back pain? Is she seeing a chiropractor currently, or has she ever been treated for a strained back or slipped disk? Are there problems with lower extremity weakness, parasthesias, or numbness? Urologically, are there problems with dysuria, hematuria, or recurrent urinary tract infections? Gynecologically, have there been any changes with her menstrual flow with regard to either heaviness or regularity? Sexually, has there been a change in libido or activity? Are there any associated psychological stressors associated with the onset or recurrence of the chief complaint? B. Past Medical History In addition to reviewing all current and prior medical illnesses, the past medical history should focus on specific conditions that affect pelvic organ and pelvic floor function. Asthma, bronchitis, and chronic obstructive pulmonary disease all can exacerbate the symptoms of stress urinary incontinence. Diabetes, congestive heart failure, and venous insufficiency all can increase urinary output, resulting in frequency, urgency, and nocturia. A history of lower extremity swelling is a sign of excess fluid that can produce specific complaints of nocturia and nighttime incontinence when in the recumbent position. Fibromyalgia, endometriosis, and irritable bowel syndrome all are associated with the pelvic pain syndrome. In addition, hormone status plays an integral part in all pelvic floor and sexual dysfunction and should be specifically investigated. The neurological history is especially important in pelvic floor dysfunction. Closed head injuries, strokes, multiple sclerosis, and Parkinson’s disease all need to be recognized and considered in any assessment of pelvic floor complaints. With a history of urgency incontinence or uncoordinated voiding, additional neurologic symptoms, such as visual disturbances, numbness, tingling, or lack of coordination, should prompt a neurological referral if not already established.

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Lower urinary tract involvement may constitute the sole initial complaint in about 10% of patients eventually diagnosed with multiple sclerosis [8]. Past obstetrical and surgical history is also important. Women commonly have altered pelvic support following even a single vaginal delivery. Based on the POP-Q system described above, studies have shown that a new mother may exhibit stage 2 support with respect to the anterior vaginal wall in the standing, straining position [9]. Many of these women have few or no symptoms; however, 23% of women who have a single, spontaneous vaginal delivery exhibit some level of stress urinary incontinence [9]. Difficulties associated with delivery must also be investigated, including prolonged labor, large birth weight, breech presentation, forceps extraction, or twin gestation. Commonly, these difficulties are not discussed if the patient is queried only about “complications” of delivery. Previous pelvic surgery must also be reviewed. Was the hysterectomy vaginal or abdominal? Was the uterus removed for benign disease or cancer? Was external or interstitial radiation given? Were the ovaries removed? Was antiincontinence surgery performed at the same time? Changes in vesicourethral function can occur after simple hysterectomy [10] and, prior to considering therapeutic options, need to be recognized as an indication of possible denervation. Finally, consideration must be given to extraurethral incontinence from a vesicovaginal or ureterovaginal fistula if the onset of incontinence occurs within days of a hysterectomy or other pelvic surgery. C.

Medications

A complete list of prescription and over-the-counter medication is important. Daytime frequency and urgency are commonly associated with morning diuretics and may be decreased by changing to a lower dose on a twice-a-day basis. Antihypertensive medications such as prazosin or terazosin may precipitate incontinence due to α-blockade effects relaxing the bladder neck. Conversely, over-the-counter cold and flu medications may cause hesitancy or urgency symptoms secondary to α-agonist effects on the bladder neck. Sedative-hypnotic medications can decrease perception of the bladder signals, leading to overflow incontinence, or impair mobility in getting to the bathroom, leading to functional incontinence. Antidepressant medication may contribute to leakage because of its anticholinergic side effects. In addition, the most frequently used medications for uncomplicated depression are the selective serotonin reuptake inhibitors (SSRIs). Women receiving these medications often complain of decreased sexual desire, decreased arousal, decreased genital sensation, and difficulty achieving orgasm. Finally, estrogen status must be reviewed in all postmenopausal patients. Dysfunction of the hypothalamic/pituitary axis, surgical or medical castration, menopause, premature ovarian failure, and chronic birth control use are the most common causes of hormonally based female pelvic floor and sexual dysfunction. D.

Family History

Extensive review of conditions of family members and relatives contributes relatively little to the evaluation of the pelvic floor dysfunction. Some psychosocial and neurological conditions may be passed from one generation to the next, but other causes of dysfunction are usually not familial.

Diagnostic Evaluation of the Female Patient

E.

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Social History

Habits such as chronic alcohol use, tobacco smoking, or illicit drug use may contribute to the presenting complaint. Excessive alcohol commonly produces a diuretic effect and may exacerbate urgency and frequency. Tobacco is a common cause of pulmonary disease and can lead to a chronic cough, resulting in worsening of stress-related incontinence. In addition, frequency and urgency symptoms with a history of tobacco use warrant cystoscopic evaluation for indolent urothelial cancer, especially when hematuria is present. Illicit stimulant drug use can also exacerbate symptoms of an overactive bladder. A patient’s work history may prove very revealing in evaluating the presenting complaint. Teachers and nurses are notorious in postponing micturition. After a career of essentially ignoring normal bladder signals, these women commonly present with complaints of voiding dysfunction and an overactive bladder. Women involved in heavy labor in their occupations may present with urinary incontinence and prolapse at a much younger age due to repetitive abdominal and pelvic strain. Investigation of the patient’s social dynamic is often useful in uncovering problems with sexual dysfunction. In addition to the medical/physiological evaluations, all patients should be evaluated for emotional and relational issues that may be contributing to the problem. This includes the context in which the patient experiences her sexuality, her self-esteem and body image, and her ability to communicate her sexual needs with her partner. This is an integral component of the female sexual function evaluation. F.

Review of Systems

A thorough review of systems is an important part of the diagnostic evaluation of any patient, and this is especially true in the workup of the female patient. Often, this step can be completed with a written questionnaire, but it must be reviewed with specific conditions in mind. Recurrent fevers or weakness may imply undiagnosed urinary tract infections secondary to abnormalities in the urinary tract. Shortness of breath or chest pain may uncover underlying medical conditions that can exacerbate urinary problems. Gastrointestinal complaints may suggest problems with chronic constipation or inflammatory bowel disease. Musculoskeletal problems such as arthritis or back pain may limit a patient’s ability to get to the bathroom, resulting in functional incontinence. Ultimately, a thorough review of systems must be completed. G.

Voiding Diary

The International Continence Society (ICS) has advised that the inclusion of a frequency-volume chart is an essential component of the patient’s clinical assessment [1]. With respect to the overactive bladder, Payne describes the voiding diary as the single most important piece of information in the patient evaluation [6]. The particular information recorded in the diary depends on the patient’s symptoms, but all dairies should include at least the time and amount of the patient’s micturition. From this record alone, information regarding the patient’s total daily urinary output, frequency of daytime and nighttime voids, longest interval be-

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tween voids, largest single void, and diurnal variation can be measured. The maximum voided volume on the diary has a good correlation with cystometric capacity [11]. Furthermore, additional notations about fluid intake, as well as the character, time, and severity of episodes of incontinence can be included. This provides information regarding total daily intake, the amount of caffeine introduced, and the quality and severity of incontinence, if present. This record provides invaluable objective confirmation of the information obtained through simple patient history alone. H.

Pad Tests

Several different types of pad tests have been described [12,13]. Unfortunately, none have met the standards of good reproducibility. Blavias [14] considers the test as “exceedingly useful” but does add the caveat that the results must be kept in perspective with the patient’s symptoms. We do not routinely perform a pad test. I.

Multisymptom Questionnaires

Outcomes research has become increasingly important in the assessment of therapeutic interventions undertaken for a patient’s presenting complaint. The instruments needed for this task must be validated, reproducible, and well-accepted tools to assess the presenting complaint and subsequently measure the efficacy of therapy. For urinary incontinence, the Incontinence Quality of Life (I-QOL) instrument developed by Patrick et al. has proven to be valid, reproducible, and responsive to treatment for urinary incontinence in women [15]. For pelvic prolapse, the POP-Q system described by Bump et al. is an attempt to create a reproducible description of pelvic floor anatomy, as discussed in Sec. II.B [4]. The Brief Index of Sexual Functioning for Women (BISF-W) inventory is a validated, 21item, self-reported inventory of sexual interest, activity, satisfaction, and preference and discriminates among depressed, sexually dysfunctional, and healthy patients [16]. Recently, Rodgers et al. introduced a condition-specific, reliable, validated, and self-administered instrument to evaluate sexual function in women with pelvic organ prolapse or urinary incontinence [17]. Certainly, this does not represent a complete list of instruments available at the present time. In addition, as outcomes research takes on a greater role in the evaluation of therapeutic efficacy, even more instruments will be developed. Further work directed toward the development of these instruments is warranted. J. Physical Examination The effective clinician begins the physical examination on first encountering the patient. Careful observation of the patient’s gait as she enters the office may reveal an underlying neurological abnormality. During the interview, close observation of slurred speech, facial asymmetry, or poor coordination may imply a history of a mild stroke or other neurological condition. The formal physical examination then proceeds after the interview with an abdominal examination, a pelvic exami-

Diagnostic Evaluation of the Female Patient

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nation in the lithotomy and standing positions, a rectal examination, and a screening neurological examination. The abdomen and flanks should be examined for masses, hernias, and a distended bladder. Prior surgical incisions should be questioned if no record exists in the history. A postvoid residual is usually determined at this time using ultrasound after clean voided urine is collected. Some investigators believe that the postvoid residual should be determined by catheterization. Certainly, there are advantages to catheterizing the patient: sterile urine, which is difficult for many women to collect by clean catch alone, can be obtained for microscopic examination or culture; and the catheter can be used to perform “bedside” urodynamics. Bedside urodynamics are performed by attaching a 60-mL catheter-tipped syringe to the end of the catheter and slowly filling the bladder to 150 mL by gravity. The patient is instructed to report her sensations to the examiner without attempting to inhibit micturition. Changes in intravesical pressure are apparent as changes in the level of the fluid meniscus in the syringe and can be estimated in centimeters of water above the symphysis pubis. Any sudden rise in pressure accompanied by an urge to void indicates an involuntary bladder contraction and detrusor instability. If the patient does not have a marked urge to urinate when 150 cc have been given, filling should be stopped, the catheter removed, and the patient assessed for stress urinary incontinence. The patient is asked to cough or bear down with gradually increasing force to determine the ease with which incontinence is produced. If the patient’s complaint of urinary incontinence has not been demonstrated, the examination should be repeated in the standing position. If incontinence still is not demonstrated, further investigation with sophisticated multichannel urodynamics should be considered. The pelvic examination of women deserves further emphasis. The vaginal examination is important first for assessing the degree of estrogenization of the external genitalia and vaginal tissues. Normal vaginal tissues are moist and rugated. Atrophic tissues are dry, thin, and friable. Atrophic or infectious vaginitis is an easily reversible cause of urinary incontinence, urgency, pelvic pain, and sexual dysfunction. Second, support of the vaginal vault is assessed using two separate posterior blades of a standard vaginal speculum independently. One blade is placed posteriorly against the rectum, and the anterior vaginal wall is observed during rest, coughing, and the Valsalva maneuver. The second blade is then introduced against the anterior vaginal wall, and the apex is examined during rest, coughing, and the Valsalva maneuver. Finally, the posterior blade is removed, and the posterior vaginal wall is observed during rest, coughing, and the Valsalva maneuver. In addition, the integrity of the perineal body between the introitus and the anus is evaluated. Of course, other problems such as a mass, pelvic pain, or vaginal bleeding must be assessed with bimanual exam. Finally, assessment of pelvic floor muscle strength should be performed. The initial assessment is done during the pelvic exam and need not be complex: A simple classification of the voluntary levator contraction with two fingers in the vagina as strong, average, weak, or absent suffices. Pelvic floor muscle strength can also be assessed during the rectal examination in much the same way. In addition, rectal examination provides information on resting anal sphincter tone, bulbocavernosus reflex, and the degree of rectocele

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and perineal relaxation. A finger in the rectum can “tent up” a rectocele, but not an enterocele. The remainder of the neurological examination includes assessment of lower extremity reflexes and sensory evaluation of the lower extremities, perineum, and buttocks. K.

Provocative Tests

Specific tests that can be completed during the physical examination warrant further discussion. The stress test was briefly discussed in the description of bedside urodynamics. The bladder is filled with fluid, and the patient is asked to cough or strain while the urethra is observed for urine leak [18]. If a short spurt of urine escapes simultaneous with the cough, this suggests genuine stress urinary incontinence. A slight delay in the leakage associated with a subsequent precipitous emptying of the bladder suggests cough-induced detrusor instability. The test is limited in that incontinence may still exist in spite of negative test results. This is especially true in the presence of cystocele. If the cystocele is not elevated during coughing or straining, the stress test results may be negative despite the presence of incontinence. An additional maneuver that can be added to the stress test is elevation of the bladder neck to observe the disappearance of stress incontinence. The Bonney test involves placing two fingers in the vagina on either side of the urethra to elevate the neck of the bladder toward the pubic bone, taking care not to compress the urethra. Unfortunately, this is extremely difficult to do without compressing the urethra. The Marshall test is a variation of the Bonney test that attempts to eliminate this error. The anterior vaginal wall is anesthetized locally, and the periurethral area is grasped with two clamps and elevated in a fashion that does not compress the urethra. Nevertheless, neither the Bonney nor Marshall test is diagnostic for stress urinary incontinence. Therefore, these tests are of limited value, and we do not routinely perform them. The Q-tip test is designed for gross definition of the degree of urethral hypermobility on straining [19]. With the patient in the supine position, the meatus is cleansed, and a lubricated cotton-tipped applicator is introduced into the bladder per urethra. The applicator is then pulled back until the cotton tip encounters resistance at the urethrovesical junction. Normally, the angle of the applicator is approximately 10°–15° above horizontal at rest. The patient is then asked to strain while a change in the angle of the applicator is observed. A change in the angle of more than 35° indicates weakness in the anatomical support of the urethra and bladder neck. Although this test is very simple, it is highly subjective and nonspecific, with high false-positive rates. A more objective measure of hypermobility can be obtained from a lateral upright voiding cystourethrogram (VCUG), discussed below. It has been our experience that the Q-tip test is very uncomfortable for the patient, and we do not routinely perform the test. L.

Objective Studies

Routine laboratory tests include urinalysis, vaginal wet mount, urine culture, and renal function tests. Cytology, intravenous pyelography, and cystoscopy should be performed for the evaluation of hematuria. Renal ultrasound is useful in cases of individuals with retention or prolapse to assess for obstruction and hydrone-

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phrosis. Pelvic ultrasound can be used in the assessment of pelvic pain to rule out pelvic mass, endometriosis, or uterine abnormalities. In the case of stress urinary incontinence, the voiding cystourethrogram in the upright, straining position is useful to assess severity of incontinence, urethrovesical angle, and degree of cystocele. Recently, dynamic magnetic resonance imaging (MRI) has developed a role in the evaluation and grading of pelvic organ prolapse and pelvic floor relaxation [20]. Sophisticated multichannel urodynamics with synchronous fluoroscopy, pressure-flow, and electromyographic studies offer the most comprehensive, artifact-free means of arriving at a precise diagnosis for pelvic organ and pelvic floor dysfunction. These studies, however, are limited by their cost and availability. When multichannel studies are not performed routinely, they should be considered in the following circumstances: Simpler tests have been inconclusive. Empiric therapy has been ineffective. Incontinence cannot be demonstrated clinically. The patient has previously undergone corrective surgery for incontinence. The patient has previously undergone radical pelvic surgery. The patient has a known or suspected neurological disorder based on history or physical examination. The patient has symptoms of mixed stress and urge incontinence. The patient has evidence of urinary retention with a high postvoid residual. A comprehensive discussion regarding the techniques and interpretation of multichannel studies is beyond the scope of this chapter and is presented in Chapter 6. Cystoscopy is useful in the evaluation of urinary urgency and frequency to rule out any bladder abnormalities, especially in the setting of a significant smoking history and hematuria. In the setting of pelvic pain, cystoscopy under local anesthesia should be performed to assess the relationship of bladder filling to bladder symptoms and to exclude neoplasm, stones, urethral diverticulum, and foreign bodies. Cystoscopy under general anesthesia should be performed as both a diagnostic and therapeutic measure only in those patients who do not tolerate office cystoscopy. Female sexual dysfunction represents a whole new field of investigation. Objective evaluation of the female sexual response is in its infancy and is based on assessing the following parameters [21]: 1. Genital blood flow: Clitoral, labial, urethral, and vaginal peak systolic velocities and end diastolic velocities can be measured using duplex doppler ultrasound. 2. Vaginal lubrication: The pH increases with sexual stimulation above the acidic levels found in the normal vagina and reflects the degree of vaginal lubrication. 3. Vaginal compliance: Pressure-volume changes assess the ability of the vagina to relax and dilate with sexual stimulation. 4. Genital stimulation: Vibration perception thresholds can be measured and recorded pre- and poststimulation.

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Currently, researchers are only now beginning to define ranges of normal for these parameters. Eventually, however, definition of these parameters prior to and following medical therapy may become the standard of care. IV. CONCLUSION The diagnostic evaluation of the female patient begins in the office with a detailed history and physical examination. Through focused interviewing and active listening, the practitioner can commonly identify several categories of complaints. These include, but certainly are not limited to, urinary incontinence; pelvic floor prolapse; frequency, urgency, and nocturia; pelvic pain; and sexual dysfunction. Following accurate diagnosis of the presenting complaint, appropriate studies may then be undertaken. REFERENCES 1. Abrams P, Blavias JG, Stanton SL, Andersen JT. The standardization of terminology of lower urinary tract function. Scand J Urol Nephrol 1988; 114(S):5–19. 2. Blavias JG. Outcome measures for urinary incontinence. Urology 1998; 51(S1A):11– 16. 3. Raz S, Little NA, Juma S. Female urology. In: Walsh PC, Retik AB, Stamey TA, Vaughan ED Jr, eds. Campbell’s Urology. 6th ed. Philadelphia: W. B. Saunders, 1992: 2782–2828. 4. Bump RC, Mattiasson A, Bo K, Brubaker LP, DeLancey JOL, Klarskov P, Shull BL, Smith ARB. The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 1996; 175(1):10–17. 5. Kenton K, Shott S, Brubaker L. Vaginal topography does not correlate well with visceral position in women with pelvic organ prolapse. Int Urogynecol J Pelvic Floor Dysfunct 1997; 8(6):336–339. 6. Payne CK. Epidemiology, pathophysiology, and evaluation of urinary incontinence and overactive bladder. Urology 1998; 51(S2A):3–10. 7. Basson R, Berman J, Brunett A, Derogatis L, Ferguson D, Fourcroy J, Goldstein I, Graziottin A, Heiman J, Laan E, Leiblum S, Padma-Nathan H, Rosen R, Segraves K, Segraves RT, Shadsign R, Sipski M, Wagner G, Whipple B. Report of the international consensus development conference on female sexual dysfunction: definitions and classifications. J Urol 2000; 163(3):888–893. 8. Blavias JG, Kaplan SA. Urologic dysfunction in patients with multiple sclerosis. Semin Neurol 1988; 8(2):159–165. 9. Brubaker L. Female pelvic prolapse: pathophysiology and classification. 22nd Annual Scientific Meeting of the Society for Urodynamics and Female Urology, Anaheim, CA, June 2, 2001. 10. Parys BT, Hadlen BT, Hutton JL, Parsons KF. The effects of simple hysterectomy on vesicourethral function. Br J Urol 1989; 64(6):594–599. 11. Diokno AC, Wells TJ, Brink CA. Comparison of self-reported voided volume with cystometric bladder capacity. J Urol 1987; 137(4):698–700. 12. Lose G, Gammelgaar J, Jorgensen TJ. The one-hour pad-weighing test: reproducibility and the correlation between the test result, start volume in the bladder and the diuresis. Neurourol Urodyn 1986; 5:17–21. 13. Hahn I, Fall M. Objective quantification of stress urinary incontinence: a short, reproducible, provocative pad-test. Neurourol Urodyn 1991; 10:475–479.

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14. Heritz DM, Blaivas JG. Evaluation of urinary tract dysfunction. In: Raz S, ed. Female Urology. 2d ed. Philadelphia: W. B. Saunders, 1996:89–96. 15. Patrick DL, Martin ML, Bushnell DM, Yalcin I, Wagner TH, Buesching DP. Quality of life of women with urinary incontinence: further development of the incontinence quality of life instrument (I-QOL). Urology 1999; 53(1):71–76. 16. Mazer NA, Leiblum SR, Rosen RC. The Brief Index of Sexual Functioning for Women (BISF-W): a new scoring algorithm and comparison of normative and surgically menopausal populations. Menopause 2000; 7(5):350–363. 17. Rogers RG, Kammerer-Doak D, Villarreal A, Coates K, Qualls C. A new instrument to measure sexual function in women with urinary incontinence or pelvic organ prolapse. Am J Obstet Gynecol 2001; 184(4):552–558. 18. Marchetti AA, Marshall VF, Shultis LD. Simple vesicourethral suspension. A survey. Am J Obstet Gynecol 1957; 74:57–63. 19. Crystle CD, Charme LS, Copeland WE. Q-tip test in stress urinary incontinence. Obstet Gynecol 1971; 38(2):313–315. 20. Barbaric ZL, Marumoto AK, Raz S. Magnetic resonance imaging of the perineum and pelvic floor. Top Magn Reson Imaging 2001; 12(2):83–92. 21. Berman JR, Berman LA, Lin H, Marley C, Goldstein I. Female sexual dysfunction: new perspectives on anatomy, physiology, evaluation and treatment. AUA Update Ser 2000; 19(34):266–271.

3 Bladder Physiology and Neurophysiological Evaluation J. THOMAS BENSON Indiana University School of Medicine Indianapolis, Indiana, U.S.A.

The bladder, just as the other pelvic organs, is intimately involved with pelvic floor function. Bladder storage and emptying, rectal storage and emptying, and sexual and reproductive functions all involve reciprocal activities between the viscera and the smooth and skeletal muscles of the pelvic floor. The coordination of these reciprocal activities is conducted by neurophysiological processes involving the central, peripheral (especially sacral), and intrinsic enteric nervous systems. These processes are established by potentiation of reflex pathways that are dynamic and capable of dramatic morphological and physiological changes reflective of neuronal neuroplasticity.

I.

BRAIN AND SUBCORTICAL PATHWAYS

For the brain and subcortical pathways (Fig. 1), positron emission tomography (PET) scanning demonstrates that prefrontal cortical areas, especially the anterior cingulate gyrus and the predominantly right-sided lateral prefrontal cortex, are activated during attempted micturition. The superomedial part of the precentral gyrus is activated with pelvic floor muscle contraction, while the superolateral portion is activated with abdominal wall contraction. In animal studies, removing these areas reduces bladder capacity by removing cortical tonic inhibition; an effect that is eliminated by administration of NMDA/(N-methyl-D-aspartate) glutaminergic receptor antagonist. 27

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Figure 1 Brain and subcortical areas involved in bladder pathways.

Basal ganglia dopamine production produces inhibition of bladder overactivity. Norepinephrine cell bodies are found in noradrenaline lateral tegmental nuclei and in the locus ceruleus. Norepinephrine tonically facilitates continencerelated reflexes. Serotonin cell bodies are in the raphe nuclei, and descending serotonin pathways suppress afferent bladder information, inhibiting the micturition reflex. Stimulation of the anterior hypothalamic region induces bladder contraction via medial pontine center parasympathetic pathway, and stimulation of the posterior hypothalamic region inhibits bladder activity via sympathetic pathways. The periaqueductal gray has strong connections between the lumbosacral cord and pons M region. The pons coordinates the activity of sacral cord parasympathetic neurons (detrusor contraction) and the nucleus of Onuf motoneurons to the sphincters (outlet relaxation) in the M region, also called the pontine micturition center or Barrington’s nucleus. Pelvic floor contraction is controlled by another region of the pons, the L region. II. REFLEX PATHWAYS Reflex pathways can act at a ganglionic level, not involving the spinal cord. Much of the gut activity is controlled by such ganglionic pathways. Bladder activity has some reflex action at the ganglionic level, but is controlled mostly by reflexes that are chiefly spinal reflexes for storage and supraspinal reflexes for voiding. The principal storage reflexes (Fig. 2) are the urethral sphincter storage reflex, which creates tonic sphincter activity that increases with bladder filling, and a direct sacral spinal reflex. The sympathetic reflex pathway depends on sacral afferents from the filling bladder and sacrolumbar intersegmental reflex activation of lumbar sympathetic preganglionic neurons. The sympathetic nerves then cause bladder outlet contraction and parasympathetic ganglionic inhibition by α-receptor activity and detrusor relaxation by β-receptor activity. Micturition reflexes (Fig. 3) include a direct spinal reflex that activates sacral parasympathetic preganglionic neurons, which may act to prolong emptying ac-

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Figure 2 Bladder storage: Sacral motoneurons activate skeletal sphincter; sympathetic postganglionic neurons activate smooth muscle of bladder base via α-adrenergic activity, which also inhibits sacral parasympathetic activity, and sympathetic β activity causes smooth muscle relaxation in bladder. a ⫽ α-adrenergic; B ⫽ β-adrenergic; N ⫽ nicotinic; S ⫽ sacral.

Figure 3 Bladder emptying: Sacral parasympathetic activity leads to detrusor contraction; sacral motoneuron activity to striated sphincter is inhibited; and sympathetic α and β activity are inhibited. Abbreviations as in Figure 2.

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tivity that is initiated by supraspinal reflexes. A “set point” in the pontine micturition center has tonic inhibitory GABA (γ-aminobutyric acid) modulation to stop tonic urethral sphincter electromyographic (EMG) activity, the first urodynamically recordable step in micturition. The parasympathetic efferent outflow to the bladder is activated via the medial pontine center. III. NEUROPHYSIOLOGICAL EVALUATION The pathways governing the functions are composed of excitable membranes. Traveling action potentials are transmitted along the membranes of the nerves and muscle cells. This bioelectrical activity acting in the nerve for transmission of information precedes the function of muscle (i.e., contraction). It is this bioelecTable 1 Localization of Nervous System Lesions with Lower Urinary Tract Sequelae Nervous lesion location

Clinical features

Superior frontal gyrus, suprapontine cortical lesions Paracentral lobule

Hesitancy, retention

Below pons, above the sacral cord

Upper motor neuron signs

Sacral cord (conus medullaris)

Symmetric saddle sensory deficit with dissociation, symmetric motor deficit without atrophy

Cauda equina

Asymmetric saddle sensory loss and motor loss with atrophy

Pelvic plexus

Perineal sensation normal, decreased bladder and rectal sensation

Pudendal nerve

Sensory loss in pudendal distribution, sphincter weakness Retention, history of overdistention

Bladder ganglia

Loss of voluntary postponement of voiding

Urodynamic features Uninhibited, coordinated, detrusor contraction

Electrodiagnostic medicine features

Abnormal bladder-based, pudendal cortical– evoked potentials Abnormal uroflow Loss of suppression of sastudies cral reflexes or sphincter EMG activity Detrusor hyperreflexia Abnormal central conducwith detrusor-sphincter tion with corticaldyssynergia evoked potentials, normal sacral reflexes with loss of suppression Detrusor areflexia, overLoss of sacral reflexes, flow incontinence, posiabnormal pudendal tive bethanechol test, conduction studies and decreased compliance sphincter needle EMG and capacity with efferent loss Abnormal voiding studVariable L5, S1 (lower ies, incontinence limb) studies, variable sacral reflex, pudendal conduction, and sphincter needle EMG Detrusor areflexia, inAbnormal visceral-anal creased compliance sacral reflexes, and capacity with afferabnormal bladderent loss base-evoked potential to cortex, normal clitoral-anal reflex Stress urinary incontiAbnormal pudendal nence, anal incontinerve conduction and nence sphincter needle EMG Detrusor areflexia, posiAbnormal bladder-anal tive bethanechol test reflex, normal urethralanal and clitoral-anal reflexes

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trical activity that makes possible the application of neurophysiological diagnostic methods. The integrity of the neurocontrol of the lower urinary tract is tested by clinical examination and several diagnostic tests, including clinical neurophysiological evaluation. Although general clinical neurophysiology is practiced in every neurology department, evaluation of the sacral component (chiefly S2, S3, and S4) is not widely available. Pelvic clinical neurophysiological evaluation requires additional clinical background knowledge that neurophysiology experts usually do not possess. Hence, uroneurophysiological techniques up to now have been most often applied to research. We are now in an era in which therapeutic manipulation of neuronal activity and neuroplasticity is possible. Nerve growth factors, neurotransmitter- and receptor-affecting agents, ion channel activity manipulators, and electrical stimulation therapies are presently available, and future applications of stem cell and gene therapies are beginning to be imagined. Care of patients with lower urinary tract dysfunction in this new era requires uroneurophysiological enhancement of information gained by clinical and urodynamic evaluation in selected patient groups. This may be accomplished by appropriate training of physicians to perform the neurophysiological tests in accordance with national policies. Interdisciplinary programs among urology, urogynecology, colorectal, and neurology departments to create “pelvic neurophysiology” or “uroneurology” sections are necessary for optimal care. Patients with pelvic disorders who may be well served by clinical neurophysiological testing include those with malformations, trauma, compression, or infiltrative or degenerative lesions involving the sacral nerves or their roots in the cauda equina. Patients with lesions in the spinal cord or supraspinal areas may have involvement of “long routed” reflexes, and combinations of urodynamic and clinical neurophysiological testing are helpful for localization of lesions (Table 1). IV. THE STUDIES Below is a description of electromyographic studies during urodynamics studies, sacral reflexes, evoked potentials, nerve conduction to the sphincters, and needle EMG of pelvic floor muscles. A. Electromyographic Activity as Part of Urodynamic Studies The bladder and bladder outlet must act in coordinated fashion for both storage and emptying. This coordination takes place chiefly in the pontine micturition center. There is continuous activity in the urethral skeletal muscle throughout bladder filling, which ceases as the first recordable event in normally coordinated voiding (Fig. 4). If there is interruption of this pathway, the urethral sphincter relaxation associated with detrusor contraction is lost, and sphincter contraction may occur (Fig. 5). This phenomenon is labeled detrusor-sphincter dyssynergia and is observable if pelvic floor electromyographic activity is recorded while simultaneously recording bladder contraction. With both suprapontine and infrapontine lesions, there may be uninhibited bladder contractions. With suprapontine lesions, the contractions will be coordinated with pelvic floor (sphincter) relaxation

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Figure 4 Urodynamic study: Qura ⫽ urine flow, Pura ⫽ urethral pressure, Pves ⫽ bladder pressure, Pdet ⫽ detrusor pressure (bladder pressure minus abdominal pressure), EMGave ⫽ surface-recorded electromyographic activity. The pelvic floor EMG activity stops at initiation of urine flow and remains suppressed during the flow.

because the pontine-to-sacral pathway is intact. With lesions below the pons and above the sacral micturition center (spinal lesions), the coordination is lost. Lesions involving the sacral cord (conus medullaris) or the cauda equina generally result in an areflexic bladder and lower motor neuron effects in the urethral skeletal muscle. Denervation of the smooth muscle of the bladder results in denervation hypersensitivity, which may be tested by cystometrically measuring the bladder’s exaggerated response to administration of bethanechol. Thus, combining urody-

Figure 5 Urodynamic study: abbreviations as in Figure 4. The pelvic floor EMG activity is activated during urine flow. Note fluctuating bladder pressures and irregular urine flow.

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Figure 6 Ring electrodes on a foley catheter. namic and pelvic floor electromyographic data is helpful in localizing central nervous system lesions associated with lower urinary tract dysfunction. Catheter-mounted ring electrodes are available mounted on a cylinder. The cylinder fits onto a Foley catheter (Fig. 6). This electrode can be used as a recording electrode to record activity during urodynamic study, to record potentials with a pudendal nerve conduction study, or can be used for stimulating when studying sacral reflexes or cortical evoked potentials. B. Sacral Reflexes The sacral reflexes are pelvic floor muscle contractions that occur in response to stimulation of a pelvic structure. Described are the urethral-anal reflex, the bladder-anal reflex, and the clitoral-anal reflex. When stimulating in the urethra or the bladder, the afferent limb of the reflex traverses the visceral fibers associated with the parasympathetic and sympathetic nerves to the sacral and thoracolumbar portion of the spinal cord, respectively. The efferent limb traverses the pudendal course, circumventing the central pelvis. When stimulating the paraclitoral regions, the afferent limb traverses pudendal pathways. All the reflexes traverse the cauda equina. Hence, abnormalities may localize lesions to the bladder wall afferents (e.g., abnormal bladder-anal reflex with the other two reflexes normal, as seen in overdistention injuries), the urethral wall afferents (abnormal urethralanal reflex with the other two reflexes normal, as seen in repeated urethral surgeries), the pelvic plexus (abnormal urethral-anal and bladder-anal reflexes with normal clitoral-anal reflex, as seen after radical pelvic surgery or radiation), or cauda equina with variable effects or pudendal injuries (e.g., from prolapse) with effect on all reflexes since the common effect pathway for all the reflexes is involved.

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Figure 7 Urethral-anal reflex: stimulus site in the urethra. Superimposed responses are (left) external anal sphincter (A1, 2, 3, 4) and (right) anal sphincter (B5, B6, B7, B8). Latency marker placed at 70.6 ms for left recording and at 72.6 ms for right recording. MA ⫽ milliamperes (stimulation level); Dur ⫽ pulse duration of stimulus; ISI ⫽ interstimulus interval (paired stimulus used). 1. Urethral-Anal Reflex The urethral-anal reflex (Fig. 7) test was reported by Bradley [1] and involves stimulating with ever-increasing amounts of current until the patient perceives the stimulus (stimulus threshold). At three to four times the stimulus threshold, stimulations are performed to obtain responses bilaterally at the external anal sphincter. The responses are recorded with surface or needle electrodes placed adjacent to or into the external anal sphincter. This reflex can be voluntarily suppressed when the patient actively tries to void, with such suppression being an evaluation of upper motor neuron function. The urethral-anal reflex has been found to be predictive of clinical response to sacral neuromodulation therapy [2]. 2. Bladder-Anal Reflex The bladder-anal reflex is performed similar to the urethral-anal reflex, with a foley catheter containing the stimulating electrodes that are placed in the bladder. Contact of the electrodes to the bladder wall is checked by measuring the impedence. 3. Clitoral-Anal Reflex The stimulation for the clitoral-anal reflex (Fig. 8) is performed using surface (prong) electrodes paraclitorally, first stimulating the patient’s left side and re-

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Figure 8 Clitoral-anal reflex: stimulus site at right paraclitoral area. Recording and abbreviations as in Figure 7. Note prolonged response to left anal sphincter. This patient had a left pudendal neuropathy.

cording both left and right anal sphincter areas, then stimulating the right side and recording both anal sphincter areas. This somatic pathway involves larger nerves than the visceral afferent pathways in the visceral-anal reflex studies and possibly involves fewer synapses. Therefore, the latency of this reflex is shorter. C. Somatosensory-Evoked Potentials Somatosensory-evoked potential studies are obtained with stimulation of a sensory nerve or the sensory component of a mixed nerve in the periphery of the body and recording the resulting potential changes over the central nervous system. Pathways studied are chiefly the posterior columns of the spinal cord. Standard stimulation is done in the lower limb over the tibial nerve, posterior to the medial malleolus, and recording may be performed over the lumbar region of the spinal cord, where the cauda equina becomes the cord near the first lumbar area, and over the cerebral cortex. The cortical recording is made with one electrode placed over the upper midforehead (Fp) and another electrode 1 cm posterior to a point halfway between the nasion and inion (CZ1). Disease processes that cause demyelination can affect the latency of the responses, and processes that cause blockade can diminish the responses. Similar responses may be obtained with stimulation of the pudendal nerve (Fig. 9), allowing assessment of the sensory genital pathway. Bladder afferent stimulation produces cortical responses also at much longer latencies since visceral afferent nerves are very small and conduct slowly. All somatosensory responses are very small and must be obtained by computer averaging.

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Figure 9 Pudendal somatosensory-evoked potential: stimulating at the pudendal nerve adjacent to the clitoris and recording at the cortex. A1 was first tested with averaging of 300 responses (N) and stimulating with 41.6 mamp. A3 is the test repeated averaging 301 responses, with 41.6-mamp stimulation, and showing replication of the first test. B5 is the control study using 0 mamp stimulation and showing lack of response. ms ⫽ milliseconds (sweep speed of trace); µV ⫽ microvolts (sensitivity of recording trace).

The clinical application of pudendal somatosensory-evoked potentials is primarily the investigation of suspected spinal cord pathologic processes relating to pelvic floor disorders of disturbed lower urinary tract, colorectal, or sexual response functions. Such a spinal cord relationship occurs with many different pathophysiological processes, the most common in ambulatory women being multiple sclerosis. Visual-, auditory-, and somatosensory-evoked potentials are sensitive studies early in the course of multiple sclerosis, and pudendal-evoked responses are frequently performed when detrusor-sphincter dyssynergia is found on urodynamic studies. Abnormalities in these studies are usually, but not invariably, associated with clinical findings such as loss of toe position sense.

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Measuring the clitoral-anal reflex and the pudendal-evoked potential allows examination of both segmental and suprasegmental neural pathways to the sacral cord. The clinical application of the bladder-evoked potential is the measurement of bladder afferent activity. At present, the presence or absence of the response is the only measurement used as latencies and amplitude are not well standardized due to the technical difficulties in obtaining the response. The presence of the response effectively rules out an afferent spinal disorder contributing to a clinical “neurogenic” bladder. D. Sphincter Nerve Conduction Studies Conduction studies of the pudendal nerve have become clinically feasible with the development of the St. Marks pudendal electrode (Fig. 10). Developed by Kiff and Swash [3] to study patients with fecal incontinence at St. Marks Hospital in London, the electrode consists of a stimulating cathode and anode and two record-

Figure 10 The St. Marks pudendal electrode: the disposable electrode is taped to a glove. The stimulating cathode and anode are located at the fingertip, and the recording electrodes are at the base of the examiner’s finger.

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ing electrodes. The electrodes are on a disposable adhesive sheet that can be applied to an examining glove so that the cathode and anode are located at the index fingertip, and the recording electrodes are at the base of the index finger. It is designed to be used rectally, with the examiner’s index fingertip stimulating the pudendal nerve at the area of the ischial spine and the recording electrodes at the base of the examiner’s finger recording the compound muscle action potential at the external anal sphincter. The latencies obtained with this study have good reproducibility, but the amplitudes have significant interexaminer variability, varying with examiner finger size. Therefore, we prefer using surface electrodes, applied as described for the sacral reflexes, to obtain the external anal sphincter response. With this methodology, the stimulation may be applied transvaginally rather than transrectally, a situation that is much more comfortable for most patients. Using two-channel recording, the responses at the external anal sphincter and the response of the perineal branch of the pudendal nerve that supplies the urethra can be simultaneously recorded using the foley catheter–mounted ring electrodes (Fig. 11). Clinical application of pudendal nerve conduction studies has increased since the latencies were first found to be prolonged in patients with idiopathic rectal and urinary incontinence [4]. It has been shown that, in most cases, stress

Figure 11 Pudendal nerve conduction study: the stimulation is at the pudendal nerve near the ischial spine, with A1 and B2 stimulating the patient’s right side and A3 and B4 the left side. The A1 recording is at the external anal sphincter with right-side stimulation. The B2 recording is at the urethra (the perineal branch of the pudendal nerve) with rightside stimulation. A3 is anal sphincter, and B4 is urethral recording with left pudendal stimulation. Hz ⫽ hertz; mA ⫽ milliamperes of stimulation; Dur ⫽ pulse width in milliseconds.

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Figure 12 Positive wave and fibrillation potential. µV ⫽ microvolt (sensitivity of recording); ms ⫽ milliseconds (sweep speed of recording).

incontinence of urine in women is associated with childbirth pelvic floor neuropathy [5]. Increases in pudendal terminal motor latency occurs in the majority of women in the first few days following vaginal delivery, resolving in about two thirds of the parturients in 2 months. Those without resolution have persistence of pudendal neuropathy that can become worse with time and with repeated vaginal delivery [6]. E.

Needle Electromyography of the Sphincters

The type of muscle EMG study performed with urodynamics is kinesthiological; surface or wire recordings give information on relatively large areas of muscle activity, and this can be related temporally to events such as bladder contraction. Needle EMG gives different types of information. Muscle tissue can be identified by yielding distinctive “insertional” type activity. Hence, one can recognize if muscle is present or replaced by fibrosis or the like. In the absence of innervation, muscle fibers have increased receptivity to ubiquitous neurotransmitters and develop abnormal spontaneous activity, referred to as fibrillations or “positive waves” (Fig. 12), which can be recognized with the needle examination. Other types of abnormal spontaneous activities due to varying pathophysiological processes may also be identified. The needle examination also allows description of the motor unit action potentials and the way in which they are recruited when muscular effort is made. The recruitment processes are different in neuropathic conditions and myopathic situations. Knowledge of the structure and function of the motor unit is fundamental to understanding the application of needle EMG studies. The motor unit is composed of the motor neuron (in the anterior gray spinal cord), its axon, the axonal branches, and all the muscle fibers innervated by that axon and its branches. The muscle fibers belonging to an individual motor unit are dispersed and are not adjacent to one another. In processes of denervation, reinnervation may occur, which changes the dispersed nature of the motor unit. Completely denervated muscle may be reinnervated by axonal regrowth from the proximal nerve stump, with a few muscle fibers constituting “nascent” motor units. In partially denervated muscle, collateral reinnervation takes place. Surviving motor axons will sprout and grow to reinnervate those muscle fibers that have lost their nerve supply. This results in a change in the arrangement of muscle fibers within the unit. These structural changes lead to changes in the amplitudes, durations, phases,

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Figure 13

Benson

Motor unit action potential: morphological considerations depicted.

and stability of the motor unit potentials (Fig. 13). Whereas in healthy muscle it is unusual for two adjacent muscle fibers to be part of the same motor unit, following reinnervation, several muscle fibers, all belonging to the same motor unit, come to be adjacent to one another. Needle EMG gives information on the morphology and stability of the motor unit, enabling one to recognize reinnervation processes and even to gain insight into the stability of the process. Thus, the ongoing activity of the process is identifiable, allowing prognostic information to be obtained frequently. The contraction properties of a motor unit depend on the nature of its constituent muscle fibers. Muscle fibers can be classified according to their twitch tension, speed of contraction, and histochemical staining properties. Although there is some regional variation, the pelvic floor muscles and sphincters consist predominantly of type 1 muscle fibers [7]. The fatigue-resistant type 1 fibers constitute motor units, which conceivably fire for prolonged periods of time at lower firing frequencies (see below). Sphincter muscle differs from other skeletal muscle in many respects. The anterior horn cells in Onuf’s nucleus, which supply the sphincters, differ from other anterior horn cells in morphology and physiology. They are smaller, have a rich content of norepinephrine and serutonin receptors, and are relatively resistant to diseases that affect anterior horn cells, such as polio and amyotrophic lateral sclerosis. The muscle fibers of the sphincters are smaller and have a higher content of type 1 muscle, aerobic, and suited to sustained activity. The urethral sphincter is in fact completely composed of type 1 fiber. The sphincters fire continuously at all times, even during sleep, and are quiet only at the onset of micturition or defecation. The other muscles of the pelvic floor levator group, the pubococcygeus and the puborectalis, also fire tonically. The superficial muscles (e.g., the bulbocavernosus) frequently do not have continuous tonic activity.

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In conjunction with a pudendal nerve conduction study, concentric needle EMG of the external anal sphincter offers clinical adjunctive evidence of lower motor neuron disease with respect to localization, extent, temporal duration, activity, and prognosis of the pathophysiological process. Upper motor neuron processes can also be assessed by determining the patient’s ability to activate and depress the tonic sphincter activity. Needle EMG “mapping” of the external anal sphincter has been used to assist the surgeon in knowing where skeletal muscle is located so the sites of sphincter rupture can be better repaired. This technique now, however, has been largely replaced by anal ultrasound. Selection of puborectalis muscle for use in the sphincter repair can be aided by needle EMG evidence of healthier status of puborectalis compared to external anal sphincter muscle. Significant changes in motor unit potential morphology occur in pelvic floor muscle following labor and vaginal delivery. The neurological insult may persist and increase with time and with subsequent deliveries or with straining at defecation. The amount of damage to the urethra, measurable by electrodiagnostic medicine consultation, is directly related to the extent of stress urinary incontinence. Needle EMG studies of the urethral sphincter augment urodynamic information by assessing extent, activity, temporal duration, and prognosis of the pathological process. F.

“Supersensitivity” Testing

Whereas the main consequence of denervation in striated muscle is paralysis and atrophy, smooth muscle responds to postganglionic denervation with denervation “supersensitivity” [8]. This process is an exaggerated response to the specific neurotransmitter due in part to upregulation of postjunctional receptors. Testing is performed by injection of bethanechol chloride (Urecholine, 5 mg subcutaneously) after baseline cystometry, followed by rapid gas cystometric studies at 5-min intervals. A positive test is indicated by a rise in intravesical pressure more than 15 cm H 2 O. V.

SUMMARY

Female pelvic floor disorders are intimately associated with neuropathic processes. Electrodiagnostic medicine consultation augments the physical and manometric examination of patients with such disorders by adding evaluation parameters for the neuropathic processes. These evaluation parameters include localization (see Table 1), determination of extent, temporal duration, activity, and prognosis of the process. Patients particularly helped by electrophysiological testing include those being evaluated for anal sphincter repair; those with voiding disorders, detrusor-sphincter dyssynergia, overflow incontinence, stress incontinence (especially when intrinsic sphincter deficiency is suspected), spinal myelopathies, peripheral or autonomic neuropathies; diabetic patients with bladder or bowel symptoms; those with pelvic floor trauma from childbirth or other sacral injuries; and patients with unexplained perineal numbness or pain or with failure of diagnosis on standard evaluations for bladder or rectal dysfunction. The pelvic clinical neurophysiological studies have not been widely used clinically and lack controlled data leading to international standardization. Con-

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tinued research is expected to lead to greater clinical application and increased understanding of the pathophysiology of female pelvic floor disorders. REFERENCES 1. Bradley WE. Detrusor and urethral electromyelography. J Urol 1972; 108:563–564. 2. Mastropietro M, Fuller E, Benson JT. Electrodiagnostic predictors of outcome with sacral test stimulation. American Urogynecological Association Annual Meeting, Hilton Head, NC, October 28, 2000. 3. Kiff ES, Swash M. Normal proximal and delayed distal conduction in the pudendal nerves of patients with idiopathic (neurogenic) faecal incontinence. J Neurol Neurosurg Psychiatry 1984; 47:820–823. 4. Snooks SJ, Swash M. Abnormalities of the innervation of the urethral striated sphincter musculature in incontinence. Br J Urol 1984; 56:401–405. 5. Allen RE, Hosker GL, Smit ARB, Warrell DW. Pelvic floor damage and childbirth: a neurophysiological study. Br J Obstet Gynaecol 1990; 97:770–779. 6. Snooks SJ, Swash M, Mathers SE, Henry MM. Effect of vaginal delivery on the pelvic floor: a five year follow-up. Br J Surg 1990; 77:1359–1360. 7. Hale DS, Benson JT, Brubaker L, Heidkamp MC, Russell B. Histologic analysis of needle biopsy of urethral sphincter from women with normal and stress incontinence with comparison of electromyographic findings. Am J Obstet Gynecol 1999; 180:342b. 8. Cannon WB. A law of denervation. Am J Med Sci 1959; 198:737.

4 Diagnosis and Assessment of Female Voiding Function J. THOMAS BENSON Indiana University School of Medicine Indianapolis, Indiana, U.S.A.

Therapy of female voiding dysfunction is dependent on understanding the pathophysiological process underlying the specific problem. This is not always possible as our methodologies of assessing the dysfunctions are not comprehensive enough to discern the discordant activity in every patient. In general, the etiologies of the dysfunctions will fall into three categories: neuropathic, mechanically obstructive, and idiopathic.

I.

NEUROPATHIC PROCESSES RELATED TO VOIDING DYSFUNCTION

Neuropathic processes that affect the voiding phase of lower urinary tract activity do so by disturbing the micturition reflexes (Chap. 3). Since these reflexes are both spinal and supraspinal, the underlying process may involve the central or the peripheral nervous system. Therapy of the voiding dysfunction is secondary to localizing, diagnosing, and treating, when possible, the underlying process. Cortical and subcortical involvements are characterized by uninhibited, coordinated detrusor and urethral activity with less effect on disturbance of voiding abilities. Disturbances in the paracentral cortical areas may result in loss of sphincter inhibition with the resulting clinical symptom of hesitancy. Subpontine, suprasacral processes, by affecting the long-loop micturition reflexes, lead to voiding disturbance with loss of detrusor-urethral coordination. Some spinal cord disorders capable of such disturbance are given in Table 1. The 43

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Table 1 Causes of Myelopathy Congenital or developmental: dysraphism (neural tube defects), craniocervical junction abnormalities, syringomyelia, cervical spinal stenosis Degenerative: spondylosis, spinocerebellar degeneration, hereditary spastic paraplegia Demyelinating: multiple sclerosis Infectious: poliomyelitis, bacterial, syphilis, tuberculosis, fungus, trichinosis, viral, herpes, HIV, cytomegalovirus Inflammatory: postvaccination, arachnoiditis, sarcoidosis, lupus erythematosus Metabolic: B12 deficiency, pellagra, chronic liver disease Trauma: vertebral subluxation or fracture, transection, hemorrhage, contusion Toxic: ethanol, arsenic, intrathecal contrast or chemotherapy Vascular: arterial or venous infarction, hemorrhage, vascular malformations, vasculitides, aneurysm, radiation

loss of detrusor-urethral coordination should be qualified by stating the location and type of the urethral muscles (striated or smooth) involved. If the type is periurethral skeletal muscle, the term detrusor-sphincter-dyssynergia may be employed in the presence of neurological features. This diagnosis is questionable if neurological (upper motor neuron) features are not present. Detrusor contraction in association with demonstrated failure of urethrovesical junction opening is termed detrusor-bladder neck dyssynergia. Overactivity of the urethral sphincter in the absence of detrusor contraction during voiding is termed dysfunctional voiding, a diagnosis implying absence of neurological features. Processes involving sacral outflow (Table 2), such as conus medullaris or cauda equina disturbances, may lead to profound voiding dysfunction. The dysfunction may be characterized by detrusor underactivity (detrusor contraction during voiding that has inadequate magnitude and/or duration to effect bladder emptying) or detrusor acontractility (no demonstration of detrusor contraction during voiding study). Detrusor acontractility due to an abnormality of nervous control is termed detrusor areflexia. With detrusor areflexia secondary to loss of sacral nerve supply, the detrusor muscle is described as decentralized, a term prefTable 2 Causes of Sacral Nerve Outflow Dysfunction Conus medullaris lesions: ankylosing spondylitis, ependymomas, lipomas, dermoid cysts, transverse myelitis, arteriovenous malformations, congenital meningomyelocele with cord tethering, prolonged aortic clamping with abdominal aortic aneurysm surgery Cauda equina lesions: central disk protrusions, congenital caudal aplasia, congenital and acquired spinal stenosis (pseudoclaudication syndrome), ankylosing spondylitis, schwannomas, primary and metastatic malignancies, lymphomas, meningiomas, neurofibromas, chordomas, AIDS, cytomegalovirus, distal aortic occlusive disease, arachnoiditis Lumbosacral and pelvic plexopathy: malignancies (cervical, rectal, lymphoma), hematomas, radiation damage Polyneuropathy: Autonomic neuropathy: diabetes, amyloidosis, porphyria, acute inflammatory demyelinating polyradiculoneuropathy, Shy-Drager syndrome, vincristine, thallium, perhexiline Sensory neuronopathy: cis-platinum, metronidazole, nitrofuradantin, pyridoxine toxicity, paraneoplastic

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erable to “denervated” as postganglionic neurons supplying the bladder are still present. II. MECHANICALLY OBSTRUCTIVE PROCESSES RELATED TO VOIDING DYSFUNCTION Mechanically obstructive processes leading to voiding disturbance in the female are certainly less common than in men, but the actual incidence is unknown and probably is underestimated. There are no standard definitions for the diagnosis of bladder outlet obstruction, which further complicates the issues of prevalence and incidence. Groutz et al. [1], using the definition of a persistent, low, maximum “free” flow rate of less than 12 mL/s in repeated noninvasive uroflow studies combined with high detrusor pressure at maximum flow (⬎20 cm H 2 O) during instrumented flow studies, diagnosed bladder outlet obstruction in 6.5% of their female patients. Detrusor-sphincter dyssynergia was present in 5%, and detrusor–bladder neck dyssynergia and dysfunctional voiding comprised 13%. The remaining obstructive processes were secondary to previous anti-incontinence surgery, the leading cause of female voiding dysfunction in most reported series. Genital prolapse is the next most common cause of mechanical outlet obstruction in the female and can be associated with life-threatening ureteral obstruction. Urethral stricture is certainly less common in the female than the male and was present in 13% of the patients in Groutz’s series. The micturition symptoms relevant to the obstructive processes were found to be nonspecific. Therapy of the mechanically obstructive processes is removing the obstruction. Transvaginal or transabdominal urethrolysis for obstruction related to antiincontinence procedures, surgical or pessary therapies for prolapse, and surgical therapies of stricture are considerations that require individualization and careful analysis. III. IDIOPATHIC FEMALE VOIDING DYSFUNCTION Idiopathic urinary retention is not uncommon and is usually seen in younger women. In the absence of physical obstruction, the retention is due to failure of detrusor contraction, urethral relaxation, or both. Fowler et al. [2] described a syndrome of finding complex repetitive discharges, a phenomenon that sounds like a race car or motorbike on the audio amplifier of the electromyography (EMG) machine, on needle EMG examination of the urethral sphincter in young women with idiopathic urinary retention. Many of these women also had polycystic ovaries. The hypothesis was that hormonal imbalance may affect the sphincter muscle membrane, leading to the complex repetitive discharges, and that this urethral skeletal muscle activity may be the cause of the detrusor acontractility and subsequent retention. Other centers have corroborated the findings of the EMG abnormality and voiding disturbances [3]. However, we have also found complex repetitive discharges in the urethral sphincter of about 10% of normal control subjects with no voiding disturbances. Treatment for nonobstructive urinary retention has been markedly improved with the recently U.S. Food and Drug Administration approved sacral

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neuromodulation therapy. In a multicenter study, 38 patients with retention who were implanted with sacral nerve stimulators had a 77% successful outcome, defined as over 50% reduction in urine volume obtained by self-catheterization. Of the patients, 61% had zero catheterizations after being implanted [4]. IV. EVALUATION OF VOIDING FUNCTION History and physical examination, supplemented frequently by urethrocystoscopic study, is necessary for clinical decisions in patients with voiding dysfunctions. The chief adjuncts at our disposal today for such evaluations are the uroflow study and the instrumented voiding study, with or without visualization (videourodynamics). Unfortunately, there are limitations to these evaluations. A very common clinical scenario involves a patient with retention following an anti-incontinence procedure who presents the treating physician with the decision of whether the patient is obstructed. The decision may be assisted by the voiding studies, but frequently the patient cannot void. A possible solution to this dilemma was suggested when Elbadawi et al. published reports of electron microscopic studies of bladder biopsies that yielded a distinctive myohypertrophy structural pattern correlating with urodynamically diagnosed outlet obstruction [5]. However, in a clinical trial to test the usefulness of bladder biopsy for diagnosing voiding dysfunctions, such correlation with urodynamic diagnoses could not be obtained [6]. The first recordable event in normal voiding is the cessation of the tonic electromyographic activity in the skeletal urethral sphincter. Immediately following is relaxation of smooth muscle in the urethra and resultant lowering of urethral pressure, followed in 2–3 s with elevation of bladder pressure secondary to contraction of the detrusor muscle. The elevated bladder pressure is dissipated as urine flow ensues. The pressure recorded at the onset of flow is the “opening” bladder pressure. Normally, the temporal duration of the detrusor contraction and the urethral relaxation will be adequate to effect bladder emptying.

Figure 1 A continuous urine flow recording with nomenclature recommended by the ICS. (From the ICS.)

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A. Uroflometry For uroflometry, (Fig. 1), measurement of the urine flow may be described in terms of rate and pattern, recorded by having the patient void into a special commode that funnels the urine into a device that measures the volume voided over time. The nomenclature recommended by the International Continence Society (ICS) [7] includes the volume voided, the voiding time, the flow time, the maximum flow rate, the average flow rate, and the time to maximum flow. The patient environment and position, method of bladder fill, and the type of filling medium are to be specified. The voiding time is the total duration of micturition and is synonymous with the flow time if there is a continuous flow. If the flow is intermittent, the time intervals between the flows are disregarded in determination of the flow time, but are included in determination of the voiding time. Normal urine flow rates are related to the volume voided and are not significantly influenced by parity, age, or weight. There is general clinical agreement that “abnormal” values in a study with less than 200 cc volume are not to be

Figure 2 A pressure-flow recording of micturition with nomenclature recommended by the ICS. A fifth channel containing surface-recorded EMG activity is generally added to evaluate simultaneous pelvic floor skeletal muscle activity during the void. (From the ICS.)

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considered for interpretation. Flow times of less than 20 s with maximum flow rates over 20 mL/s, average flow rates over 10 mL/s, and with smooth, continuous flow patterns are considered “normal,” although precise definitions are not agreed upon uniformly. B.

Instrumented Voiding Study

The specifications for the instrumented voiding study (bladder pressure measurements during micturition) (Fig. 2) are the fluid medium, access (transurethral or percutaneous); temperature of fluid; patient position; filling method and rate; number, size, and type of catheters; and the measuring equipment. The opening time is the time from the initial rise in detrusor pressure to the onset of flow (initial isovolumetric contraction period of micturition). The pressure parameters are for the intravesical, the abdominal, and the detrusor pressures and include the premicturition pressure (before the initial isovolumetric contraction), the opening pressure (pressure at onset of flow), the maximum pressure (maximum value of recorded pressure), the pressure at maximum flow (recorded pressure at maximum flow rate), and the contraction pressure at maximum flow (difference between pressure at maximum flow and premicturition pressure). The term urethral resistance factor, a ratio of the pressure and flow rate, is no longer used as it refers to a rigid tube concept. However, graphs may be applied (Fig. 3) to postulate obstructed, equivocal, and unobstructed parameters. Measurements of urethral pressures during voiding, with or without visualization of urethral flow with fluoroscopy and/or ultrasound (videourodynamics), are becoming more developed, but need wider usage and technical advances before standardization. Residual urine determination, the measurement of urine remaining in the bladder after a voluntary void, is an indirect measurement of bladder contractility.

Figure 3 Example of commercially available graph to denote data areas suggesting obstruction, nonobstruction, or equivocal findings with instrumented voiding study.

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The absence of residual urine is clinically significant, whereas the presence may be caused by many conditions, including voiding in a “laboratory” situation, and requires repetition for confirmation. Residual urine less than 50 cc is probably considered normal by most physicians. The residual urine may be determined by catheterization or by noninvasive ultrasound methodologies. Cystourethroscopy remains an important adjunct in evaluation of female voiding disorders. Many obstructive disorders have a concomitant irritative component. With skilled observation, the significance of either or both may be better evaluated. REFERENCES 1. Groutz A, Blaivas JG, Chaikin DC. Bladder outlet obstruction in women: definition and characteristics. Neurourol Urodyn 2000; 19:213–220. 2. Fowler CJ, Christmas TJ, Chapple CR. Abnormal electromyographic activity of the urethral sphincter, voiding dysfunction and polycystic ovaries: a new syndrome? Br Med J 1988; 297:1436–1438. 3. Jensen D, Stein R. The importance of complex repetitive discharges in the striated female urethral sphincter and male bulbocavernosus muscle. Scan J Urol Nephrol Suppl 1996; 179:69–73. 4. Siegel SW, Catanzaro F, Dijkema HE, Elhilali MM, Fowler CJ, Gajewski JB, Hassouna MM, Jankwegt RA, Jonas V, Vankerrebroeck PE, Lucklama a Nijeholt AA, Oleson KA, Schmidt RA. Long term results of a multicenter study on sacral nerve stimulation for treatment of urinary urge incontinence, urgency-frequency, and retention. Urology 2000; 56(suppl 1):87–91. 5. Elbadwi A, Yalla SC, Resnick NM. Structural basis of geriatric voiding dysfunction. IV. Bladder outlet obstruction. J Urol 1993; 150:1681–1695. 6. Mastropietro M, Geary W, Fuller E, Benson JT. Detrusor biopsy as a potential clinical tool. Int J Urogynecol 2001; 12:355–360. 7. Abrams P, Blaivas JG, Stanton S, Andersen JT. The standardization of terminology of lower urinary tract function. Scand J Urol Nephrol Suppl 1988; 114:5–19.

5 Radiological Evaluation HUY Q. TRAN, VAMSIDHAR R. NARRA, and CARY LYNN SIEGEL Mallinckrodt Institute of Radiology Washington University School of Medicine St. Louis, Missouri, U.S.A.

I.

INTRODUCTION

The radiological evaluation of the female pelvic floor disorders includes many examinations and multiple imaging modalities, including conventional radiography, ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI). Within each modality are different examinations, ranging from general screening studies to specific examinations optimized to address a particular clinical question. There is no single ideal radiological examination capable of addressing the many issues related to the female pelvis. Assessment of a patient with pelvic-related complaints should begin with a thorough history and physical examination. This provides not only a basis for possible etiologies, but also is essential in guiding the radiological evaluation. In some cases, the radiological workup may not resolve a clinical question, but when combined with other diagnostic tests such as neuromuscular testing, manometry, endoscopy, and the like, the combination may provide valuable insight into the patient’s underlying pathology, possible therapy, and prognosis. This chapter focuses on the imaging examinations utilized with the most common female pelvic floor pathologies: (1) stress incontinence, (2) urethral diverticulum, (3) urinary fistulas, and (4) pelvic floor relaxation. With each disease entity, the technique and imaging findings are reviewed.

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II. STRESS INCONTINENCE AND VOIDING DYSFUNCTION A.

Conventional Radiography

Conventional radiographic techniques include the cystogram and voiding cystourethrogram (VCUG). These are utilized in the evaluation of stress urinary incontinence. These imaging tests provide the basic anatomy of the bladder and urethra and show urethral movement. The low cost, wide availability, and general familiarity with these techniques are their major advantages. Cystography and VCUG do have disadvantages: they require catheterization, and the images contain no information about the pelvic musculature and adjacent soft tissue structures. Only structures in direct contact with the urethral and bladder lumen opacify with contrast. 1. Voiding Cystourethrography For the VCUG, a catheter is placed in the bladder, and contrast material (20–30% weight/volume) is instilled into the bladder. Fluoroscopy is used to record the bladder emptying and the appearance of the female urethra in the anteroposterior view. The bladder base is normally at or cephalad to the superior margin of the pubic symphysis. A cystocele is when a significant portion of the bladder lies below the symphysis pubis. The posterior urethrovesical (PUV) angle is normally less than 100°. When this angle increases beyond 100°, it results in stress incontinence from posterior and inferior rotation of the posterior bladder wall [1]. The bladder neck is usually closed. An open bladder neck or bladder neck descent has also been associated with stress incontinence. If the bladder neck descends outside the pelvic cavity, increased intravesical pressure may be transmitted to the urethra, resulting in urine leakage. However, these criteria have been questioned as being diagnostic for stress urinary incontinence given the large degree of overlap among continent women, incontinent women, and women with prolapse [2,3]. Cystograms can be used to identify vesicalization of the urethra, or an incompetent bladder neck, which can predict poor response to simple suspensory operations [4]. 2. Cystoproctography In cystoproctography, patients drink 500 mL of a barium mixture 30–60 min prior to the examination to opacify the small bowel loops deep in the pelvis. Subsequently, water-soluble contrast is instilled in the bladder. The position of the vagina is indicated by the placement of high-density barium suspension either by directly injecting a small amount in the vagina or by having a barium-soaked tampon inserted. The tampon is removed before the exam commences. The anterior and posterior margins of the anus are marked with adhesive metallic markers. The bladder and urethra should be imaged before opacification of the rectum since a distended rectum can elevate the bladder. Finally, thick barium paste is instilled into the rectum to the level of the sacral promontory using a large syringe or caulking device. The patient is seated on a radiolucent commode, and images are recorded during straining, coughing, and defecation. Cystoproctography can document the presence of a rectocele, cystocele, or enterocele and abnormal perineal decent and

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abnormal movements of the rectal or vaginal wall [4]. These may coexist with stress urinary incontinence and represent global weakening of the pelvic support. The positive and negative predictive values of cystoproctography are 70% and 50%, respectively [5], but the interobserver variations can be as high as 25–50% [6]. B. Ultrasonography Compared to conventional radiography, US can provide more information concerning the soft tissues of the pelvis. Continuous real-time imaging with no exposure to ionizing radiation and widespread availability make it an attractive technique. Originally, transabdominal sonography was used to investigate the urethra, but its use has been limited because the urethra disappears from the field of view during descent [4]. Transperineal, transrectal, and transvaginal US are used to assess the urethrovesical junction and the entire urethra. Imaging can be done with the patient in the supine, sitting, or upright positions or during voiding. The sitting position may offer a more accurate assessment, with gravity favoring pelvic descent. Typically, transperineal imaging uses either a 3.5-MHz curved sector probe or a 5- to 10-MHz linear array. Transvaginal imaging uses an endovaginal 5- to 9-MHz tightly curved array, and transrectal scanning uses an endorectal probe with an end-firing 3.5-MHz linear array transducer. Normally, the urethra is parallel to the pubic symphysis, but it is mildly bowed and points anteriorly at its distal aspect. Descent of the bladder neck and proximal urethra during the valsalva maneuver is greater in patients with stress incontinence [7]. Greater than 1 cm decent on transrectal sonography indicates stress urinary incontinence [8]. Urethral funneling or beaking with straining is present in 93% of patients with stress urinary incontinence [4]. Funneling is present if there is slight separation of the internal urethral orifice with straining. In more severe instances, urethral beaking may be extensive or seen at rest. The urethra may rotate out of the pelvis in stress incontinence. Initially, the urethra rotates as a unit, but in later stages, the anterior wall rotates much less than the posterior wall of the urethra as the puborectalis ligaments and subpubic fascial complex limit it. With the differential rotation of the anterior and posterior walls, the urethra twists and causes physical separation of the luminal surfaces, with resultant incontinence [4]. Schaer et al. completed preliminary examinations demonstrating that bladder neck anatomy and urethral funneling may be more easily evaluated using ultrasound contrast (Echovist) instilled into the bladder [9]. Finally, using three-dimensional ultrasound and a transvaginal approach, Athanasiou et al. were able to document the urethral anatomy in great detail [10]. They noted a smaller, thinner, and shorter striated urethral sphincter in women with stress incontinence, but its etiology and implications for treatment have not been elucidated. C. Magnetic Resonance Imaging Imaging by magnetic resonance provides soft tissue contrast and the ability for multiplanar and dynamic imaging. It may be performed with an intravaginal coil. This provides optimal signal to noise and resolution necessary to evaluate the urethra, bladder neck, and pelvic support [11]. Recently, with the introduction of fast imaging techniques, it has become possible to obtain MR images in a dynamic

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(a)

(b)

Figure 1 Dynamic MRI examination of the pelvis in a patient with urinary incontinence. Sagittal T2 images (a) at rest and (b) during straining and (c) an axial image at the level of the symphysis pubis during straining demonstrate a cystocele (arrow) and a large enterocele (arrowheads).

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(c)

fashion. These techniques allow the acquisition of a series of images at rest and during straining [12]. Dynamic imaging is best performed with a pelvic coil as an intravaginal or intrarectal coil may inhibit organ prolapse. Dynamic MRI can document the presence of other pelvic pathology, such as cystocele or enterocele (Fig. 1). The technique of MRI is elaborated in Section V. Mostwin et al. compared MR images with dynamic fast-scan MR during straining. Using the pubococcygeal line in the sagittal plane as a reference, they found that women with stress incontinence had significant organ displacement from this reference line during straining, while asymptomatic women did not [4]. Descent of the bladder neck below the superior pubic ramus and separation of the symphysis and urethra have been associated with urethral hypermobility and stress incontinence [13]. As with sonographic examination, rotation of the urethra as manifested by an increased urethrovesical angle was greater in women with stress incontinence [14]. Loss of the hammock configuration of the anterior vaginal wall, where it is normally concave toward the symphysis pubis (as seen on sagittal images on MRI), has been noted more frequently in women with either stress incontinence or pelvic prolapse [12]. This configuration change may reflect loss of lateral supports, including the pubovesical ligament [15] or flaccidness of the fibromuscular tissue between the pubococcygeal muscle and the vagina, which may play a major role in the pathogenesis of incontinence [16]. Also, loss of the normal “H” shape of the vagina on the transverse view has been associated with prolapse. Fielding et al. studied women in the sitting position [15]; they used open MR systems with the intent of duplicating a more physiological appearance of the pelvis during rest and straining. Supine imaging appears to have a better signal-to-noise ratio as this allows the surface coil to be wrapped around the pelvis. The sitting position suffers from signal loss on axial images above the ischial spines because the patient sits on the coil rather than having it wrapped around the pelvis. However, Fielding et al. could clearly visualize the bladder neck and

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proximal urethra with the patients in sitting position and were able to document an increase in the posterior urethrovesical angle by an average of 14° in normal women [15]. Their preliminary work documents the presence of bladder neck widening, descent of the bladder neck, and increased posterior urethrovesical angles while straining in the sitting position in incontinent women. Although the findings were also present on supine images, they were best revealed in the sitting position, especially for bladder descent [14]. The main limitations of MRI are cost and availability. Furthermore, a small number of patients cannot be imaged due to the presence of pacemakers and cochlear implants, which are a contraindication for MRI. In addition, patients with claustrophobia and obese patients cannot be optimally evaluated. III. URETHRAL DIVERTICULUM Most commonly, diverticula emanate from the midurethra, near the location of the periurethral glands from which they may have originated. If filling defects are visualized within the diverticular sac, stones, debris neoplasm, both benign and malignant, should be considered. Urethroscopy frequently visualizes the communication between the urethral lumen and the diverticular sac. This alone

Figure 2 VCUG demonstrating a urethral diverticulum (arrow).

(a)

(b)

Figure 3 (a) A spot image from a VCUG in a patient with urethral diverticulum (arrows). Notice the faint opacification of the diverticulum, which is secondary to the diverticulum being partially filled with fluid. (b) Transperineal ultrasound image of the urethra demonstrates the diverticulum (arrows).

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(a)

(b)

Figure 4 (a) VCUG demonstrates a urethral diverticulum (arrow). (b) Transvaginal ultrasound examination depicts a fluid-filled diverticulum (arrowhead).

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(a)

(b)

Figure 5 (a) Postvoid image from a VCUG demonstrates accumulation of contrast in a urethral diverticulum (arrow). (b) Axial T1- and (c) T2-weighted MR images depict the entire diverticulum (arrows) encasing the urethra (curved arrow). The MR images were obtained using an endovaginal coil.

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(c)

Figure 5 Continued

may not be adequate since the neck of a diverticulum may be hidden between coapted urethral folds [17] or missed because of inflammatory changes or an obstructed orifice [18]. Urethroscopy cannot evaluate the size or appearance of the diverticular sac. Radiological evaluation serves as an important complement to physical examination and urethroscopy. A.

Conventional Radiography

The conventional radiography of VCUG is a commonly performed examination for the evaluation of the urethral diverticulum (Fig. 2). The technical aspects of VCUG were described in Section II. VCUG has a sensitivity of 65% in diagnosis of urethral diverticulum [18]. The false negative rate for the diagnosis of urethral diverticulum can be as high as 35% [19]. When a lesion is suspected but the VCUG is normal, suboptimal, or equivocal, a double-balloon retrograde examination may be considered as it shows a higher sensitivity (90%) [19,20]. The double-balloon retrograde exam utilizes a specialized catheter with a distal and a proximal balloon. The proximal balloon may be fixed or free to slide along the catheter. A side port is located between the proximal and distal balloons. The catheter is inserted into the urethra and the distal balloon is inflated. Traction is placed on the catheter to seat it firmly near the internal urethral meatus. The external balloon is then inflated and pressed firmly against the external urethral meatus to limit the leakage of contrast material. Several milliliters of contrast are injected into the urethra under fluoroscopy.

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(a)

(b)

Figure 6 (a) Coronal T2-weighted image demonstrates a large exophytic mass lesion (arrows) in a patient with carcinoma of the urethral diverticulum. (b) Note the enhancement on the postcontrast T1 images (arrows).

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(a)

(b)

Figure 7 Lateral image from (a) a VCUG reveals an extrinsic impression (arrow) on the urethra. (b, c) Transvaginal ultrasound images demonstrate a solid lesion. (d) T1-weighted postcontrast MR image clearly depicts the periurethral leiomyoma (arrow) and the urethra (arrowhead).

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(c)

(d)

On VCUG or double-balloon urethrography, diverticula appear as round or ovoid sacs adjacent to the urethra with a neck of variable length connecting the sac to the urethral lumen. Diverticula may be in multilobular shape or may appear as elongated tubular structures that wrap around the urethra. The complex urethral diverticulum may be difficult to appreciate on VCUG alone [17].

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If a diverticulum is demonstrated, the patient may benefit from US or MRI [21]. US or MRI may depict the exact location of the diverticular neck and determine if a diverticula wraps around the urethra, which can affect surgical planning [17]. US and MRI may evaluate any filling defects and adjacent inflammatory soft tissue to exclude the possibility of a malignant neoplasm. B.

Ultrasonography

Urethral diverticula are usually anechoic or hypoechoic to the adjacent periurethral tissues. Occasionally, diverticula may be filled with echogenic debris. A urethral diverticulum may be diagnosed with confidence when the neck connecting the diverticula to the urethral lumen is identified. In a series by Siegel et al. using a combination of sonographic approaches, US correctly identified the precise location of the neck in 13 of 15 patients, while VCUG visualized the neck in 2 of these 13 patients [17]. They also noted that US allowed easier evaluation of complex diverticula that wrapped around the urethra. Advantages of US over conventional radiography include its ability to assess the contents of diverticula (Figs. 3 and 4), evaluate the diverticular wall, and provide alternative diagnoses such as Gartner’s duct cyst, vaginal inclusion cyst, or Skene’s gland abscesses. C.

Magnetic Resonance Imaging

When imaging urethral diverticula, an endovaginal or endorectal coil is utilized. Small field of view T1- and T2-weighted images are obtained in the axial plane, which is the most useful imaging plane (Fig. 5). Postcontrast T1-weighted images are useful in depicting the neck of the diverticulum. Additional images in the sagittal and coronal planes may be needed for evaluation of cases complicated by mass lesions. With surgical findings as the gold standard, MRI had the best sensitivity when compared with urethroscopy or urethrography. MRI detected 70% of urethral diverticula, while urethroscopy and urethrography correctly identified only 55% [18]. Like ultrasonography, MRI can visualize the extent of the diverticulum and its relation to the bladder neck, which are important in surgical planning [22], and can image the contents of diverticula (Figs. 6 and 7). IV. URINARY FISTULAS Because of the many types of fistulas that can develop between the urinary tract and the adjacent pelvic viscera, imaging of a fistula is tailored to a particular clinical presentation and situation. The urinary fistulas include vesicovaginal, rectovaginal, enterovaginal, and urethral fistulas. Vesicovaginal fistulas are usually secondary to gynecological surgery, with 75% of all fistulas forming after abdominal hysterectomy [23]. The remainder are the result of cervical, vaginal, or bladder malignancies or subsequent radiation therapy [24]. The majority of rectovaginal fistulas are the result of obstetrical injury, cryptoglandular abscess, Crohn’s disease, surgical trauma, or intestinal disorders such as diverticulitis, tuberculosis, or even obstruction [24,25]. A.

Conventional Radiography

There are numerous radiographic examinations that may be helpful in delineating urinary fistulas, depending on its communications with the pelvic viscera. Fistulas

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Figure 8 Lateral image from a VCUG depicts contrast opacification of the vagina (arrowheads) in a patient with a vesicovaginal fistula.

are frequently “unidirectional” during conventional radiographic imaging; for example, a rectovesical fistula may only be visualized during cystography and not during a barium enema [26] (Fig. 8). At other times, fistulas may not be evident by either route of contrast administration. If communication with the colon (Fig. 9) or small bowel is suspected, a barium enema or small bowel study may be needed. To evaluate fistulas that communicate with the bladder or urethra, an intravenous urogram or VCUG may be indicated. Vaginography or colpography performed with contrast directly instilled into the vagina using a balloon catheter to tamponade the vaginal orifice may be helpful to study fistulas that enter the vagina. However, fistulas to the vagina frequently fail to opacify given their small size and tortuous, oblique course [27]. In cases of fistulas with a cutaneous communication, a sinogram or fistulogram can be performed with gentle injection of water-soluble contrast after the careful placement of a small-caliber, soft-tip catheter within the sinus tract. The combination of these widely available techniques may demonstrate the course and appearance of a fistula. Although conventional radiography can document the presence of a fistula, it provides little information concerning the nature and extent of the extraluminal disease process causing the problem [28]. Other disadvantages of conventional imaging include exposure to ionizing radiation, occasional use of intravenous contrast agents, and patient discomfort with the placement of catheters for contrast instillation into the rectum, vagina, bladder, and sinus tracts. B. Ultrasonography Transabdominal, transvaginal, transperineal, and transrectal ultrasonography have all occasionally been used to document pelvic fistulas, but these are usually

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(a)

(b)

Figure 9 (a, b) Images from a hypaque enema examination demonstrate a colovesical fistula (arrows) in a patient with cervical carcinoma postradiation therapy.

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difficult to visualize because they are often short with thin communications [29]. Transperineal imaging is comfortable for patients of either sex. Transvaginal scanning with a partially full bladder is especially useful for patients with bladderrelated symptoms or rectal and perirectal disease [30,31]. Although transrectal ultrasound may successfully document a pelvic fistula, in a patient with Crohn’s disease or other rectal pathology, it is often painful and noncontributory. Yee et al. performed endoanal ultrasound (EAUS) with patients in a prone, jackknife position using a 360° rotating, 10-MHz probe covered with a waterfilled plastic cap. They demonstrated that only 28% of rectovaginal fistulas were identified, and only those above or at the dentate line were seen. However, they noted that the usefulness of EAUS derives from its ability to document coexistent anal sphincter defects, which can alter surgical management. EAUS correctly identified 92% of sphincter injuries seen with rectovaginal fistulas [25]. In a case report, Yang et al. used a 5-MHz transvaginal probe and successfully documented a vesicovaginal fistula in two patients. The fistulous tracts had echogenic walls, and bladder wall thickening secondary to pelvic radiation therapy was noted. Using a Valsalva maneuver or cough, they were able to induce a flow wave of urine into the fistula, which helped to localize the fistula. A small amount of urine pooled within the upper vagina also assisted in localizing the fistula [23]. Fistulas to the bladder appear as linear bands of varying echogenicity: If air is present within the tract, it will appear echogenic with or without ring-down artifact, but if the tract is collapsed or empty, it may appear as an anechoic or hypoechoic tract [30,31]. If the fistula connects the bladder to the skin, vagina, or bowel, nondependent air can be seen, which indicates its presence. Furthermore, palpation of the abdomen during real-time scanning can cause gas to percolate through the fistula and increase the detection rate [31]. C. Computed Tomography The CT imaging of urinary fistulas requires optimal technique with judicious use of oral and intravenous contrast media. The depiction of fistulas by CT relies on the presence of contrast in a space where it should not be present. Contiguous thin axial sections through the abdomen, pelvis, and perineum should be obtained. Rectal contrast can be administered if opacification of the sigmoid colon is needed. If a sinus tract to the skin is present, an injection of the fistula with contrast and repeat CT imaging of the pelvis can determine the location and extent of the sinus tract. If an enterovaginal fistula is suspected, oral contrast should be given to opacify the distal bowel loops within the pelvis. Intravenous contrast should not be given in these cases so that if contrast medium is seen within the vagina, its enteric origin can be documented with certainty. Delayed images after 5–15 min may be useful in demonstrating contrast within the vagina if only air or fluid was seen in initial scanning. This can be particularly helpful in detecting small communications [28]. Similarly, in suspected cases of vesicovaginal fistula, intravenous but not oral contrast should be administered so that the origin of any contrast seen within the vagina is certain. Delayed imaging may also aid in finding small com-

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Figure 10 An axial postcontrast CT image demonstrates a fistulous communication (arrow) between the bladder (curved arrow) and sigmoid (arrowhead) secondary to carcinoma of the sigmoid colon.

munications. False-positive scans can result from the use of a bedpan or from the reflux of urine into the vagina of an incontinent patient [28]. For identifying enterovesical fistulas, CT outperforms both barium enema and cystoscopy and is the imaging modality of choice (Fig. 10). CT not only can identify fistulas, but also can suggest the underlying etiology (e.g., malignancy if there is an associated mass, radiation injury, or inflammatory bowel disease) as well as show the extent of the disease. Both of these factors can greatly influence surgical planning in terms of which procedure should be done and whether surgical repair is even possible [28,32]. D.

Magnetic Resonance Imaging

Fast spin-echo (FSE) sequences may be helpful in imaging fistulas since they produce heavily T2-weighted images with shorter imaging times, allowing for the use of higher resolution acquisition matrices. With the intrinsic contrast between the small amount of fluid within a fistulous tract and the surrounding soft tissues on heavily T2-weighted images, intravenous contrast is rarely required [33]. However, on early postgadolinium images, the fistula wall may be enhanced with high signal intensity surrounding a tract of low signal intensity, and these findings are more conspicuous with fat suppression. With delayed postgadolinium images, high-intensity fluid may be seen within the fistula tract [34]. Enterovesical fistulas are best demonstrated in the sagittal and coronal planes given their usual superior-to-inferior course. They appear as high-intensity, fluid-filled tracts on long-TR/TE sequences, connecting the lumens of the bladder and intestine. A diagnostic feature of enterovesical fistulas is the discontinuity of the low signal intensity muscularis of the bladder wall at the entry site

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of the fistula. A similar disruption can be seen in the muscularis of the bowel wall, but is more difficult to recognize [33]. Vesicovaginal fistulas can be demonstrated on T2-weighted sequences (Fig. 11). The urine within the fistula will appear as high signal intensity, and urine may also be present within the vagina. The bladder may be collapsed with decom-

(a)

(b)

Figure 11 (a) Sagittal T2-weighted image demonstrates the vesicovaginal fistulous tract (arrow). (b) Postcontrast T1-weighted image shows a large communication (arrows) between the bladder and vagina, which is filled with a necrotic mass (arrowhead) secondary to carcinoma of the cervix. Also note the involvement of the rectum posteriorly.

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pression into the fistula and vagina. On T2-weighted images, a focal discontinuity is present in the bladder wall and the vaginal muscularis such as seen with enterovesical fistulas [33]. Enterovaginal fistulas include rectovaginal and sigmoidovaginal fistulas. Fistulas can result in focal disruptions in the muscularis of the posterior vaginal wall or the anterior rectal wall, which are best appreciated on T2-weighted images [33]. The fat plane separating the rectum and vagina may also be disrupted. The lumen can have high signal intensity if fluid is present, but can appear as a signal void if gas is trapped within the lumen. Like CT, MR is capable of defining the fistula tract as well as the underlying pathology. The presence of pelvic abscesses, bowel disease, changes from radiation, or viable tumor is easily demonstrated by MR imaging and can affect surgical management. V.

PELVIC FLOOR RELAXATION

A thorough evaluation of the female pelvis includes assessment of the anterior, middle, and posterior compartments. Various imaging methods have become available over the years for the evaluation of pelvic floor descent. These include VCUG, defecography, colpocystodefecography, and recently dynamic MRI. VCUG and defecography have been described elsewhere. Bethoux and colleagues introduced colpocystodefecography [35]. This technique includes opacification of the bladder, vagina, and rectum. The small bowel is also opacified with barium. Dynamic evaluation is performed under fluoroscopy with the patient seated on a special chair and empties the bladder and rectum. This technique allows comprehensive evaluation of the pelvic floor and evaluates the degree of pelvic floor descent and the compartments it involves. However, the limitation with this technique remains the lack of visualization of the soft tissues outside the contrast-filled lumen. Recent advances in MRI fast-imaging sequences have made it possible to evaluate the pelvic floor in a real-time fashion. Real-time imaging allows one to obtain images at rest and during straining and relaxation. These images are then run together on a cine loop and viewed as a dynamic evaluation. Typically, T2weighted FSE sequences such as HASTE (half Fourier acquisition of single-shot turbo spin echo) are used. These sequences allow acquisition of a single slice in less than a second and are relatively insensitive to breathing motion. The inherent bright signal of urine within the urinary bladder and the ability to visualize soft tissues allows one to perform this technique without the need for any additional contrast opacification (Figs. 12 and 13). The images are typically obtained at rest and during the Valsalva maneuver. The limitation of this technique is the suboptimal evaluation of the rectum. As a result, some investigators have suggested the use of aqueous sonographic gel instilled in the rectum and dynamic MR evaluation performed during straining and evacuation [36]. Defecation during MRI is best performed on vertical configuration open scanners. The degree of visceral organ prolapse and pelvic floor descent is evaluated by drawing a line from the symphysis pubis to the sacrococcygeal junction and measuring the degree of descent of the bladder, uterocervical junction, vagi-

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(a)

(b)

Figure 12 Dynamic MRI images of a patient with pelvic floor relaxation obtained (a) at rest and (b) under stress demonstrate a large cystocele (arrow).

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(a)

(b)

Figure 13 Dynamic MRI images obtained (a) at rest and (b) during straining demonstrate a cystocele (arrow) and descent of the uterovaginal junction (arrowheads) in a patient with pelvic floor relaxation following a traumatic vaginal delivery.

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nal vault, enterocele, and rectocele [36]. Comiter et al. designed a grading method for evaluating the pelvic floor prolapse and relaxation when using dynamic MRI [37]. The advantage of MRI is that it permits complete analysis of the three pelvic compartments in a single procedure without exposure to ionizing radiation. Given the inherent soft tissue contrast, MRI does not require additional application of contrast material into the vagina, small bowel, or bladder [38]. Goodrich et al. confirmed the clinical relevance of dynamic MRI in analyzing and assessing pelvic floor relaxation and in understanding anatomical changes that occur before and after surgical repair or uterovaginal and vaginal vault prolapse. Lienemann et al. showed that MRI was clearly superior to colpocystodefecography and accurately depicted pelvic floor descent and prolapse in women [38]. However, a recent study by Vanbeckevoot et al. that focused on a comparison between MRI and colposystodefecography concluded that dynamic singleshot MRI is not as accurate as colpocystodefecography in the evaluation of pelvic floor descent [36]. They encountered false-negative MRI studies in the anterior and middle compartments and to a lesser extent in the posterior compartment. Of the 33 cases finally evaluated, the sensitivity of MRI was 74% for cystocele, 60% for vaginal vault descent, 100% for enterocele, 62% for rectocele, and 97% for rectal descent. The specificity of MRI was 100%. The decreased sensitivity of MRI was felt likely to be due to the supine position in which the MRI was performed in contradistinction to the more physiological sitting position used for colpocystodefecography. In addition, they noted that the pelvic floor muscles reach their greatest degree of relaxation during defecation. This is probably the physiological basis for the greater sensitivity of colpocystodefecography in the detection of pelvic floor defects compared to MRI. Use of MRI in the erect position in an open system should reveal new perspectives. REFERENCES 1. Dunnick NR, Sandler CM, Newhouse JH, Amis S. In: Textbook of Uroradiology. Philadelphia: Lippincott Williams and Wilkins, 2001:352–393. 2. Bergmann A, McKenzie C, Ballard CA, Richmond J. Role of cystourethrography in the preoperative evaluation of stress urinary incontinence in women. J Reprod Med 1988; 33:372–376. 3. Versi E. The significance of an open bladder neck in women. Br J Urol 1991; 68:42– 43. 4. Mostwin JL, Yang A, Sanders R, Genadry R. Radiography, sonography, and magnetic resonance imaging for stress incontinence. In: Klutke CG, Raz S, eds. The Urologic Clinics of North America: Evaluation and Treatment of the Incontinent Female Patient. Philadelphia: W. B. Saunders, 1995:539–549. 5. Fischer-Rasmussen W, Hansen RI, Stage P. Predictive values of diagnostic tests in the evaluation of female urinary stress incontinence. Acta Obstet Gynecol Scand 1986; 65: 291–294. 6. Mouritsen L, Strandberg C, Jensen AR, Berget A, Frimodt-Moller C, Folke K. Interand intraobserver variation of colpo-cysto-urethrography diagnoses. Acta Obstet Gynecol Scand 1993; 69:55–59. 7. Chen GD, Su TH, Lin LY. Applicability of perineal sonography in anatomical evaluation of bladder neck in women with and without genuine stress incontinence. J Clin Ultrasound 1997; 25:189–194.

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8. Bergman A, Ballard CA, Platt LD. Ultrasonic evaluation of urethrovesical junction in women with stress urinary incontinence. J Clin Ultrasound 1989; 16:295–300. 9. Schaer GN, Koechli OR, Schuessler B, Haller U. Usefulness of ultrasound contrast medium in perineal sonography for visualization of bladder neck funneling—first observations. Urology 1996; 47:452–453. 10. Athanasiou S, Khullar V, Boos K, Salvatore S, Cardozo L. Imaging the urethra sphincter with three-dimensional ultrasound. Obstet Gynecol 1999; 94:295–301. 11. Yang A, Mostwin J, Genadry R, Saunders R. High-resolution magnetic resonance imaging of urethra and periurethral structures using intravaginal surface coil and quadrature phased array surface coil. Neurourol Urodyn 1993; 12:329–330. 12. Tunn R, Paris S, Fischer W, Hamm B, Kuchinke J. Static magnetic resonance imaging of the pelvic floor muscle morphology in women with stress urinary incontinence and pelvic prolapse. Neurourol Urodyn 1998; 17:579–589. 13. Carey MP, Dwyer PL. Position and mobility of the urethrovesical junction in continent and stress incontinent women before and after successful surgery. Aust N Z J Obstet Gynaecol 1991; 31:279–284. 14. Fielding JR, Griffiths DJ, Versi E, Mulkern RV, Lee MTL, Jolesz FA. MR imaging of pelvic floor continence mechanisms in the supine and sitting positions. Am J Roentgenol 1998; 171:1607–1610. 15. Fielding JR, Versi E, Mulkern RV, Lerner MH, Griffiths DJ, Jolesz FA. MR imaging of the female pelvic floor in the supine and upright positions. J Magn Reson Imaging 1996; 6:961–963. 16. DeLancey JOL. Anatomy and mechanics of structures around the vesical neck: How vesical neck position might affect its closure. Neurourol Urodyn 1988; 7:161–162. 17. Siegel CL, Middleton WD, Teefey SA, Wainstein MA, McDougall EM, Klutke CG. Sonography of the female urethra. Am J Roentgenol 1998; 170:1269–1274. 18. Romanzi LJ, Groutz A, Blaivas JG. Urethral diverticulum in women: diverse presentations resulting in diagnostic delay and mismanagement. J Urol 2000; 164:428–433. 19. Lee TG, Keller FS. Urethral diverticulum: diagnosis by ultrasound. Am J Roentgenol 1977; 128:690–691. 20. Davis HJ, Cian LG. Positive pressure urethroscopy: a new diagnostic method. J Urol 1956; 75:753–757. 21. DiSantis DJ. Inflammatory conditions of the urethra. In: Pollack HM, McClennan BL, eds. Clinical Urography. 2nd ed. Philadelphia: W. B. Saunders, 2000:1041–1057. 22. Siegelman E, Banner M, Ramchandani P, Schnall M. Multicoil MR imaging of symptomatic female urethral and periurethral disease. Radiographics 1997; 17:349–365. 23. Yang JM, Su TH, Kuo-Gon W. Transvaginal/sonographic findings in vesicovaginal fistula. J Clin Ultrasound 1994; 22:201–203. 24. Thorvinger B, Horvath G, Samuelsson L. CT demonstration of fistulae in patients with gynecologic neoplasms. Acta Radiologica 1990; 31:357–360. 25. Yee LF, Birnbaum EH, Read TE, Kodner IJ, Fleshman JW. Use of endoanal ultrasound in patients with rectovaginal fistulas. Dis Colon Rectum 1999; 42:1057–1064. 26. Davidson AJ, Hartman DS, Choyke PL, Wagner BJ. The urinary bladder. In: Davidson’s Radiology of the Kidney and Genitourinary Tract. 3rd ed. Philadelphia: W. B. Saunders, 1999:485–515. 27. Hudson CN, Chir M. Acquired fistulae between the intestine and the vagina. Ann R Coll Surg Engl 1970; 46:20–39. 28. Kuhlman JE, Fishman EK. CT evaluation of enterovaginal and vesicovaginal fistulas. J Comput Assist Tomogr 1990; 14:390–394. 29. Thurston W, Wilson SR. The urinary tract. In: Rumack CM, Wilson SR, Charboneau JW, eds. Diagnostic Ultrasound. 2nd ed. St. Louis, MO: Mosby, 1998:329–397.

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30. Wilson SR. The gastrointestinal tract. In: Rumack CM, Wilson SR, Charboneau JW, eds. Diagnostic Ultrasound. 2nd ed. St. Louis, MO: Mosby, 1998:279–327. 31. Damani N, Wilson S. Non-gynecologic applications of transvaginal sonography. Radiographics 1999; 19:179–200. 32. Alexander ES, Weinberg S, Clark RA, Belkin RD. Fistulas and sinus tracts: radiographic evaluation, management, and outcome. Gastrointest Radiol 1982; 7:135–140. 33. Outwater E, Schiebler ML. Pelvic fistulas: findings on MR images. Am J Roentgenol 1993; 160:327–330. 34. Semelka RC, Hricak H, Kim B, Forstner R, Bis KG, Ascher SM, Reinhold C. Pelvic fistulas: appearances on MR images. Abdom Imaging 1997; 22:91–95. 35. Bethoux A, Bory S, Huguier M, Sheao SL. LE colpocystogramme. J Chir (Paris) 1965; 8:809–828. 36. Vanbeckevoort D, Van Hoe L, Oyen R, Ponette E, De Ridder D, Deprest J. Pelvic floor descent in females: comparative study of colpocystodefecography and dynamic fast MR imaging. J Magn Reson Imaging 1999; 9:373–377. 37. Comiter CV, Vasavada SP, Barbaric ZL, Gousse AE, Raz S. Grading pelvic prolapse and pelvic floor relaxation using dynamic MRI. Adult Urol 1999; 54(3):454–457. 38. Lienemann A, Anthuber A, Baron A, Kohz P, Reiser M. Dynamic MR colpocystorectography assessing pelvic-floor descent. Eur Radiol 1997; 7:1309–1317.

6 Urodynamic Evaluation of Pelvic Floor Dysfunction SUMANA KODURI University of Wisconsin—Milwaukee Clinical Campus Milwaukee, Wisconsin, U.S.A. PETER K. SAND Northwestern University Medical School Evanston, Illinois, U.S.A.

I.

INTRODUCTION

The evaluation of the incontinent woman must yield a proper diagnosis. Complications after incontinence operations related to preoperatively unrecognized detrusor instability or voiding dysfunction are not acceptable. Multichannel urodynamics provide a comprehensive evaluation of the underlying conditions related to incontinence and urinary retention. While researchers might like to perform urodynamic testing of every incontinent patient, the cost-effectiveness and feasibility must be addressed. Simple evaluation in the office can be helpful in most cases. However, if these evaluations do not help arrive at a comprehensive diagnosis that fully explains the patient’s symptoms, then more sophisticated testing in a urodynamics laboratory is warranted. II. BASIC OFFICE EVALUATION It is important to recognize that history alone is a poor predictor of urodynamically achieved diagnoses. While some authors have found that, in patients with isolated symptoms, diagnoses could be achieved based on history alone [1,2], most others have found no correlation between history and diagnosis [3–7]. Jensen and colleagues [8] reviewed the English literature from 1975 to 1987 and found 29 studies that compared history to diagnosis. Of these, 19 were acceptable for comparison. The data on 3092 patients evaluated for genuine stress incontinence showed the symptom of stress incontinence to have a sensitivity of 90.6% 77

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and a specificity of only 51.1%. A history of urge incontinence in 2950 patients had a sensitivity of 73.5% and a specificity of only 55.2%. Lemack and Zimmern [9] felt that taking a history with a validated questionnaire (Urogenital Distress Inventory-6 [UDI-6]) could help identify women with stress incontinence symptoms who required further urodynamic studies. With this questionnaire, they were able to show that 91% of critical diagnoses (mixed incontinence, intrinsic sphincteric deficiency, and detrusor instability alone) could be predicted. Addition of a physical examination with lumbosacral evaluation, measurement of residual urine, urine culture, assessment of urethral mobility, along with some simple office testing can be more helpful than history alone in achieving a diagnosis. The pelvic examination should include assessment of urogenital atrophy, infection, and inflammation that can lead to irritative voiding symptoms such as urgency, frequency, and dysuria. Urethral deformity such as diverticula or fistulae can also be assessed, as can the presence of genital prolapse. Anterior and posterior vaginal wall prolapse can mask genuine stress incontinence in 36– 73% of women, which can be found by reduction of the prolapse with a pessary or Sim’s speculum [10–13]. Neurological evaluation is important in understanding the integrity of upper cortical and spinal tracts as well as peripheral innervation of the lower urinary tract. A Q-tip test should be done to evaluate for urethral hypermobility, which can identify women with anatomical genuine stress incontinence. Additional tools that can be used in the office include uroflowmetry studies, stress testing, pad testing, dynamic urethroscopy/cystoscopy, and singlechannel cystometry. Spontaneous uroflowmetry is the study of the voiding velocity and is used as a screening test in women to detect abnormalities of micturition. It is more useful in men than in women because of its ability to detect an obstructive outflow problem, and in the female for whom physical obstruction is less likely, the absolute flow rate is not as important as the pattern of flow. A bell-shaped, continuous pattern of flow is normal. Intermittent flow patterns are usually a sign of voiding dysfunction, but may occur spontaneously in normal asymptomatic women [14]. Further testing may be warranted when obstructive patterns or intermittent patterns of flow occur consistently or any pattern is accompanied by urinary retention (ⱖ50 mL). Stress testing and pad testing are also useful diagnostic tests. Stress testing is used to demonstrate objectively the sign of stress incontinence; when performed supine at a low bladder volume (ⱕ50 mL), it may be predictive of a low-pressure urethra or low leak point pressure [15,16]. While stress testing done at maximum cystometric capacity can help diagnose genuine stress incontinence, it can be confused with stress-induced detrusor instability [17]. Pad testing, similarly, cannot distinguish between genuine stress incontinence and detrusor instability. Pad testing is a good measure to quantitate losses [18–20] and can be used to follow patients’ progress on a treatment regimen. Dynamic urethroscopy, described by Robertson [21], can be used to observe the bladder neck during filling to diagnose detrusor overactivity and during the Valsalva maneuver and coughing to identify passive opening of the bladder neck, as seen in genuine stress incontinence. This technique clearly requires some amount of expertise, and several authors have found it to be a fairly specific,

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but not very sensitive, test for diagnosing detrusor instability and genuine stress incontinence [22,23]. Urethroscopy and cystoscopy are indicated in evaluating patients with prior surgery, hematuria, and irritative voiding symptoms to look for foreign bodies, urolithiasis, as well as inflammatory, neoplastic, and hypoestrogenic changes. These endoscopic examinations are frequently used in conjunction with other diagnostic tests for incontinence. Single-channel cystometry can be easily done in the office setting. It is an important diagnostic test used to measure the change in bladder pressure during filling (antegrade or retrograde). Simple cystometry usually involves filling the bladder in a retrograde fashion through the urethra while measuring bladder pressure. In its simplest form, it can be done by pouring water into an open syringe connected to an inserted urethral catheter held approximately 15 cm above the pubic bone and, while watching for rises in the meniscus, denoting rises in intravesical pressure. Ouslander et al. [24] found this method to have a sensitivity of 75% and a specificity of 79% with a positive predictive value of 85% when compared with multichannel urodynamic studies for the diagnosis of detrusor instability in geriatric patients. Manometric transducers may be attached to the catheter for direct pressure measurements. Leakage or symptoms of marked urgency associated with rises in intravesical pressure suggest detrusor instability. The catheter can be removed and, in the absence of rise in intravesical pressure, the patient can be stress tested to look for genuine stress incontinence. The sensitivity of simple, retrograde cystometry can be increased from 85% to 92.3% if repeated a second time [25]. False-positive tests can result from intraabdominal pressure increases that cannot be differentiated from vesical pressure increases with single-channel cystometry. The sensitivity of simple retrograde cystometry is also limited by the failure to diagnose low-pressure detrusor instability. The above techniques are useful in many cases to arrive at a diagnosis and initiate treatment. If, however, the patient’s symptoms are not completely explained or the patient fails treatment based on these initial tests, multichannel urodynamic testing should be considered. III. INDICATIONS FOR MULTICHANNEL URODYNAMIC TESTING Multichannel urodynamic evaluation of urinary incontinence involves the recording of urethrocystometry, sphincter electromyography (EMG), urethral closure pressure profiles, leak point pressures, and voiding pressure studies. These studies are not indicated for every incontinent patient. They can add cost and can be time consuming. Where to draw the line between who has multichannel studies and who undergoes single-channel standing cystometry, stress testing, and simple clinical tests is difficult. Lemack and Zimmern [9] felt that patients who needed urodynamic studies could be screened with a history and the UDI-6 questionnaire, with an overall cost savings of 15%. However, they did not include voiding dysfunction and postoperative complications in their cost analysis. Weber and Walters [26] also performed cost-effective analysis on urodynamic studies and found that, in a select population undergoing surgery for prolapse and stress incontinence symptoms, multichannel urodynamic studies are

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not cost effective. Nonsurgical treatments, other lower urinary tract symptoms, and potential incontinence in patients with large prolapse were not included in this analysis. Looking retrospectively at surgical outcomes over a period of 14 years, Thompson et al. [27] found no difference in outcomes in women younger than 50 years whether they had multichannel urodynamic testing or simple testing. Single-channel cystometry can have a sensitivity as low as 60%. This can be concerning, especially in the elderly population, for whom the prevalence of detrusor instability can be as high as 60% [25]. While the presence of detrusor instability may not be crucial to diagnose in the nonsurgical patient, it is more important in the patient undergoing antiincontinence surgery. Patients with detrusor instability have been found to have more problems postoperatively, with lower cure rates for genuine stress incontinence as well as persistent urge incontinence [28]. Those with higher pressure detrusor instability (⬎15 cm H 2 O) and sensory urgency have a lower chance of resolving their detrusor instability when compared to lower pressure detrusor instability (⬍15 cm H 2 O) following a sling procedure [29]. Cystometry can also provide many false-positive diagnoses of detrusor instability because of the effect of the intra-abdominal pressure recorded intravesically. Urethrocystometry avoids this by recording true detrusor (bladder minus abdominal) pressure and negating the intra-abdominal pressure artifact. Urethral pressure profiles have been found to be useful by some authors [30– 32]. They provide a glimpse at the intrinsic sphincteric mechanism by recording pressures along the urethra in the static phase. Those with low urethral closure pressure have been found to be at risk for failing retropubic urethropexies [33]. Postmenopausal patients and those with prior anti-incontinence procedures are at risk of low urethral closure pressure and may benefit from urethral pressure profiles. Dynamic phase urethral pressure profiles with cough and/or the Valsalva maneuver can provide information in relation to changes in intra-abdominal pressure. Performance of EMG testing with voiding pressure studies is essential in the patient with urinary retention. Recent studies show a high prevalence of functional bladder outlet obstruction in women [34,35]. Kuo [34] found associated pathologies in patients identified with obstructive voiding and was able to treat most of the patients successfully. Voiding pressure studies can also provide useful information about the voiding mechanism and the risk of postoperative voiding dysfunction in a patient about to undergo antiincontinence surgery. Despite many studies, indications for multichannel urodynamics continue to be debated. Various laboratories have their own criteria as to who needs multichannel urodynamic studies after their initial evaluation in the office. If some aspect of the patient’s symptoms remains unexplained after the simple office evaluation, then multichannel urodynamics are indicated. Other indications for complex urodynamic studies are not as clear, but may include prior failed anti-incontinence operations, age over 60 years, continuous and/or insensible (unconscious) urine loss, suspicion of neuropathic dysfunction, mixed incontinence symptoms, and apparent stress incontinence in women who do not have evidence of urethral hypermobility.

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IV. MULTICHANNEL URODYNAMICS A. Equipment and Setup Multichannel urodynamic testing means many things to different people. The basic testing usually includes the performance of urethrocystometry. This can be augmented with urethral pressure profilometry, measuring leak point pressures, and voiding pressure studies with EMG. These basic studies can be enhanced with fluoroscopy or ultrasound for videourodynamics. Use of an ambulatory monitor allows these studies to be performed outside the laboratory in the patient’s own environment, which increases its sensitivity. The basic urodynamic studies are described here. The urodynamics laboratory may be set up with many different commercial products. Standard components include a urodynamics chair, uroflowmeters (to measure voiding velocity), an EMG apparatus (electrodes, cables, amplifier, filter, and internal converters), pressure catheters and transducers, withdrawal profilometer (to move urodynamic catheters through the urethra), infusion pump (to fill the bladder with liquid), and recorder or computer (to chart results). Various companies market full urodynamic systems that range in cost from $30,000 to $95,000 depending on the sophistication of the system. Ultrasound and fluoroscopy (to image the lower urinary tract) add to the cost considerably. B. Catheters Various catheters are available for urodynamic studies. Some utilize external pressure transducers, while others have pressure transducers on the catheter itself at the site of pressure measurement. With external transducer systems, the recording catheter is placed inside a body cavity in which pressure or force is transmitted along a fluidfilled or gas-filled tube back to the transducer at some distance. The force generated on the external transducer membrane is then converted into an electronic signal that can be transmitted over electronic cables to a physiological recorder or computer. These signals are then converted into graphic and digital information. Internal pressure transducers such as the microtip catheters first described by Millar and Baker [36] have revolutionized multichannel urodynamics by improving the frequency response of pressure transducer measurements. Increased frequency response (15 Hz) has allowed for the accurate measurement of rapid pressure changes such as those associated with a cough. Transmission of pressure along a catheter to an external transducer system can blunt the measurement of a cough pressure spike and introduce artifact that can be avoided with good semiconductor, strain-gauge, microtip transducer catheters [36]. Good catheters are able to measure pressures accurately over a wide range of pressures (0 to 300 cm H 2 O) with little drift (⬍0.1%ρ C) or hysteresis (⫾1% over 100 cm H 2 O). Hysteresis is the change in pressure-measuring accuracy caused by varying previously applied pressures. In addition, the catheter should be small and flexible to help avoid flexion and tension artifacts, especially during urethral pressure measurements [37–39]. Addition of a filling channel to the pressure-measuring channel to avoid the use of a second catheter is also important in the avoidance of artifact [38]. The ideal catheter would also be able to measure

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pressure circumferentially and would be strong and durable. Work continues on the development of an affordable ideal catheter, but in the meantime, each available system appears to have its limitations. External transducer catheters are usually of the water infusion or balloon type and are both limited in similar ways. The infusion catheters have a unique limitation in that they may become plugged at their pressure-measuring inlets. In non-fluid-filled closed systems like the urethra, they (like microtransducer catheters) measure the force generated by contact with the urethral wall rather than pressure. While these catheters are inexpensive and disposable, they are not adequate to measure rapid pressure changes such as coughing and therefore cannot be used for dynamic urethral profilometry. Motion in the catheter tubing may also introduce unnecessary artifact, and pressure measurements may be dampened by faulty connections and air bubbles. These catheters and transducers are more difficult to set up, calibrate, and maintain than the microtip transducer catheters. The microtip transducers, while more accurate because of their decreased volume displacement and greater frequency response, are far more expensive ($1000 to $4000). They are also far more fragile and, more temperature sensitive, and they introduce more drift [38]. Fiber-optic disposable catheters have been developed that incorporate some of the advantages of both microtip and balloon catheters. Early catheters had only a side-mounted membrane monitored by fiber-optic light, which dampened pressure responses [40–41]. The more recent catheters added small circumferential membranes to help alleviate this problem. While these new fiber-optic transducers were found to provide measurements comparable to microtip measurements in fluid-filled spaces such as the bladder during cystometry, pressure measurements in the urethra were not comparable to those of microtip catheters [42,43]. Until replaced by a better catheter, the microtip catheters continue to be the gold standard in urodynamic testing. C.

Preparation for Test

All components must be calibrated and tested properly prior to starting the test as recommended by the International Continence Society (ICS) [44]. Calibration of all catheters to atmospheric pressure, which is defined as zero, is important. The vesical and abdominal pressures should be equal prior to initiating the study. Equal pressure transmission to the bladder and the abdominal transducers is checked by asking the patient to cough. No change should be seen on the true detrusor pressure channel if there is equal pressure transmission. Empty resting pressures (bladder pressure and abdominal pressure) tend to be around 5–20 cm H 2 O if the patient is in the supine position, 15–35 cm H 2 O in the sitting position, and 30–50 cm H 2 O in the standing position (depending on obesity). If these baseline parameters are not consistent, all catheters and connections should be checked again. Calibration should be carefully monitored through the study also as the catheters may have some drift. V.

URETHROCYSTOMETRY

Multichannel urethrocystometry is our most valuable tool in diagnosing storage phase pathology. It involves the measurement of abdominal pressure, urethral

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pressure, and bladder pressure during filling with or without the recording of electromyographic activity. The urethral and bladder pressure may be measured by two sensors on the same small microtransducer catheter (7F) with a filling channel through the center of the catheter. This dual transducer placed through the urethra has a transducer at the tip that measures the vesical pressure and another transducer 6 cm distally that measures the urethral pressure. The abdominal pressure can be measured with a single transducer catheter placed in the vagina or the rectum. In the multichannel study, subtracted recordings can also be made. The true detrusor pressure is calculated by subtracting the abdominal pressure from the vesical pressure. This helps distinguish true changes in the bladder pressure from artifacts caused by changes in the abdominal pressure, which are also recorded by the vesical transducer. The urethral closure pressure is the difference between the urethral pressure and the bladder pressure. This helps to understand the constant relationship between the bladder and the urethral responses to filling during the storage phase. This may be further augmented by the use of periurethral or perianal electromyography to evaluate skeletal muscle function in the pelvis during the storage phase. These five or six recordings together constitute the multichannel urethrocystometry study. Water or physiological saline are the most commonly used media for filling during multichannel urodynamic testing. Contrast may be added if videourodynamics are being undertaken. Carbon dioxide is a medium that is used by some investigators during single-channel cystometry, but as stress testing and voiding studies are also studied here, a liquid medium is preferred. The patient is usually catheterized prior to starting the urethrocystometry study to start at a bladder volume of zero and to check her postvoid residual after a spontaneous void. Retrograde filling is done at various rates, and the patient is asked to report her sensations. The first sensation to void is noted when the patient first feels the presence of any fluid in the bladder, which she feels she could urinate. The patient is then asked about fullness, when she feels the strong urge to void (i.e., she would go out of her way to find a toilet). Maximum cystometric capacity (MCC) is when the patient cannot tolerate any more fluid in the bladder (i.e., when it is painful or she has piloerection). Studies done in normal volunteers show an average MCC of 594 mL and first sensation to void at about 32% of capacity [45]. Of the subjects, 95% note the first desire to void before filling to 300 mL of water. During a normal filling study, such as in Fig. 1, the patient is noted to have no increase in true detrusor pressure during the entire filling study. Small changes in intra-abdominal pressure (rectal pressure) are seen, which are reflected in the bladder pressure also, but the true detrusor pressure remains unchanged. Increased EMG activity signifies increased recruitment of pelvic floor muscle fibers in response to increasing volume in the bladder (MCC ⫽ 418 mL). Provocative maneuvers during this study do not stimulate a bladder contraction. Detrusor instability is defined as the presence of spontaneous or provoked involuntary bladder contractions during filling that cannot be suppressed. It is the second most common cause of urinary incontinence in adult women. The term is used when the condition is idiopathic, that is, without known cause. When the cause is felt to be due to a lesion in the brain or spinal cord that affects the upper motor neurons involved with bladder control, the term detrusor hyperreflexia is

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Figure 1 Normal filling study. used. Originally, the condition was defined by an involuntary contraction measuring 15 cm H 2 O or more. It then became apparent that even smaller contractions could cause incontinence and urgency. This led to a change in the definition of detrusor instability by the ICS to reflect that any symptomatic, involuntary, detrusor contraction (not necessarily ⱖ15 cm H 2 O) can be defined as an unstable contraction.

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Figure 2 Abnormal filling study denoting detrusor instability. Figure 2 shows an abnormal filling study. The patient leaks urine in response to a phasic, involuntary contraction of the bladder. Note the pressure change in the urethra that relaxes in response to this contraction. Detrusor instability can be from a phasic contraction, like the one shown, or a tonic one that slowly increases in pressure and eventually results in leakage. The patient usually complains of an urge to urinate from the onset of the contraction. She tries to prevent

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leakage by contracting her pelvic floor muscles (which can be seen on the EMG if this is being recorded), and may leak when she cannot hold back anymore. The leakage occurs when the urethral closure pressure falls to zero, when there is pressure equalization between the urethra and the bladder. EMG response can also be seen as a steady rise in the activity of the pelvic floor skeletal muscle as the patient tries to prevent leakage, followed by sudden relaxation as the pelvic floor musculature reflexively relaxes at the time of leakage, and then by bursts of EMG activity again to try to inhibit the leakage. Detrusor instability can also be stimulated with provocative maneuvers such as running water, hand washing, coughing, the Valsalva maneuver, or a heel jolt. These provocative maneuvers are used during or at the end of the filling phase if detrusor instability has not been observed. These maneuvers increase the sensitivity of the study, with hand washing being the strongest provocative technique [46]. Detrusor instability may sometimes be difficult to detect during free flow of urine through a low-resistance urethra. The stop test helps detect isometric contractions of the bladder [47]. This can help differentiate detrusor instability from stress incontinence through a low-pressure urethra. This is done by asking the patient to attempt to stop the flow of urine. This increases urethral resistance and allows recording of an isometric contraction. This can be seen as an increase in the bladder pressure on both the vesical and true detrusor channels. Mechanically obstructing the urethra with a finger in the vagina, suburethrally, can also achieve the same results. Although the most common pathology seen during urethrocystometry is detrusor instability or detrusor hyperreflexia, other unusual causes of urinary leakage can also be diagnosed. Urethral instability, low bladder compliance, uninhibited urethral relaxation, and overflow incontinence may also be seen. Normally, the bladder is a very compliant organ that can hold large volumes of water. Bladder compliance is defined as the change in volume ∆V divided by the change in pressure ∆P. The low-compliance bladder results from intrinsic disease processes within the bladder wall, which result in fibrosis and decreased elasticity. This is reflected in the urodynamic tracing as a loss of accommodation of the bladder wall, with a gradual continuous pressure increase during cytometry. This is frequently associated with diminished bladder capacity and can be seen in conditions such as radiation cystitis [48] or advanced interstitial cystitis. The opposite situation is the acontractile bladder, which has an ability to accept large volumes of fluid with little or no increase in bladder pressure [49]. Although the absence of detrusor contractions may be seen as a sign of normal detrusor control, large cystometric capacities may be a sign of detrusor muscle decompensation. This may be due to diabetic neuropathy, other lower motor neuron lesions, or habituation to delayed voiding for social reasons. This results in urinary retention and often recurrent urinary tract infections from the inability to evacuate bacteriuria. Many of these patients also have complaints of stress incontinence, which may in fact be due to overflow incontinence. Urethral instability is another condition diagnosed on urethrocystometry; it is defined as oscillations in the continuously measured urethral pressure of greater than 15 cm H 2 O with or without associated incontinence [50,51]. This is demonstrated in Fig. 3. There is no change in the true detrusor pressure or abdominal

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Figure 3 Urethral instability.

pressure with the changes in urethral pressure. At the end of the tracing, a detrusor contraction can be seen. Urethral pressure oscillations have been shown to be from skeletal muscle activity, smooth muscle activity, or a combination of the two. It has been associated with urgency and frequency and detrusor instability and also is included in the differential diagnosis of genuine stress incontinence [52]. When urine loss is only due to urethral relaxation, the term uninhibited urethral

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relaxation is preferred. Ambulatory urodynamic studies suggest that urethral instability may just be a precursor of detrusor instability, with involuntary bladder contractions eventually being found in almost all of these patients. Sensory abnormalities of urinary storage function may also be diagnosed. Sensory urgency mimics detrusor instability symptomatically with urgency and frequency. Urodynamically, the patient has reduced volumes at first sensation, first desire to void, and maximum cystometric capacity. No involuntary detrusor contractions are seen, but the patient complains of severe pain or urgency at a reduced cystometric capacity and may voluntarily void to relieve the pressure. This is then termed sensory urge incontinence. These women may also have pain with insertion of the catheter. Such patients should also be evaluated with endoscopy to evaluate for urethral inflammation, bladder lesions, or chronic cystitis responsive for this hyperalgesia.

VI. URETHRAL PRESSURE PROFILES Patients maintain urinary continence by having adequate intrinsic sphincteric activity and tone as well as equal or positive pressure transmission to the proximal urethra during increases in intra-abdominal pressure. Most patients with genuine stress incontinence have a condition in which there is urethral hypermobility, which results in decreased pressure transmission to the proximal urethra. This deficit in the extrinsic continence mechanism may be corrected by surgery and compensated for by some nonsurgical treatments. However, deficits in the intrinsic urethral resistance and sphincteric function are not usually corrected by routine, anti-incontinence operations. Intrinsic skeletal muscle, smooth muscle, and elastic and collagenous tissues contribute to the resting intraurethral pressure and tone [53]. In addition, the periurethral vasculature and periurethral skeletal muscle add to the intrinsic urethral resistance. Mucosal coaptation also appears to play a role in the intrinsic sphincteric function. These mechanisms can be studied with urethral pressure profilometry. Urethral pressure profiles are measurements of integrated pressure curves from the entire length of the urethra and are obtained by the slow withdrawal of a pressure-measuring catheter through the urethra at a constant rate. Urethral closure profiles may be static, done with the patient at rest in the supine, sitting, or standing position; or, they may be dynamic, done with the patient coughing, performing a Valsalva maneuver, or squeezing to prevent passage of flatus or urine. Measurement of static urethral closure pressure profiles allows the investigator to make comparisons of preoperative and postoperative measurements or between different positions and states of bladder fullness in the same patient. Such static assessment, although not diagnostic for genuine stress incontinence, may still provide the examiner with useful information. Comparisons of dynamic profiles during coughing and the Valsalva maneuver allow the examiner to make the diagnosis of genuine stress incontinence when pressure equalization is noted in the absence of an increase in detrusor pressure. A low urethral closure pressure, defined as 20 cm H 2 O or less, has been determined to be a useful predictor of surgical failure with retropubic urethropexy and needle suspensions.

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Figure 4 Theoretical static urethral pressure profile.

Figure 4 demonstrates a theoretical static urethral closure pressure profile. Measurements may be made of the total or anatomical urethral length, the functional length, the urethral pressure, the maximal urethral pressure, the bladder pressure, the urethral closure pressure, the maximal urethral closure pressure, the integrated area underneath the curve (representing total urethral closure pressure), and the length to maximal pressure as well as the length from maximal pressure to the external meatus. The total urethral length is a measurement made from the first rise in urethral closure pressure at the urethrovesical junction until the pressure reaches zero atmospheric pressure at the external urethral meatus. Normal anatomical length in the female ranges from 3 to 5 cm. The closure pressure represents the difference between urethral pressure and bladder pressure. When this is positive along any or all of the urethra, the patient will remain continent. If there is no positive closure pressure, then the patient will be incontinent of urine. The functional length is the length of the urethra that has a positive closure pressure. This is the portion of the urethra that maintains continence. The bladder pressure is the pressure measured within the bladder. This differs from the true detrusor pressure, which is the difference between the bladder pressure and the intra-abdominal pressure. The integrated area under the curve or total closure pressure and measurements of partial urethral lengths are used primarily for research purposes. The urethral pressure study is usually done by slowly withdrawing a dualtransducer catheter from the bladder until the urethral pressure-measuring transducer reaches the urethral meatus. The catheter is withdrawn at the same rate as the speed of the recording paper, and the lengths being measured can easily be read from the paper. In Figure 5, the catheter was withdrawn at a rate of 1 mm/s, the same speed of the paper. The small boxes along the X axis represent 1 mm

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or 1 s of elapsed time. The length of the urethra can be obtained by counting the small boxes from the onset of the profile. When augmented studies or Valsalva profiles are done, the speeds of the catheter and paper are changed to 5 mm/s, and the calibration of the boxes remains the same. Figure 5 shows normal urethral closure pressure profiles of a postmeno-

Figure 5 Normal urethral pressure profiles in a postmenopausal woman.

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pausal woman in the sitting position. Resting or static profiles are measured a minimum of three times until a fairly consistent tracing is obtained. The figure shows one example of resting, coughing, and the Valsalva maneuver profiles. Measurement of these closure pressure profiles shows that this woman had a maximum urethral closure pressure of 62 cm H 2 O. The total urethral length was 46 mm, and the functional urethral length was 28 mm. The length to maximal pressure was 9 mm, and the length from the maximal pressure to the urethral meatus was 37 mm. The urethral closure pressure was zero when the urethral transducer was still in the bladder, and as it was slowly withdrawn and entered the urethra, the urethral closure pressure profile was seen. It should be noted that the urethral pressure tracing was identical to the urethral closure pressure tracing. This is because the bladder pressure remained stable throughout the profile. If the bladder pressure increased, the two tracings would not be identical. In fact, this is an important point, as the urethral pressure profile is invalid if there is an ongoing bladder contraction as the catheter is withdrawn. The coughing urethral closure pressure profile is the next profile shown in Figure 5. The patient is asked to cough repetitively every 2 or 3 s while the urethral pressure transducer is slowly withdrawn. With each cough, a measure of pressure transmission to the urethra and bladder can be made at the point of the transducer in the urethra. Positive spikes on the closure pressure profile indicate positive pressure transmission to the urethra, for which the increased pressure in the urethra is greater than the pressure added to the bladder in response to coughing. This differential in added urethral pressure compared to bladder pressure is from equal passive transmission of intra-abdominal pressure to both urethra and bladder augmented by a further increase in urethral pressure from reflex contraction of the periurethral skeletal muscle. The figure shows positive pressure transmission throughout the urethra. Negative pressure transmission would be seen as downward spikes along the urethral closure pressure profile, implying decreased transmission of pressure to the urethra in comparison to the bladder. If the urethral closure pressure falls to zero with a cough, then there is pressure equalization, and the patient leaks urine, signifying genuine stress incontinence. Pressure transmission ratios (PTRs) are used to define quantitatively the relative transmission of pressure to the urethra and bladder during stress. The pressure transmitted is measured by the urethral pressure increment over the urethral pressure profile curve u and the bladder pressure increment b during the coughing profile. The ratio of these pressures is then calculated and multiplied by 100% (PTR ⫽ u/b ⫻ 100%). Positive pressure transmission is the hallmark of continence (PTR ⱖ 100%), while negative pressure transmission (PTR ⬍ 100%) is indicative of failure of the extrinsic continence mechanism (passive transmission of intraabdominal pressure and reflex contraction of the periurethral skeletal muscle). This is associated with genuine stress incontinence unless the intrinsic continence mechanism (tonic smooth muscle, skeletal muscle, vascular muscle, and fibrous connective tissue components) represented by the resting closure pressure is able to compensate for this negative pressure gradient. Positive pressure transmission at one point along the urethra is theoretically enough to maintain continence. Bump et al. [54] found a significant difference in pressure transmission ratios in stress continent and stress incontinent women. In their study, a PTR of 90% or less

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had a sensitivity of 90% and a specificity of 56% for stress incontinence. Pressure transmission ratios are used heavily in research studies, especially for understanding the effects of medical or surgical management on urethrovesical function. The next profile in Figure 5 is the Valsalva urethral closure pressure profile. This is done at higher speed (5 mm/s) as the patient is asked to hold her breath and bear down. This is accompanied by an increase in EMG activity and an increase in abdominal pressure. Figure 5 shows an increase in the closure pressure, implying positive pressure transmission to the urethra and bladder and no evidence of genuine stress incontinence. No leakage is seen. Urethral closure pressure profiles can also be augmented by urethral and rectal squeeze. This studies the effect of contraction of the levator muscles. This is also done at a higher speed (5 mm/s) as the patient may not be able to hold the squeeze for too long. The expected response would be an increase in the closure pressure and the functional length. A lack of this increase would suggest partial denervation to the pelvic floor musculature; rigidity of the urethral wall, which does not allow for extrinsic compression; or an inability to understand or comply with this command. These augmented profiles are difficult to obtain and reproduce reliably and therefore are not routinely done. The patient should contract her levator ani muscles without contracting her rectus abdominis muscles. This can be confirmed as an augmented EMG response without increase in intraabdominal pressure. Genuine stress incontinence is the most common form of urinary incontinence. It is defined by the ICS as the involuntary loss of urine that occurs as a result of an increase in intravesical pressure that exceeds the intraurethral pressure in the absence of a bladder contraction. This can be seen in Figure 6 in the coughing and Valsalva profiles. As a result of the cough, intra-abdominal (and hence intravesical) pressure increases, and the patient leaks. The true detrusor pressure shows no rise. Urethral pressure rises in response to the cough, but not as much as the bladder pressure. This differential pressure transmission to the urethra and bladder is part of the pathophysiology of genuine stress incontinence and results in the urethral closure pressure decreasing to zero when the patient leaks as a result of this negative pressure transmission. The Valsalva profile also demonstrates negative urethral pressure transmission with a decrease in the urethral closure pressure to zero, with resultant leakage. The true detrusor pressure remains unchanged throughout the Valsalva profiles. Artifactual increases in urethral closure pressure may be seen in association with genuine stress incontinence. When positive pressure transmission is seen in association with urinary leakage, one must suspect either artifact or a urethrovaginal fistula. This phenomenon is usually due to a direct force artifact of the pressure transducer being bumped against the urethral wall in response to the cough or Valsalva maneuver. This will produce a momentary increase in pressure recorded, which returns to normal once the increase in intraabdominal pressure is relieved. This artifact is minimized by orienting the pressure transducer laterally (at the 3 o’clock or 9 o’clock position) [55], such that it is at a right angle to the vertical force caused by the cough or Valsalva maneuver. When positive pressure transmission is seen despite recalibrating and reorienting catheters, in association with urinary leakage, other pathology such as a urethrovaginal fistula or a vesicovagi-

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Figure 6 Static and dynamic urethral pressure profiles seen in genuine stress incontinence.

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nal fistula should be strongly suspected. The site of leakage should be carefully observed to see if it is vaginal. Positive pressure transmission is usually seen in women with significant genital prolapse who do not complain of stress incontinence [10,11]. Particularly in association with urethral hypermobility, it is important to perform urodynamic testing with support of the prolapse. Certain patients may develop stress incontinence following surgical repair of the genital prolapse if sufficient attention is not paid to providing permanent support to the urethrovesical junction [56]. The prolapse may protect the patient from stress incontinence by a mechanical kinking effect in the urethra during periods of increased intra-abdominal pressure from coughing or the Valsalva maneuver [10,11]. The prolapse should be supported during the study carefully without obstructing the urethra. A pessary, proctoswabs, or vaginal packing may be used to support the prolapse. Figure 7 shows the static and dynamic urethral pressure profiles, with and without support of a pessary, of a woman with a cystocele to the hymenal ring. This patient was noted to have positive pressure transmission as a result of the mechanical kinking from the prolapse, which was abolished by support of the prolapse. The PTR changed from 167% to 98% with support of the prolapse with resultant leakage. Potential genuine stress incontinence was seen in this patient with no complaints of stress incontinence, but negative pressure transmission and associated leakage from stress with support of the prolapse. This patient should be considered for an antiincontinence procedure along with her prolapse surgery. Stress-induced detrusor instability is another important entity diagnosed by urethral pressure profilometry. Of patients, 2–11% can have this as the sole cause of their urinary incontinence [9,26]. These women complain of stress incontinence, but the etiology of the leakage is entirely from detrusor instability. This can be confusing to diagnose, and the urethral meatus should be carefully observed for leakage coincident with the cough or Valsalva maneuver, signifying genuine stress incontinence versus leakage following or continuing after the cough or Valsalva maneuver, signifying stress-induced detrusor instability. The true detrusor pressure will show an increase in pressure during the profile coincident with leakage and can continue afterward. Urethrovaginal fistulas and urethral diverticula can produce similar resting urethral closure pressure profiles [57]. At the site of the fistula or diverticulum, there is a loss of integrity of the wall of the urethra, creating a pressure sink in that area, which is reflected as a decrease in the urethral pressure profile. This decrease in pressure is seen following return of normal urethral pressures in the distal urethra. In the case of the urethrovaginal fistula, urinary leakage through the vagina may be seen in association with positive pressure transmission during the dynamic profiles, as mentioned above. VII. LEAK POINT PRESSURES Leak point pressures (LPPs) are used for a relatively new urodynamic test to quantify defective sphincteric function in patients with genuine stress incontinence. The LPP was originally defined as the lowest total bladder pressure at which urinary leakage occurs during progressive increases in intra-abdominal pressure by the Valsalva maneuver [58]. The LPP is an indirect measure of the resistance

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Figure 7 Static and dynamic urethral pressure profiles without and with support of prolapse.

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of the urethra to outflow of urine. It may also be thought of as the urethral opening pressure, the pressure necessary to force urine out of the bladder into the urethra. LPPs may be done with progressively harder coughs also and then are called cough leak point pressures. They can be performed following a subtracted cystometry study by removing the transurethral catheter and measuring intra-abdominal pressure with a rectal or vaginal catheter. The abdominal pressure is slowly increased by performing a Valsalva maneuver with gradually increasing force or with incrementally stronger coughs. The threshold of the abdominal pressure at the point of urinary leakage is the abdominal leak point pressure. Alternatively, a small transurethral catheter may be used to measure the bladder leak point pressure. Many variables can affect the LPP, and a lack of standardization of this test only increases the confusion [59]. A rigorous attempt should be made to perform the test in a similar fashion each time. Variability in the test can be caused by position, bladder volume, whether a cough or the Valsalva maneuver is used, and what pressure is measured (the change in abdominal pressure or the total abdominal pressure measurement that causes urinary leakage) [60,61]. If a bladder LPP is performed, the catheter size can also change the measurement [60]. All of these factors should be carefully described when reporting LPPs. If done carefully, LPP testing is simple and reproducible [62] and can be used for monitoring therapy for genuine stress incontinence. If the intrinsic factors of the continence mechanism are compromised, then resting urethral pressure or resistance will be decreased. It has been demonstrated that loss of resting urethral resistance or pressure may cause urinary incontinence even when the proximal urethra is well supported. This is known as type III stress incontinence; as described by McGuire [63], it is defined as a LPP of 60 cm H 2 O or less. When urethral hypermobility and decreased urethral resistance coexist, we use the term low-pressure urethra [33]. This condition is the single largest risk factor for failure of routine anti-incontinence operations. The low-pressure urethra has been defined as one with a resting urethral closure pressure of 20 cm H 2 O or less in the sitting position at maximum cystometric capacity. Sand et al. [33] showed that patients who have a low-pressure urethra may have up to a 54% risk of failing anti-incontinence operations, such as retropubic urethropexies and needle suspensions. There have been conflicting reports regarding the correlation between LPPs and maximal urethral closure pressure [64–66]. While low leak point pressures and low urethral closure pressures define intrinsic sphincteric deficiency in a different manner, one thing is certain: It is a more difficult entity to treat. It has been suggested that these patients not only need support of the proximal urethra, but also need something to compensate for their lost intrinsic sphincteric function. Obstructive procedures such as slings and artificial urinary sphincters have been used in these patients [67,68]. VIII. VOIDING PRESSURE STUDIES The same equipment used to analyze the storage phase during urethrocystometry may be used to study the emptying phase. The dual-channel microtransducer system or external transducer-catheter system can be used to measure the urethral

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and bladder pressures simultaneously by placing the urethral transducer at the point of maximal urethral pressure. The abdominal pressure may be measured vaginally or rectally, and EMG activity may be measured with needle, wire, patch, or ring electrodes at the anus or urethra. By adding uroflowmetry to this equipment, one can analyze the patient’s voiding mechanism and function. The normal male voids by urethral relaxation, followed within seconds by a detrusor contraction. Because the longitudinal muscle fibers of the detrusor continue on into the proximal urethra, contraction of the bladder results in elevation and opening of the urethrovesical junction. This normal activity is modulated by numerous reflex pathways, which allow for the smooth initiation of voiding by urethral relaxation coordinated with a bladder contraction. These reflexes also allow for the normal cessation of voiding with termination of the detrusor contraction following contraction of the urethral and periurethral striated musculature. Although abnormal voiding in the male is almost always due to physical obstruction, this is rare in the female. Women, especially those with decreased urethral resistance, may appear to void normally according to simple uroflowmetry studies by five different mechanisms [69]: (1) urethral relaxation alone, (2) urethral relaxation with detrusor contraction, (3) urethral relaxation with a detrusor contraction plus a Valsalva maneuver, (4) urethral relaxation and the Valsalva maneuver in the absence of a detrusor contraction, and (5) the Valsalva maneuver alone with markedly decreased urethral resistance. Valsalva voiding is common in women with genuine stress incontinence and can cause prolonged urinary retention and catheterization following antiincontinence surgery [70]. In women who have suburethral sling procedures, permanent retention can occur if Valsalva voiding persists [71]. Therefore, it is important to rule out Valsalva voiding. Up to 30% of women who void normally at home may not do so in the urodynamics laboratory. They may void by Valsalva maneuver in this setting if not encouraged to relax and void as they normally would at home. This is because of the uncomfortable nature of having catheters in the vagina and bladder and having strangers in the room. The patient should be left alone when possible to obtain reliable voiding pressure studies. The patient should be asked if the void was typical for the patient. Voiding pressure studies are used primarily to evaluate patients with paruresis or retention. While acute retention is often attributed to patient anxiety, many women carefully evaluated with voiding pressure studies and EMG will have significant underlying pathology. Preminger et al. [72] found that 55% of 27 women seen for acute retention over a 7-year period were found to have a nonpsychological etiology: 19% had myelitis, 11% diabetes, 11% other neuropathies, and 15% late postoperative retention. Fowler and Kirby [73] found that 72% of all patients with retention (acute and chronic) had EMG abnormalities on concentric needle testing. These investigators would suggest that careful evaluation and neurological workup are indicated for all women with urinary retention. Electromyography allows us to observe the electrical potentials, individually or on summation, that are generated during the depolarization of skeletal muscle. This activity gives us insight into the electrical activity of the urethra, while measurement of urethral pressure gives us a summation of the mechanical properties of the skeletal and smooth muscle of the urethra. EMG studies may be done with concentric needles, which allow for analysis of individual motor units. Hooked

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wires allow pickup from an area of muscle fibers reliably, but no individual assessment. Surface electrodes or patches transcutaneously pick up generalized pelvic floor muscle activity. Surface electrodes can be of the patch type, which may be placed perianally or transvaginally, or the ring electrode type, which is placed on a plug in the anus or on a catheter in the urethra. Surface electrodes are less invasive, but observe only global activity and are more susceptible to interference and artifact [74]. Wire electrodes offer the advantage of reliable EMG activity observation and are not affected by urinary leakage like surface patch electrodes may be. Therefore, needle or wire electrodes are more advisable when evaluating urinary retention to allow for uninterrupted EMG recording during voiding. The urethral transducer of the dual-channel catheter is placed midurethrally at the point of maximal urethral pressure to observe urethral pressure changes during voiding. The EMG response is calibrated by asking the patient to perform a rectal squeeze maneuver. The patient is then asked to void in a sitting physiological position. The vesical pressures at various points during the flow are included in a study, including premicturition pressure, opening pressure at the onset of flow, the maximum voiding pressure recorded during the study, and the pressure at maximum flow. The times between urethral relaxation and detrusor pressure increase, and then the times to the start of urine flow are noted. The maximum flow rate, the average flow rate, the time to maximum flow, and the total flow time are recorded. If an interrupted flow is present, the voiding time is the total time that the patient voids from onset of flow to the point that all flow ceases, and the flow time is the incremental total of the time during which flow is actually recorded. Normally, the urethra relaxes first, followed by the onset of a detrusor contraction 3–5 s later, followed by initiation of flow in another 3 s. While the Liverpool nomograms attempt to establish normal voiding parameters for men and women [75], abnormal parameters are not well established in women who have various pathologies associated with voiding dysfunction. Figure 8 shows a normal voiding mechanism in a woman about to undergo a Burch procedure for genuine stress incontinence. The urethral pressure drops from 64 cm H 2 O to 22 cm H 2 O. Meanwhile, the bladder pressure rises approximately 4 s later, and urine flow begins in another 5 s. The EMG, measured by perianal patches, shows appropriate relaxation of the pelvic floor, and there is no rise in intraabdominal pressure, implying no use of the Valsalva maneuver here. The maximum flow rate achieved is 25 mL/s, which is achieved in 4 s, and the whole flow is completed in 14 s. The postvoid residual is 10 mL. Abnormal voiding with retention may simply be characterized as occurring because of either ineffective detrusor activity or deficient urethral relaxation. Some patients may have a complete absence of detrusor activity during voiding studies, which is called an acontractile detrusor. Before making this diagnosis, one must be sure that an isometric contraction is not being missed due to decreased urethral resistance at the time of the void. A stop test should be done to rule out this possibility. Obstruction of the urethra, by having the patient voluntarily contract the urethral musculature or by physically obstructing the urethra with the urodynamicist’s finger, will allow for the measurement of the isometric detrusor pressure. Detrusor areflexia is the term used to describe the neurogenic problem for which bladder contractions are absent because of an absence of central control, as with spinal cord lesions. In the absence of a bladder contraction, the patient

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Figure 8 Normal void.

may use a Crede maneuver or Valsalva maneuver to force urine out. This may be seen urodynamically as increases in intra-abdominal pressure intermittently during the void. The underactive detrusor is one that is unable to contract long enough and/or strongly enough to bring about bladder emptying in a normal amount of time. This may be more prevalent with aging. Inadequate urethral relaxation that causes urinary retention may be detected

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by the use of EMG of the pelvic floor or urethra with the measurement of the urethral pressure. Usually, rises in urethral pressure will be paralleled by increases in the skeletal muscle activity as noted on EMG. EMG activity can help make the diagnosis of detrusor sphincter dyssynergia, for which there is a lack of coordination between bladder and urethra, preventing adequate relaxation of the urethra during a bladder contraction. This is usually because of inadequate relaxation or contraction of the periurethral skeletal muscle and is caused by decentralization from spinal cord lesions. Needle or wire EMG can give a direct indication of the periurethral skeletal muscle activity and shows simultaneous contraction of the urethral sphincter and the bladder (Fig. 9). Siroky and Krane [76] hypothesized that detrusor sphincter dyssynergia represents an abnormal flexor reflex response in patients with spinal cord lesions below the pons. It is seen commonly with detrusor hyperreflexia. Most investigators believe that true detrusor sphincter dyssynergia is a neurological disease of skeletal muscle control, but other functional and autonomic variants have been described as causes of urinary retention [77]. Functional discoordination may be a result of an exaggerated guarding response to involuntary bladder contractions. Women or girls with long-standing detrusor instability habitually try to voluntarily constrict the urethra and pelvic floor muscles to guard against urinary leakage. Habituation to this response over time may interfere with voluntary attempts at voiding. Treating the underlying detrusor instability or using behavior modification has been effective in resolving this “nonneurogenic neurogenic” bladder. It has been theorized that other women interrupt voiding in a spastic pattern because of inflammation or spasm, which can be treated with diazepam, α-blockers, and treatment of chronic urethrotrigonitis [78]. IX. ENHANCED URODYNAMIC STUDIES As mentioned, urodynamic studies can be enhanced by fluoroscopy, ultrasound, or ambulatory monitoring. Videourodynamics add fluoroscopic visualization of the bladder and the urethra during the standard urodynamic studies. This obviously adds to the cost, with needed additional equipment including a fluoroscopy-compatible chair, television camera, television, and video recording equipment and the use of radioopaque material for the study. While some find little utility to the addition of fluoroscopy [79], others find it useful as a comprehensive test of lower urinary tract function and anatomy [80]. Descent of the bladder neck, bladder neck funneling, vesicoureteral reflux, prolapse, fistulas, and diverticula can all be assessed. Other fluoroscopic evaluations such as defecography studies may also be performed with this equipment. The major disadvantages to videourodynamics include its cost, exposure to radiation, and need for extra space and radiology personnel. Ambulatory monitoring is a means of performing urethrocystometry in a more physiological setting, much like Holter monitoring of the heart. The catheters are taped in place and attached to a recorder worn by the patient. The data can then be downloaded after the patient has been performing her normal activities for a specified period of time, including several filling and emptying cycles. It is an ideal tool if standard office urodynamics fail to explain the patient’s symp-

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Figure 9 Abnormal void with retention from detrusor sphincter dyssynergia. toms. A higher frequency of detrusor contractions and larger voiding pressures have been documented on ambulatory monitoring [81–83]. These studies also correlate better with the patient’s symptoms [83]. This type of study may become the gold standard for evaluating filling and emptying phase pathology. Ultrasound can also be used for the dynamic evaluation of the lower urinary tract. Recent studies have shown good reliability of color Doppler ultrasound in

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the evaluation of bladder outlet obstruction and vesicoureteral reflux [84,85]. Bladder neck mobility is also well documented by translabial ultrasound [86]. While ultrasound evaluation in urogynecology sounds promising [87], further studies are needed to compare it with fluoroscopy.

X.

CONCLUSION

Urodynamic studies provide a comprehensive evaluation of the filling and emptying phases as well as pressure dynamics under stress and at rest. Whether such complete testing is required for every patient is debatable, and this decision should be individualized. The main objective should be to obtain a diagnosis that is consistent with the patient’s symptomatology and can improve treatment outcomes. Cost analysis is also an important factor in targeting patients that need comprehensive urodynamic evaluation. Future research should help individualize such testing.

REFERENCES 1. Farrar DJ, Whiteside CG, Osborne JL, et al. A urodynamic analysis of micturition symptoms in the female. Surg Gynecol Obstet 1975; 141:875–883. 2. Hastie KJ, Moisey CU. Are urodynamics necessary in female patients presenting with stress incontinence? Br J Urol 1989; 63:155–156. 3. Sand PK, Hill RC, Ostergard DR. Incontinence history as a predictor of detrusor stability. Obstet Gynecol 1988; 71:257–260. 4. Cardozo LD, Stanton SL. Genuine stress incontinence and detrusor instability—a review of 200 patients. Br J Obstet Gynaecol 1980; 87:184–190. 5. Webster GD, Sihelnik SA, Stone AR. Female urinary incontinence: the incidence, identification, and characteristics of detrusor instability. Neurourol Urodyn 1984; 3:235– 242. 6. Flezerman M, Glasner M, Rikover M, et al. Evaluation of reliability of history in women complaining of urinary stress incontinence. Eur J Obstet Gynecol Reprod Biol 1986; 21:159–164. 7. LeCoutour X, Jung-Faerber S, Klein P, et al. Female urinary incontinence: comparative value of history and urodynamic investigations. Eur J Obstet Gynecol Reprod Biol 1990; 37:279–286. 8. Jensen JK, Nielsen FR Jr, Ostergard DR. The role of patient history in the diagnosis of urinary incontinence. Obstet Gynecol 1994; 83:904–910. 9. Lemack GE, Zimmern PE. Identifying patients who require urodynamic testing before surgery for stress incontinence based on questionnaire information and surgical history. Urology 2000; 55(4):506–511. 10. Richardson DA, Bent AE, Ostergard DR. The effect of uterovaginal prolapse on urethrovesical pressure dynamics. Am J Obstet Gynecol 1983; 146:901–905. 11. Bump RC, Fantl JA, Hurt WG. The mechanism of urinary continence in women with severe uterovaginal prolapse: results of barrier studies. Obstet Gynecol 1988; 72:291– 295. 12. Bergman A, Koonings PP, Ballard CA. Predicting postoperative urinary incontinence development in women undergoing operation for genitourinary prolapse. Am J Obstet Gynecol 1988; 158:1171–1175. 13. Myers DL, Lasala CA, Hogan JW, et al. The effect of posterior wall support defects

Urodynamics of Pelvic Floor Dysfunction

14. 15. 16. 17. 18. 19. 20. 21. 22.

23.

24.

25. 26.

27.

28. 29. 30. 31.

32. 33. 34. 35.

103

on urodynamic indices in stress urinary incontinence. Obstet Gynecol 1988; 91(5):710– 714. Fantl JA, Smith PJ, Schneider V, et al. Fluid weight uroflowmetry in women. Am J Obstet Gynecol 1983; 145:1017–1024. Lobel RW, Sand PK. The empty supine stress test as a predictor of intrinsic urethral sphincter dysfunction. Obstet Gynecol 1996; 88(1):128–132. McLennan MT, Bent AE. Supine empty stress test as a predictor of low valsalva leak point pressure. Neurourol Urodyn 1998; 17(2):121–127. Mayer R, Wells T, Brink C, et al. Handwashing in the cystometric evaluation of detrusor instability. Neurourol Urodyn 1991; 10:563. Jorgensen L, Lose F, Andersen JT. One hour pad-weighing test for objective assessment of female urinary incontinence. Obstet Gynecol 1987; 69:39. Klarskov P, Hald T. Reproducibility and reliability of urinary incontinence. Assessment with a 60 min test. Scand J Urol Nephrol 1984; 18:293–298. Lose G, Versi E. Pad-weighing tests in the diagnosis and quantification of incontinence. Int Urogynecol J 1992; 3:324. Robertson JR. Dynamic urethroscopy. In: Ostergard DR, Bent AE, eds. Urogynecology and Urodynamics. Baltimore, MD: Williams and Wilkins, 1991:115–121. Sand PK, Hill RC, Ostergard DR. Supine urethroscopic and standing cystometry as screening methods for the detection of detrusor instability. Obstet Gynecol 1987; 70: 57–60. Scotti RJ, Ostergard DR, Guillaume AA, et al. Predictive value of urethroscopy as compared to urodynamics in the diagnosis of genuine stress incontinence. J Reprod Med 1990; 35:772–776. Ouslander J, Leach G, Abelson S, et al. Simple versus multichannel cystometry in the evaluation of bladder function in an incontinence geriatric population. J Urol 1988; 140:1482–1486. Sand PK, Brubaker LT, Novak T. Simple standing incremental cystometry as a screening method for detrusor instability. Obstet Gynecol 1991; 77:453–457. Weber AM, Walters MD. Cost-effectiveness of urodynamic testing before surgery for women with pelvic organ prolapse and stress urinary incontinence. Am J Obstet Gynecol 2000; 183(6):1338–1347. Thompson PK, Duff DS, Thayer PS. Stress incontinence in women under 50: does urodynamics improve surgical outcome? Int Urogynecol J Pelvic Floor Dysfunct 2000; 11(5):285–289. Sand PK, Bowen LW, Ostergard DR, et al. The effect of retropubic urethropexy on detrusor stability. Obstet Gynecol 1988; 71:818–822. Schrepferman CG, Griebling TL, Nygaard IE, et al. Resolution of urge symptoms following sling cystourethropexy. J Urol 2000; 164(5):1628–1631. Constantinou CE. Resting and stress urethral pressures as a clinical guide to the mechanism of continence in the female patient. Urol Clin North Am 1985; 12:247–258. Hilton P, Stanton SL. Urethral pressure measurement by microtransducer: the results in symptom-free women and in those with genuine stress incontinence. Br J Obstet Gynaecol 1983; 90:919–933. Versi E, Cardozo L, Studd J, et al. Evaluation of urethral pressure profilometry for the diagnosis of genuine stress incontinence. World J Urol 1986; 4:6. Sand PK, Bowen LW, Panganiban R, et al. The low pressure urethra as a factor in failed retropubic urethropexy. Obstet Gynecol 1987; 69:399. Kuo HC. Videourodynamic study for diagnosis of bladder outlet obstruction in women. J Formos Med Assoc 2000; 99(5):386–392. Lemack GE, Zimmern PE. Pressure flow analysis may aid in identifying women with outflow obstruction. J Urol 2000; 163(6):1823–1828.

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36. Millar HD, Baker LE. A stable ultraminiature catheter-tip pressure transducer. Med Biol Eng 1973; 11:86–89. 37. Teague CT, Merrill DC. Laboratory comparison of urethral profilometry techniques. Urology 1979; 13(2):221–228. 38. Sand PK, Bowen LW, Ostergard DR. The effect of a filling catheter during urodynamics. Int Urogynecol J 1990; 1:124–127. 39. Bump RC. The urodynamic laboratory. Obstet Gynecol Clin North Am 1989; 16(4): 795–816. 40. Fossberg E, Rud T. Fiber-optic versus microtip transducers in simultaneous urethrocystometry. Eur Urol 1988; 14:27–29. 41. Ask P, Hok B. Pressure measurement techniques in urodynamic investigations. Neurourol Urodyn 1990; 9:1–15. 42. Culligan PJ, Rackley R, Koduri S, Thompson RB, Schwabe L, Sand PK. Is it safe to reuse a syringe of GAX collagen? A microbiologic study. J Urol 2001; in press. 43. Elser DM, London W, Fantl WA, et al. A comparison of urethral profilometry using microtip and fiberoptic catheters. Int Urogynecol J Pelvic Floor Dysfunct 1999; 10(6): 371–374. 44. Lewis P, Abrams P. Urodynamic protocol and central review of data for clinical trials in lower urinary tract dysfunction. Br J Urogynecol Int 2000; 85(1):20–31. 45. Abdel-Rahman M, Coulombe A, Devroede G, et al. Urorectodynamic evaluation of healthy volunteers. Urology 1982; 19(5):559–564. 46. Mayer R, Wells T, Brink C, et al. Handwashing in the cystometric evaluation of detrusor instability. Neurourol Urodyn 1991; 10:563–569. 47. Frigerio L, Ferrari A, Candiani GB. The significance of the stop test in female urinary incontinence. Diagn Gynecol Obstet 1981; 3:301–304. 48. Farquharson DIM, Shingleton H, Sanford SP, et al. The short-term effect of pelvic irradiation for gynecologic malignancies on bladder function. Obstet Gynecol 1987; 70:81–84. 49. Sand PK. The acontractile bladder. In: Sand PK, Ostergard DR, eds. Urodynamics and the Evaluation of Female Incontinence, 2nd ed. London: Springer-Verlag. 50. Vereecken RL. Physiological and pathological urethral pressure variations. Urol Int 1996; 57(3):145–150. 51. Weil A, Miege B, Rottenberg R, et al. Clinical significance of urethral instability. Obstet Gynecol 1986; 68:106–110. 52. Vereecken RL, Das J. Urethral instability: related to stress and/or urge incontinence. J Urol 1985; 134:698–701. 53. DeLancey JO. Anatomy and physiology of urinary continence. Clin Obstet Gynecol 1990; 33:298–307. 54. Bump RC, Copeland WE, Hurt WG, et al. Dynamic urethral pressure/profilometry pressure transmission ratio determinations in stress-incontinent and stress-incontinent subjects. Am J Obstet Gynecol 1988; 159(3):749–755. 55. Anderson RS, Shepherd AM, Feneley RCL. Microtransducer urethral profile methodology: variations caused by transducer orientation. J Urol 1983; 130:727–728. 56. Beck RP, McCormick S, Nordstrom L. A 25-year experience with 519 anterior colporrhaphy procedures. Obstet Gynecol 1991; 78:1011–1018. 57. Urethrovaginal fistulas, urethral diverticula. In: Sand PK, Ostergard DR eds. Urodynamics and the Evaluation of Female Incontinence, 2nd ed. London: Springer-Verlag. 58. McGuire EJ, Fitzpatrick CC, Wan J, et al. Clinical assessment of urethral sphincter function. J Urol 1993; 150:1452–1454. 59. Swift SE, Utrie JW. The need for standardisation of the valsalva leak-point pressure. Int Urogynecol J 1996; 7(4):227–230. 60. Bump RC, Elser DM, Theofrastous JP, et al. Valsalva leak point pressure in women

Urodynamics of Pelvic Floor Dysfunction

61. 62. 63. 64.

65. 66.

67.

68.

69. 70.

71. 72. 73. 74. 75.

76. 77. 78. 79.

80. 81.

105

with genuine stress incontinence: reproducibility, effect of catheter caliber and correlations with other measures of urethral resistance. Am J Obstet Gynecol 1995; 173: 551–557. Miklos JR, Karram MM. A critical appraisal of methods of measuring leak point pressures in women with stress incontinence. Obstet Gynecol 1995; 86:349–352. Heritz DM, Blaivas JG. Reliability and specificity of the leak point pressure. J Urol 1995; 153:492A. Abstract 1055. McGuire EJ. Urodynamic findings in patients after failure of stress incontinence operations. Prog Clin Biol Res 1981; 78:351–360. Bump RC, Coates KW, Cundiff G, et al. Diagnosing intrinsic sphincteric deficiency: comparing urethral closure pressure, urethal axis, and valsalva leak point pressures. Am J Obstet Gynecol 1997; 177(2):303–310. Sultana CJ. Urethal closure pressure and leak-point pressure in incontinent women. Obstet Gynecol 1995; 86(5):839–842. Swift SE, Ostergard DR. A comparison of stress leak-point pressure and maximal urethral closure pressure in patients with genuine stress incontinence. Obstet Gynecol 1995; 85(5):704–708. Summit RL, Bent AE, Ostergard DR, et al. Suburethral sling procedure for genuine stress incontinence and low urethral closure pressure. A continued experience. Int Urogynecol J 1992; 3:18–21. Horbach NS, Blanco JS, Ostergard DR, et al. A suburethral sling procedure with polytetrafluoroethylene for the treatment of genuine stress incontinence in patients with low urethral closure pressure. Obstet Gynecol 1988; 71:648–652. Rud T, Ulmsten U, Andersson KE. Initiation of voiding in healthy women and those with stress incontinence. Acta Obstet Gynecol Scand 1978; 57:457–462. Bhatia NN, Bergman A. Use of preoperative uroflowmetry and simultaneous urethrocystometry for predicting risk of prolonged postoperative bladder drainage. J Urol 1986; 28:440–445. Rud T, Ulmsten U, Anderson KE. Initiation of voiding in healthy women and in those with stress incontinence. Acta Obstet Gynecol Scand 1978; 57:457–462. Preminger GM, Steinhardt GF, Mandell J, et al. Acute urinary retention in female patients: diagnosis and treatment. J Urol 1983; 130:112–113. Fowler CJ, Kirby RS. Electromyography of urethral sphincter in women with urinary retention. Lancet 1986; 1:1455–1457. Vereecken RL, Mulders JV. Techniques and value of sphincter electromyography in urological problems. Urol Int 192; 37:152–159. Haylen BT, Ashby D, Sutherst JR. Maximum and average urine flow rates in normal male and female populations—the Liverpool nomograms. Br J Urol 1989; 64:30– 38. Siroky MB, Krane RJ. Neurologic aspects of detrusor-sphincter dyssynergia with reference to the guarding reflex. J Urol 1982; 127:953–957. Allen TD. The non-neurogenic neurogenic bladder. J Urol 1977; 117:232–238. Vereecken RL, Poppel HV, Boeckx G, et al. Long term alpha-adrenergic-blocking therapy in detrusor-urethra dyssynergia. Eur Urol 1983; 9:167–169. Rud T, Ulmsten U, Westby M. Initiation of micturition: a study of combined urethrocystometry and urethrocystography in healthy and stress incontinent females. Scand J Urol Nephrol 1979; 13:258–264. Carlson KV, Rome S, Nitti VW. Dysfunctional voiding in women. J Urol 2001; 165(1): 143–148. Porru D, Usai E. Standard and extramural ambulatory urodynamic investigation for the diagnosis of detrusor instability-correlated incontinence and micturition disorders. Neurourol Urodyn 1994; 13:237–242.

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82. Vereecken RL, Van Nuland T. Detrusor pressure in ambulatory versus standard urodynamics. Neurourol Urodyn 1998; 17(2):129–133. 83. Bhatia NN, Bradley WE, Haldeman S. Urodynamics: continuous monitoring. J Urol 1982; 128:963–968. 84. Ding YY, Ozawa H, Yokoyama T, et al. Reliability of color Doppler ultrasound urodynamics in the evaluation of bladder outlet obstruction. Urology 2000; 56(6):967–971. 85. Farina R, Arena C, Pennisi F, et al. Vesico-ureteral reflux: diagnosis and staging with voiding color Doppler US: preliminary experience. Eur J Radiol 2000; 35(1):49–53. 86. Howard D, Miller JM, DeLancey JO, et al. Differential effects of cough, Valsalva, and continence status on vesical neck movement. Obstet Gynecol 2000; 95(4):535–540. 87. Dietz HP, McKnoulty L, Clarke B. Translabial color Doppler for imaging in urogynecology: a preliminary report. Ultrasound Obstet Gynecol 1999; 14(2):144–147.

7 Injectable Agents for the Treatment of Stress Urinary Incontinence in Females* NATANIA Y. PIPER and R. DUANE CESPEDES Wilford Hall Medical Center San Antonio, Texas, U.S.A.

I.

HISTORICAL PERSPECTIVE

The use of bulking agents dates to 1938, when Murless injected sodium morrhuate, a sclerosing agent, into the anterior vaginal wall of 20 incontinent women [1]. The inflammatory response compressed the urethra and provided improved continence in 17 women; however, complications precluded its further use. In 1955, Quackels successfully treated two patients with periurethral paraffin injections [2]. Sachshe utilized Dondren, a sclerosing agent, in 1963; however, pulmonary emboli complicated the procedure [3]. The modern era of bulking agents began when Berg and later Politano and associates popularized the use of polytetrafluoroethylene (PTFE; Teflon, Polytef, and Urethrin) in the early 1970s [4,5]. This agent is a thick paste, with most of the particles ranging in size from 4 to 100 µm. PTFE was extensively used until 1984, when animal studies demonstrated particle migration and granuloma formation in the brain, liver, spleen, and lungs dampening enthusiasm for this agent. PTFE is not currently approved by the Food and Drug Administration (FDA) as a bulking agent.

* The opinions contained herein are those of the authors and are not to be construed as reflecting the views of the Air Force or the Department of Defense.

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In 1989, autologous fat was first described as an injectable bulking agent by Gonzales and colleagues [6]. A report by Santarosa and Blaivas on 15 patients noted that 5 patients were cured and 5 more significantly improved at 11-month follow-up [7]. In contrast, others have reported high reabsorption rates and poor long-term viability [8]. In addition, one fatal case of pulmonary fat embolism has been reported [9]. Because of the poor long-term results and potential complications, autologous fat injection is not commonly used in the treatment of incontinence. In 1993, the FDA approved the use of bovine collagen as a new, minimally invasive treatment for stress incontinence. Glutaraldehyde cross-linked (GAX) collagen (Contigen, CR Bard Co., Covington, GA) is a highly purified bovine dermal collagen cross-linked with glutaraldehyde and suspended in a phosphate base. GAX collagen contains 3.5% collagen by volume and contains approximately 95% type 1 collagen and 1–5% type 3 collagen. It is prepared by selective hydrolysis of the nonhelical amino terminal and carboxyl terminal segments (telopeptides) of the collagen molecules. Since the telopeptides are the antigenic markers for collagen, GAX collagen has less antigenicity. The glutaraldehyde cross-linking also reduces hydrolysis by fibroblast-secreted collagenases. As a result, GAX collagen is reabsorbed much slower than previous collagen compounds used in cosmetic surgery [10]. GAX collagen is biocompatible and does not cause foreign body reaction, and particle migration has not been demonstrated. A mild inflammatory reaction does occur that appears to result in replacement of the bovine collagen by the patient’s own collagen [11]. Last, GAX collagen is easily injected through a small needle, allowing precise placement of the collagen using standard equipment and local anesthesia. Because GAX collagen is the most commonly used injectable agent in the treatment of stress urinary incontinence in females, this chapter focuses on its use. II. PATIENT SELECTION There are two general etiologies for urinary incontinence: dysfunction of the bladder or dysfunction of the urethral sphincter. Bladder conditions that can produce incontinence include detrusor instability and poor detrusor compliance. Detrusor instability (also called an “overactive bladder”) is common in elderly patients and is manifested by a sudden urge to void that cannot be inhibited. If severe, urgency may result in urge incontinence. Poor detrusor compliance is characterized by an abnormal increase in detrusor pressure as a result of filling [12]. This condition is most commonly seen in patients with neurogenic bladders and after pelvic irradiation. It is important to distinguish these forms of incontinence from stress urinary incontinence as neither condition is treatable with injectable agents. The classification of patients with stress urinary incontinence has undergone many changes over the last decade [13]. An analysis of abdominal (or Valsalva) leak point pressure (LPP) data using fluoroscopic imaging in a prospective study of females with stress incontinence found three relatively distinct groups of patients [14]. Some incontinent patients demonstrated high abdominal LPPs (⬎100 cm H2O); another group demonstrated very low LPPs (⬍60 cm H2O); and a smaller group of patients was found to be in the “gray zone” (abdominal LPP

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Figure 1 Intrinsic sphincter deficiency in a 63-year-old female previously treated with a retropubic suspension. During a Valsalva maneuver, minimal mobility of the bladder neck was noted; however, the bladder neck opened, with resulting incontinence.

between 60 and 100 cm H2O) [15]. Type III stress incontinence, more recently termed intrinsic sphincter deficiency (ISD), is characterized by a low ALPP (less than 60 cm H2O) and little or no urethral mobility with straining (Fig. 1). It is well established that patients with type III stress incontinence are at an increased risk of failing a suspension procedure, and treatment with one of the sling procedures or an injectable agent is recommended [16–20]. As ISD is most often associated with prior failure of a surgical procedure or elderly females, collagen injections provide a minimally invasive method of attaining continence. Early studies demonstrated that patients successfully treated with collagen injections had an average increase in the abdominal LPP of 31 cm H2O; however, there was little change in the voiding pressure since muscular relaxation allowed the bladder neck to open widely [21]. Type II stress incontinence is associated with urethral hypermobility, and incontinence occurs at higher pressures, usually greater than 100 cm H2O (Fig. 2). On physical examination, the urethra is mobile in conjunction with prolapse of the adjacent vaginal wall. All incontinence procedures that provide support and immobilize the urethra work reasonably well. Although collagen has shown some efficacy in treating patients with hypermobility, it is rarely used because sling procedures are associated with better long-term results in this younger group of patients. As with any procedure, proper patient selection is the key to therapeutic success and patient satisfaction. The ideal candidate for collagen injections is one

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Figure 2 Fluorourodynamic study demonstrating incontinence secondary to urethral hypermobility. During a Valsalva maneuver, the bladder neck (at the arrows) rotates posteriorly, and incontinence occurs. with ISD, minimal urethral mobility, and normal detrusor function. Clinically, these patients are often elderly patients with some degree of detrusor instability. Detrusor instability that coexists with stress urinary incontinence is not a contraindication for collagen injection; however, it is prudent to medically treat the instability before continuing to collagen injections. The patient must also know that multiple injections 4–6 weeks apart will be required, and that transient urinary retention requiring intermittent catheterization may occur in rare circumstances. In most cases, only two or three total injections will be required to achieve dryness. In addition, as collagen is slowly reabsorbed and replaced by the patient’s own collagen, some patients will require reinjection at some time in the future even if they are continent for many years. If the patient is unwilling to undergo a minimum of two injections and perform transient self-catheterization if retention occurs, other therapies should be discussed. The only absolute contraindications to collagen injections are an untreated urinary tract infection and hypersensitivity to the material. Therefore, all patients are skin tested using 0.1 mL of the more immunogenic non-cross-linked collagen 30 days before collagen treatments are started. The overall hypersensitivity rate has been reported as between 2% and 5% [22]. Extra caution should be used in immunocompromised patients and patients on steroids because they may not react to the skin test even if they are allergic to bovine collagen. Last, collagen injections have not been well studied in pregnant women, and other alternatives should be considered.

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III. SURGICAL TECHNIQUE Collagen may be injected using either a periurethral or a transurethral approach (Fig. 3). The initial studies were performed using the periurethral approach; however, now that specialized transurethral instrumentation exists, the transurethral approach has become more popular [23]. The endoscopic injection procedure can be performed in the outpatient setting using a local anesthetic with minimal patient discomfort. If performed in the operating room, sedation or general anesthesia is usually favored as spinal anesthesia may cause prolonged urinary retention. The patient normally takes a single dose of a fluoroquinolone antibiotic preinjection and an additional dose the next day. The patient is then placed in the lithotomy position, and the perineum and vagina are prepped and draped. We use the Wolf 21F panendoscope, which has a Nesbit-type working element and rigid 23gauge needle (Richard Wolf Instruments, Vernon Hills, IL) (Fig. 4). The key to obtaining good results with collagen is the precise placement of the transurethral needle, ensuring accurate placement of the collagen. In addition, less collagen is wasted, improving cost-effectiveness. Collagen injections in females usually require only two injection sites as the collagen usually dissects circumferentially around the bladder neck if the proper plane is found. Normally, the 4 and 8 o’clock positions are selected at the bladder neck. A small amount (0.2–0.5 mL) of 1% plain lidocaine is injected first to decrease pain and to help in dissecting the appropriate plane for the collagen to fill. Without withdrawal of the needle, the collagen syringe is attached, and the collagen is injected very slowly. It usually takes at least 2–3 min to inject each syringe. Collagen will fill the submucosal plane and effectively “close off” the bladder neck (Fig. 5). Resist the temptation to overinject as the mucosa will rupture, and all the collagen will be lost. The injection of collagen requires tissue “expansion”

Figure 3 A syringe of GAX collagen (Bard, Covington, GA) shown with both the periurethal and transurethral injection needles.

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Figure 4 Transurethral collagen injections are most efficiently performed using a specialized injection cystoscope such as the Wolf aspiration injection cystoscope. (Richard Wolf Instruments, Vernon Hills, IL). This injection cystoscope features a rigid needle system (as seen in the inset photograph), a Nesbit-style working element that allows the needle to be advanced, and a smooth sheath.

and as such must be done slowly over a relatively long period of time to decrease the chances of tissue rupture. Certain technical aspects of the injection are important to understand. If the needle is placed too deep, collagen is wasted, and the desired bulging of the urethral mucosa does not occur. Generally, only 1–2 mL need to be injected before this bulging is evident. Conversely, if the needle depth is too shallow, a small amount of collagen will cause a mucosal “bleb,” identified by the lack of blood vessels in the lining of the tissue. This bleb will eventually rupture, creating a defect with loss of all collagen injected. Ideally, the collagen should be injected slowly using the fewest injection sites possible. Avoid injecting directly into the external sphincter as this may result in dysuria and perineal pain. Usually, one syringe (2.5 mL) and occasionally two syringes are used depending on the degree of coaptation achieved. The end point of the procedure is visual closure of the bladder neck without leakage of urine in response to increased intraabdominal pressure. To test how efficacious the injection is, leave the bladder full, remove the scope, and have the patient cough. If leakage occurs, more collagen can be given, but keep in mind that if more than two syringes are required to close the bladder neck completely, the injection is in the wrong plane. Postoperatively, an indwelling catheter should be avoided as molding of the collagen around the catheter may occur, with subsequent loss of efficacy. All patients must be able to void prior to leaving the clinic or be taught clean intermittent catheterization using a 10–14 Fr catheter. IV. RESULTS Multiple studies have reported good results using collagen in selected patients (Table 1). In 1990, the initial studies using collagen reported that 78% of females

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Figure 5 In this series of intraoperative photographs, the open bladder neck is shown sequentially by a collagen injection. (A) The preoperative view; (B) the needle has been inserted into the right side of the bladder neck, with bulging of the mucosa to the midline seen. (C) The left side of the bladder neck is closed with collagen; (D) final result. Normally, only two injection sites are needed in female patients, and only one or two syringes of collagen are injected per visit.

became dry; overall, 93% were significantly improved [24]. Dryness was achieved in 88% using three or fewer injections, and 58% required only one injection. At 2 years, of patients rendered initially dry, 78% remained dry, demonstrating the durability of collagen injections in females. Monga and colleagues reported a 68% subjective cure rate and 48% objective cure rate at 24 months after collagen injection [19]. This group was also the first to report a sustained decrease in the symptoms of urge incontinence; although unexpected, this may greatly benefit these hard-to-treat patients. Steele and colleagues compared the results of using collagen in patients with and without urethral hypermobility [25]. Of 40 patients, 9 were diagnosed with hypermobility. Steele et al. reported a subjective dry rate of 76% in the hypermobile group compared to 46% of the nonmobile group. It is clear that patients with hypermobility can be treated successfully in some cases using collagen; however, it is important to remember that this group of patients are typically younger and usually have pelvic prolapse in other areas. Therefore, a sling procedure and prolapse repair should be considered in this group of patients.

149 31 50 16 42

Appell [31] Hershorn et al. [20] Stricker and Haylen [36] Kieswetter et al. [37] Richardson et al. [38]

N/A ⫽ not available.

44 29 139

No. of patients

12 8.4 11 4.5 46

N/A 24 18

Mean Follow-up (months)

19.2 12.7 14.4 N/A 28.3

9.1 10.8 N/A

Mean (cc) cumulative volume

Results Using GAX Collagen for Incontinence in Females

O’Connell et al. [18] Monga et al. [19] Cross [28]

Authors

Table 1

45 48 74 (Dry⫹significantly improved) 80.8 48 42 43 40

Cured (%)

N/A 41 40 50 43

18 20 N/A

Significantly improved (%)

N/A 9 14 18 17

12 N/A 5

Failed (%)

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In a review of a small urban practice, Tschopp and colleagues examined the durability of collagen injection in 99 women [26]. A success rate of 56% with a follow-up of 9 months was reported. They concluded that collagen injection has minimal morbidity with good success in appropriate patients. In 1995, O’Connell et al. reported the results of their use of collagen injections. Patient response to treatment was evaluated by the change in the number of pads required to effect significant improvement. Cure was effected for 63%, with four patients having previously used greater than 10 pads per day prior to injection. No major complications were noted [18]. Moore et al. provided an objective report of collagen injections; their study used exams, pad tests, and urodynamic evaluation in postoperative follow-ups [27]. They found significant decreases in pad number and weight from baseline, with no difference in residual volume, voided volume, or flow rate. Interestingly, two women reported only “improvement,” yet were objectively cured; conversely, one patient felt she was cured, yet leaked 11 g of urine on pad testing. Two patients developed cystitis; however, no patients experienced urinary retention. Most recently, Cross et al. reported their long-term follow-up of patients treated with collagen injections over a period of 36 months [28]. Through telephone interviews and chart review, they reported an overall 74% dry or improved rate, with 72% achieving continence after two or fewer injections. Reinjections were required in 11 patients to regain dryness in this series. It is important to note that the results of collagen injection therapy cannot be directly compared to other modalities used to treat ISD because it is a biodegradable bulking agent [29]. In some cases of treatment “failure,” the procedures were in fact not failures, but incomplete treatments. Simply injecting once or twice to “see what happens” is inappropriate, and all patients should receive at least three injections and 10 mL of collagen before being declared a treatment failure and having another therapy initiated. In addition, a patient who is dry for 2 years and then begins to leak again is not a treatment failure. The patient simply needs another injection. Therefore, in reviewing the results of any collagen studies, these caveats should be kept in mind. V.

COMPLICATIONS

Overall, collagen injection has few side effects, and most are minor. The risk of postoperative urinary tract infection probably varies depending on whether preoperative antibiotics are given; however, this has not been proven in controlled trials. The risk of urinary tract infections appears to vary between 1.4% and 6% [22,24,30]. A periurethral abscess has been reported, but these are fortunately rare [30]. Symptomatic hematuria or prolonged perineal pain is uncommon and selflimited [22]. Transient postinjection urinary retention requiring intermittent catheterization was reported in 4% by Cross et al. [28], while permanent retention in the non-neurological patient has been reported in only one patient [30,31]. The fear of particle migration has concerned users of injectable materials since the initial reports by Malizia et al. [32]; however, there have been no such reports using GAX collagen as an injectable agent. The immunogenicity of GAX collagen has also been extensively evaluated. In 1998, Leonard et al. found that

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3 of 10 children developed antibodies to the bovine collagen, but there was no seroconversion to antibodies that cross reacted with human collagen [33]. Hypersensitivity has previously been shown to be in the range of 2% to 5%; however, Stothers and Goldenberg recently reported three cases of delayed patient hypersensitivity to the agent [34]. Despite initial negative skin tests, each of these patients developed distinct induration at the forearm test site after they received their first transurethral injection 4 weeks later. Two of the three reported arthralgias, and all responded to conservative management. VI. FUTURE DEVELOPMENTS Durasphere is the newest FDA-approved injectable bulking agent, with shortterm clinical data expected soon [35] (Fig. 6). It is a nonantigenic material (no skin test required) designed to be biocompatible and is composed of nonmigratory and nonabsorbable pyrolytic, carbon-coated zirconium oxide beads suspended in a glucan carrier gel. The majority of particles are in the range of 251 to 300 µm, more than three times larger than the 80-µm threshold for particle migration. From 1996 to 1998, 355 women were enrolled in a randomized controlled double-blind study to compare the safety and efficacy of this material with GAX collagen [37]. At 12 months, the investigators found that 66.1% of Durasphere patients were dry compared to 65.8% of collagen patients. Adverse events were similar in the two groups. Theoretical advantages suggested by this new agent are improved durability compared to GAX collagen and the ability to treat immediately as skin

Figure 6 A syringe of Durasphere and the required specialized needle are seen on the left side of the photograph. On the right side, a close-up view of the Durasphere particles and carrier can be seen.

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testing is not required. The particles are suspended in a viscous carrier that requires specialized injection techniques, making it more difficult to inject than collagen.

VII. CONCLUSION As with any procedure, the results obtained with collagen injection therapy depend heavily on patient selection, expertise in performing the procedure, and the use of specialized equipment. Patient satisfaction depends on understanding the treatment options, and if collagen is selected, knowing that multiple injections will be necessary at greater than 4-week intervals with periodic reinjections after dryness is achieved to restore continence. In addition, when performed in the clinic using local anesthesia, injectable agents give patients who are poor surgical candidates the opportunity to achieve continence. Overall, collagen injections are easy to perform, minimally morbid, and remain very cost effective, especially when performed in the outpatient office setting. Nonetheless, the search for an inexpensive, easily injected, durable, but equally innocuous, injectable bulking agent continues.

REFERENCES 1. Murless BC. The injection treatment of stress incontinence. J Obstet Gynecol Br Emp 1938; 45:521–524. 2. Quackels R. Deux incontineces apre`s adenoectomic queries par injection de paraffine dans le perinee. Acta Urol Belg 1955; 23:259–262. 3. Sachse H. Treatment of urinary incontinence with sclerosing solutions. Indications, results, complications. Urol Int 1963; 15:225–229. 4. Berg SL. Polytef augmentation urethroplasty: correction of surgically incurable urinary incontinence by injection technique. Arch Surg 1973; 107:379–381. 5. Politano VA, Small MP, Harper JM. Periurethral Teflon injection for urinary incontinence. J Urol 1974; 111:180–183. 6. Gonzales-Garibay S, Jimeno C, York M, Gomez P, Borrwell S. Endoscopic autotransplantation of fat tissue in the treatment of urinary incontinence in the female. J Urol (Paris) 1989; 95:363–366. 7. Santarosa RP, Blaivas JG. Periurethral injection of autologous fat for the treatment of sphincter incontinence. J Urol 1994; 151:607–608. 8. Trockman BA, Leach GE. Surgical treatment of intrinsic urethral dysfunction: injectables (fat). Urol Clin North Am 1995; 22:665–671. 9. Currie L, Drutz HP, Oxorn D. Adipose tissue and lipid drop embolism following periurethral injection of autologous fat: case report and review of the literature. Int Urogynecol J 1997; 8:923–926. 10. Stegman SJ, Chu S, Bensch K. A light and electron microscopic evaluation of Zyderm collagen and Zyplast implants in aging human facial skin. Arch Dermatol 1987; 123: 1644–1649. 11. Canning D, Peters C, Gearhart J, Jeffs RD. Local tissue response to glutaraldehyde crosslinked collagen in the rabbit bladder. J Urol 1988; 139(5):258 (abstr 381). 12. Cespedes RD, McGuire EJ. Proper diagnosis: a must before surgery for stress incontinence. J Endourol 1996; 10:201–205.

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13. Blaivas JG, Olsson CA. Stress incontinence: classification and surgical approach. J Urol 1988; 139:737–741. 14. McGuire EJ, Fitzpatrick CC, Wan JH, et al. Clinical assessment of urethral sphincter function. J Urol 1993; 150:1452–1455. 15. Cespedes RD, McGuire EJ. Leak point pressures. In: Nitti V, ed. Practical Urodynamics. Philadelphia: W. B. Saunders, 1998:94–107. 16. McGuire EJ, O’Connell HE. Surgical treatment of intrinsic sphincter dysfunction: slings. Urol Clin North Am 1995; 22:657–664. 17. Blaivas JG, Jacobs BZ. Pubovaginal fascial sling for the treatment of complicated stress urinary incontinence. J Urol 1991; 145:1214–1217. 18. O’Connell HE, McGuire EJ, Aboseif S, Usui A. Transurethral collagen therapy in women. J Urol 1995; 154:1463–1465. 19. Monga AK, Robinson D, Stanton SL. Periurethral collagen injections for genuine stress incontinence: a two year follow-up. Br J Urol 1995; 76:156–160. 20. Herschorn S, Steele D, Radomski S. Long term follow-up of intraurethral collagen for female stress incontinence. J Urol 1995; 153:433 (abstr 818). 21. Appell R. Periurethral collagen injection for female incontinence. Probl Urol 1991; 5: 134–140. 22. Winters JC, Appell R. Periurethral injection of collagen in the treatment of intrinsic sphincter deficiency in the female patient. Urol Clin North Am 1995; 22:673–678. 23. McGuire EJ, English SF. Periurethral collagen injection for male and female sphincteric incontinence: indications, techniques and results. World J Urol 1997; 15:306– 309. 24. CR Bard Company. PMAA submission to U.S. FDA for IDE G850010, 1990. 25. Steele AC, Kohli N, Mickey MM. Periurethral collagen injection for stress incontinence with and without urethral hypermobility. Obstet Gynecol 2000; 55:357–358. 26. Tschopp PJ, Wesley-James T, Spekkens T, Lohfeld L. Collagen injections for urinary stress incontinence in a small urban urology practice: time to failure analysis of 99 cases. J Urol 1999; 162:779–782. 27. Moore KN, Chetner MP, Metcalfe JB, Griffiths DJ. Periurethral implantation of glutaraldehyde cross-linked collagen (Contigen) in women with type II or III SUI: quantitative outcome measures. Br J Urol 1995; 77:359–363. 28. Cross C, English SF, Cespedes RD, McGuire EJ. A follow-up on transurethral collagen injection therapy for urinary incontinence. J Urol 1998; 159:106–108. 29. McGuire EJ, Appell RA. Transurethral collagen injection for urinary incontinence. Urology 1994; 43:413–415. 30. McClennan MT, Bent AE. Suburethral abscess: a complication of periurethral collagen injection therapy. Obstet Gynecol 1998; 92:650–652. 31. Appell R. Use of collagen injections for treatment of incontinence and reflux. Adv Urol 1992; 5:145–165. 32. Malizia AA Jr, Reiman HM, Myers RP, Sande JR, Barham SS, Benson RC Jr, Dewanjee MK, Utz WJ. Migration and granulomatous reaction after periurethral injection of polytef (Teflon). JAMA 1984; 251:3277–3279. 33. Leonard MP, Dector R, Hills K, Mix LW. Endoscopic subureteral collagen injection: are immunological concerns justified? J Urol 1998; 160:1016–1022. 34. Stothers L, Goldenberg SL. Delayed hypersensitivity and systemic arthralgia following transurethral collagen injection for stress urinary incontinence. J Urol 1998; 159: 1507–1510. 35. Lightner D, Diokno A, Snyder J, et al. Study of Durasphere in the treatment of stress urinary incontinence: a multi-center, double blind randomized, comparative study. J Urol 2000; 163:166 (abstr 739).

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36. Stricker P, Haylen B. Injectable collagen for type 3 female stress incontinence: the first 50 Australian patients. Med J Aust 1993; 158:89–92. 37. Kieswetter H, Fischer M, Wober L, Flamm J. Endoscopic implantation of collagen (GAX) for the treatment of urinary incontinence. Br J Urol 1992; 69:22–25. 38. Richardson TD, Kennelly MJ, Faerber GJ. Endoscopic injection of glutaraldehyde cross-linked collagen for the treatment of intrinsic sphincter deficiency in women. Urology 1995; 46:378–381.

8 Transabdominal Procedures for the Treatment of Stress Urinary Incontinence ALAN D. GARELY Winthrop University Hospital Mineola, New York LEAH KAUFMAN Long Island Jewish Medical Center New Hyde Park, New York

Proper evaluation with a thorough physical exam and urodynamic assessment is the first step in approaching patients with stress incontinence. There are several procedures that have been used to treat these patients once nonsurgical management of their symptoms has failed. Surgical treatment of stress urinary incontinence can be approached abdominally, vaginally, transurethrally, or laparascopically. Assuming that the goal of treatment is not to trade incontinence with continence caused by total urethral outlet obstruction, the surgeon must tailor the operative approach for each individual patient. If the patient is continent at rest (sitting or lying down), the ideal treatment will be to simulate this situation while the patient is active (walking, coughing, sneezing, etc.). Transabdominal procedures can achieve this by stabilizing the anterior vaginal wall and, especially, the tissue next to and around the urethra. Starting with the Kelly plication, this chapter follows the evolution from the Marshall-Marchetti-Kranz (MMK) to the Burch procedure, along with some of its common modifications, and ends with a description of the paravaginal repair. Almost all abdominal approach procedures involve placing sutures lateral to the urethra and then anchoring them to another pelvic structure. The main 121

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differences between any of these are how closely the sutures are placed to the urethra, how many sutures are used, what type of suture is used, which pelvic structure is used for support, and how tight the sutures are tied. When doing any incontinence procedure, there exist three possible surgical outcomes: (1) The results of the operation are too loose (causing continued incontinence); (2) the operation results are too tight (causing outflow obstruction, resulting in urinary retention); or (3) the operation results are just right (curing incontinence and allowing appropriate voiding to occur). While success rates vary from one operation to another, surgical technique is a factor in the eventual outcome of a procedure, making comparison between two different approaches difficult. Clearly, suture tension is a dominant factor in overall success and failure. Dedicated practitioners of pelvic reconstructive surgery who routinely do incontinence procedures understand the importance of learning how to adjust the tension for each operation. With the advent of better surgical instruments and materials, and better understanding of the physiology of incontinence, we have reached overall success rates in the range of 85% to 95% [1,2]. Today, any procedure that cannot produce this cure rate consistently is usually not worth attempting. I.

MARSHALL-MARCHETTI-KRANZ PROCEDURE

In 1946, Marshall, later with Marchetti and Kranz (1949), developed a suprapubic approach to elevate and fix the urethrovesical junction. The first procedure was performed on a man who suffered from urinary incontinence after a transurethral prostatectomy and resection of the rectum for carcinoma. Lifting the bladder neck to the pubic symphysis achieved the first retropubic urethrovesicopexy [3,4]. Marshall, Marchetti, and Kranz developed testing to choose their patients for the MMK procedure. The patient’s bladder was filled with 250 cc water, and the patient was then asked to cough or perform the Valsalva maneuver. The test was then repeated with a finger or a clamp lifting the urethrovesical junction. The test was performed without excessive pressure on the urethra to avoid false positives. Patients found to have improvement with the above testing were considered candidates for the procedure. In 1949 the group’s initial results were published, reflecting improvement in 92% of the first 50 patients to undergo the procedure [3–5]. The original procedure is performed through a vertical suprapubic incision with the patient in Trendelenburg position to allow wide exposure of the retropubic space of Retzius. Light pressure is applied to the bladder and urethra with a sponge stick to separate the bladder from the posterior aspect of the pubic symphysis and rectus muscle (Fig. 1). Excessive bleeding in this area is managed with packing as it is usually venous in origin. Three no. 1 chromic sutures are then placed symmetrically, lateral to the urethrovesical junction, into the vaginal sidewall (Fig. 2). To avoid trauma to the urethra, it should either be palpated with a Foley catheter in place or be retracted by an assistant’s hand within the vagina (Fig. 3). The most distal of these sutures is placed at the level of the urethral meatus. After placing these sutures, cystoscopic evaluation is performed to ensure no stitches are placed within the bladder or urethra. Once placement is confirmed, these sutures are tied, and the long end of the sutures are then placed on a Mayo needle and single bites are taken into the cartilage or periosteum of the pubic

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Figure 1 A sponge stick is used to gently pull the bladder medially, avoiding bladder injury with the sutures. symphysis (Fig. 4). Each suture is placed serially until the space of Retzius is closed, lifting the urethra and vesical neck from the introitus. This portion of the procedure has also been described using nonabsorbable suture on double needles. Closure of the abdominal incision is then performed in the usual fashion, leaving a drain in the space of Retzius for 48 h postoperatively [4–6]. In the late 1960s, surgeons began to use permanent suture during the MMK as the procedure failures were thought to be a result of using absorbable suture. In 1964, O’Leary described osteitis pubis as a complication of the MMK (found in 3% of postoperative patients). O’Leary described osteitis pubis as “an uncommon, self-limited, subacute or chronic inflammatory disease of the symphysis pubis capable of producing severe and prolonged discomfort and disability.” Symptoms occurred 2–12 weeks after surgery and included “pubic pain—a constant, dull ache—accompanied by spasms of the adductor and rectus muscles. Walking, sitting, defecating, urinating and coughing may be painful.” Patients often had separation or changes in the symmetry of the symphysis on radiological studies, as well as a degeneration of hyaline cartilage. Leukocytosis was common, and urine cultures were often positive for Pseudomonas, Proteus, or Escherichia coli. The disease was found to be self-limiting over the course of 2–3 years, but antimicrobial therapy often facilitated improvement [7,8]. Because of these complications from the attachment of the sutures to the symphysis pubis, surgeons began to seek other structures in the pelvis with which

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Figure 2 The classic Marshall-Marchetti-Krantz (MMK) procedure. The original description of the MMK procedure involved placement of sutures directly into the urethra to provide direct anatomic support. Later modifications, however, avoid placement of sutures directly into the urethra.

Figure 3 The surgeon’s finger in the vagina is used to help elevate the tissue lateral to the bladder.

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Figure 4 The MMK sutures are tied. The pubocervical fascia is tied tightly to the back of the pubic symphysis.

to perform their colposuspension. In 1961, Burch first described his procedure that attached the vagina to Cooper’s ligament. II. BURCH PROCEDURE In 1961, Burch published an article in the American Journal of Obstetrics and Gynecology entitled “Urethrovaginal Fixation to Cooper’s Ligament for Correction of Stress Incontinence, Cystocele, and Prolapse” [9]. When this article was written, the MMK operation was the major technique used to treat female urinary stress incontinence. Burch was pleased with the MMK, but experienced problems that he felt could be overcome by a few modifications. He stated that the MMK was “not always easy to perform, the field is often deep and bloody, the edges of the urethra are difficult to define, and the periosteum on the posterior aspect of the symphysis is far from ideal as a holding structure” [9–11]. In most surgical specialties, changes and improvements to existing techniques occur because of frustration or difficulty experienced by the current operator. Burch reached this point while trying to affix his paraurethral sutures to the periosteum during the MMK. He noted that the sutures would not hold, and rather than take the chance that the operation might fail because of weak attachment points, he looked for an alternative. Initially, his modification of the MMK placed the paraurethral sutures to the arcus tendineous, or the “white line,” which simultaneously corrected the anterior vaginal wall cystocele. After seven operations utilizing the arcus tendineous as the main support site, Burch again modified the procedure so that the paraurethral sutures went instead to the iliopectineal

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Figure 5 The Burch sutures are lateral to the urethra and are stitched to the Coopers ligament.

ligament (Sir Astley Cooper’s ligament), which is located on the superior ramus of the pubic bone (Fig. 5). Burch justified his switch to Cooper’s ligament because he felt that the arcus tendineous had inherent weakness, similar to the periosteum. At the time, Burch was unaware that he was obviating the risk of osteitis pubis by staying away from the periosteum [9,10]. Initially, Burch made his suture tension tight, putting the paraurethral tissue on so much tension that it abutted Cooper’s ligament. This caused the urethral vesical junction angle to be overly corrected from a resting angle of 0° to one of 25° to 30°. Because this overcorrection resulted in urinary outflow obstruction, he revised his technique 7 years later to eliminate suture tension. By leaving visible “violin strings” of suture, this allowed the anterior vaginal wall to behave as if it were constantly in a state of rest. Biomechanically, during stress events, there was little movement of the anterior vaginal wall [9,10,12,13]. The first step in this retropubic urethropexy is positioning the patient on the operating room table. The patient must be in the dorsal lithotomy position in candy cane or Allen stirrups, with the thighs abducted just far enough apart to allow the surgeon’s hands access to the vagina. The patient’s legs do not need to be elevated any higher than 0° relative to the patient’s torso. After positioning, the patient is prepped and draped with an appropriate setup that allows both abdominal and vaginal exposure. Because the Foley will be manipulated throughout the procedure, it is preferable to place it after the patient is draped. Surgically, the operation starts with exposure of the space of Retzius. This can be achieved using either a vertical or a transverse skin incision. If a vertical

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incision is made, it is best to carry it down to the superior aspect of the pubic symphysis. Unfortunately, a traditional Pfannenstiel incision does not allow adequate access to the retropubic space, especially the pubic symphysis. Modification of this incision can be made to accommodate both intrabdominal pelvic surgery and retropubic procedures. This is achieved by making the skin incision only 1 cm above the pubic bone and making the fascial incision at the inferior margin of the skin incision. Greater exposure can also be obtained by using the Maylard or Cherney incisions. In a nonobese patient without concurrent malignancy, the Pfannenstiel skin incision is usually adequate. After exposure to the retropubic space is obtained, identification of anatomical structures is necessary. In patients who have had previous surgery in this area, normal anatomy is often grossly distorted. An O’Connor-O’Sullivan or a Balfour retractor with the lateral blades placed under the rectus muscles will help with exposure. Meticulous dissection may be required prior to starting the actual urethropexy. The urethrovesical junction is usually identified by palpating the Foley balloon with one hand in the retropubic space, while two fingers of the other hand are in the vagina, gently putting traction on the Foley. With good exposure, the urethrovesical junction can sometimes be seen by the outline of the Foley without palpation (Fig. 6). Burch initially described his vaginal attachment points as lateral to the urethra and close to the pelvic side wall. Using no. 2 chromic catgut, three pairs of sutures are placed transabdominally directly through the pubocervical fascia lateral to the bladder by pushing the vagina up toward Cooper’s ligament with the intravaginal fingers (Fig. 7). Ideally, they would be full thickness bites going to, but not through, the surgeon’s gloved fingers. Tanagho’s modification to this portion of the procedure was described in 1976. He substituted no. 1 Dexon (delayed-absorbable) suture and changed the placement of the sutures from the lateral anterior vaginal wall to lateral to the urethra. Also, only two sutures were placed on each side instead of three. The first was placed at the midurethra, and the second was placed just lateral to the urethrovesical junction. Experience with this procedure shows that, by using the intravaginal fingers to first identify the urethra (by palpating the Foley between two fingers), these fingers can then be moved together to the side of the urethra that will be sutured. By placing the sutures over these two fingers, risk of injury to the urethra itself is minimized [14,15]. Once all sutures have been placed, injury to bladder, urethra, or ureters must be ruled out. Burch originally evaluated unintentional cystotomy by filling the bladder with sterile milk and looking for spillage at sites of injury. Unfortunately, this method will not give information about ureter injuries, which have been observed to be as high as 2% [16,17]. Also, some suture placement may cause a compressive effect on the tissue, eliminating milk spillage. Current recommendations based on the incidence of lower urinary tract injury may justify routine cystoscopy with intravenous injection of indigo carmine dye to visualize ureteral patency and to search for intravesical sutures [18]. After the sutures have been successfully placed through the pubocervical and vaginal tissue, placement to Cooper’s ligament can be completed. Once Cooper’s ligament has been exposed, each suture can be placed through this structure. Because the fibers of the ligament run transversely along the pubic bone, it is important that the suture needle is placed at a perpendicular

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Figure 6 Note the outline of the Foley catheter in the bladder. This helps orient the junction of the urethra and the bladder.

angle. This ensures the strongest suspension with little chance of pull through. Starting with the most inferior suture lateral to the urethra, stitches should be placed through Cooper’s ligament 1 to 2 cm lateral to the pubic tubercle on the same side, and the remaining sutures should be placed about 1 to 2 cm apart moving laterally (Fig. 5). After all sutures have been placed through Cooper’s ligament, they can be tied down. Tension on the sutures should be just enough to remove any slack from the suture bridge. This can be accomplished by gently placing a surgeon’s air knot and then carefully following this by succeeding knots, which will not advance the surgeon’s knot. This will prevent the suture from synching down, causing an overcorrection of the repair. A notable change to the original and modified Burch procedure is the change from absorbable to nonabsorbable sutures. Most surgeons today utilize polyester, Ethibond, or Prolene suture. However, a review of 17 studies indicates similar success rates for both absorbable and nonabsorbable sutures [19]. Although it seems unexpected that the absorbable sutures would have a high success rate, it

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Figure 7 Similar to placement of the MMK sutures lateral to the urethra, the surgeon’s fingers help elevate the tissue lateral to the urethra, decreasing urethral and bladder injury. has been suggested that a mild inflammatory reaction with subsequent scarring will adequately support the urethra [20]. After the Burch has been completed, if there is still a small amount of bleeding, gel foam or surgicell can be placed. Prior to closing the abdomen, the choice of bladder drainage must be determined. Some surgeons prefer a suprapubic catheter, especially when they are anticipating slow resumption of normal voiding. During long periods of bladder drainage, suprapubic catheters have the following advantages over transurethral Foley drainage: (1) less risk of ascending bacterial colonization, (2) more comfortable for the patient, (3) easier to complete repetitive voiding trials without having to reinsert the catheter. However, surgeons who attempt early postoperative voiding trials often will use a transurethral Foley. III. PARAVAGINAL REPAIR In 1912, George White described the arcus tendineous fascia as the lateral supportive ligament of the anterior vaginal wall. His dissections showed that the pubocervical segment of the endopelvic fascia, lateral to the vagina, attached itself to the pelvic side wall via the arcus tendineous (commonly referred to as the “white

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line,” but was not named after George White [21]. The white line runs laterally from the pubic symphysis to the ischial spine. It separates the iliococcygeus muscle from the obturator internus muscle. As the pubocervical fascia tears away from the white line, the anterior wall of the vagina begins to descend (Fig. 8). Similar to the weakening of the wires in a suspension bridge, the anterior vaginal wall will sag. This is the anatomic cause of most cystoceles, described as a lateral defect, causing a drop in the midline (Fig. 9). In addition, descent of the posterior urethrovesical junction results in a weakening of the normal continence mechanism. In 1976, Richardson et al. postulated that supporting the anterior vaginal wall from the ischial spine to the symphysis by reattachment of the torn pubocervical fascia to its normal anatomic insertion would eliminate the cystocele and restore continence [22]. In 1981, Richardson published the results of using the paravaginal repair to treat stress incontinence. With 2 to 8 years of follow-up, 95% of all patients reported satisfaction or improvement of their symptoms [22]. The majority of these patients reported total cure. These data were further supported by Shull and Baden’s results in 1989, which showed a 97% cure of stress incontinence with the paravaginal repair [23]. Bruce et al. compared the paravaginal repair alone to the same procedure with the addition of a bladder neck sling in patients with stress incontinence. Their results showed that, at the 17-month follow-up, 72% of the paravaginal repair group was continent compared to 85% of the patients who also received a sling [24]. While the paravaginal repair is considered to be the “gold standard” for cystocele repair, few surgeons rely on it as a primary incontinence treatment procedure. The procedure is started similar to the Burch operation as access to the space of Retzius is essential. A Foley catheter is placed into the bladder for continuous

Figure 8 The pubocervical fascia has separated from its lateral attachment on the arcus tendineus.

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Figure 9 Anatomic relaxation of the bladder base (cystourethrocele) and fibromuscular floor of the urethra (urethrocele) with posterior rotation of the urethrovesical junction.

drainage. A self-retaining retractor is placed so that the lateral blades are under the rectus muscle, but above the peritoneum. Access to the pelvic side wall is best gained by standing on the contralateral side. Using gentle traction medially, a sponge on a ring forceps can be used to gently open up the space directly over the lateral pelvic sidewall. It is best if the white line can be visualized, but this is not always possible because of attenuation or poor exposure. If the white line cannot be seen running from the ischial spine to the public symphysis, reliance on anatomical landmarks will suffice as the course of the white line is predictable. Once the white line is either visualized or outlined, sutures can be placed through it for lateral suspension to the paravaginal tissue. The “key stitch,” the most cephalad suture, is placed just inferior to the ischial spine and is used to support the uppermost portion of the pubocervical fascia. Using an automatic suture driver such as the Capio (Boston Scientific, Natick, MA) for this portion allows suturing to be done in tight spaces, taking advantage of reliance on tactile confirmation of anatomic landmarks. Also, there is low risk of losing a needle. A total of three to five sutures should be placed on each white line, using permanent suture material to ensure a long-lasting repair. After each suture is placed, it should be held with a clamp and kept in the order in which placed. After all of the sutures on one side have been tagged, they are ready for placement onto the pubocervical fascia. Working from the contralateral side, the surgeon inserts the hand closest to the vagina and uses a sponge stick with the other hand to sweep the bladder medially, always giving countertraction with the intravaginal hand. The assistant will then take the sponge stick, and the sur-

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Figure 10 The paravaginal repair is done by re-approximating the torn pubocervical fascia to the arcus Tendineus with sutures. The “key stitch” will help elevate the lateral aspect of the vaginal Apex. geon will pick up the suture. This maneuver will decrease the chances of suturing into the bladder or around the ureter. Starting with the key stitch, each suture is placed into the lateral pubocervical tissue. Full-thickness bites should be encouraged, and the needle itself should be palpable with the intravaginal hand (Fig. 10). Care should be taken to avoid suturing into the vaginal hand. After all the sutures have been placed on both sides, the abdominal wall retractor is relaxed, and cystoscopy is performed. The bladder is inspected for inadvertent sutures, which must be removed by simply pulling them out from the abdominal side. Next, 5 cc of intravenous indigo carmine dye is given to ensure patency of both ureters by observing spillage of dye from the ureteral orifices. If a ureter appears to be obstructed, passing a small ureteral stent can confirm patency, or the sutures on the affected side should be removed. Either way, confirmation of ureteral spillage is paramount to completing the operation. After cystoscopy, the bladder is drained, the retractor is replaced, and the sutures are tied tightly so that the pubocervical tissue abuts the arcus tendineous. In cases in which there is some bleeding secondary to small vessel abrasions, Gelfoam or Surgicel can be placed into the space prior to tying. After both sides have been tied, the retractor is removed, and the abdomen is closed. Use of the automatic suture driver often requires less dissection, so that placement of a drain into the retropubic space is often not necessary. IV. CONCURRENT SURGERY Most incontinence procedures rely on stabilization of the bladder neck. Distortion of the urethral vesical angle and movement of the urethra itself can have an impact

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on the continence mechanism. Incontinence surgery is best left to be done at the end of any concurrent surgical procedures. The exception to this occurs when the abdominal portion of the case can be completed with only a posterior repair remaining. V.

POSTOPERATIVE CARE

Patients undergoing uncomplicated incontinence surgery can be expected to recover rapidly. The major decision is how quickly to initiate the voiding trial. As there are few data to support a delayed trial, many surgeons will initiate this on the first postoperative day [25]. However, patients who have had an abdominal approach procedure should probably wait 24 to 48 h because of immediate tissue swelling and incisional pain, which can decrease the function of the bladder and urethra. In cases in which the urine is bloody, bladder drainage should continue until the urine has been clear for at least 24 h. Because there is a steep learning curve on how tight to make the suture bridges, most experienced surgeons rarely have patients who will not void within 5 to 7 days. The easiest technique for a voiding trial with a transurethral Foley is to fill the bladder retrograde with at least 200 cc of sterile water, remove the catheter, and have the patient immediately void. Measuring the voided volume and subtracting it from the amount placed into the bladder will give you the postvoid residual. Alternatively, a passive voiding trial can be completed by removing the Foley and then waiting either 4 to 6 h or until the patient has a strong urge to void. The patient’s void is measured and then straight catheterization or ultrasound of the bladder volume is done to check the postvoid residual. If an ultrasound bladder scanner is available, repeat catheterization is not necessary. The trial is usually considered successful when the postvoid residual is less than 75 cc [26]. To avoid overdistention in patients who fail the voiding trial, the catheter can be replaced, or patients can be taught intermittent self-catheterization. To decrease the chance of urinary tract infection, catheterized patients should be on low-dose antibiotic prophylaxis such as nitrofurantoin 50 mg once daily or Ciprofloxin 250 mg once daily. In addition, 1 g of vitamin C can be used to acidify the urine to decrease both the risk of infection and the amount of mucus accumulation around the catheter tip [27]. VI. CONCLUSION Prior to collaborative training and research, urologists preferred sling procedures, and gynecologists utilized abdominal approach incontinence repairs for genuine stress urinary incontinence. With the advent of specialized training in female pelvic medicine and pelvic reconstruction, skilled practitioners must now be familiar with all types of incontinence operations. The ideas of “one man, one operation” and “one size fits all” will no longer be acceptable. Each operation must be tailor-made for the patient. While urodynamic assessment may guide the surgeon toward one particular approach, other variables such as concurrent procedures, age, physical activity, health status, and previous incontinence surgery may alter the plan. Urodynamic studies have been used to quantitate the degree and severity of stress incontinence by looking at the urethral closure pressure profile and at the leak point pressure (LPP) of the bladder. Broad definitions have been used to qualify which type of procedure should be used to repair the incontinence based

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on objective data. It is generally accepted that patients with low urethral closure pressure (less than 20 cm of water) and/or low LPP (less than 60 cm of water) would benefit from a sling procedure [28,29]. The logic is that these patients need more support for the urethra directly, rather than laterally placed support. In the past, abdominal retropubic bladder neck suspensions have been used for patients with higher LPPs and higher urethral closure pressures. These patients would not be exerting high-pressure forces into the pelvis during times of physical stress. For patients who did not need a sling based on the urodynamic assessment, the abdominal approach was considered superior. This was because the sling required a large dissection and had associated morbidity (blood loss, urinary retention, and bladder injury). With the advent of the minimally invasive sling technique, this paradigm has shifted in favor of the sling as a primary and preferred approach that can now be utilized more liberally. Incontinence procedures done abdominally are well suited for patients who will be having an abdominal incision for reasons other than primary incontinence. Patients with pelvic prolapse who need an abdominal approach vault suspension are the best candidates, assuming they have no risk factors that may contribute to failure. Patients with high LPPs have the highest success rates [30]. The MMK, Birch, and Paravaginal repairs all depend on sutures holding tight to vaginal epithelium and pubocervical fascia. In many patients, this tissue has attenuated and is one of the main causes of the patient’s incontinence and concurrent prolapse. These operations depend on suture material holding tight to this tissue for the remainder of the patient’s life. Risk factors, which decrease long-lasting success, must be considered. During the 19th century, the average life expectancy for American women did not exceed 60 years. Over the past 100 years, this life expectancy has approached 80 years. In the past, operations with a 15-year cure rate were considered the gold standard. With patients living much longer, we need to look toward cure rates that remain high after 20 years. Younger patients are now more likely to outlive the success of their incontinence repair. These patients are probably better candidates for operations that do not depend on the strength of their own tissues. Physical activity will greatly influence the success of a particular operation. Patients who are sedentary will not exert the same intra-abdominal forces to the pelvis as an active patient. While our population ages, our older citizens are engaging in many of the same sports and activities that they did when they were younger. Active patients have a far greater chance of ripping suture out of the vaginal and paravaginal tissue because of constant and sudden forces applied to the pelvis. Patients who are considered athletes are probably not good candidates for abdominal approach procedures. Patients who are obese (defined by body mass index) are also at high risk of ripping suture from pelvic tissues, even at rest. Simple tasks, such as walking, may be enough to disrupt a repair. This is probably one of the reasons that incontinence is more prevalent in overweight populations. Some surgeons prefer not to operate on obese patients because of high failure rates. If the abdominal approach is abandoned in favor of the sling procedure, success rates can be very high. Either way, it is unrealistic to believe that patients will lose weight to have an operation that will change the quality of their life, not simply to save it. While we ask patients to lose weight prior to surgery, it is expected that they will not succeed, and the operation is planned based on this premise.

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Smokers and patients with pulmonary diseases such as chronic obstructive pulmonary disease (COPD) and asthma are at high risk of failure for reasons similar to those for athletes. These patients frequently cough, and this results in very high intra-abdominal pressures (which can be seen on urodynamic assessment). Regardless of surgical approach, these patients must have strong cough suppression in the immediate 8 week postoperative period. Smokers and patients with pulmonary conditions should be considered to have relative contraindications for abdominal approach procedures [31–34]. Previous incontinence surgery that has failed is probably a good indication that aggressive support of the bladder neck is needed. Patients so affected will benefit from a sling rather than a retropubic urethrapexy. Entering the space of Rhetzius abdominally in a patient who has had previous surgery can be very difficult. Scar tissue will obliterate normal tissue plains, and neovascularization can present tortuous and dilated veins, which are very friable. It is not uncommon to experience large blood loss and increased risk of entering the bladder. Because of the associated morbidity with previous incontinence repair failures, it is wise to consider staying out of this space unless absolutely necessary. A vaginal approach sling procedure can facilitate minimal entry into this space. Most incontinence procedures have a place in the surgical armamentarium. If the surgeon has eliminated and minimized all of the patient’s contributing risk factors, a retropubic urethrapexy can be very useful. In the properly selected patient, abdominal approach incontinence procedures should yield long-lasting and successful results [35,36]. REFERENCES 1. Consensus conference. Urinary incontinence in adults. JAMA 1989; 261:2685–2690. 2. Langer R, Ron-El R, Neuman M, Herman A, Bukovsky I, Caspi E. The value of simultaneous hysterectomy during Burch colposuspension for urinary stress incontinence. Obstet Gynecol 1988; 72(6):866–869. 3. Marshall UF, Marchetti AA, Kranty KE. The corrections of stress incontinence by simple vesico-urethral suspension. Surg Gynecol Obstet 1949; 88:509–518. 4. Mainprize TC, Drutz HP. The Marshall-Marchetti-Krantz procedure: a critical review. Obstet Gynecol Surv 1988; 43(12):724–729. 5. Marchetti A, Marshall V, O’Leary J. Suprapubic vesico-urethral suspension and urinary stress incontinence. Clin Obstet Gynecol 1963; 6:195. 6. Parnell JP, Marshall VF, Vaughn E Jr. Primary management of urinary stress incontinence by the MMK vesico-urethroprexy. J Urol 1982; 127(4):679–682. 7. Ball TL, Wright KL. Stress incontinence: complications and sequelae of the MarshallMarchetti operation. Pac Med Surg 1965; 73:290. 8. Lee RA, Symmonds RE, Goldstein RA. Surgical complications and results of modified Marshall-Marchetti-Krantz procedure for urinary incontinence. Obstet Gynecol 1979; 53(4):447–450. 9. Burch JC. Urethrovaginal fixation to Cooper’s ligament for correction of stress incontinence, cystocele, and prolapse. Am J Obstet Gynecol 1961; 81:281. 10. Burch JC. Cooper’s ligament urethrovesical suspension for stress urinary incontinence. Am J Obstet Gynecol 1968; 100:764. 11. Raz S, Maggio AJ Jr, Kaufman JJ. Related articles. Why Marshall-Marchetti operation works . . . or does not. Urology 1979; 14(2):154–159. 12. Walters MD. Retropubic repair of urethral incontinence. In: Kursh ED, McGuire EJ, eds. Female Urology. Philadelphia: Lippincott, 1994.

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13. Hilton P, Stanton SL. A clinical and urodynamic assessment of the Burch colposuspension for genuine stress incontinence. Br J Obstet Gynaecol 1983; 90(10):934–939. 14. Green TH Jr. Vaginal repair. In: Stanton SL, Tanagho EA, eds. Surgery of Female Incontinence. New York: Springer-Verlag, 1980. 15. Tanagho EA. Colpocystourethropexy: the way we do it. J Urol 1976; 116(6):751–753. 16. Harris RL, Cundiff GW, Theofrastous JP, Yoon H, Bump RC, Addison WA. The value of intraoperative cystoscopy in urogynecologic and reconstructive pelvic surgery. Am J Obstet Gynecol 1997; 177(6):1367–1369, discussion 1369–1371. 17. Galloway NT, Davies N, Stephenson TP. The complications of colposuspension. Br J Urol 1987; 60(2):122–124. 18. Gill EJ, Elser DM, Bonidie MJ, Roberts KM, Hurt WG. The routine use of cystoscopy with the Burch procedure. Am J Obstet Gynecol 2001; 185(2):345–348. 19. Bidmead J Cardozo L. Retropubic urethropexy (Burch colposuspension). Int Urogynecol J Pelvic Floor Dysfunct 2001; 12(4):262–265. 20. Bhatia NN, Bergman A. Modified Burch versus Pereyra retropubic urethropexy for stress urinary incontinence. Obstet Gynecol 1985; 66(2):255–261. 21. White GR. An anatomical operation for the cure of cystocele. Am J Obstet Dis Women Child 1912; 65:286–290. 22. Richardson AC, Lyon JB, Williams NL. A new look at pelvic relaxation. Am J Obstet Gynecol 1976; 126:568–573. 23. Shull BL, Baden WF. A six-year experience with paravaginal defect repair for stress urinary incontinence. Am J Obstet Gynecol 1989; 160:1432–1440. 24. Bruce RG, El-Galley RE, Galloway NT. Paravaginal defect repair in the treatment of female stress urinary incontinence and cystocele. Urology 1999; 54(4):647–651. 25. Wall LL. Hewitt JK. Voiding function after Burch colposuspension for stress incontinence. J Reprod Med 1996; 41(3):161–165. 26. Sze EH, Miklos JR, Karram MM. Voiding after Burch colposuspension and effects of concomitant pelvic surgery: correlation with preoperative voiding mechanism. Obstet Gynecol 1996; 88(4 Pt 1):564–567. 27. Hilton P. Bladder drainage: a survey of practices among gynaecologists in the British Isles. Br J Obstet Gynaecol 1988; 95(11):1178–1189. 28. McGuire EJ, Bennet C, Konnak J, et al. Experience with pubovaginal slings for urinary incontinence at the University of Michigan. J Urol 1987; 138:525–528. 29. Hsieh GC, Klutke JJ, Kobak WH. Low Valsalva leak-point pressure and success of retropubic urethropexy. Int Urogynecol J Pelvic Floor Dysfunct 2001; 12(1):46–50. 30. Cespedes RD, Cross CA, McGuire EJ. Selecting the best surgical option for stress urinary incontinence. Medscape Womens Health 1996; 1(9):3. 31. Olsen AL, Smith VJ, Bergstrom JO, Colling JC, Clark AL. Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence. Obstet Gynecol 1997; 89(4): 501–506. 32. Bump RC, McClish DM. Cigarette smoking and pure genuine stress incontinence of urine: a comparison of risk factors and determinants between smokers and nonsmokers. Am J Obstet Gynecol 1994; 170(2):579–582. 33. Bump RC, McClish DK. Cigarette smoking and urinary incontinence in women. Am J Obstet Gynecol. 1992; 167(5):1213–1218. 34. Galloway NT, Davies N, Stephenson TP. The complications of colposuspension. Br J Urol 1987; 60(2):122–124. 35. Drouin J, Tessier J, Bertrand PE, Schick E. Burch colposuspension: long-term results and review of published reports. Urology 1999; 54(5):808–814. 36. Webster GD, Ramon J. Procedure selection in the management of stress urinary incontinence. Prob Urol 1990; 4:37–53.

9 Transvaginal Surgery for Stress Urinary Incontinence TRACEY S. WILSON and GARY E. LEMACK University of Texas Southwestern Medical Center Dallas, Texas, U.S.A.

I.

INTRODUCTION

Stress urinary incontinence is the involuntary loss of urine related to increases in abdominal pressure. It has been suggested that urethral hypermobility and/or intrinsic sphincter deficiency (ISD) contribute to most forms of stress urinary incontinence. Urethral hypermobility results when the vaginal musculofascial attachments that support the bladder neck and urethra in a retropubic position lose integrity. On increases in abdominal pressure, this loss causes the proximal urethra and bladder neck to descend into the vagina. ISD, on the other hand, refers to a deficiency in the function of the urethral sphincter that is unrelated to urethral support [1]. This leads to poor coaptation of the urethral mucosa and incontinence with minimal stress activities. Intrinsic sphincteric weakness can result from neurologic deficit, or it may merely be a secondary effect of aging. ISD may also be related to previous attempts at surgical repair or exposure to pelvic radiation. DeLancey proposed a unifying theory known as the “hammock hypothesis” that suggests that a poor muscular backing to the posterior aspect of the urethra results in failure of effective urethral coaptation, excessive urethral mobility, and urinary leakage [2]. ISD has only recently been recognized as an independent etiological factor for the development of stress urinary incontinence. Historically, surgical procedures to treat this incontinence were designed to suspend the urethra and thereby reposition it to a more correct anatomical location and restore the urethrovesical angle. One of the first transvaginal procedures for incontinence was the 1914 Kelly plication. This procedure involved a subvesical urethral plication that used the 137

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urethropelvic fascia and anterior vaginal wall to restore support to the floor of the urethra and bladder neck [3]. Kelly performed lateral dissection of the vaginal wall via a midline incision and then reapproximated the lateral tissues to reduce the diameter of the urethra. He reported an 80% success rate in his initial series of 20 patients [2]. But, despite this initial report, overall results were suboptimal (61% after 48 months) [1]. The general approach toward the treatment for incontinence began to change. Presently, the surgical goal of correction of stress urinary incontinence is to enhance outlet resistance. In patients with urethral hypermobility, this can be accomplished by stabilizing the bladder neck and proximal urethra. In patients with ISD, this is accomplished by improving urethral support [3]. There is often overlap of these two conditions, and ISD, as some suggest, exists in all forms of stress urinary incontinence. Thus, the type of procedure used is often more dependent on surgeon preference than on the presumed mechanism of incontinence. In addition, the surgical approach should reflect patient comorbidities, concomitant surgical procedures to be performed, and experience of the surgeon. Surgical approaches include abdominal, transvaginal, or combined abdominal-transvaginal procedures. In this chapter, we discuss the transvaginal approach to the correction of stress urinary incontinence. These procedures continue to evolve as our understanding of the pathophysiology of stress urinary incontinence improves. II. NEEDLE SUSPENSION PROCEDURES A.

Pereyra

Pereyra described the first transvaginal needle suspension in 1959 [4]. He used stainless steel wires to suspend the pericervical fascia from the anterior abdominal wall fascia near its junction with the symphysis pubis. This elevated the periurethral tissues in the desired position and restored the vesicourethral angle. Over time, the steel wires cut through the tissues; thus, permanent urethral support depended on periurethral scarring. In his first series of 31 patients, Pereyra’s success rate was 90% after 14 months of follow-up. He later modified this procedure (in 1967) to include incision of the endopelvic fascia to facilitate the passing of the trochar through the retropubic space. To decrease suture pull through, he incorporated a vaginal wall plication, and he exchanged the wire for chromic suture material [5]. These modifications improved the success rate to 94%. But, others were unable to duplicate these results, and follow-up data at 3 years revealed a 15% to 18% failure rate due to sutures pulling from the endopelvic fascia. Pereyra continued to modify his procedure in hopes of decreasing the rate of pull out of the suspensory sutures. In 1982, he described a method of detaching the attenuated endopelvic fascia from the pubis to expose the pubourethral ligaments [6]. He bound the strong pubourethral ligaments to the enfolded endopelvic fascia and suspensory ligaments to provide maximal resistance to suture pullout. This procedure, known as the modified Pereyra procedure, resulted in a cure or marked improvement rate of 94.5% after 4 to 6 years of follow-up. B.

Stamey

Recognizing the high rate of suture pull through with the Pereyra procedure, Stamey introduced a transvaginal needle suspension designed to restore the ur-

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ethrovesical angle using cystoscopic guidance [7]. With this technique, needles are passed from two suprapubic incisions to a T-shaped vaginal incision. Because dissection of the bladder or bladder neck is not required, the endopelvic fascia is not disrupted. Dacron pledgets (placed well away from the vaginal suture line) are used to buttress the vaginal suture loop (preventing direct apposition of the pledget and suture line is thought to decrease the likelihood of erosion). The addition of the pledget bolster was felt to be most critical in those patients whose pubocervical tissue was poor and unlikely to hold, especially among elderly patients. Stamey’s technique was considered a fairly easy operation that necessitated a minimal learning curve, required a short hospital stay, and was associated with low morbidity. The reported efficacy of the Stamey endoscopic bladder neck suspension varies between 40% and 93% [7,8]. This disparity is due to many factors: the definition of cure, the method of measuring cure (subjective or objective), technical modifications to the original procedure, diagnostic errors, and surgeon experience. Elapsed time since the surgery also seems to affect success. In 1980, Stamey reviewed the results of 203 patients who had undergone the procedure, 47 of whom had been followed for at least 4 years [9]. He found that operative failures occurred early rather than late (only 1 failure after 1 year). In contrast, however, other authors reported a gradual increase in the recurrence of leakage over time [8,10,11]. This late failure rate may be secondary to the suspensory sutures giving way or to these sutures cutting through the rectus or pubocervical fascia. Patient age also affects the reported success rate of the Stamey procedure. Peattie and Stanton found an objective cure rate of 41% in a group of 44 women over the age of 65 years [12]. Hilton and Mayne reported higher long-term success rates in patients over 65 years old (76%) compared to those aged less than 65 years (53%) [13]. Their results indicate that, on an actuarial basis, cure is better maintained in older rather than in younger patients, and this finding has been supported [14]. Some attribute the disparity to differences in operative technique; others attribute it to the lower level of activity among elderly patients. Factors possibly placing patients at increased risk for postoperative failure include multiple prior procedures for stress urinary incontinence, obesity, menopausal status, presence of pulmonary disease, and a concomitant abdominal hysterectomy [14]. Complications associated with the Stamey procedure are common to all transvaginal suspensions, but some are unique (Table 1 lists complications associated with various antiincontinence procedures). Use of monofilament nylon suture material minimizes the incidence of suprapubic wound infection. The occurrence of detrusor instability (DI) is difficult to assess because postoperative urodynamic studies have not been done consistently. However, as with many anti-incontinence procedures, success rates for the Stamey procedure are diminished in those patients with preoperative DI [15,16]. The presence of DI postoperatively may represent persistence of preoperative findings or de novo occurrence. De novo DI may be secondary to bladder outlet obstruction or to irritation from suture or pledget materials. If overcorrection of the urethrovesical angle has occurred, cutting or loosening the suspensory sutures may relieve the obstruction and preserve continence. However, many believe the degree of postoperative scarring may preclude any effective release. Long-term erosion of the suture and bolster material may, in rare cases, cause acute onset of irritative voiding, urinary tract infection, hematuria, or stone formation [17].

Bladder injury

NR 1 NR NR 7

3 NR NR NR 6

18 9 4 40 11

11 7 14 6 15

UTI

7 8 3 31 10

6 12 8 6 7

Wound complication

1 NR NR NR 15

NR 41 4 NR NR

Dysuria

NR NR 4 NR

27 12 2 NR 5

Pain

NR NR NR NR 2

NR 8 16 3 4

Sexual dysfunction

Source: Adapted from Ref. 1. AVWS ⫽ anterior vaginal wall sling; MP/R ⫽ modified Pereyra/Raz; NR ⫽ not reported; UTI ⫽ urinary tract infection.

5 4 3 4 13

Bleeding

3 NR 1 NR NR

Urethral injury

Complication (%)

Complications Associated with Transvaginal Anti-Incontinence Procedures

Transvaginal suspensions Pereyra 4 Stamey 12 MP/R 4 Gittes 8 Four corner 6 Pubovaginal slings Rectus fascia 21 Fascia lata 12 AVWS 3 Allograft 11 Synthetic 8

Procedure

Table 1

NR NR NR NR 3

1 9 1 NR 0

Fistula

NR 6 NR NR 3

NR 16 NR NR NR

Stone

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C. Modified Pereyra/Raz In 1981, Raz described his modification of the Pereyra suspension procedure [18]. In this procedure, an inverted-U incision is made along the anterior vaginal wall to facilitate dissection lateral to the urethra. In addition, the urethropelvic ligament, pubocervical fascia, and vaginal wall (without its epithelium) are incorporated in the helical suspensory sutures. The initial report, based on 100 patients, found a 96% cure rate. In 1992, Raz reviewed the results of 206 patients who had 15 months of follow-up [19]. According to this report, the success rate dropped to 90.3%, and the procedure was most effective in patients with mild stress urinary incontinence (leakage occurring with forceful abdominal exertion or with exercise) and a minimal, if any, cystocele. Unfortunately, other surgeons have been unable to reproduce Raz’s results [20]. Data from long-term follow-up suggest the success rate of the modified Pereyra procedure varies from 50% to 90%, owing largely to various definitions of cure and study methodology [21]. Sirls et al. highlighted the importance of study methodology in a report in which surgical results of the modified Pereyra bladder neck suspension were compared using questionnaire-based outcomes versus retrospective chart review [22]. Success rates determined by questionnaire were consistently lower than rates suggested by chart review (64% and 89%, respectively). D. Gittes In 1987, Gittes introduced his “incisionless” bladder neck needle suspension [23]. He eliminated lower abdominal and/or vaginal incisions after reviewing animal studies that showed suture material made from nonabsorbable monofilament can be absorbed into body sinuses without causing infection or foreign body reaction [24]. Gittes described passing a long needle (30° Stamey needle) through a small stab wound on the anterior abdominal wall, past the posterior aspect of the pubic bone, then lateral to the bladder neck and through the anterior vaginal wall mucosa. Using no. 2 polypropylene or no. 2 nylon suture material, the bladder neck is suspended by creating an autologous buttress. This is accomplished by taking a full-thickness bite through the vaginal wall that stretches between the first and second needle passes. This technique is based on the idea that the monofilament suture heals as an autologous pledget as it is pulled through the vaginal wall, which then creates an internal bolster that tethers the anterior vaginal wall and prevents rotational descent during the Valsalva maneuver. Figure 1 shows the position of the suspensory sutures for the Gittes procedure compared to the position used in other transvaginal needle suspension procedures. Gittes reported a success rate of 87% in his first series of 38 patients, who were followed for 2 to 29 months [23]. A recurrence rate of 16% occurred within the first 12 months before the incorporation of the autologous buttress. Further evaluation revealed no recurrence of stress incontinence after 29 months. Subsequent studies confirmed a high rate of success with the autologous buttress (81.5% to 94%), and these same patients experienced a high rate of transient postoperative retention (58% to 81%) [26,27]. The rate of retention may be elevated with the Gittes procedure because, until the sutures loosen by moving into the vaginal submucosa, it is an “obstructing” technique [26]. Because of the high rate of postoperative retention, suprapubic tubes were placed in all patients. Factors such as

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Figure 1 Position of various anchoring sutures used in transvaginal needle suspension procedures. (A) modified Pereyra procedure; (B) Raz procedure; (C) Stamey procedure; (D) Gittes procedure; (E) anterior vaginal wall sling with bone anchor fixation. (From Ref. 25.)

mild stress urinary incontinence (as classified by Stamey), no prior surgeries for stress urinary incontinence, and premenopausal status improve the success rate of the no-incision endoscopic urethropexy [26]. E.

Four-Corner Bladder Neck Suspension

Raz further modified his approach to the treatment of stress urinary incontinence by adding another set of sutures. Known as the four-corner bladder neck suspension, this procedure is best suited for patients with lateral defects or a moderate cystocele. The proximal suture is placed at the bladder base and includes the anterior vaginal wall (minus the epithelium), the vesicopelvic fascia, and the cardinal and uterosacral ligaments adjacent to the cervix. This first set of sutures supports the upper vagina and serves to correct a moderate cystocele. The distal suture is placed at the level of the bladder neck and proximal urethra to correct urethral hypermobility. This suture incorporates the vaginal wall (minus the epithelium), the vesicopelvic fascia, and the urethropelvic fascia [28]. Dmochowski et al. reported results for 47 women who had the procedure and had been followed for a mean of 37 months. Surgical outcome was assessed by questionnaire and physical examination. Of these patients, 83% reported little to no incontinent episodes (less than 1 per week); however, 57% had low-grade cystoceles, half of which were symptomatic [29].

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A modification of the four-corner bladder neck suspension, referred to as the anterior vaginal wall suspension, utilizes two distal sutures, placed in a helical fashion, at the level of the bladder neck. Two additional sutures are placed proximal to incorporate the cardinal ligament complex (if the uterus is present) or the apical scar at the vaginal fornices (if the patient has had a hysterectomy). Recent reports based on data from a validated, anonymous questionnaire demonstrate a 77% incidence of no to minimal incontinence after 2 years [30]. Initial reviews of many transvaginal suspensions were promising. Longterm results, however, have been disappointing: Cure/dry rates drop to 65% to 69% after 48 months of follow-up, at which time retropubic suspensions and slings appear to be more efficacious [1]. III. PUBOVAGINAL SLINGS The pubovaginal sling (PVS) is the most common procedure used to correct ISD, and its indications are expanding to include urethral hypermobility with or without ISD. A successful PVS should restore sufficient outlet resistance to the intrinsically compromised urethra to prevent urine loss on increases in abdominal pressure, while avoiding urethral obstruction and allowing spontaneous micturition [31]. These goals are accomplished by placing the sling suburethrally—traditionally at the level of the bladder neck/proximal urethra—and suspending the ends from one of several points of fixation (i.e., rectus fascia, Cooper’s ligament, and pubic bone). Figures 2 and 3 illustrate the position of the fascial sling and its fixation to the pubic bone. Although different materials have been utilized as slings, the most important influences on the procedure’s outcome are patient selection, proper positioning of the sling, and determination of the correct amount of tension once the sling has been positioned. In this section, we discuss the variety of sling materials available and their comparative efficacy and rate of complication. A sling procedure is suitable for patients of any age, provided they or a caregiver can perform intermittent catheterization should it be necessary. However, a sling should not be performed in patients with poor bladder compliance. A sling does not block leakage driven by increase in bladder pressure. In fact, this type of leakage may occur at lower bladder volumes following a sling procedure. Thus, in patients with ISD and poor compliance, a sling procedure must be combined with treatment to either increase bladder capacity or decrease bladder pressure (i.e., augmentation cystoplasty). In addition, patients who cannot generate a detrusor contraction (as is seen with some forms of neurological diseases and in those who void with a low-pressure/low-flow state) should be informed of the increased risk of permanent urinary retention and the need for intermittent catheterization. Von Giordano is credited with creating the first pubovaginal sling, when in 1907, he wrapped a gracilis graft around the urethra [32]. From then until the early 1970s, many materials were used, including the pyramidalis, gracilis, and rectus and levator ani muscles [33]. In 1933, Price described the first sling using a fascia lata strip [34]. He passed the fascia beneath the urethra from the suprapubic approach and fixed the ends of the sling to the rectus muscle. In 1943, Aldridge constructed a sling from rectus fascia by suturing the ends of the fascia strips

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Figure 2 Transvaginal view of a fascial sling positioned at the bladder neck. (From Ref. 31.)

Figure 3 Fascial pubovaginal sling anchored to the pubic bone. (From Ref. 31.)

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together underneath the urethra to provide urethral compression during coughing and straining [35]. At that time, the goal of surgery was to restore a high urethral position by attaching the sling to the abdominal muscles. Consequently, the sling operation met with poor success rates and multiple complications. It was not therefore routinely performed for stress urinary incontinence until McGuire and Lytton reintroduced it in 1978 [36]. In the early 1970s, physicians began recognizing stress urinary incontinence in the absence of urethral hypermobility. Using a combined vaginal and abdominal approach, McGuire and Lytton performed the PVS with rectus fascia on 52 women who had proper anatomical position of the proximal urethra but low urethral closing pressures. They reported an 80% success rate after 2.3 years, when the urethral pressure was increased by 10 to 20 cm H2O in the area of the sling [36]. These findings emphasize the importance of preoperative identification of patients with type III stress urinary incontinence (ISD). The PVS was historically reserved for those patients with complex stress urinary incontinence, that is, patients who failed previous incontinence operations, who had associated pelvic prolapse or neurogenic disorders, or who had associated urethral diverticulae or fistulae. However, the PVS is now recommended by some as a first-line procedure for all types of stress urinary incontinence regardless of the presence of urethral hypermobility. A. Autologous Fascia Fascia, either rectus or fascia lata, is the most common autologous material used today. Those who advocate use of fascia lata do so because it is uniformly strong, regardless of patient age or condition, and has a tensile strength three to four times that of rectus fascia [37]. Moreover, fascia lata may achieve better sling tension and more uniform urethral closure; it eliminates the need for abdominal dissection, which thereby obviates the possibility of abdominal wall herniation [38]. Initially, using fascia lata included the disadvantages of prolonged postoperative discomfort and the need for additional incisions to harvest a long fascial strip (24 to 28 cm ⫻ 2.5 cm). The dissection of the fascial strip itself risked incurring peroneal nerve injury, lateral thigh pain, and wound infection [28]. But this procedure has been modified to reduce the size of the fascial strip required, thereby significantly reducing complications associated with harvesting. Initial objections to using rectus fascia involved the increased risk of abdominal wall hernias and the inability to harvest fascia from this location in patients having had multiple abdominal procedures (but others have encountered no problems with such patients) [39]. The procedure first called for a Pfannenstiel incision to harvest an 8 to 10 cm ⫻ 1.5 cm strip of fascia. This larger incision led to increased postoperative discomfort, longer convalescence, and the potential for wound infections. It was later realized that replacing a portion of the sling with sling sutures that traverse the retropubic space allows a smaller piece of fascia to be harvested through a smaller incision without apparent reduction in efficacy [40]. As a result, complications—including the possibility of entrapment of the genital branch of the genitofemoral nerve—have declined significantly. The success rate of the autologous fascial sling remains 85% to 97% [1]. Most failures occur within the first year and can be identified as occurring in those

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patients who never achieve dryness or, rarely, patients who feel a “popping” sensation within the first month postoperatively. The most common reasons for failure of the fascial sling are broken sutures, failure to place the sling in the retropubic space to achieve adequate scarring, and tying the sling too loosely [36]. The complication rate for the autologous PVS is quite low (Table 1). The most common postoperative complication is acute, transient urinary retention. All patients should therefore receive preoperative instruction on clean intermittent catheterization or should have a suprapubic tube placed during the operation. Most patients regain the ability to void spontaneously within 72 h, with the majority (⬎90%) voiding by 4 weeks. The risk of long-standing voiding dysfunction or permanent retention is less than 5% [1]. Another common complication is postoperative urgency. De novo urgency may develop in up to 25% of patients, while de novo urge incontinence may develop in up to 10%. These irritative symptoms are likely secondary to the obstructive nature of the PVS. No standard parameters exist that identify appropriate sling tension. In the past, to reduce the rate of obstruction, surgeons have performed intraoperative cystoscopy or intraoperative pressure flow studies and have tied the sling with little to no tension. But, none of these measures has ensured adequate sling tension. Therefore, all patients should be counseled preoperatively about this potential complication. Urodynamic changes seen after sling surgery are discussed in more detail in Section V. It is also important to distinguish patients with pure stress urinary incontinence from those with mixed (stress and urge) incontinence. Patients with continued urgency and/or urge incontinence after the sling procedure will report the lowest rates of satisfaction. However, about 70% of patients with preoperative urgency may have complete resolution of their symptoms [41]. The risk of erosion with the use of an autologous fascial sling is practically nonexistent (only one case is reported in the literature) [42]. The most likely predisposing factor to erosion from a fascial sling is the concomitant performance of a urethral reconstructive procedure. B.

Anterior Vaginal Wall

Raz introduced the anterior vaginal wall sling in 1989 [43]. Factors leading to its development were twofold: Morbidity associated with harvesting autologous fascia was well recognized, and there was an increased understanding of the anatomy of the bladder neck and midurethra as it relates to the pelvic floor. Since the bladder neck is not the only area controlling continence, any defects in the support of the midurethra needed to be addressed. Thus, the goal was to construct a sling from the anterior vaginal wall and underlying fascia that provided both compression and support for the urethra [44]. This procedure was unique in that it required no extra incision for sling harvesting, and it eliminated suburethral dissection. As a result, postoperative morbidity and convalescence were reduced. The procedure involved creation of a rectangular island of anterior vaginal wall beneath the proximal urethra and bladder neck. The size of the flap was tailored to the length and caliber of the urethra while maintaining an autonomous vascular supply. The four corners of the rectangle were then anchored with nonabsorbable sutures to the entire vaginal wall. The sutures were transferred to the

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suprapubic area and tied over a 1-cm segment of rectus fascia, and a proximal vaginal wall flap was then advanced to cover the island. Initially, Raz et al. reported 85% success, with success defined as minimal to no incontinence and no need for pads [43]. They later reported results of 160 patients with both ISD and urethral hypermobility after a median follow-up of 17 months. That success rate was 93% [44]. Because the anterior vaginal wall sling relied, in part, on the quality of the vaginal wall mucosa, the procedure was relatively contraindicated in elderly patients with atrophic vaginitis, and sexually active patients with short vaginas were discouraged from undergoing this procedure. In 1996, Kaplan et al. compared the efficacy and safety of an anterior vaginal wall sling to the autologous rectus fascial sling [45]. They reported that both procedures were equally effective in treating stress urinary incontinence. The use of the vaginal wall sling resulted in a significantly shorter hospital stay and decreased postoperative morbidity. In addition, Kaplan et al. recently reported a 93% cure rate for stress urinary incontinence using a modified anterior vaginal wall sling in 373 consecutive patients after a mean of 40 months of follow-up [46]. De novo detrusor instability and urge incontinence, which responded to medical therapy in most instances, were present in 8% of patients. A potential complication inherent to the vaginal wall sling is the development of epithelial inclusion cysts. Although this complication is rare (only one reported thus far) [47], its potential is real. In most descriptions, the mucosa of the vaginal wall sling is completely covered by a vaginal flap. The anterior vaginal wall sling was modified in 1998 by Vasavada and colleagues and is referred to as the in situ vaginal wall sling [48]. With this technique, the anterior vaginal wall patch is anchored to the pubic tubercle using only two sutures, and the endopelvic fascia is preserved. These modifications were believed necessary to reduce the rate of suture pull through from the vaginal side and to reduce the rate of prolapse caused by breakdown of the endopelvic fascia. Bone anchors were also incorporated to help fix the suspensory sutures. Appell et al. reported that the pubic bone fixation decreased the rate of suture-related pain and the risk of entrapping the ilioinguinal nerve [48,49], but long-term results for this procedure are pending. C. Synthetic Sling Materials Initial indications for synthetic sling material were for patients who experienced recurrent stress urinary incontinence despite multiple procedures to correct it. These patients usually had considerable pelvic and vaginal scarring that precluded elevating the anterior vaginal wall by routine colposuspension procedures, which were in favor when the synthetic sling was introduced. Although many sling materials have been used, synthetic materials became less popular because of their association with multiple complications, most notably rejection, erosion, and infection (Table 2 compares the different sling materials and their associated complications). As a result, the use of synthetics was virtually abandoned for several years. Recently, treatment of stress urinary incontinence has come full circle: Certain authorities are again advocating synthetic material. Contemporary use of arti-

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Table 2 Complications of Sling Procedures by Sling Material Sling material Complication Vaginal erosion Urethral erosion Fistula Wound sinus Wound infection Seroma

Autologous (N ⫽ 1715)

Homologous (N ⫽ 414)

Synthetic (N ⫽ 1515)

1 (0.01%) 5 (0.3%) 6 (0.3%) 3 (0.2%) 11 (0.6%) 6 (0.3%)

0 0 0 0 9 (2%) 0

10 (0.7%) 27 (2%) 4 (0.2%) 11 (0.7%) 15 (0.9%) 1 (0.07%)

Source: From Ref. 1.

ficial sling material has been encouraged to improve the ease of sling surgery and to offer patients a less-morbid procedure. The most popular use of the material today may be the tension-free vaginal tape (TVT) procedure, which uses polypropylene mesh. Mersilene polyethylene was the first synthetic material used to support the urethra and bladder neck to correct stress incontinence [50]. In 1962, Williams and TeLinde advocated use of a 5-mm wide piece of Mersilene (Dacron) ribbon. They reported an 83% success rate, although the sling had to be removed in one patient due to urethral erosion. Moir modified this procedure in 1968 by using Mersilene gauze to provide a broader band of support to the bladder neck and vesicourethral junction [51]. This procedure became known as the gauze hammock operation. It was named such to distinguish it clearly from the fascial sling described by Aldridge in 1943 [35]. Moir believed that the Aldridge fascial sling and the Mersilene ribbon were fraught with complications because they utilized narrow sling materials. These allowed the sling to become cordlike and thereby increased the likelihood of postoperative retention and the development of urethrovaginal fistulas caused by transection of the urethra. Therefore, Moir fashioned a strip of sterilized Mersilene gauze (approximately 30 cm long) to serve as his “hammock.” The belly or widest portion (2.5 cm) of the hammock was placed at the level of the bladder neck, and the two ends were secured to the rectus fascia. He evaluated the results in 71 patients after a few months to 5 years of follow-up. Of the patients, 83% reported that they were cured or substantially improved, 11% were improved with occasional incontinence, and 5% experienced failure. In addition, Nichols published results in 1973 and reported 21 cures in 22 cases. All cases with 2 or more years of follow-up were cured, although cure was based on physician assessment and thus was poorly defined [52]. In 1970, Morgan, employing the same concept as Moir, described a Marlex gauze hammock operation for the treatment of recurrent stress urinary incontinence that was designed to overcome the problem of urethral fixation and scarring caused by prior procedures [53]. He utilized a wide strip (2 cm) of polypropylene mesh for the sling material and anchored this to the ileopectineal line (Cooper’s ligament). In this initial report, he achieved a success rate of 100% after 3 to 23 months. In 1985, Morgan reported a 77.4% success rate with 208 patients with at least

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5 years of follow-up [54]. When he excluded patients who underwent a Marlex sling procedure in conjunction with construction of a neourethra, the success rate increased to 80.9%. Others reported similar outcomes [55]. However, although the success rate of the procedure was acceptable, many of the same complications seen with the Mersilene gauze hammock were encountered. In Morgan’s report of 208 patients, urethral erosion occurred in 12 patients, chronic retention occurred in 12 patients, and postoperative urgency and frequency occurred in 10. No slings were rejected or required removal [53]. Additional sling materials have been utilized. Stanton introduced the use of Silastic in 1985 [56]. This material is made from layers of silicone sheet that are reinforced with Dacron. Silastic was thought to be preferable to either Mersilene or Marlex because of its smooth surface, which prevents it from being bound by living tissues. In theory, after several weeks, a thin fibrous sheath surrounds the silicone sling, and if at any time the sling requires removal, the sheath persists and continues to provide the support necessary for continued continence. In contrast, dense scar tissue is encountered on removal of Mersilene and Marlex slings. This scar has to be sacrificed to release the synthetic sling. As a result, any support that the scar provides to the urethra and bladder neck is lost, and recurrent incontinence ensues. Stanton reported an objective and subjective cure rate of 83% in 30 patients after 3 months of follow-up. However, the long-term results of the silicone sling were not as impressive: 71% cure rate at 5 years [57]. But, on removing the silicone sling, 70% to 80% of patients remained continent, which confirms the durability of a fibrous sheath [56,58]. As with all synthetic materials, the silicone sling was also associated with a high rate of complications (Table 2). Although it proved easy to remove, silicone was associated with a high rate of sinus formation and rejection due to foreign body reaction. Gore-tex (expanded polytetrafluoroethylene) was introduced as an additional synthetic material because of its success as a vascular conduit. It is a nonabsorbable, inert material that facilitates the incorporation of tissues without provoking excessive reaction to a foreign body. Thus, unlike prior synthetic materials, it allows infection to be treated without having to remove the graft. Horbach et al. achieved an 84% objective success rate in 17 patients after 3 months of followup [59]. Weinberger and Ostergard achieved a lower success rate on longer evaluation: 61% objective cure rate after a mean of 38 months [60]. Despite its porous microstructure, which led many to believe that Gore-tex would reduce the rate of foreign body reactions, Gore-tex is associated with a high rate of erosion and rejection. Reaction and removal rates for Gore-tex slings have been reported as high as 23% [61], and the incidence of postoperative wound infection has been as high as 40% [60]. Consequently, Norris et al. modified the procedure and developed the Goretex patch sling [62]. They believed that reducing the amount of sling material could decrease the infection rate. After 24 months of follow-up, they reported a success rate of 88% in 122 patients. However, 4% experienced vaginal erosion, and 5% experienced prolonged postoperative retention that required sling incision. In 1999, Choe and Staskin reported an overall success rate of 90% in 141 patients after a mean follow-up of 51 months [63]. Of the patients, 7% experienced prolonged (greater than 3 months) urinary retention. Fifty percent remained conti-

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nent following sling lysis. Due to adverse tissue reaction, 5% of patients had to have their sling removed. Only 20% of these remained continent. D.

Allograft Fascia

In 1942, Aldridge described the use of “transplanted” autologous fascia to correct urinary incontinence [35]. Fascia allografts have been used in clinical practice for more than 25 years, and their efficacy and safety are clearly documented. Ophthalmologists have used allograft fascia lata in the reconstruction of the orbital floor, while orthopedists have used it extensively in repair of the anterior cruciate ligament [64,65]. However, it was not until 1996 that Handa et al. introduced the use of cadaveric allograft fascia for the treatment of incontinence [66]. This approach was well received because of the need for a sling material that was free of (1) the infectious and erosive complications associated with synthetic materials and (2) the additional morbidity associated with harvesting autologous material. Allografts are tissues harvested from a human donor, usually cadavers, that are transplanted into human recipients. The allograft is obtained from a licensed tissue bank regulated by the American Association of Tissue Banks (AATB), and a multistep sterilization process is conducted to eliminate the risk of disease transmission. Several processing techniques for allograft fascia include fresh frozen, freeze-dried, and Tutoplast—a unique chemical process followed by irradiation (Mentor, Santa Monica, CA). Fresh frozen allografts must be stored at ⫺70 °C and reconstituted 24 h prior to use. Freeze-dried grafts are incubated in 70% isopropyl alcohol to inactivate any virus and then frozen (in a process known as lyophilization). This freeze-drying process eliminates the antigenicity of soft tissue allografts, and thus donor and recipient matching are not required. Further sterilization is achieved through γ-radiation. Although the risk of disease transmission is remote, it is imperative that this risk be explained to patients. Several studies have attempted to quantify this risk. Only one case of transmission of the human immunodeficiency virus (HIV) has been reported from tissue transplantation since screening for HIV and other viral pathogens has been initiated. This one case occurred in a woman who received a bone allograft from a seronegative donor in 1985 [67]. If the guidelines for tissue banking set forth by the Food and Drug Administration are followed, the risk of acquiring tissue from a properly screened donor with HIV is estimated to be 1/1,667,600 [68]. By comparison, the risk of HIV infection from a blood transfusion is much higher, at 1/ 440,000 to 1/600,000 per unit transfused [69]. Another potential risk of cadaveric fascia transplantation is the transmission of prion diseases. Prions are protein molecules located in the central nervous system that harbor infection within a host protein. They have been associated with transmissible spongioform encephalopathy, the most common form being Creutzfeldt-Jakob disease. Unfortunately, prions resist conventional means of virus inactivation [i.e., γ-irradiation or extreme heat exposure (such as by autoclaving)]. However, they may be susceptible to processes that denature proteins, such as chaotropic ions or denaturing detergents [70]. Strong alkaline treatment is also capable of inactivating prions [71], and the Tutoplast process utilizes this method. Extensive review of the literature has failed to document any transmissible spongioform encephalopathy associated with the use of cadaveric fascia lata.

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Pubovaginal slings created using allograft fascia lata have proven as efficacious as autologous fascia in short-term follow-up studies. Handa et al. reported subjective success in 14 of 16 patients after 6 to 12 months of follow-up [66]. In 1998, Wright et al. reported results for 59 patients: There was a 98% success rate after an average of 9 months of follow-up versus a 94% success rate for 33 patients who had undergone an autologous fascia lata sling procedure by the same surgeon [72]. Recently, Brown and Govier reported the results for 121 patients 12 months after surgery and compared these results to those for 46 women who underwent an autologous fascia lata sling [73]. Of the patients receiving an allograft fascia lata sling, 85% were cured of stress incontinence, compared to 90% of those receiving an autologous graft. Durability of allograft fascia lata slings has been called into question. Chaikin and Blaivas reported the first failure of a cadaveric fascial sling in 1998 [74]. Three days postoperatively, the patient had recurrent stress urinary incontinence. The edges of the graft had frayed, and the sutures had pulled out. The authors questioned whether the tissue processing technique had weakened the fascia. Additional reports raise the same question. Fitzgerald et al. reported 8 failures for 35 patients who received a cadaveric fascial sling [75]. Seven of these had an initial subjective cure lasting 6 to 16 weeks. On reoperation, 7 of the 8 slings were found to have undergone some form of degeneration or autolysis. In fact, 5 showed no visible remnants of the fascial graft. Histologic examination did not reveal the expected changes leading to graft maturation, and the etiology for autolysis has yet to be determined. Some authors have implicated the tissue-processing technique, suggesting that irradiation may be associated with a decrease in graft strength [76,77]. Overall, despite the established safety and efficacy of cadaveric allograft fascia, its role in incontinence surgery awaits clarification from more long-term clinical data and further research into the phenomenon of autolysis. Other recently introduced allograft materials include decellularized dermis known as Duraderm (Bard, Inc., Covington, GA) and Repliform (Microvasive, Boston Scientific, Natick, MA). Stratasis (Cook Urological, Bloomington, IN), a graft derived from the submucosa of porcine small intestine, has also been recently developed. At this point, until clinical data supporting both the long-term safety and efficacy of these new allografts emerge, their use cannot be endorsed without caution.

IV. USE OF BONE ANCHORS IN INCONTINENCE SURGERY The point of fixation must also be considered in addition to the suspensory material used in incontinence procedures. Marshall et al. originally popularized pubic bone fixation when they described their retropubic approach to bladder neck suspension in 1949 [78]. On the many modifications of the Pereyra procedure, the anterior rectus fascia became a common point of fixation. Over the last decade, however, pubic bone fixation has again gained in popularity. Its proponents recognize that a major cause of failure of incontinence procedures using rectus fascia as their point of fixation is because of suture pull through. During increases in abdominal pressure, tension is placed on the suspensory sutures, which allows the sutures to saw through the periurethral and vaginal tissues [79]. In contrast,

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the pubic bone serves as a medial, stationary point of fixation and reduces the amount of tension placed on the suspensory sutures. Leach was among the first to describe the use of bone anchor fixation in transvaginal surgery stress urinary incontinence, doing so in 1988 [80]. In his series of 115 patients, he manually attached the suspensory sutures to the pubic bone and found that postoperative discomfort and the risk of ileoinguinal nerve entrapment were dramatically reduced. Since this initial description, various devices for bone anchor fixation have been introduced. Instruments utilizing the suprapubic approach for the placement of bone anchors have given way to the infrapubic or transvaginal devices that minimize the invasiveness of this procedure. Transvaginal devices help preserve the endopelvic fascia and decrease retropubic dissection. Figures 4 and 5 illustrate the infrapubic placement of bone anchors using the In-Fast Female Sling Fixation System (American Medical Systems, Inc., Minnetonka, MN). The introduction of bone-anchoring devices has allowed transvaginal anti-incontinence procedures to be done easily and with decreased patient morbidity [46]. Table 3 lists their advantages and disadvantages as compared to rectus fascial fixation.

Figure 4 Transvaginal bone anchoring using the In-Fast Female Sling Fixation System. (Courtesy of American Medical Systems, Inc., Minnetonka, MN. Medical illustrations by Michael Schenk.)

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Figure 5 Final position of a pubovaginal sling using the In-Fast Female Sling Fixation System. (Courtesy of American Medical Systems, Inc., Minnetonka, MN. Medical illustrations by Michael Schenk.)

To date, use of bone anchors has not shown to improve the long-term durability of bladder neck suspension procedures [81], and long-term data assessing their effectiveness with slings are lacking. Some preliminary reports of their usage with cadaveric fascia are disappointing: There was a 10.4% failure rate after 6 months of follow-up [77]. In this series, as in most, it is unclear whether it is the mode of sling fixation, the sling type, or other factors that are responsible for the high failure rate. Complications associated with bone anchor fixation remain of concern. The incidence of osteitis pubis, a painful inflammation of the periosteum of the pubic bone, following an Marshall-Marchetti-Kranz (MMK) procedure is as high as 0.9% to 10% [82–85]. Adding the transvaginal (nonsterile) approach would seem to increase the incidence, but Leach did not report any cases of osteitis pubis or osteomyelitis in his original series of 115 patients [80]. Moreover, bone anchors

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Table 3 Controversies in Sling Technique Potential advantages Sling material Autograft

Allograft

Synthetic

Fixation point Fascia

Bone

Potential Disadvantages

↑ Durability Biocompatible ↓ Cost Readily available No harvesting ↓ Operative time Readily available No harvesting ↓ Operative time

↑ Morbidity (harvesting) ↑ Operative time ↑ Risk nerve entrapment ? ↓ Durability ? ↑ Infection (HIV, prions) ↑ Cost ↑ Erosion Tissue rejection ↑ Infection (wound) ↑ Cost

↓ Cost ↓ Infection

↑ Suture tension ↑ Risk nerve entrapment Retropubic dissection ↑ Infection (osteitis pubis, osteomyelitis)

↓ Suture tension ↓ Nerve entrapment ↓ Operative time No retropubic dissection

↑ Bone pain ↑ Cost

had to be removed due to infection in only 5 of 7000 operations [86]. Patients presenting with complications related to bone anchors often complain of suprapubic pain, difficulty walking, wound drainage, or fever. Plain radiographs may demonstrate widening of the symphysis pubis or bone erosion. Magnetic resonance imaging or computerized tomography scans will show inflammation of the symphysis pubis and possibly retropubic fluid. Cases of osteitis pubis can often be managed with oral antibiotics, but the more serious condition of osteomyelitis must be treated with intravenous antibiotics, debridement of necrotic bone, and removal of the bone anchors. Enzler et al. reported four cases of osteomyelitis following bladder neck suspension procedures [87]. All four patients experienced recurrent stress urinary incontinence following surgical debridement and removal of the bone anchors. At this time, whether the benefits of bone anchors outweigh the risks associated with their use is uncertain. V.

URODYNAMIC CHANGES FOLLOWING INCONTINENCE SURGERY

Unfortunately, voiding dysfunction following surgery for incontinence is not rare. It is well documented that antiincontinence procedures may aggravate preexisting urgency and/or DI and are associated with their de novo occurrence. However, preoperative identification of DI or urgency is not a contraindication to incontinence surgery. In fact, it has been shown that approximately 70% of patients with preoperative detrusor instability will have resolution of their symptoms following

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surgery for stress urinary incontinence [19,88]. It would appear that those who do have resolution of the instability with the stress urinary incontinence procedure are those in whom the cause of the instability was Valsalva maneuver induced [89]. However, patients with preoperative urgency or urge incontinence must be informed that these symptoms may persist following surgery for stress incontinence, and that their success rate may be lower than those with stable bladders [1,39,76]. The etiology of de novo DI following surgery for stress urinary incontinence is yet to be determined. Some believe it is secondary to irritation of the bladder base induced by extensive vaginal dissection. Others believe it is due to the obstructive nature of the procedures themselves [90]. Still others believe that the bladder neck is left incompetent, which allows urine to leak into the proximal urethra and thereby initiate a reflex detrusor contraction [91]. An extensive metanalysis of over 250 articles revealed that there is no major statistical difference with regard to postoperative urgency among transvaginal suspensions, sling procedures, and retropubic suspensions. Some patients may complain of voiding with a slow stream, of feelings of incomplete emptiness, or of having to void in a particular position (i.e., bending forward, standing, etc.) following anti-incontinence procedures. Along with urgency and urge incontinence, these are all signs of postoperative obstruction. The diagnosis of obstruction in a female patient is often difficult, and pressure flow studies are the most reliable. Lemack and Zimmern propose cutoff pressure flow values for identifying women with bladder outlet obstruction as maximum flow rate Qmax of less than 11 cc/s and maximum detrusor pressure at Qmax as greater than 21 cm H2O [92]. Using this definition, as many as 20% of women with overactive bladder symptoms may be obstructed. Table 4 further illustrates the pressure flow changes seen following various incontinence procedures. In all cases, postoperative detrusor pressure at maximum flow was increased. The longterm significance of this finding remains uncertain. Treatment options for bladder outlet obstruction following incontinence procedures include sling incision or urethrolysis, possibly coupled with a repeat antiincontinence procedure. Following urethrolysis, 77% to 100% of patients will have resolution of their obstructive voiding symptoms without recurrent stress incontinence [96,97]. However, urethrolysis is not as effective in patients with irritative Table 4 Pressure-Flow Changes Following Anti-Incontinence Procedures Procedure Stamey* Modified Pereyra† Burch‡ Sling§

Preop Pdet at Q max (cm H2O)

Postop Pdet at Q max (cm H2O)

P

26 37 21.6 24

57 51 27.7 38

.4 ⬎.05 ⬍.001 ⬍.001

Pdet ⫽ maximum detrusor pressure; Qmax ⫽ maximum flow rate. * From Ref. 92. † From Ref. 94. ‡ From Ref. 95. § From Ref. 96.

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voiding symptoms. Goldman et al. found 19% of patients had recurrent stress incontinence after urethrolysis, but these patients could be managed with collagen injections [98].

VI. CONCLUSION Many questions remain unanswered with regard to the pathophysiology of stress urinary incontinence. As our understanding of this entity improves, new procedures will continue to be introduced. It is therefore imperative that each new technique be scrutinized before being accepted and incorporated into routine practice. Regardless of the choice of antiincontinence procedure, the keys to success continue to be proper patient selection, thorough preoperative evaluation and counseling, and diligent attention to detail intraoperatively.

REFERENCES 1. Leach GE, Dmochowski RR, Appell RA, Blaivas JG, Hadley HR, Luber KM, Mostwin JL, O’Donnell PD. Report on the Surgical Management of Female Stress Urinary Incontinence Clinical Practice Guidelines. Baltimore, MD: American Urological Association, 1997. 2. DeLancey JO. Structural support of the urethra as it relates to stress urinary incontinence:the hammock hypothesis. Am J Obstet Gynecol 1994; 170(6):1713–1720. 3. Kelly HA, Dumm WM. Urinary incontinence in women, without manifest injury to the bladder. Surg Gynecol Obstet 1914; 444–450. 4. Pereyra AJ. A simplified surgical procedure for the correction of stress incontinence in women. West J Surg Obstet Gynecol 1959; 67:223–226. 5. Pereyra AJ, Lebherz TB. Combined urethrovesical suspension and vaginourethroplasty for correction of urinary stress incontinence. Obstet Gynecol 1967; 30(4):537–546. 6. Pereyra AJ, Lebherz TB, Growdon WA, Powers JA. Pubourethral supports in perspective: modified Pereyra procedure for urinary incontinence. Obstet Gynecol 1982; 59(5): 643–648. 7. Stamey TA. Endoscopic suspension of the vesical neck for urinary incontinence. Surg Gynecol Obstet 1973; 136:547–554. 8. Mundy AR. A trial comparing the Stamey bladder neck suspension procedure with colposuspension for the treatment of stress incontinence. Br J Urol 1983; 55:687–690. 9. Stamey TA. Endoscopic suspension of the vesical neck for urinary incontinence in females: report on 203 consecutive patients. Ann Surg 1980; 192(4):465–471. 10. Walker GT, Texter JH. Success and patient satisfaction following the Stamey procedure for stress urinary incontinence. J Urol 1992; 147:1521–1523. 11. Mills R, Persad R, Ashken MH. Long-term follow-up results with the Stamey operation for stress incontinence of urine. Br J Urol 1996; 77:86–88. 12. Peattie AB, Stanton SL. The Stamey operation for correction of genuine stress incontinence in the elderly woman. Br J Obstet Gynecol 1989; 96:983–986. 13. Hilton P, Mayne CJ. The Stamey endoscopic bladder neck suspension: a clinical and urodynamic investigation, including actuarial follow-up over four years. Br J Obstet Gynecol 1991; 98:1141–1149. 14. Griffith-Jones MD, Abrams PH. The Stamey endoscopic bladder neck suspension in the elderly. Br J Urol 1990; 65:170–172.

Transvaginal Surgery for Stress Incontinence

157

15. Wujanto R, O’Reilly PH. Stamey needle suspension for stress urinary incontinence. Br J Urol 1989; 63:162–164. 16. Gofrit ON, Landau EH, Shapiro A, Pode D. The Stamey procedure for stress incontinence: long term results. Eur Urol 1998; 34:339–343. 17. Bihrle W, Tarantino AF. Complications of retropubic bladder neck suspension. Urology 1990; 35(3):213–214. 18. Raz S. Modified bladder neck suspension for female stress incontinence. Urology 1981; 17(1):82–85. 19. Raz S, Sussman EM, Erickson DB, Bregg KJ, Nitti VW. The Raz bladder neck suspension: results in 206 patients. J Urol 1992; 148:845–850. 20. Kelly MJ, Knielsen K, Bruskewitz R, Roskamp D, Leach GE. Symptom analysis of patients undergoing modified Pereyra bladder neck suspension for stress urinary incontinence. Urology 1991; 37(3):213–219. 21. Korman HJ, Sirls LT, Kirkemo AK. Success rate of modified Pereyra bladder neck suspension determined by outcomes analysis. J Urol 1994; 152:1453–1457. 22. Sirls LT, Keoleian CM, Korman HJ, Kirkemo AK. The effect of study methodology on reported success rates of the modified Pereyra bladder neck suspension. J Urol 1995; 154:1732–1735. 23. Gittes RF, Loughlin KR. No-incision pubovaginal suspension for stress incontinence. J Urol 1987; 138:568–570. 24. Gittes RF, Roreman R. Transcutaneous incorporation of nonabsorbable monofilament sutures. Surg Gynecol Obstet 1988; 166(6):545–548. 25. Kohli N, Karram MM. Surgery for genuine stress incontinence. In: Walters MD, Karram MM, eds. Urogynecology and Reconstructive Surgery. St. Louis, MO: Mosby, 1999:178. 26. Kursch ED. Factors influencing the outcome of a no-incision endoscopic urethropexy. Surg Gynecol Obstet 1992; 175:254–258. 27. Kursch ED, Angel AH, Resnick MI. Evolution of endoscopic urethropexy: seven-year experience with various techniques. Urology 1991; 37:428–431. 28. Raz S, Stothers L, Chopra A. Raz techniques for anterior vaginal wall repair. In: Raz S. Female Urology. Philadelphia: W. B. Saunders, 1996:344–366. 29. Dmochowski RR, Zimmern PE, Ganabathi K, Sirls L, Leach GE. Role of the four-corner bladder neck suspension to correct stress incontinence with a mild to moderate cystocele. Urology 1997; 49(1):35–40. 30. Lemack GE, Zimmern PE. Questionnaire-based outcome after anterior vaginal wall suspension for stress urinary incontinence. J Urol 2000; 163(4), 321A:73. 31. Leach GE, Sirls L. Pubovaginal sling procedures. In: Leach GE, ed. Atlas of the Urologic Clinics of North America, Vaginal Surgery for the Urologist. Philadelphia: W. B. Saunders, 1994:61–71. 32. Ridley JH. The Goebel-Stockel sling operation. In: Mattingly RF, Thompson JD, eds. TeLinde’s operative gynecology. Philadelphia: Lippincott, 1985. 33. Goebel R. Zur operativen beseitigung der angeborenen incontinenz Vesicae. Ztsch.f.gynak. U Urol 1910; 2:187. 34. Price PB. Plastic operations for incontinence of urine and feces. Arch Surg 1933; 26: 1043. 35. Aldridge AH. Transplantation of fascia for relief of urinary stress incontinence. Am J Obstet Gynecol 1943; 44:398–411. 36. McGuire EJ, Lytton B. Pubovaginal sling procedure for stress incontinence. J Urol 1978; 119:82–85. 37. Crawford JS. Nature of fascia lata and its fate after implantation. Am J Ophthalmol 1969; 67:900–907. 38. Govier FE, Gibbons RP, Correa RJ, Weissman RM, Pritchett TR, Hefty TR. Pubovagi-

158

39. 40. 41. 42. 43. 44.

45. 46.

47. 48.

49. 50. 51. 52. 53. 54. 55.

56. 57. 58. 59.

60.

Wilson and Lemack nal slings using fascia lata for the treatment of intrinsic sphincter deficiency. J Urol 1997; 157:117–121. Cross CA, Cespedes RD, McGuire EJ. Our experience with pubovaginal slings in patients with stress urinary incontinence. J Urol 1998; 159:1195–1198. Gormley EA, Bloom DA. Pubovaginal slings for the management of urinary incontinence in female adolescents. J Urol 1994; 152(2 Pt 2):822–825. Morgan TO, Westney OL, McGuire EJ. Pubovaginal sling: four-year outcome analysis and quality of life assessment. J Urol 2000; 163:1845–1848. Beck RP, Grove D, Arnusch D, Harvey J. Recurrent urinary stress incontinence treated by the fascia lata sling procedure. Am J Obst Gynecol 1974; 120(5):613–621. Raz S, Siegel AL, Short JL, Synder JA. Vaginal wall sling. J Urol 1989; 141:43–46. Raz S, Stothers L, Young GPH, Short J, Marks B, Chopra A, Wahle GP. Vaginal wall sling for anatomical incontinence and intrinsic sphincter dysfunction: efficacy and outcome analysis. J Urol 1996; 156:166–170. Kaplan SA, Santarosa RP, Te AE. Comparison of fascial and vaginal wall slings in the management of intrinsic sphincter deficiency. Urology 1996; 47(6):885–889. Kaplan SA, Te AE, Young GPH, Andrade A, Cabelin MA, Ikeguchi EF. Prospective analysis of 373 consecutive women with stress urinary incontinence treated with a vaginal wall sling: the Columbia-Cornell university experience. J Urology 2000; 164: 1623–1627. Baldwin DD, Hadley HR. Epithelial inclusion cyst formation after free vaginal wall swing sling procedure for stress urinary incontinence. J Urology 1997; 157:952. Vasavada SP, Rackley RR, Appell RA. In situ vaginal wall sling formation with preservation of the endopelvic fascia for treatment for stress urinary incontinence. Int Urogynecol J 1998; 9:379–384. Appell RA. In situ vaginal wall sling. Urology 2000; 56(3):499–503. Williams TJ, TeLinde RW. The sling operation for urinary incontinence using mersilene ribbon. Obstet Gynecol 1962; 19(2):241–245. Moir JC. The gauze-hammock operation. J Obstet Gynaecol Br Commonw 1968; 75(1): 1–9. Nichols DH. The mersilene mesh gauze-hammock for severe urinary stress incontinence. Obstet Gynecol 1973; 41(1):88–93. Morgan JE. A sling operation, using marlex polypropylene mesh for treatment of recurrent stress incontinence. Am J Obstet Gynecol 1970; 106:369–377. Morgan JE. The marlex sling operation for the treatment of recurrent stress urinary incontinence: a 16-year review. Am J Obstet Gynecol 1985; 151:224–226. Bryans FE. Marlex gauze hammock sling operation with Cooper’s ligament attachment in the management of recurrent urinary stress incontinence. Am J Obstet Gynecol 1979; 133(3):292–294. Stanton SL. Silastic sling for urethral sphincter incompetence in women. Br J Obstet Gynaecol 1985; 92:747–750. Chin YE, Stanton SL. A follow up of silastic sling for genuine stress incontinence. Br J Obstet Gynaecol 1995; 102:143–147. Duckett JRA, Constantine G. Complications of silicone sling insertion for stress urinary incontinence. J Urol 2000; 163:1835–1837. Horbach NS, Blanco JS, Ostergard DR, Bent AE, Cornella JL. A suburethral sling procedure with polytetrafluoroethylene for the treatment of genuine stress incontinence in patients with low urethral closure pressure. Obstet Gynecol 1988; 71:648–652. Weinberger MW, Ostergard DR. Long-term clinical and urodynamic evaluation of the polytetrafluoroethylene suburethral sling for treatment of genuine stress incontinence. Obstet Gynecol 1995; 86:92–96.

Transvaginal Surgery for Stress Incontinence

159

61. Bent AE, Ostergard DR, Zwick-Zaffuto M. Tissue reaction to expanded polytetrafluoroethylene suburethral sling for urinary incontinence: clinical and histologic study. Am J Obstet Gynecol 1993; 169:1198–1204. 62. Norris JP, Breslin DS, Staskin DR. Use of synthetic material in sling surgery: a minimally invasive approach. J Endourol 1996; 10(3):227–230. 63. Choe JM, Staskin DR. Gortex patch sling: seven years later. Urology 1999; 54(4):641– 646. 64. Bedrossian EH. Banked fascia lata as an orbital floor implant. Ophthal Plast Reconstr Surg 1993; 9(1):66–70. 65. Noyes FR, Barber-Westin SD. Reconstruction of the anterior cruciate ligament with human allograft. Comparison of early and later results. J Bone Joint Surg Am 1996; 78(4):524–537. 66. Handa VL, Jensen JK, Germain MM, Ostergard DR. Banked human fascia lata for the suburethral sling procedure: a preliminary report. Obstet Gynecol 1996; 88(6):1045– 1049. 67. Simonds RJ, Holmberg SD, Hurwitz RL, Coleman TR, Bottenfield S, Conley LJ, Kohlenberg SH, Castro KG, Dahan BA, Schable CA. Transmission of human immunodeficiency virus type I from a seronegative organ and tissue donor. N Engl J Med 1992; 326(11):726–732. 68. Buck BE, Malinin TI, Brown MD. Bone transplantation and human immunodeficiency virus. An estimate of risk of acquired immunodeficiency syndrome (AIDS). Clin Orthop 1989; 240:129–136. 69. Tomford WW. Transmission of disease through transplantation of musculoskeletal allogafts. J Bone Joint Surg 1995; 77(11):1742–1754. 70. Cashman NR. A prion primer. Can Med Assoc J 1997; 157(10):1381–1385. 71. Diringer H, Braig HR. Infectivity of unconventional viruses in dura mater. Lancet 1989; 1(8635):439–440. 72. Wright EJ, Iselin CE, Carr LK, Webster GD. Pubovaginal sling using cadaveric allograft fascia for the treatment of intrinsic sphincter deficiency. J Urol 1998; 160:759–762. 73. Brown SL, Govier FE. Cadaveric versus autologous fascia lata for the pubovaginal sling: surgical outcome and patient satisfaction. J Urol 2000; 164:1633–1637. 74. Chaikin DC, Blaivas JG. Weakened cadaveric fascial sling: an unexpected cause of failure. J Urol 1998; 160:2151. 75. Fitzgerald MP, Mollenhauer J, Brubaker L. Failure of allograft suburethral slings. BJU Int 1999; 84:785–788. 76. Fitzgerald MP, Mollenhauer J, Bitterman P, Brubaker L. Functional failure of fascia lata allografts. Am J Obstet Gynecol 1999; 181(6):1339–1346. 77. Carbone JM, Kavaler E, Raz S. Disappointing early results with bone-anchored cadaveric fascia pubovaginal sling. J Urol 2000; 163(4), 736A:166. 78. Marshall VF, Marchetti AA, Krantz KE. The correction of stress incontinence by simple vesicourethral suspension. Surg Gynecol Obstet 1949:509–518. 79. Appell RA. The use of bone anchoring in the surgical management of female stress urinary incontinence. World J Urol 1997; 15:300–305. 80. Leach GE. Bone fixation technique for transvaginal needle suspension. Urology 1988; 31(5):388–390. 81. Schulteiss D, Hofner K, Oelke M, Grunewald V, Jonas U. Does bone anchor fixation improve the outcome of percutaneous bladder neck suspension in female stress urinary incontinence? Br J Urol 1998; 82:192–195. 82. Lee RA, Symmonds RE, Goldstein RA. Surgical complications and results of modified Marshall-Marchetti-Krantz procedure for urinary incontinence. Obstet Gynecol 1979; 53(4):447–450.

160

Wilson and Lemack

83. McDuffie RW, Litin RB, Blundun KE. Urethrovesical suspension (Marshall-MarchettiKrantz). Experience with 204 cases. Am J Surg 1981; 141(2):297–298. 84. Parnell JP, Marshall VF, Vaughn ED. Management of recurrent urinary stress incontinence by the Marshall-Marchetti-Krantz vesicourethropexy. J Urol 1984; 132(5):912– 914. 85. Peters WA, Thornton WN. Selection of the primary operative procedure for stress urinary incontinence. Am J Obstet Gynecol 137(8):923–930. 86. Leach GE. Local anesthesia for urologic procedures. Urology 1996; 48:284–288. 87. Enzler M, Agins H, Kogan M, Kudurna J, Sand P, Wurts R, Culligan P. Osteomyelitis of the pubis following suspension of the neck of the bladder with use of bone anchors: a report of four cases. J Bone Joint Surg Am 1999; 81A(12):1736–1740. 88. McGuire EJ. Abdominal procedures for stress incontinence. Urol Clin North Am 1985; 12:285–290. 89. Sereles SR, Rackley RR, Appell RA. Surgical treatment for stress urinary incontinence associated with Valsalva induced detrusor instability. J Urol 2000; 163:884–887. 90. Kelly MJ, Zimmern PE, Leach GE. Complications of bladder neck suspension procedures. Urol Clin North Am 1991; 18(2):339–348. 91. Haab F, Sananes S, Amarenco G, Ciofu C, Uzan S, Gattegno B, Thibault P. Results of the tension-free vaginal tape procedure for the treatment of type II stress urinary incontinence at a minimum follow-up of one year. J Urol 2001; 165:159–162. 92. Lemack GE, Zimmern PE. Pressure flow analysis may aid in identification of women with outflow obstruction. J Urol 2000; 163:1823–1828. 93. Pope AJ, Shaw PJR, Coptcoat MJ, Worth PHL. Changes in bladder function following a surgical alteration in outflow resistance. Neurourol Urodynam 1990; 9:503–508. 94. Leach GE, Yip CM, Donovan BJ. Mechanism of continence after modified Peveyra bladder neck suspension. Prospective urodynamic stray. Urology 1987; 29(3):328–331. 95. Belair G, Tessier J, Bertrand PE, Schick E. Retropubic cystourethropexy: is it an obstructive procedure? J Urol 1997; 158:533–538. 96. Fulford SCV, Flynn R, Barrington J, Appanna T, Stephenson TP. An assessment of the surgical outcome and urodynamic effects of the pubovaginal sling for stress incontinence and the associated urge syndrome. J Urol 1999; 162:135–137. 97. Foster HE, McGuire EJ. Management of urethral obstruction with transvaginal urethrolysis. J Urol 1993; 150(5 Pt 1):1448–1451. 98. Goldman HB, Rackley RR, Appell RA. The efficacy of urethrolysis without resuspension for iatrogenic urethral obstruction. J Urol 1999; 161(1):196–198.

10 Laparoscopic Approaches to Female Incontinence, Voiding Dysfunction, and Prolapse JAIME LANDMAN Washington University St. Louis, Missouri, U.S.A. ELSPETH M. McDOUGALL Vanderbilt University Nashville, Tennessee, U.S.A.

I.

INTRODUCTION

No longer can the surgeon consider only the management or elimination of disease. The surgeon of today has available the tools to manage disease with great efficacy, while inflicting minimal pain and allowing an expeditious convalescence. Advances in both minimally invasive surgical technology and surgical skills have made many traditional management strategies obsolete. Specifically, advances in reconstructive laparoscopic surgery have dramatically altered the standard of care in almost every surgical subspecialty. In this chapter, we outline the current state of the art of laparoscopic management of female urinary incontinence, voiding dysfunction, and prolapse. The evolution and specific surgical technique of each procedure are described. In addition, the most current available literature is presented with specific attention to the efficacy and efficiency of each procedure. When available, comparative studies contrasting the results of open and laparoscopic procedures are presented. II. LAPAROSCOPIC URINARY INCONTINENCE SURGERY The 1996 Agency for Health Care Policy and Research estimated that approximately 14 million Americans suffer from urinary incontinence, with an estimated 161

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annual cost of $46 billion [1]. While these data were not stratified to reflect only surgically correctable stress urinary incontinence, this population certainly reflects a significant component of the figure. In addition, quality of life is decreased in these individuals. Multiple surgical procedures have been developed to suspend or support the bladder neck and thereby correct female stress incontinence. These procedures include anterior colporraphy, anterior cystourethropexies, endoscopic needle suspensions, and sling procedures. Laparoscopic bladder neck suspension was first described in 1991 as a transperitoneal approach by Vancaillie and Schuessler [2]. At present, laparoscopic bladder neck suspension is usually performed in an extraperitoneal retropubic fashion. Access is gained to the extraperitoneal space via a 2-cm incision that is created approximately one-third of the way caudal, between the symphysis pubis and the umbilicus. A dilating balloon is used to dilate and establish the retropubic working space. A laparoscopic trocar is placed, and carbon dioxide insufflation is performed. Two additional trocars are placed just lateral to the lateral border of the left rectus abdominus muscle; one is opposite the initial trocar placement, and another is several centimeters above the pubic ramus. Using an intracorporeal suturing technique, sutures are placed on either side of the bladder neck and are then passed through the midline cartilagenous notch of the posterior symphysis (modified Marshall-Marchetti-Krantz [MMK]), through Cooper’s ligament bilaterally (modified Burch), or through the ileal pectinate line (modified Richardson) (Figs. 1–3). The sutures are tightened to elevate the bladder neck and proximal urethra behind the pubic symphysis, and the sutures are secured with an anchoring device (e.g., LaparoTy clip) or by

Figure 1 Laparoscopic Marshall-Marchetti-Krants procedure.

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Figure 2 Laparoscopic modified Burch procedure.

Figure 3 Laparoscopic modified Richardson.

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intracorporeal or extracorporeal knotting techniques. A Foley catheter is placed in the bladder for 24 h. Albala and coworkers reported results of 22 bladder neck suspensions using transperitoneal MMK (n ⫽ 22) or Burch (n ⫽ 10) procedures [3]. There were 29 (91%) procedures successfully accomplished laparoscopically. Two conversions resulted from inability to place sutures, and one conversion was the result of bladder injury during dissection of the space of Retzius. All three of these patients were discharged on the third postoperative day without further complication. Mean operative times for the Burch and MMK procedures were 105 and 65 min, respectively. Estimated blood loss and analgesic requirements were not reported. There were 28 patients (88%) discharged in less than 18 h postoperatively. Of these, 19 (59%) patients were discharged home without a Foley catheter, while 13 (41%) had catheters placed for 3 days. In the MMK group, all patients were cured of their incontinence over 1 year after surgery. With a mean follow-up of only 7 months, all patients in the Burch group were also cured of their incontinence. Postoperative complications included urinary retention in 2 patients (6%) that required cystotomy tube placement. Ou and coworkers reported results of 40 women with stress incontinence treated with a modified laparoscopic Burch procedure [4]. A transperitoneal approach was used, and Proline hernia mesh was stapled to both the periurethral tissues and Cooper’s ligament. Operative times and estimated blood loss were not reported. All 40 procedures were successfully accomplished laparoscopically. Average length of hospital stay was 1.2 days, and average duration of catheterization was less than 24 h. Minor complications were reported in 6 of 40 (15%) patients: hematuria, low-grade fever, urinary retention, and urinary tract infection. All complications were self-limiting and were successfully managed without intervention or transfusion. With a mean follow-up of 16 months, all patients had resolution or improvement of incontinence. Specific details regarding postoperative leakage of urine were not reported [4]. Expediting the laparoscopic Burch procedure with the application of proline mesh and staples is appealing. However, we are aware of at least two cases in which the staples migrated into the bladder and urethra, leading to complications. These cases, however, have not been documented in the minimally invasive literature. Soygur and colleagues recently described a modified approach to bladder neck suspension involving 35 patients with type I and II stress urinary incontinence who underwent an extraperitoneal bladder neck suspension [5]. Polypropylene mesh was bilaterally tacked from Cooper’s ligament to digitally elevated periurethral vaginal tissues. The procedure was expedited by the application of a tacking device. Mean operative time was 40 min. There were two intraoperative complications, bladder perforations that were closed using intracorporeal suturing techniques. Four patients (11.4%) experienced postoperative urinary retention, with one requiring self-catheterization for 3 months. With a mean follow-up of only 28 months, 80% of patients were totally dry; the remaining 7 patients reported mild stress incontinence [5]. While there was great initial enthusiasm for laparoscopic bladder neck suspension, the success of the procedure began to unravel when it was reevaluated in the light of longer follow-up. In this regard, Su and coworkers reported a pro-

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spective comparison of laparoscopic and open bladder neck suspension [6]. Fortysix women were randomly chosen for extraperitoneal laparoscopic bladder neck suspension, and 46 women were randomly chosen for the open procedure. Of note, 14 (30%) patients in the laparoscopy group underwent laparotomy for hysterectomy immediately after the laparoscopic procedure. Similarly, there were 14 (30%) patients in the open group that underwent hysterectomy for concomitant gynecological diseases. Operative times were not significantly different for laparoscopic and open procedures (66.5 min and 72.8 min, respectively). However, mean estimated blood loss was significantly decreased in the laparoscopic population (53 mL and 134 mL, respectively). Bladder drainage was present significantly longer in the open group compared to the patients managed laparoscopically (6.8 days and 3.9 days, respectively). Analgesic requirements were not reported. With a minimum of 1-year follow-up, postoperative urodynamic evaluation revealed both groups to have a significant increase in leak point pressure. Comparison between the two groups demonstrated no significant difference. The continence rate was significantly better in the patient population managed with the open technique. Specifically, the continence rate for the laparoscopic group was 80.4% compared to 95.6% for the open group. In the laparoscopic group, there was a complication rate of 10.8%. Two patients (4.3%) experienced outflow obstruction, two (4.3%) experienced de novo detrusor instability, and one (2.2%) patient had a urinary tract infection. In the open group there was a 17.2% complication rate, including two patients (4.3%) with outflow obstruction, two patients (4.3%) with hematuria, and three patients (6.5%) with either detrusor instability, and one (2.2%) patient with a urinary tract infection. Das performed a retrospective nonrandomized comparison of abdominal colposuspension, laparoscopic colposuspension, and vaginal needle suspension [7]. There were 10 women in each group, and all patients were followed for 3 years. Patients undergoing the laparoscopic colposuspension experienced a shorter hospital stay and urinary catheterization and required only low doses of parenteral analgesics. Initial results were promising, with continence rates 10 months postoperatively 90% in the laparoscopic group and 100% in the open colposuspension and needle suspension groups. However, despite these excellent initial outcomes, these results deteriorated significantly thereafter. At 36-month follow-up, laparoscopic colposuspension, abdominal colposuspension, and needle suspension manifested success rates of only 50%, 40%, and 20%, respectively. Subsequent studies with even longer follow-up have shown further reduction in the success of the laparoscopic bladder neck suspension. Specifically, McDougall and colleagues compared results of 58 patients undergoing laparoscopic extraperitoneal bladder neck suspension to results of 42 patients managed by transvaginal Raz bladder neck suspension [8]. Mean follow-up was the longest of any reports on this procedure: 45 months in the laparoscopy group and 59 months in the transvaginal group. Of 58 patients, 50 (86%) were available for follow-up in the laparoscopy group, and 29 of 42 (69%) of the transvaginal group were available for follow-up. Operative time was significantly longer in the population managed laparoscopically: 100 min versus 45 min. Estimated blood loss was similar between patients managed with laparoscopic and vaginal technique (84 mL and 74 mL, re-

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spectively). Mean days of postoperative catheterization was 0.9 days for the laparoscopic bladder neck suspension group and 13.2 days for patients managed transvaginally. Using the strict definition of absolutely no stress incontinence, 15 of 50 (30%) patients in the laparoscopy group were completely dry, while another 20% had occasional stress incontinence requiring no pads or were improved. This was not quite as sanguine an outcome as in the transvaginal group, among whom 10 of 29 (34%) were completely dry, and 28% had occasional stress incontinence requiring no pads or were improved. In the remainder of the laparoscopy group, 23 (46%) patients were using one to two pads daily, and 2 (4%) patients required more than two pads per day. Of the 19 remaining patients in the transvaginal group, 9 (31%) were using one to two pads daily, and 2 (7%) required more than two pads per day. In the laparoscopy and transvaginal groups, 14 (28%) and 11 (38%) patients, respectively, experienced postoperative urge incontinence. As with any reconstructive procedure, it is important to determine that point in time when the “success” of the procedure becomes durable. For bladder neck suspension, it would appear that follow-up of less than 2 years is not sufficient. Indeed, in a review of the literature, Spencer and O’Conor established that failures occurred anywhere between 6 months and 23 years after surgery [9]. They concluded that accurate determination of the efficacy of continence surgery should be established only after 5 years of follow-up. While laparoscopic bladder neck suspension offers women with incontinence the advantages of minimally invasive surgery, the scarce available literature demonstrating long-term results suggests that the procedure as it presently exists likely does not offer women reasonable long-term continence. In addition, data suggest a significant population of women with type I and type II incontinence will also manifest some degree of intrinsic sphincter deficiency. As such, many incontinence surgeons currently favor sling procedures that are efficacious in the management of both forms of stress urinary incontinence and have withstood the 5-year test of time [10]. Another minimally invasive treatment option for intrinsic sphincter deficiency (type III) stress urinary incontinence has been the laparoscopic pubovaginal sling. The pubovaginal sling has also become a primary modality for repair of type I and type II stress incontinence. In an attempt to minimize the postoperative pain associated with the transvaginal and transabdominal approaches, and to expedite convalescence, the laparoscopic approach has been applied to the procedure. Kreder and Winfield described the initial laparoscopic sling placement for stress urinary incontinence via an extraperitoneal approach [11]. Fascia lata was harvested from the patient’s thigh in the usual fashion. Five trocar sites were placed in the lower abdomen, and a plane was created between the bladder neck and the vagina. The fascial sling was passed through the defect at the bladder neck and anchored to the rectus fascia 0.5 cm above the pubis with nonabsorbable sutures passed through two of the previously placed trocar sites. Two cases were described; one had to be converted to open due to an inadvertent urethrotomy. The successful laparoscopic case had an operative time of 6.5 h with an estimated blood loss less than 100 mL. The patient required 16 mg of intramuscular morphine postoperatively. Sluggish return of bowel function resulted in a 5-day hospital stay. At 3-week follow-up, the patient was doing well and had a normal

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voiding cystourethrogram, and the catheter was removed. At 4-month follow-up, the patient was continent. A laparoscopic pubovaginal sling procedure is technically feasible. However, with the evolution of a transvaginal approach in conjunction with synthetic or allograft materials for sling construction, the open procedure has become minimally invasive. Indeed, most of these patients are now treated on an outpatient basis. As such, it is unlikely there will be any advantage to patients in the application of laparoscopic technology for this purpose.

III. BLADDER AUGMENTATION Augmentation cystoplasty is performed for conditions associated with reduced bladder compliance or for detrusor hyperreflexia-instability. These conditions, in which the bladder has a markedly decreased capacity, are common in a variety of clinical settings, including spinal cord disease, myelodysplasia, interstitial cystitis, idiopathic detrusor instability, radiation cystitis, and neurogenic bladder. Procedures to correct these pathological entities are performed with two primary goals in mind: creation of a functional urinary reservoir and preservation of renal function. A consistent feature of bladder augmentation has been the application of components of the alimentary tract as a vascularized source of graft material. Aside from the morbidity of harvest, the use of bowel for urologic reconstruction is associated with significant late sequelae, including segment-specific metabolic disturbances arising from chronic contact with urine, pouch rupture, urolithiasis, and, rarely, carcinogenesis [12–14]. Ideally, alternative techniques for bladder augmentation should both decrease operative time and reduce the morbidity associated with interposing bowel segments into the urinary tract while making the entire procedure amenable to a minimally invasive surgical approach (i.e., laparoscopy). Vesicomyotomy or vesicomyomectomy (autoaugmentation) represents an alternative approach to increasing the capacity of the urinary bladder while avoiding the application of heterotopic epithelium. This technique entails the incision or excision of the detrusor layer of the bladder to create a large, wide-mouth diverticulum of urothelium. First described by Couvelaire in 1955, the technique has undergone a significant evolution with variable results [15]. In the next sections, we review the current state of the art of laparoscopic bladder augmentation and laparoscopic autoaugentation. A. Bladder Autoaugmentation (Cystomyotomy and Cystomyomectomy) In 1989, Cartwright and Snow introduced autoaugmentation by myomectomy in a dog model [16]. Five of the six dogs survived and were evaluated with urodynamics. Four of the five animals demonstrated an increase in pressure-related bladder capacity. The remaining animal manifested decreased bladder capacity. While these results were intriguing, their significance remained unclear as all animals had normal bladder function preoperatively. In the same article, the authors

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described autoaugmentation in a 5-year-old boy with posterior urethral valves [16]. Animal models evaluating the feasibility and efficacy of laparoscopic autoaugmentation are presented in Table 1. The body of available evidence clearly demonstrates the technical feasibility of laparoscopic bladder augmentation in animal models and establishes the foundation for clinical progress. The efficacy of bladder autoaugmentation in the laboratory, whether performed open or laparoscopically, is difficult to determine because no animal model has approximated the conditions of the human bladder pathology that is to be treated. However, it is quite apparent from the available studies that autoaugmentation of a normalcapacity bladder does not increase the bladder capacity. The technique of laparoscopic autoaugmentation was first described by Ehrlich and Gershman [17]. A pneumoperitoneum is established to 10 mmHg. A 10mm trocar is placed beneath the umbilicus. Under direct vision, three additional trocars are placed. Two 10-mm trocars are placed in the midclavicular line, halfway between the umbilicus and the iliac crest. One 10-mm trocar is placed in the right lower quadrant 3 cm medial to the other 10-mm trocar. The bladder is distended via a urethral catheter. Using curved laparoscopic scissors or a laparoscopic hook and low-power cutting current, the posterior wall of the bladder is incised until the urothelium is visualized (Fig. 4). Using graspers, the bladder muscle is teased laterally, exposing additional urothelium. Any bleeding detrusor muscle is carefully coagulated to avoid coagulation of the urothelium. The incision is extended posteriorly to the cul de sac and superiorly to the anterior fusion of the peritoneum and bladder. The bladder muscle is teased laterally for approximately one third the bladder circumference. Inspection of the cut muscular edge with the bladder deflated should demonstrate no bleeding. A drain is left in the space of Retzius. The bladder is drained with a urethral catheter until a cystogram 5 to 7 days postoperatively demonstrates no extravasation. Overall outcome with bladder autoaugmentation has been highly variable. A summary of results of clinical trials is presented in Table 2. Cartwright and Snow reported the first series of bladder autoaugmentations in a pediatric population [18]. Seven patients who failed conservative management of poorly compliant bladders of different etiologies underwent open autoaugmentation with myomectomy. Patient follow-up ranged from 4 to 24 months. There was a single case described as a “technical failure” that led to subsequent enterocystoplasty. In this case, an autoaugmentation was performed successfully; however, there was no augmenting effect, and clinical symptoms persisted. Another patient had not yet returned for follow-up urodynamic evaluation at the time of their report. Bladder capacity was described as the volume at which severe discomfort or urethral leakage occurred. Two patients experienced significant increases in bladder capacity, and two patients experienced no change in bladder capacity. In one case, there was some decrease in the bladder capacity, which was explained by the authors as the result of correction of bilateral grade 5 reflux [18]. When bladder capacity was compared at a controlled pressure of 40 cm H 2 O, a significant increase in capacity (75% to 350%) was documented in four of five patients tested. One of the five patients tested had no alteration in bladder capacity at this pressure. Postoperatively, all patients were dry, and three no longer required clean intermittent catheterization (CIC). Overall, six of seven (86%) previously incontinent patients

Animal

Canine Canine Sheep Porcine Canine

Britansky et al. Cartwright and Snow Dewan et al. Figenshau et al. Garibay et al.

9 6 10 12 5

N Virgin Virgin Virgin Virgin Talc

Bladder Seromyotomy Myomectomy Seromyotomy Seromyotomy Myomectomy

Technique Lap Open Open Lap Open

Open/ laparoscopic

Laparoscopic Autoaugmentation: Laboratory Results

Author

Table 1

6 weeks 2–6 weeks 1–16 weeks 4 months 6 months

Follow-up Increase 8/9 (89%) Increase 2/5 (40%) Decrease 5/5 (100%) Mean increase Mean decrease

Capacity

Increase 7/9 (78%) Increase 4/5 (80%) Mean decrease Mean decrease NA

Compliance

1 Animal died Omentum applied 1 Animal died Extensive myomectomy

Comment

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Figure 4 Laparoscopic autoaugmentation.

were dry, even though only two of five patients tested had increased absolute bladder capacities as demonstrated by urodynamics. The patient described as a technical failure actually represented a failure of the technique as the procedure was successfully performed, and a urothelial diverticulum was achieved, yet the patient remained incontinent and had no alteration in bladder capacity. Snow and Cartwright subsequently described a series of 25 adult and pediatric patients with diverse bladder pathologies who were followed for at least 2 years [19]. Of 24 patients with preoperative incontinence, 58% became dry, 17% were improved, and 25% remained wet after autoaugmentation. All patients were on CIC preoperatively. After autoaugmentation, 80% of patients continued to require CIC, 12% voided spontaneously, and 8% voided spontaneously with only an occasional requirement for CIC. Of 24 patients who required pharmacological bladder relaxation preoperatively, 18 continued to require medication [19]. Follow-up urodynamic evaluation performed at variable intervals demonstrated inconsistent alterations in bladder capacity. A more consistent change was demonstrated in the pressure-filling curve, with most patients manifesting improved compliance at 20, 30, and 40 cm H 2 O. Overall results were judged to be good in 52%, acceptable in 28%, and poor in 20% of the patients. Subsequently, Skobejko-Wlodarska and colleagues reported their experience with 21 children with myelodysplasia who failed conservative management and underwent autoaugmentation [20]. All patients had low-compliance neurogenic bladders and underwent open autoaugmentation. The authors’ technique involved seromyotomy with fixation of the detrusor flaps to the psoas muscle bilat-

Myotomy Myotomy Myomectomy Myotomy

Mytomy Myotomy

50 5 55

Technique

21 12 7 6 46

Number

36 47 37

9.5 4–14 4–17 4–10

Mean age (years) Etiology

Mixed Motor urge incont. Mixed

Myelodysplasia Mixed Mixed Myelodysplasia Mixed

Laparoscopic Autoaugmentation: Clinical Trials

Pediatric trials Skoberjko-Wlodarska et al. Stothers et al. Cartwright and Snow Dattani and Bondarenco Total Adult trials Stohrer et al. Ter Meulen et al. Total

Author

Table 2

37/37 (100%) 0/5 (0%) 37/42 (88%)

13/17 (76%) 12/12 (100%) 3/6 (50%) NA 28/35 (80)

Improved bladder capacity

34/34 (100%) NA 34/34 (100%)

14/17 (82%) NA 4/6 (67%) NA 18/23 (78%)

Improved bladder compliance

24 Months 3 Months 22 Months

NA 4–8 Weeks 4–24 Months NA

Follow-up

NA 0/5 0/5

NA NA 3/7 (43%) NA 3/7 (43%)

Complete cure*

NA 0/5 0/5

14/17 NA 6/7 (86%) 4/6 (67%) 24/30 (80%)

Cure with CIC

NA 0/5 0/5

NA NA NA NA NA

Cure with CIC and medications

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erally. Follow-up ranged from 3 months to 8 years. Only 17 of 21 (81%) of children underwent urodynamic assessment after autoaugmentation. Bladder capacity was increased in 13 of 17 (76%) by a mean of 60 mL. Intravesical pressure was found to decrease a mean of 65 cm H 2 O (down to 35 cm H 2 O) in 14 of 17 (82%). Continence was achieved in 14 of 17 (82%) with CIC; of 6 patients with vesicoureteral reflux preoperatively, 2 achieved resolution. The mean length of follow-up was not described, and unfortunately, the longevity of the procedure was not specifically addressed as patients who were more than 1 year postoperative were not separately examined. The role of autoaugmentation in the pediatric population was also explored by Stothers and coworkers [21]. In this study, 12 pediatric patients with neurogenic bladders and incontinence, despite conservative management with medication and CIC, underwent seromyotomy autoaugmentation. There were no major complications reported. One patient experienced fever that resolved, and 2 patients had urinary tract infections. All patients had an increase in bladder capacity. The increase ranged from 15% to 70% over preoperative values, with a mean increase of 40%. All patients experienced improved continence. However, the length of clinical follow-up and requirements for continued medications were not reported [21]. Ter Meulen and coworkers evaluated the role of seromyotomy autoaugmentation in five adult patients with motor urge incontinence [22]. Complications included a wound infection and two urinary tract infections. Four of five patients experienced significant increases in bladder capacity. The fifth patient had only a minimal increase in capacity from 50 to 60 mL. Three of five patients experienced only transient improvement from incontinence and subsequently returned to baseline incontinence. The fifth patient experienced no improvement postoperatively. One patient experienced resolution of incontinence despite an ultimate bladder capacity of only 160 mL [22]. The authors concluded that autoaugmentation does not cure the unstable bladder. In 1993, Ehrlich and Gershman were the first to perform clinical laparoscopic seromyotomy bladder autoaugmentation [17]. This initial case report described the technique of laparoscopic autoaugmentation in an 8-year-old boy with a nonneurogenic neurogenic bladder. The patient underwent an uncomplicated laparoscopic autoaugmentation. The procedure was accomplished in 1.2 h, and the patient tolerated a regular diet on the day of surgery. The patient was discharged in less than 24 h, and the drain was removed on postoperative day 2. On postoperative day 8, the patient’s urethral catheter malfunctioned, resulting in a small bladder perforation that was treated with a percutaneous cystotomy tube. A voiding cystourethrogram at 2 weeks demonstrated no extravasation. The patient’s persistent day and nighttime incontinence had markedly improved 1 year postoperatively, with only minor leakage with high-performance athletic activity. Unfortunately, the patient’s parents refused follow-up urodynamic evaluation [17]. McDougall and colleagues also reported their initial experience with retroperitoneal laparoscopic autoaugmentation in a 26-year-old female with traumatic spinal cord injury [23]. Urodynamic evaluation revealed poor compliance, a decreased leak point pressure, and a bladder capacity of 85 mL. An extraperitoneal laparoscopic seromyotomy autoaugmentation was performed using a 3F right-

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angle Greenwald electrode. The bilateral detrusor flaps were sutured to Cooper’s ligament bilaterally with 1-zero polyglactin suture. Operative time was 6.5 h, and estimated blood loss was 75 mL. The patient tolerated oral intake 12 h after surgery and was discharged home on postoperative day 2 with bladder drainage in position. Bladder drainage was continued for 1 month, at which time a cystogram revealed no extravasation. The patient experienced a urinary tract infection 9 weeks postoperatively that responded to appropriate antibiotics. At 6-month follow-up, the patient had a normal cystogram, good compliance, a bladder capacity of 285 mL, and improved leak point pressure [23]. The patient had day and nighttime continence and was catheter-free voiding by Valsalva with a residual of 30 cc. Subsequently, Poppas and coworkers reported two cases of laparoscopic seromyotomy autoaugmentation that were performed with KTP laser assistance [24]. Two children with myelodysplasia and high-pressure neurogenic bladders unresponsive to conservative management underwent laparoscopic autoaugmentation. The detrusorotomy was performed with the KTP laser. A right-angle backstop device was used for the final portions of the detrusorotomy after initial access to the urothelium had been achieved. There were no reported complications. Initial results were promising, with improvement in symptoms, decreased peak detrussor pressures, and increased bladder capacity in both cases. However, the improvement was only transitory, and both cases required enterocystoplasty within 5 months [24]. Results with autoaugmentation have been highly variable; whether this is due to the method employed, patient selection criteria, or both has yet to be determined. Optimizing the techniques used to perform the procedure and defining the most suitable population will require systematic, controlled clinical study. Both open and laparoscopic autoaugmentation are feasible, yet the viability of this form of management has yet to be firmly established. In this regard, it becomes imperative that these patients be carefully characterized prior to surgery with regard to the small-capacity bladder etiology (i.e., whether inflammatory, postradiation, postsurgical, or neurogenic), the bladder capacity at different pressures (i.e., compliance curves), and the leak point pressure. Likewise, in each case, a detailed description of the technique used is imperative. The differences among simple seromyotomy, anchored seromyotomy, and myomectomy have not been explored. Finally, follow-up needs to incorporate similar parameters, specifically the amount of antispasmotic medications, thorough urodynamics studies to determine compliance, leak point pressure, maximal bladder capacity, and, finally, a proper questionnaire regarding incontinence, use of clean intermittent catheterization, and quality of life. While it has not been formally addressed in the past, the status of the urothelium should be seriously considered in both animal models and clinical practice. Autoaugmentation is, at least in part, dependent on the quality of the urothelium for increasing bladder capacity. If the urothelium is limited by fibrosis or other pathological processes, it is unlikely to yield optimal results. Future animal models should consider techniques that limit bladder capacity by means that do not damage the urothelial layer. Similarly, preoperative bladder biopsy to determine the status of the urothelium may be of value in patients who would be

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considered candidates for an autoaugmentation procedure. Documentation of this sort may ultimately improve patient selection and thereby better define the ultimate role of both open and laparoscopic autoaugmentaiton. Autoaugmentation is an attractive, minimally invasive method for the treatment of the contracted, high-pressure bladder. However, to date this approach has been plagued by inconsistent results. Whether this is due to variations in technique, problems in patient selection, or difficulties in obtaining detailed and/ or long-term follow-up is as yet undetermined. Further detailed studies in the laboratory and clinical arena are needed to determine the overall value of autoaugmentation surgery. B.

Enteric Bladder Augmentation

Open enteroplasty is the most commonly used technique for augmentation of bladder capacity. Anastomosis of a well-vascularized patch of detubularized bowel can significantly and durably increase the storage capacity of the urinary bladder. Several investigators have described laparoscopic enterocystoplasty with different segments of the gastrointestinal tract. Docimo and colleagues described gastrocystoplasty in a young female with a neurogenic bladder. The patient had a small, poorly compliant bladder with a capacity of 150 mL [25]. The stomach was chosen as the source for augmentation as the authors believed it would be more technically straightforward. Using blunt and sharp dissection, the anterior bladder wall was dissected free of surrounding structures to the level of the urethra. Attention was turned to the stomach, where the greater omentum was divided distal to the gastroepiploic arcade, and the transverse mesocolon was displaced posteriorly. The right gastroepiploic pedicle was dissected free of the right side of the greater curvature of the stomach to the level of the pylorus. After division of the omentum, a gastric wedge 20 cm long was removed using five firings of a laparoscopic stapler. An Endo-Stitch suturing device was used to oversew the stomach. An Endo-Stitch device with 3-0 vicryl suture was used to run the edges of the anastomosis of the gastric segment to the bladder. A 24F Malecot suprapubic tube and a 20F Foley urethral catheter were left to drain the bladder. The patient also underwent a needle bladder neck suspension. Total operative time was 10 h 55 min. The patient received a transfusion of two units of packed red blood cells despite an estimated blood loss of 250 mL. Postoperatively, the patient received 247 mg morphine via a patient-controlled analgesia device. Due to a transient urine leak, she was not discharged until postoperative day 13. Urodynamic evaluation 3 months after surgery revealed a bladder capacity of 315 mL. She remained dry on intermittent catheterization. Gill and colleagues reported results of laparoscopic-assisted enterocystoplasty in three patients with reduced bladder capacity [26]. Augmentation was performed with ileum in the first case described and sigmoid colon in the second. The third patient underwent augmentation with cecum and right colon, and the terminal ileum was refashioned to create a continent conduit, which was brought out at the umbilicus as a catheterizable stoma. After selection of the appropriate bowel segment, 15 cm of bowel were delivered outside the abdomen via a 2-cm extension of the umbilical trocar site. Using open surgical techniques, each bowel segment with its mesenteric pedicle was isolated, bowel continuity was reestab-

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lished, and the mesenteric window was closed. After detubularization, the bowel segments were anastomosed to the bladder with intracorporeal suturing. In the third patient, the terminal ileum was narrowed, the ileocecal junction was imbricated, and the ileum was brought out the umbilicus as a catheterizable stoma. Mean operative time was 6.8 h. Mean estimated blood loss was 150 mL. The only intraoperative complication was a rectus sheath hematoma, which was controlled laparoscopically. Postoperative Jackson-Pratt drainage was minimal in all three cases, and drains were removed on postoperative days 3, 5, and 4, respectively. The first patient developed an ileus that delayed his discharge until postoperative day 7. The subsequent two patients were discharged on postoperative days 4 and 5. Analgesic requirements were 44, 55, and 229 mg morphine. Follow-up bladder capacities and long-term patient outcomes were not reported. Pure laparoscopic and laparoscopic-assisted procedures for enterocystoplasty are feasible; however, in only one case has long-term data been provided as to the efficacy of the procedure. Further experience and eventual comparison with traditional open techniques are needed. At present, this laparoscopic approach remains under study. IV. VAGINAL WALL PROLAPSE Vaginal wall prolapse has been managed by abdominal sacral colpopexy or transvaginal sacrospinous ligament vaginal vault suspension. In an attempt to apply minimally invasive technology to vaginal wall prolapse, laparoscopic sacralcolposuspension has been described. The procedure, as described by Ostrzenski, is performed by entering the retropubic space bilaterally between the urachus and the medial umbilical folds. The space of Retzius is opened until the obturator foramen is visualized bilaterally [27]. The vagina is digitally elevated to its normal position, and using 0-polydioxanone suture, it is anchored to the surrounding pelvic structures. Posteriorly, the vaginal apex is suspended to the deep layer of the uterosacral ligaments. The posterolateral vaginal cuff is suspended to the cardinal ligaments. Anteriorly, the vaginal vault is suspended to the pubocervical fascia. Finally, the pubocervical fascia and the anterolateral vaginal sulci are suspended to the fascia of the obturator internus muscle and tendinous arch bilaterally. Ostrzenski reported the use of this technique in 27 patients with iatrogenic total vaginal prolapse after hysterectomy [27]. The initial 17 patients underwent the procedure without suspension of the pubocervical fascia to the obturator internus and tendinous arches. The procedure was subsequently modified, and the two groups were compared. All procedures were successfully accomplished laparoscopically, and estimated blood loss was minimal. Mean operative time was 3.6 h. There were 24 (89%) patients discharged on the day of surgery, with the remaining 3 (11%) discharged on postoperative day 1. No intraoperative complications were described. Postoperative urinary tract infections were experienced by 2 patients (7%). Of the initial 16 patients, 1 patient (6%) experienced complete vaginal prolapse within 6 months of the procedure, 11 (69%) had no significant laxity of the vaginal apex or walls, and 4 (25%) patients displayed some degree of vaginal cuff descent postoperatively. After modification of the procedure, an additional 11

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patients were evaluated. No patients experienced prolapse of the vaginal apex over a 42-month follow-up period. There were 10 (91%) patients who displayed no laxity of the vaginal apex or walls, and 1 (9%) patient demonstrated moderate vaginal wall descent. Presently, there are limited data on laparoscopic sacral colposuspension. However, the procedure appears to be safe and feasible. Preliminary results are promising, and patients may benefit from a more rapid convalescence with decreased pain. Data comparing open and laparoscopic techniques are required before a more definitive conclusion can be drawn.

V.

SUMMARY

The recent increased growth and popularity of minimally invasive techniques have dramatically altered the management of many surgical diseases. For many procedures, an endoscopic, percutaneous, or laparoscopic approach has decreased patient pain and expedited convalescence while providing equivalent results for disease control. Clearly, however, each procedure must be studied and evaluated individually. It is the surgeon’s responsibility to consider all management options, incorporating the efficacy of treatment as well as the level of invasiveness. Laparoscopic management of urinary incontinence remains an example of how initial enthusiasm for a new, minimally invasive approach must be tempered by thoughtful evaluation and reevaluation of efficacy. Similarly, autoaugmentation, laparoscopic enteric bladder augmentation, and laparoscopic colposuspension will require close scrutiny to determine their ultimate utility. As technology and surgical techniques continue to evolve, it is imminent that all procedures will become amenable to a minimally invasive approach.

REFERENCES 1. Fantl JA, Newman DK, Colling J. Urinary Incontinence in Adults: Acute and Chronic Management. Clinical Practice Guideline. Update 2. Rockville, MD: U.S. Department of Health and Human Services, Agency for Health Care Policy and Research, 1996. 2. Vancaillie TG, Schuessler W. Laparoscopic bladder neck suspension. J Laparoendoscop Surg 1991; 1:169–172. 3. Albala DM, Schussler WW, Vancaillie TG. Laparoscopic bladder neck suspension. J Endourol 1992; 6:137–141. 4. Ou C, Presthus J, Beadle E. Laparoscopic bladder neck suspension using hernia mesh and surgical staples. J Laparoendoscop Surg 1993; 3:563–566. 5. Soygur T, Safak M, Yeilli C, Arikan N, Gogus O. Extraperitoneal laparoscopic bladder neck suspension using hernia mesh and tacker. Urol 2000; 56:121–124. 6. Su T, Wang K, Hsu C, Wei HJ, Hong BK. Prospective comparison of laparoscopic and traditional colposuspension in the treatment of genuine stress incontinence. Acta Obstet Gynecol Scand 1997; 76:576–582. 7. Das S. Comparative outcome analysis of laparoscopic colposuspension, abdominal colposuspension, and vaginal needle suspension for female urinary incontinence. J Urol 1998; 160:368–371. 8. McDougal EM, Heidorn CA, Portis AJ, Klutke CG. Laparoscopic bladder neck suspension fails the test of time. J Urol 1999; 162:2078–2081.

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9. Spencer JR, O’Conor VJ Jr. Comparison of procedures for stress urinary incontinence. AUA Update Series 1987; 6(28). 10. Chaikin DC, Rosenthal J, Blaivas JG. Pubovaginal fascial sling for all types of stress urinary incontinence: long-term analysis. J Urol 1998; 160:1312–1316. 11. Kreder KJ, Winfield HN. Laparoscopic urethral sling for treatment of intrinsic sphincter deficiency. J Endourol 1996; 10:255–260. 12. McDougal W. Metabolic complications of urinary intestinal diversion. J Urol 1992; 147:1199–2003. 13. Desgrandchamps F, Cariou G, Barthelemy Y. Spontaneous rupture of orthotopic detubularized ileal bladder replacement: report of five cases. J Urol 1997; 158:798–804. 14. Filmer R, Spencer J. Malignancies in bladder augmentations and intestinal conduits. J Urol 1990; 143:671–674. 15. Couvelaire R. Agrandir la vessie. In: Chirurgie de la Vesie. Paris: Masson, 1955:200– 221. 16. Cartwright PC, Snow BW. Bladder autoaugmentation: partial detrusor excision to augment the bladder without use of bowel. J Urol 1989; 142:1050–1054. 17. Ehrlich RM, Gershman A. Laparoscopic seromyotomy (auto-augmentation) for nonneurogenic neurogenic bladder in a child: initial case report. Urology 1993; 42:175– 176. 18. Cartwright PC, Snow BW. Bladder autoaugmentation. Urol Clin North Am 1996; 23: 323–329. 19. Cartwright PC, Snow BW. Bladder autoaugmentation: early clinical experience. J Urol 1989; 142:505–508. 20. Skobejko-Wlodarska L, Strulak K, Nachulewicz P, Szymkiewicz C. Bladder autoaugmentation in myelodysplastic children. Br J Urol 1998; 81:114–116. 21. Stothers L, Johnson H, Arnold W. Bladder autoaugmentation by vesicomyotomy in the pediatric neurogenic bladder. Urology 1993; 44:110–114. 22. Ter Meulen PH, Heesakkers JP, Janknegt RA. A study of the feasibility of vesicomyotomy in patients with motor urge incontinence. Eur Urol 1997; 32:166–172. 23. McDougall EM, Clayman RV, Figenshau RS, Pearl MS. Laparoscopic retropubic autoaugmentation of the bladder. J Urol 1995; 153:123–126. 24. Poppas DP, Uzzo RG, Britanisky RG, Mininber DT. Laparoscopic laser assisted autoaugmentation of the pediatric neurogenic bladder: early experience with urodynamic follow-up. J Urol 1996; 155:1057–1060. 25. Docimo SG, Moore RG, Adams J, Kavoussi LR. Laparoscopic bladder augmentation using stomach. Urology 1995; 46:565–569. 26. Gill IS, Rackley RR, Meraney AM, Marcello PW, Sung GT. Laparoscopic enterocystoplasty. Urology 2000; 55:178–181. 27. Ostrzenski A. Laparoscopic colposuspension for total vaginal prolapse. Int J Gynecol Obstet 1996; 55:147–151.

11 Diagnosis and Management of Obstruction Following Anti-Incontinence Surgery MICHAEL VOLPE and MOHAMED A. GHAFAR College of Physicians and Surgeons Columbia University New York, New York, U.S.A. ALEXIS E. TE Weill Medical College of Cornell University New York, New York, U.S.A.

I.

INTRODUCTION

Urinary incontinence can result from either detrusor or sphincteric dysfunction. Sphincteric dysfunction can be caused by either anatomic malposition of an intact sphincteric unit (urethral hypermobility) or a damaged urethral sphincter (intrinsic sphincter deficiency). Numerous surgical procedures have been devised to correct this life-altering disorder. The rationale behind the surgical treatment of urethral hypermobility is to reposition and stabilize the bladder, bladder neck, and urethra in an appropriately supported retropubic position. When intrinsic sphincter deficiency is diagnosed, the rationale of surgery is to provide a support that provides appropriate urethral coaptation and compression during increases in intra-abdominal pressure (Valsalva events). However, the mechanism of most of these techniques generally increases urethral resistance and as a consequence may result in bladder outlet obstruction postoperatively. The dilemma for treatment of bladder outlet obstruction after incontinence surgery is to remove the obstruction while maintaining sufficient continence support. 179

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Table 1 Types of Anti-Incontinence Surgery Vaginal reconstructive surgery for prolapse

Bladder neck/paraurethral suspension surgery

Anterior repair/Kelly plication

Transabdominal retropubic bladder neck suspension 1. Marshall-MarchettiKrantz (MMK) 2. Burch Transvaginal needle urethropexy 1. Raz 2. Stamey 3. Gittes

Surgery for intrinsic sphincteric deficiency (slings) Pubovaginal slings 1. Transabdominal 2. Transvaginal a. Percutaneous retropubic needle suture b. Retropubic bone anchor c. Tension-free vaginal tape (TVT)

Periurethral bulking agent 1. Collagen

In this chapter, we review the various continence procedures utilized today (Table 1), their risk for post-treatment obstruction, approaches to diagnosis and treatment, and finally, caveats toward decreasing the risk of postsurgical bladder outlet obstruction.

II. SURGERY FOR PELVIC FLOOR PROLAPSE Pelvic floor prolapse has long been associated with voiding symptoms, particularly urinary incontinence. The prolapse that often affects voiding function is bladder prolapse, or a cystocele with or without cervical descent. Reconstructive surgery to repair this prolapse is described generally as an anterior vaginal wall repair. This cystocele repair is commonly performed via a transvaginal approach, and the various techniques (e.g., a Kelly plication) generally consist of repairing the central defect by reducing the cystocele through a surgical plication of one pubocervical ligament to the other. Because the technique stabilizes the bladder base, it can correct urethral hypermobility sufficiently to return continence. Since the procedure does not suspend the area of the bladder neck and urethra, it rarely results in obstruction. In fact, the procedure may actually result in worse incontinence in patients with intrinsic urethral sphincter deficiency whose descending cystocele provided an obstructive component prior to pessary correction or surgical reduction. In only rare instances of aggressive plication near the bladder neck can bladder outlet obstruction result [1].

III. RETROPUBIC SUSPENSION SURGERY A.

Transabdominal Approach

Paraurethral/parabladder neck suspension or suspension urethropexy provides the treatment rationale for a host of procedures. These procedures all attempt to cure incontinence by restoring the urethra and bladder neck to their normal retropubic position, and they can be generally categorized according to their surgical approach (transabdominal vs. transvaginal).

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The traditional continence procedure that has gained acceptance as a standard for comparison to other continence procedures is the Marshall-MarchettiKrantz (MMK) cystourethropexy. In 1949, Marshall and coworkers [2] described their retropubic vesicourethral suspension. In this procedure, a transabdominal approach is utilized to expose the space of Retzius through a lower abdominal midline incision. The bladder neck, anterior vaginal wall, and urethra are identified and dissected in this manner. As originally described, chromic catgut sutures were used to suspend the paraurethral anterior vaginal wall to the back of the symphysis pubis. Marshall described three pairs of sutures being placed on each side of the urethra, the most proximal pair being at the level of the bladder neck; each suture is passed close to, but not through, the urethra, and each suture is passed through the cartilaginous portion of the symphysis. A guiding principle behind the rationale of this technique in effecting continence is the restoration of the bladder neck to its retropubic position with an appropriate urethrovesical angle. The other popular transabdominal retropubic urethropexy suspension procedure is the Burch colosuspension. In 1961, Burch [3] reported on his experience with the Cooper’s ligament repair. He was dissatisfied with the fixation of the vaginal wall to the symphysis pubis as described by Marshall, and he attached the paravaginal fascia to the “white line” of the pelvis, the arcus tendineus, to which the obturator internus muscle and fascia and pubovesical muscle attach to the side wall. Still hampered by insecure fixation, Burch changed his point of suspension to the ileopectineal ligaments, which are thick bands of fibrous tissue running along the superior surfaces of the superior rami of the pubic bones. An advantage of the Burch procedure is that it simultaneously corrects a lateral defect and corrects urinary incontinence by the repositioning of the vesicourethral region within the abdomen, but does not compress the urethra [4]. B. Transvaginal Approach The morbidity and invasiveness of the transabdominal retropubic suspensions encouraged the development of less invasive procedures. To this goal, a host of transvaginal retropubic needle urethropexies were developed. These procedures generally utilized a suture to support the paraurethral tissue and bladder neck to stabilize them in their normal retropubic location, and they differ only in their fixation techniques. The first transvaginal suspension procedure was described by Pereyra in 1959. For this technique Pereyra designed an angulated, partly hollow point cannula with a needle stylet, which he used to pass a suture from a vaginal incision to the retropubic space [5]. In 1981 and 1985, Raz and colleagues [6,7] presented a modification of the Pereyra needle suspension that improved exposure and anchoring of sutures into the urethropelvic ligament. An inverted, U-shaped incision in the anterior vaginal wall was developed to create increased exposure. The retropubic space was opened to permit placement of a pair of permanent helical sutures into the urethropelvic ligament, incorporating both its vaginal and abdominal sides. The Raz operation is indicated for patients with stress incontinence due to urethral and bladder neck hypermobility with minimal/grade 1 or no cystocele. This pro-

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cedure may be combined with a four-corner bladder-and-bladder neck suspension for patients with moderate cystocele (grade 2 or 3). In this approach, the bladder base and neck are suspended by permanent sutures that anchor the urethropelvic fascia, pubocervical fascia, cardinal ligaments, and vaginal wall. The other popular needle suspension urethropexies are the Gittes [8] and Stamey [9] procedures. In 1987, Gittes and Loughlin described their modification of the Pereyra needle suspension, simplifying the technique by obviating the need for vaginal incisions. To achieve support of the bladder neck, suspension sutures placed into the vaginal wall become incorporated over time, creating an “autologous pledget.” To provide better and more durable support at the paravesical neck/paraurethral anchoring suspension site, Stamey introduced the use of synthetic pledgets at the paraurethral/paravesical neck site, which has been called the endopelvic fascia, to help suspend the urethra/bladder neck. In general, the advantages of these various procedures are that they correct urinary incontinence by repositioning the vesicourethral region into the retropubic position through suspension and they cause less morbidity than their transabdominal counterparts. These procedures should not compress the urethra. In fact, they are not recommended for patients with intrinsic sphincter deficiency since a pure suspension will only correct incontinence due to urethral hypermobility and not address incontinence due to intrinsic sphincter deficiency. However, it is possible to obstruct the urethra with an overaggressive suspension, inappropriate suture placement, or the development of postsurgical urethral strictures. These transvaginal procedures had become less popular due to the higher rate of recurrent incontinence over time.

IV. SURGERY FOR INTRINSIC SPHINCTERIC DEFICIENCY A.

Pubovaginal Slings

It became apparent after careful investigation through a variety of videourodynamic techniques that, despite the correction of urethral hypermobility, stress incontinence may still occur. The cause of the failures was identified as weakness in the urethral sphincteric mechanism and was identified during fluoroscopy as an open bladder neck at rest or a low Valsalva leak point pressure despite lack of urethral hypermobility. It was apparent that coaptation during a Valsalva event was insufficient, and this deficiency was diagnosed as intrinsic sphincter deficiency. This has also been classified as stress incontinence type 3. This type of incontinence has led to the development of the pubovaginal sling, described by Morgan et al. [10]. The continence rationale behind a pubovaginal sling is to provide a backboard support under the urethral sphincteric unit to provide increased coaptation and support during Valsalva events. This backboard would also limit urethral hypermobility. However, the intrinsic mechanism of this procedure inherently produces an increase in outflow resistance by the sling. This accounts for the increased risk of bladder outlet obstruction with this procedure. The traditional pubovaginal sling was performed using a transabdominal approach in which autologous rectus fascia was harvested in a long strip. Through a combination open transabdominal approach and transvaginal approach, this

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autologous sling was placed under the bladder neck and anchored to the anterior abdominal wall for support. A key maneuver was to place the sling in a position for adequate continence support without the inappropriate tension that would lead to bladder outlet obstruction [11]. Over the years, many modifications of this surgical technique have been made to increase its durability and decrease its invasiveness, much like the cystourethropexy suspension procedures. Many types of sling material have been applied and are associated with different rates of morbidities, especially with regard to durability, infection, and urethral erosion. Applied autologous grafts have included rectus fascia, fascia lata, and vaginal wall. Applied allografts have included cadaveric fascia lata, pericardium, and dermis [12–14]. Synthetic graft materials have included Gore-tex, Mersilene, Marlex, and polypropylene [15]. Generally, the synthetic slings have caused increased risk of urethral erosion, infection, and obstruction due to their less flexible and nonbiodegradable nature. In addition, the trend to less invasive approaches has led to the incorporation of minimally invasive transvaginal techniques for pubovaginal sling placement. Currently, either a percutaneous retropubic needle is used to pass the sling’s suture through the anterior abdominal wall or bone anchors are used to fix the sling to a retropubic location. In 1989, Raz et al. [16] described a percutaneous needle technique for the treatment of urinary incontinence due to intrinsic sphincter deficiency; their procedure uses an autologous sling constructed from the vaginal wall. This vaginal wall sling consists of a rectangular island of in situ anterior vaginal wall underlying the urethra and bladder neck. The four corners of the sling are anchored with polypropylene sutures. These sutures are guided in a retropubic path to the anterior abdominal wall with needles. These sutures are then tied over the anterior abdominal wall with the appropriate sling tension. An anterior vaginal wall flap is then advanced to cover the sling. In 1996, the tension-free vaginal tape (TVT) was introduced by Ulmsten et al. [17]. This minimally invasive procedure involves the placement of a sling providing urethral support with a synthetic polypropylene mesh. The sling is introduced with the aid of a trocar via a transvaginal route through a small incision at the level of the midurethra. The trocar with the attached sling mesh is guided just lateral to the urethra and bladder neck and hugs the pubic bone in a retropubic path through the anterior abdominal wall. The mesh tape is covered by a plastic sheath that allows free passage through the tissue and is separated at its midpoint so that it can be removed once the sling is in place. The placement of the sling is at the midurethra, and the procedure is performed under local anesthesia with intravenous sedation. During the procedure, a key maneuver is the adjustment of sling tension and positioning with a voluntary Valsalva maneuver by the conscious patient without a regional or general anesthetic. B. Periurethral Collagen Injections Collagen is a highly purified bovine dermal collagen cross-linked with gluteraldehyde. It has been developed for use as a periurethral bulking agent. It does not begin to degrade until approximately 12 weeks after injection. Compared with other injectable agents, there have been no reports of granuloma formation or

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migration. It has been approved by the U.S. Food and Drug administration for the treatment of stress incontinence arising from intrinsic sphincter deficiency [18]. Initial results suggested a 64% subjective short-term cure rate and a subjective cure rate of 38–80% at the 1–2 year follow-up. Long-term obstruction has not been associated with this procedure. V.

BLADDER OUTLET OBSTRUCTION

A.

Incidence

Bladder outlet obstruction in women is an infrequently diagnosed urological condition. However, obstruction and voiding dysfunction after antiincontinence procedures are not uncommon (Table 2). Previous studies reported a 2.58 to 24% prevalence rate among women referred for evaluation of lower urinary tract symptoms [20]. Several factors may predispose a patient to voiding dysfunction after an antiincontinence procedure, but most of them are unproven since the criteria to diagnose these dysfunctions are themselves not widely accepted. Generally, it has been shown that large urinary bladder capacity and large residual urine volumes predispose to retention after stress incontinence procedures. It is probable that impairment in detrusor function is the primary etiology in these patients. The female patient who develops urinary retention or symptoms consistent with obstruction still currently present as a diagnostic dilemma since urodynamic criteria for bladder outlet obstruction in women are not well defined. As such, any published data on the subject can be criticized on this basis, and therapy is often based on a stepwise empirical approach to improving symptoms. B.

Symptoms

Absolute criteria for bladder outlet obstruction in women are not available. However, patients may present with classic obstructive symptoms, such as straining to void, slow stream, hesitancy, incomplete emptying, and complete urinary retention. The majority of patients may just present with irritative symptoms, such as frequency, urgency, urge incontinence from detrusor instability, or an overactive bladder. These may be associated with recurrent urinary tract infections and often coexist with incomplete bladder emptying. Lower urinary tract symptoms

Table 2 Probability Estimates for Procedure Categories Cure/dry (%)

Treatment Transabdominal retropubic suspensions Transvaginal retropubic suspensions Anterior repairs Slings Source: Ref. 19.

Urgency (%)

Retention (%)

12–23 24–47 48 months Longer than months months and longer Continued De Novo 4 weeks Permanent 84

84

84

66

11

5

⬍5

79

65

67

54

6

5

⬍5

68 82

65 82

61 83

46

7

⬍5 8

⬍5 ⬍5

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in women with previous anti-incontinence surgery regardless of their continence status should raise suspicion for obstruction [21], and video pressure flow data for a complete urodynamic evaluation can provide important diagnostic insight for clarifying the diagnosis. The precise cause of symptoms in these patients is not well established, and there are no universally accepted urodynamic criteria for evaluating lower urinary tract symptoms in women. Currently, several issues still remain undetermined. An AUA symptom index score was used as a bothersomeness index in women with bladder outlet obstruction, similar to its use in men. The mean score was higher in women with obstruction than in those with stress incontinence or no symptoms, 15.8 versus 10.3, respectively. However, no correlation was found between the index score and urodynamic parameters. Thus, the index score should not be used as a reliable measure of clinical severity. C. Diagnostic Problems Voiding dynamics are different in women, and diagnosis becomes more difficult, especially when one attempts to evaluate obstruction after anti-incontinence procedures. Often, preoperative voiding parameters (quantitative urodynamics) are not available since it is not considered an essential component of preoperative assessments. The diagnosis of obstruction after anti-incontinence procedures cannot be made on the basis of urodynamic pressure flow criteria alone. Several studies have failed to show any correlation between urodynamic parameters of pressure and flow and the likelihood of successful voiding after urethrolysis. Even patients who failed to demonstrate contractility or who have low detrusor pressures with poor flow seem to have a success rate equal to those with classic high-pressure, low-flow voiding characteristics of urodynamic obstruction. Therefore, the diagnosis of obstruction must be made using a combination of urodynamic and radiographic criteria (i.e., a sustained detrusor contraction with radiographic evidence of obstruction between the bladder neck and urethra). In the case of a contractile bladder, the diagnosis can be inferred, without certainty, only by considering the patient’s history of normal voiding and emptying before surgery [22,23]. D. Urodynamic Diagnosis Obstruction in men is defined by high pressure (⬎45 cm H 2 O) of adequate force, speed, and duration with a low peak flow rate (⬍12 mL/min). However, obstruction in many women would be missed based on these parameters since many women void with low detrusor pressure or by relaxing pelvic floor muscles, and they are able to empty their bladder completely with a good flow rate. Some women augment voiding by abdominal straining, and even a mild elevation in bladder outlet resistance can cause relative obstruction and lead to significant voiding dysfunction. Farrar et al. [24] used only flow rates to diagnose obstruction. They defined obstruction as maximum pressure flow rates less than 15 mL/s with a voided volume of 200 mL or greater. They believed that low-pressure flow rate associated with normal or low detrusor pressures may be an indication of obstruction. Axelord and Blaivas [25] in 1987 defined bladder outlet obstruction as a sustained

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contraction of at least 20 cm H 2 O with a peak flow rate of less than 10 cm H 2 O. Massey and Abrams [26] in 1988 proposed using two or more of the following four parameters: flow rate less than 12 mL/s, detrusor pressure at peak flow greater than 50 cm H 2 O, urethral resistance (detrusor pressure at maximum flow rate divided by the square of maximum flow rate) greater than 0.2, or significant residual urine in the presence of high pressure or resistance. Bass and Leach [27] in 1991 reported that a normal peak flow greater than 15 mL/s with a voided volume of 100 mL or greater could exclude bladder outlet obstruction diagnosis in women. Nitti et al. [28] reported diagnosis of obstruction in women that was confirmed by fluoroscopy. The average maximum flow was 9 cc/s, and the detrusor pressure at maximum flow was 40.8 cm H 2 O. Lemack et al. [29] also reported on a group of 84 women with bladder outlet obstruction and a group of 124 women with stress urinary incontinence as controls. In the control group, the average maximum flow rate was 23 cc/s and the average detrusor pressure was 21.9 cm H 2 O, whereas the corresponding values in those with clinical obstruction were 10.7 cc/s and 40.8 cm H 2 O. Based on these findings, they proposed a diagnostic cutoff of less than 11 mL/s and an average detrusor pressure of greater than 21 cm H 2 O for defining bladder outlet obstruction. Using these criteria in a prospective analysis of 108 women undergoing urodynamic studies for voiding symptoms, 20% fulfilled these criteria. Recent data showed that a 7F transurethral catheter has a profound effect on uroflowmetry parameters, as well as on establishing an accurate diagnosis of bladder outlet obstruction in women; it will falsely increase the diagnosis of obstruction in women. Based on that, Blaivas and Groutz [30] in 2000 constructed a nomogram to diagnose obstruction in women using pdet.max and free flow. The nomogram consists of four zones: no obstruction and mild, moderate, and severe obstruction (Fig. 1). We tried to construct a bladder outlet obstruction nomogram for women by reviewing the videourodynamic studies of 905 consecutively seen women [31]. Of these women, 54 were diagnosed with bladder outlet obstruction. Diagnosis was based on one of two criteria: (1) maximum voiding detrusor pressure during voiding (maxPdet) greater than 20 cm H 2 O with a maximum flow (Qmax) less than 12 mL/s (39 women) (72%) or (2) obvious fluoroscopic evidence of obstruction combined with a sustained detrusor contraction period of greater than 120 s (regardless of magnitude of maxPdet or Qmax) (15 women) (28%). These women were then compared to another 52 women (average age 66 ⫾ 8 years), all of whom had stress urinary incontinence, a maxPdet less than 25 cm H 2 O, a Qmax greater than 12 mL/s, no evidence of prolapse on physical exam, and no radiologic evidence of obstruction. The maxPdet and Qmax of the patients in each group were then plotted on a scatter graph. Considerable overlap of maxPdet and Qmax was found between the two groups in the scatter graph. The lack of any significant clustering between the groups prevented the creation of a reliable nomogram. Using the criterias described above, women with videourodynamic evidence of obstruction have demonstrated various maxPdet and Qmax. These data demonstrate that the urodynamic diagnosis of bladder outlet obstruction based on pressure flow data alone is currently unreliable. It is clear that more investigation into understanding the physiology and

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Figure 1 Nomogram for diagnosing obstruction in women showing four zones. (Adapted from Blaivas et al. Neurourol Urodynam 2000; 19:213.)

pathophysiology of voiding dynamics needs to be completed. It has been suggested that the placement of a sling at the bladder neck and related retropubic dissection with consequent scarring may alter the normal funneling/emptying dynamics. As such, patients, especially after a sling, are apt to be dysfunctional voiders with difficulty emptying because they cannot “naturally” relax and open the bladder neck to funnel and empty the bladder. This rationale is the basis for the modification of the TVT sling technique position at the midurethra. This midurethral position is thought to maintain the normal funneling dynamics of the bladder neck. The procedure is also performed under a local anesthetic, and sling tension is adjusted to maintain continence while the patient coughs in a conscious voluntary state. Maintaining these technical points is thought to be the explanation for the TVT patient being sent home the same day of surgery without a catheter and voiding naturally. VI. MANAGEMENT OF VOIDING SYMPTOMS FOLLOWING AN ANTI-INCONTINENCE PROCEDURE The incidence of voiding complaints after surgery has been reported [20] to be 2.4–24%. About 73–100% of these patients complain of irritative symptoms, and about 51–60% complain of obstructive symptoms [22,32,33]. There is a 1.5–13% incidence of urinary retention for more than 1 month after surgery [8,15–17] (Fig. 2).

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Figure 2 Algorithm for management of post op voiding dysfunction after an anti-incontinence procedure.

Almost all patients, however, will have urinary retention immediately following an antiincontinence procedure [34]. For this reason, a suprapubic tube (SPT) is commonly placed during surgery. On the morning of postoperative day 1, a voiding trial and a postvoid residual measurement are performed. About 50% of patients are able to void to completion at this time; subsequently, their catheters are removed [34]. The other 50% are taught how to use their SPT and are then discharged home. At follow-up on postoperative day 5, another voiding trial is performed. At this time, approximately 80–96% of these patients are able to urinate to completion and have their catheters removed [34]. Those with elevated postvoid residuals (greater than 10% of their voided volume or more than 50 cc) are given a voiding diary and are followed up in 1 month for another voiding trial. If the patients are not voiding to completion by 1 month postoperatively, they are taught clean intermittent catheterization (CIC). They have SPTs removed and are scheduled for follow-up in 3 months. At 3 months postoperatively, if they still have elevated postvoid residuals, they undergo videourodynamics. Patients with symptoms of obstruction (straining to urinate, slow stream, incomplete emptying), high-pressure (greater than 50 cm H 2 O) and low-flow (less than 12 cc/s) urodynamics, an elevated postvoid residual, and fluoroscopic evidence of ob-

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struction undergo urethrolysis. If the urodynamics are equivocal or normal, but the fluoroscopy shows obvious signs of obstruction, then urethrolysis is also considered. Nitti et al. showed that voiding symptoms can completely resolve after urethrolysis in patients with evidence of obstruction on fluoroscopy, even if they have low-pressure urodynamics [28]. If the patient complains mainly of obstructive symptoms and the videourodynamic results are equivocal for obstruction, or if the videourodynamics are completely normal, then the patients continue intermittent catheterization and are placed on an α-blocker for another 3 months. The rationale for the use of α-blockers in this group comes from the work of Kumar et al., who successfully treated 50% of women with bladder neck obstruction with α-blockers alone [35]. If there are no improvements in the postvoid residual measurements at the end of this time (6 months postoperatively), and they are still significantly bothered by their obstructive symptoms, then urethrolysis is also performed. Some patients in this group refuse urethrolysis, preferring instead to catheterize a few times a day to facilitate bladder emptying. These are usually patients who had severe incontinence preoperatively who would rather catheterize and be dry rather than risk being wet again. Some patients are unable to mount a detrusor contraction on urodynamics and have urinary retention or have elevated postvoid residuals. These patients are also placed on CIC and an α-blocker for 3–6 months. If there is no improvement in symptoms after this time, then these patients can also be offered urethrolysis. However, these retention patients do not have a urodynamic confirmation of bladder outlet obstruction and have evidence of a detrusor contractility dysfunction. It is reasonable to offer these patients a trial with neuromodulation (percutaneous sacral nerve stimulation evalutions) prior to urethrolysis. Patients who have primarily irritative symptoms postoperatively are treated slightly differently. About 8–36% of patients with voiding complaints postoperatively will have de novo or continued irritative voiding without an elevated postvoid residual [22,32,33]. These patients are placed on anticholinergic medication, instructed in Kegel exercises, put on a timed voiding regimen, given estrogen cream (if they are postmenopausal), and are told to avoid caffeine intake. If there is no improvement in symptoms 3 months postoperatively, then videourodynamics are performed. If high-pressure, low-flow urodynamics are discovered, or if there is obvious obstruction on fluoroscopy, then urethrolysis is recommended. If the urodynamics are equivocal for obstruction or if they are normal, then conservative treatments (timed voiding, Kegel exercises, estrogen cream, and avoidance of caffeine) are continued. Anticholinergic medication is also changed or increased, and pelvic floor therapy with biofeedback and electrical stimulation or the Neotonis chair is considered. Schrepferman et al. reported complete resolution of postoperative urgency in 91.3% of patients with low-pressure urodynamics versus 27.8% of patients with high-pressure urodynamics [36]. This study highlights the fact that urethrolysis is rarely necessary in patients with low-pressure urgency. However, if there is no still no improvement in symptoms after 6 months of conservative treatment, neuromodulation can also be offered prior to a possible urethrolysis. Prior to any urethrolysis, urethral dilation may be considered, but is usually unsuccessful as a durable treatment for these conditions.

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Urethrolysis Techniques

The goal of urethrolysis surgery is to decrease the outlet resistance on the urethra by replacing it in its normal anatomic position. Traditionally, this was accomplished by completely dissecting the urethra from its surrounding tissues using a retropubic or transvaginal approach. However, if the obstruction occurs after pubovaginal sling surgery, the urethra can usually be freed by simply incising the sling in its midline. Other times, when scarring is severe, it is still necessary to circumferentially dissect the urethra. To perform urethrolysis, patients are placed in the dorsal lithotomy position and prepped and draped in the normal sterile fashion. Cystoscopy is then performed to evaluate the angulation of the bladder neck and to rule out stitch or sling erosion. Cystoscopy can also be helpful in locating sling placement. Amundensen et al. suggest that the sling location can often be easily found by palpating the urethra against the firm cystoscope sheath [32]. A marking pen can then be used to score the identified site. The bladder is then filled; the cystoscope is removed, and a Crede maneuver is performed, noting how much pressure is necessary to cause leakage. A 16F Foley catheter is then placed, and the balloon is pulled back to the bladder neck. The anterior vaginal wall mucosa is then infiltrated with normal saline, and a midline incision is performed. The mucosa is dissected off the urethra and periurethral fascia. If a pubovaginal sling was performed, it is identified and isolated, then incised in the midline. The Foley catheter is then removed, and a Crede maneuver is repeated. If significant leakage is noted with minimal pressure, the dissection is completed. A suprapubic tube is then inserted, and the vaginal mucosa is closed with a running polygalactin stitch. If there is no leakage or if there is only minimal leakage, the Foley is replaced, and further dissection, lateral to the urethra along the glistening surface of the periurethral fascia, is performed. The endopelvic fascia is then reached and opened, thereby entering the retropubic space. After this, the Crede maneuver is repeated. If significant leakage is still not seen, then dissection is continued, anterior to the urethra and under the pubic bone, until the urethra is completely freed and mobile. Urethral mobility is assessed as adequate when gentle intermittent traction on the Foley catheter causes downward displacement of the posterior urethra into the vagina, and when significant leakage is noted on Crede maneuver. A Martius labia fat flap should then be placed between the urethra and the pubic symphysis to prevent refibrosis. It has been noted by several authors that vaginal wall slings and autologous fascia slings are often difficult to identify as a discreet band and are often associated with considerable fibrosis at the site of sling placement [32,37]. Bladder neck suspension procedures are also commonly found to have significant periurethral fibrosis. Therefore, urethrolysis in these situations must usually be performed by complete urethral mobilization, as previously described. Allograft slings, on the other hand, are almost always easily identified in their entirety with minimal surrounding fibrosis. It has been reported that 71% of these patients only require sling incision to resolve voiding symptoms [32]. When synthetic material is used, it must be completely freed from the urethra and incised at the level of its sutures. Sutures and bone anchors are only removed if the patient is complaining of significant suprapubic pain consistent with osteitis

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pubis. Replacement of the pubovaginal sling at the time of urethrolysis can be performed if the patient has significant stress incontinence prior to the procedure. B. Results After Urethrolysis Urethrolysis has been found to be a safe and extremely effective treatment for prolonged voiding dysfunction after anti-incontinence procedures. It has been reported that resolution of irritable symptoms occurs in 65–85%, and 50–92% void to completion [22,32,33]. Complications of the procedure are also very low. Only 0–9% of patients are reported to suffer recurrent stress urinary incontinence after urethrolysis, and hospital stay is usually only 1–2 days [22,32,33]. Austin et al. have found that patients with urge incontinence on urodynamics preoperatively did worse after urethrolysis [38]; however, other groups have not been able to confirm this finding [22,32,33]. Most report that patients do equally well after urethrolysis, regardless of their preoperative pressure flow studies [22,32,33]. Therefore, patients should not be excluded from urethrolysis even if they have low pressure, low flow, or even acontractile detrusors. Urodynamics should, however, still be performed as part of the workup for voiding dysfunction. Patients with continued urgency after urethrolysis can be helped by bladder augmentation [33]. These patients usually have intrinsic damage to the urethra as a result of surgery, and obstruction is not due to periurethral fibrosis and scarring. VII. PREVENTION OF OBSTRUCTION AFTER AN ANTI-INCONTINENCE PROCEDURE The cause of prolonged postoperative obstruction after an anti-incontinence procedure is usually due to surgical technique. For sling procedures, the most important factor is stitch tension. If the stitches are tied too tightly, they can cause kinking of the urethra and obstruction. It must also be remembered that the tension on the knot will only increase once the patient is out of the lithotomy position. But how tight is too tight? Numerous recommendations for tying knots have been made, such as “tie an air knot,” “use only minimal tension,” “place two fingers between the knot and the abdominal fascia,” but without experience, these suggestions are difficult to duplicate. A reliable recommendation seems to have been made by Rovner et al. [39]. They suggest placing a cystoscope sheath within the urethra and inclining it 20–30° relative to the horizontal position. The stiches are then tied to the rectus fascia without indenting it. The cystoscope sheath should then “be able to be easily rotated in the vertical plane within the urethral lumen.” Cystoscopy can then also be performed after tying the stitches to make sure that the urethra is not damaged or closed. In performing this technique in 160 patients, none had permanent urinary retention, and only 7% had urge incontinence [39]. Another common cause for postprocedure obstruction after an anti-incontinence procedure is the postoperative development or worsening of a cystocele. Failure to correct even a very minor cystocele during an anti-incontinence procedure may result in enlargement of the cystocele postoperatively. This may then lead to kinking at the bladder neck and bladder outlet obstruction. For suspension procedures, stitch tension is also very important, but so is suture placement. Proper placement of suspension sutures at the bladder neck

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and the proximal urethra is critical. If a suspension stitch is placed too medially, it can perforate the urethra, causing extravasation of urine and periurethral fibrosis. These stitches can also lead to recurrent urinary tract infection, stone formation, and a fistula. If the stitch is placed too distally, it may kink the midurethra and cause obstruction. It will also fail to support the bladder neck. Extreme care should be taken when performing a bladder neck suspension to place the sutures in supporting tissues lateral to the urethra at the level of the bladder neck. Finally, the understanding of bladder neck dynamics and the physiology of normal voiding still requires investigation to clarify how we can prevent obstruction. This is demonstrated by the incidence of obstruction, de novo instability, and dysfunctional voiding that is observed in women after incontinence surgery. The TVT, for example, has a midurethral position that is thought to maintain the normal funneling dynamics of the bladder neck. The procedure is optimally performed under a local anesthetic because sling tension is adjusted to maintain continence while the patient coughs in a conscious voluntary state. It is thought the nonanesthetized pelvic floor plays an important role in maintaining passive continence. By adjusting tension in a conscious state, the tension can be adjusted to provide just the right amount of tension required to return continence. Maintaining these technical points is thought to be the explanation for the TVT patient being sent home the same day of surgery without a catheter and voiding naturally. How this translates to other sling techniques still remains to be evaluated and investigated. REFERENCES 1. Raz S, Stoothers L, Chopra A. Vaginal reconstructive surgery for incontinence and prolapse. Campbell’s 1059. 2. Marshall FV, Marchetti AA, Krantz KE. The correction of stress incontinence by simple vesicourethral suspension. Surg Gynecol Obstet 1949; 88:509. 3. Burch JC. Urethrovaginal fixation to Cooper’s ligament for correction of stress incontinence, cystocele and prolapse. Am J Obstet Gynecol 1961; 81:281. 4. Webster GD, Khoury JM. Retroropubic suspension surgery for female sphincteric incontinence. In Campbell’s Urology. 1095. 5. Pereyra AJ. A simplified surgical procedure for the correction of stress incontinence in women. West J Surg Obstet Gynecol 1959; 67:223. 6. Raz S. Modified bladder neck suspension for female stress incontinence. Urology 1981; 17:82. 7. Hadley HR, Zimmern PE, Staskin DR, Raz S. Transvaginal needle bladder neck suspension. Urol Clin North Am 1985; 12:291. 8. Gittes RF, Loughlin KR. No-incision pubovaginal suspension for stress incontinence. J Urol 1987; 138(3):568. 9. Stamey TA. Endoscopic suspension of the vesical neck for urinary incontinence. Surg Gynecol Obstet 1973; 136(4):547. 10. Morgan TO, Westney OL, McGuire EJ. Pubovaginal sling: four-year outcome analysis and quality of life assessment. J Urol 2000; 163(6):1845–1848. 11. McGuire EJ, O’Connell HE. Pubovaginal slings. In Campbell’s Urology. 1103. 12. Wright EJ, Iselin CE, Carr LK, Webster GD. Pubovaginal sling using cadaveric allograft fascia for the treatment of intrinsic sphincter deficiency. J Urol 1998; 160(3 pt 1): 759–762. 13. Govier FE, Gibbons RP, Correa RJ, Weissman RM, Pritchett TR, Hefty TR. Pubovagi-

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14. 15. 16. 17.

18. 19.

20. 21.

22. 23. 24.

25. 26. 27. 28. 29. 30. 31.

32.

33. 34.

35.

36.

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nal slings using fascia lata for the treatment of intrinsic sphincter deficiency. J Urol 1997; 157(1):117–121. Brown SL, Govier FE. Cadaveric versus autologous fascia lata for the pubovaginal sling: surgical outcome and patient satisfaction. J Urol 2000; 164(5):1633–1637. Norris JP, Breslin DS, Staskin DR. Use of synthetic material in sling surgery: a minimally invasive approach. J Endourol 1996; 10(3):227–230. Raz S, Siegel AL, Short JL, Snyder JA. Vaginal wall sling. J Urol 1989; 141(1):43. Ulmsten U, Henriksson L, Johnson P, Varhos G. An ambulatory surgical procedure under local anesthesia for treatment of female urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 1996; 7(2):81. Gorton E, Stanton S, Monga A, Wiskind AK, Lentz GM, Bland DR. Periurethral collagen injection: a long-term follow-up study. BJU Int 1999; 84(9):966. Leach GE, Dmochowski RR, et al. Female Stress Urinary Incontinence Clinical Guidelines Panel summary report on surgical management of female stress urinary incontinence. The American Urological Association. J Urol 1997; 158(3 pt 1):875. Groutz A, Blaivas JG, Chaikin DC. Bladder outlet obstruction in women: definition and characteristics. Neurourol Urodyn 2000; 19:213. Chassagne S, Bernier PA, Haab F, Roehrborn CG, Reisch JS, Zimmern PE. Proposed cutoff values to define bladder outlet obstruction in women. Urology 1998; 51:408. Nitti VW, Raz S. Obstruction following anti-incontinence procedures: diagnosis and treatment with transvaginal urethrolysis. J Urol 1994; 152:93. Carr LK, Webster GD. Voiding dysfunction following incontinence surgery: diagnosis and treatment with retropubic or vaginal urethrolysis. J Urol 1997; 157:821. Farrar DJ, Osborne JL, Stephenson TP, et al. A urodynamic view of bladder outflow obstruction in the female: factors influencing the results of treatment. Br J Urol 1975; 47:815. Axelrod SL, Blaivas JG. Bladder neck obstruction in women. J Urol 1987; 137:497. Massey JA, Abrams PH. Obstructed voiding in the female. Br J Urol 1988; 61:36. Bass JS, Leach GE. Bladder outlet obstruction in women. Prob Urol 1991; 5:141. Nitti VW, Tu LM, Gitlin J. Diagnosing bladder outlet obstruction in women. J Urol 1999; 161:1535. Lemack GE, Zimmern PE, Blaivas JG, Griffiths D, Nitti VW. Pressure flow analysis may aid in identifying women with outflow obstruction. J Urol 163:1823–1828. Blaivas JG, Groutz A. Bladder outlet obstruction nomogram for women with lower urinary tract symptomatology. Neurourol Urodyn 2000; 19(5):553. Volpe M, Ghafar M, Fromer D, Te AE, Kaplan SA. Failed attempt to construct a nomogram to predict bladder outlet obstruction in women with lower urinary tract symptoms. Abstract submitted to the AUA 2001. Amundsen CL, Guralnick ML, Webster GD. Variations in strategy for the treatment of urethral obstruction after a pubovaginal sling procedure. J Urol 2000; 165: 434. Foster HE, McGuire EJ. Management of urethral obstruction with transvaginal urethrolysis. J Urol 1993; 150:1448. Kaplan SA, Te AE, Young GPH, Andrade A, Cabelin MA, Ikeguchi EF. Prospective analysis of 373 consecutive women with stress urinary incontinence treated with a vaginal wall sling: the Columbia-Cornell experience. J Urol 2000; 164:1623. Kumar A, Mandhani A, Gogoi S, Srivastava A. Management of functional bladder neck obstruction in women: use of alpha-blockers and pediatric resectoscope for bladder neck incision. J Urol 1999; 162(6):2061. Schrepferman CG, Griebling TL, Nygaard IE, Kreder KJ. Resolution of urge symptoms following sling cystourethropexy. J Urol 2000; 164:1628.

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37. Cross CA, Cespedes D, English SF, McGuire EJ. Transvaginal urethrolysis for urethral obstruction after anti-incontinence surgery. J Urol 1998; 159:1199. 38. Austin P, Spyropoulos E, Lotenfoe R, Helal M, Hoffman M, Lockhart JL. Urethral obstruction after anti-incontinence surgery in women: evaluation, methodology and surgical results. Urology 1996; 47:890. 39. Rovner ES, Ginsberg DA, Raz S. A method for intraoperative adjustment of sling tension: prevention of outlet obstruction during vaginal wall sling. Urology 1997; 50(2):273.

12 Pediatric Dysfunctional Voiding in Females PAUL F. AUSTIN Washington University School of Medicine St. Louis Children’s Hospital St. Louis, Missouri, U.S.A. YVES L. HOMSY University of South Florida School of Medicine Children’s Urology Group Tampa, Florida, U.S.A.

I.

INTRODUCTION

In this chapter, we discuss dysfunctional voiding as it applies to the pediatric population. Urinary incontinence is a normal transitional phase between infantile and adult lower urinary tract function; consequently, wetting disorders are often considered a necessary nuisance associated with the growing years. This is usually tolerated until the child is believed to lag behind peers in achieving a state of dryness. Similar to other developmental milestones, children mature and develop bladder control differently. Parental concerns about voiding are common and often supersede the child’s anxiety. Knowledge of normal acquisition of day and nighttime urinary control and significant departures from these normal patterns is important for health professionals to determine if treatment is warranted. It is interesting to speculate that pediatric dysfunctional voiding may serve as a precursor to urinary problems frequently seen in adult women. II. TERMINOLOGY The International Children’s Continence Society has provided standardization and definitions of lower urinary tract dysfunction in children [1]. Enuresis is de195

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Table 1 Disorders of Pediatric Female Dysfunctional Voiding Minor disorders Giggle incontinence Stress incontinence Postvoid dribbling

Moderate disorders

Major disorders

Lazy bladder syndrome Overactive bladder Dysfunctional elimination syndrome

Hinman syndrome Ochoa syndrome Myogenic detrusor failure

fined as normal voiding that occurs at an inappropriate time or occurs involuntarily in a socially unacceptable setting. The term enuresis is commonly associated with nighttime wetting; however, it is important to distinguish nocturnal enuresis from diurnal enuresis or daytime wetting. Nocturnal and diurnal enuresis are believed to result from different etiologic factors, but there is certainly some overlap. For example, it is not uncommon for a “bed wetter” to have diurnal enuresis nor is it unusual for a child with daytime wetting to have nocturnal enuresis. Our approach is to focus initially on the most sociably upsetting problem, diurnal enuresis, and then shift attention toward nocturnal enuresis if still present. III. CLASSIFICATION OF DYSFUNCTIONAL VOIDING The term dysfunctional voiding is typically linked with diurnal enuresis. Dysfunctional micturition may be categorized into neuropathic or nonneuropathic voiding disorders. The latter are functional problems, whereas neuropathic voiding is associated with neurological conditions such as myelodysplasia, transverse myelitis, or spinal cord trauma. This chapter focuses on the nonneuropathic spectrum of wetting disorders that commonly occur in pediatric females. Dysfunctional voiding in girls occurs in a variety of patterns (Table 1), and it is imperative to properly identify which specific pattern is present for successful treatment. IV. EPIDEMIOLOGY It is estimated that 5–10% of school-age children experience daytime wetting. This prevalence includes a range of urinary incontinence from a few times per week to multiple episodes daily. Hellstrom et al. reported that, in 3556 school-age entrants at 7 years old, 6% of girls had diurnal enuresis [2]. Bloom et al. looked at the toilet habits in a population of 1192 children and reported diurnal enuresis in 5% of 7 year olds, 10% of 6 year olds, and 10% of 8 year olds [3]. In another survey of 2292 children between the ages of 5 and 12 years, diurnal wetting was reported in 5.5% [4]. Dysfunctional voiding is often accompanied by other clinical manifestations, such as recurrent urinary tract infections (UTIs), vesicoureteral reflux (VUR), and constipation. The term dysfunctional elimination syndrome (DES) has recently been used to describe the association of constipation with diurnal enuresis [5]. V.

BLADDER MATURATION AND PATHOGENESIS

To fully appreciate dysfunctional voiding, it is important to understand how bladder control is attained in the developing child. The micturition center in the neo-

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nate is located at the sacral level; consequently, bladder emptying occurs as a result of a sacral spinal cord reflex [6]. Bladder emptying occurs when the bladder reaches a critical stretch threshold. Afferent signals are sent to the spinal cord to activate the parasympathetic outflow to the bladder and urethra and inhibit the sympathetic and pudendal storage reflex pathways [7]. Newborns void about 20 times per day or an average of once per hour with only a slight decrease in frequency during the first year of life [8,9]. The micturition reflex gradually becomes inhibited or modulated by the pontine micturition center in the brain stem via a spinobulbospinal reflex pathway, and the development of segmental interneurons further modifies the micturition reflex [10,11]. As the bladder fills to a critical threshold, the desire to empty occurs, and the child must consciously suppress this desire until he or she can get to the toilet. It has been proposed that the external sphincter serves as an “on-off ” switch that inhibits or allows reflux micturition [12]. With conscious voiding, the external sphincter is willfully relaxed just prior to initiating a bladder contraction. These two processes, sphincter relaxation and bladder contraction, must occur in a coordinated fashion for proper emptying to occur. It is important to note that the process of bladder control maturation is not uniform in children as with so many other developmental milestones. As the child matures, there is an increase in bladder capacity and voided volumes with a decrease in voiding frequency. At approximately 2 years of age, conscious sensation of bladder fullness develops, although the need to void is not yet fully mastered, resulting in a “physiological” urge incontinence [13]. It is believed that voluntary control of bladder fullness occurs from 2 to 4 years of age, and that by the age of 4 years, most children have acquired an adult pattern of voiding [14]. Two large surveys examining toilet training issues support this concept. Brazelton reviewed the charts from 1170 children and found that 26% of the parents said their children achieved daytime continence by age 24 months, and 52.5% said it was achieved by age 27 months. By age 30 months, daytime continence rose to 85.3%, with 98% of the children reportedly trained by age 36 months [15]. Bloom et al. surveyed 1186 children and found the age of toilet training ranged from 0.75 to 5.25 years, with a mean of 2.4 years [3]. In general, the usual sequence of development of bowel and bladder control is as follows: (1) nocturnal bowel control, (2) daytime bowel control, (3) daytime control of voiding, and (4) nocturnal control of voiding [16]. During this process of attaining bladder control, there are several steps in which “bad bladder” behaviors can be learned. Children develop the ability to volitionally contract the external striated sphincter at an early age. This is a powerful stimulus to inhibit the detrusor muscle. As alluded above, the external sphincter is used by the child as the on-and-off switch for the bladder. With the increase in bladder capacity during toilet training, the child begins to hold urine for very long periods. They learn holding maneuvers to suppress the desire to void. Over time, this will lead to overactivity of the detrusor with uninhibited bladder contractions that the child will also try to suppress. Subsequently, dysfunctional voiding results, and the child has difficulty relaxing the sphincter when attempting to void voluntarily. Relaxation of the sphincter is essential to initiate voiding. In general, dysfunctional voiders exhibit a dyscoordination between the bladder and the bladder outlet, resulting in inefficient bladder emptying. This dyscoordination

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is also termed dyssynergia. The clinical manifestations range from incontinence to UTIs. Because of the tonically active external urethral sphincter and pelvic floor musculature, constipation is also common due to the inability to relax the external anal sphincter through the same pelvic floor.

VI. EVALUATION A.

History

Evaluation of a dysfunctional voider begins with a detailed elimination history. It is important to address the topics of specific problems in infancy, age of toilet training, and family history of urological problems. All voiding symptoms and the present status of continence should be quantified. The most frequent complaint is urinary incontinence without any underlying structural or obvious neurological anomaly. We ascertain if the incontinence is a new development or has been present ever since toilet training. It is not uncommon to see new urinary incontinence after a stressful occurrence at home or school. Subsequently, any new changes or psychological stresses in the child’s life should be probed [17]. Characterization of the pattern of incontinence is important. A history of continuous incontinence throughout the day in a girl would suggest an ectopic ureter, inserting distal to the urethral sphincter or into the vagina. Organic factors, such as diabetes and epilepsy, that can contribute to urinary incontinence should be excluded. Other voiding symptoms commonly seen with dysfunctional voiding include urinary urgency, frequency, or dysuria (Table 2). Voiding symptoms may also be associated with sexual abuse and should be further explored if suggested during the patient interview [18]. Children often demonstrate holding maneuvers such as leg crossing, squatting, or “Vincent’s curtsey.” Although there is some overlap in the features of many voiding disorders, each has a characteristic pattern that stands out sufficiently from the rest so as to be appropriately identified. To quantitate voiding problems, the families fill out a 3-day elimination diary (Fig. 1). We send them home with a voiding and elimination record sheet, as well as a measuring “hat” that sits in the toilet to determine voided volumes. Although there are various methods to predict the maximum bladder capacity in a child, we typically use the formula for age-expected maximum bladder capacity proposed by Berger et al. [19]. Maximum bladder capacity (ounces) ⫽ Age (years) ⫹ 2 Maximum bladder capacity (mL) ⫽ [Age (years) ⫹ 2] ⫻ 30 mL/ounce

Table 2 Signs and Symptoms of Voiding Dysfunction Urinary incontinence Dysuria Frequency Infrequent voiding

Urinary tract infections Urgency Incomplete emptying Constipation

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Figure 1 Elimination diary form. Parents often have very little detailed information regarding their child’s voiding frequency, volumes, or pattern. It is also imperative to have the families record the presence of bowel movements and their appearance during the elimination diary period. In today’s society with both caregivers working, it is impractical for the child to be held out of school to attain the elimination diary. This information does not have to be on consecutive days but needs to be reflective of complete 24-h periods. Typically, the weekends are the best opportunities for the caregiver to document and record the elimination pattern. B. Physical Exam One of the most important aspects of the physical examination is to exclude occult neurological disorders. The lower back should be observed for any lipoma, sinus,

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pigmentation, or tufts of hair that may be a sign of an occult myelodysplasia. Neurological examination of the lower extremities and checking the bulbocavernosal reflex will often reflect the neurological integrity of these lower motor neuron reflex arcs. The bulbocavernosus reflex is elicited by squeezing the glans penis or clitoris and observing or feeling a reflex contraction at the external anal sphincter. Absence of this reflex is suggestive of a possible sacral neurological lesion; however 20% of normal women have a nondetectable reflex [20,21]. If a neurological abnormality is suspected, then neurological consultation and spine imaging are indicated. Abdominal palpation can detect a distended bladder or a large stool mass suggestive of constipation. Inspection of the genitalia should note the presence of labial adhesions in girls. Labial adhesions or synechiae may impede urinary flow, with subsequent urinary symptoms and infections [22]. Any signs of erythema or irritation should be noted and may be indicative of vaginal voiding. Voiding dysfunction and urinary complaints have been described with sexual abuse, and attention should be directed toward examination for any scarring, tearing, or signs of trauma [23]. Finally, if there is a history of continuous urinary incontinence in a little girl, the introitus should be examined carefully for an ectopic ureter. C.

Diagnostic Testing

Urinalysis is obtained to rule out infection as this is a common associated problem with daytime incontinence. If there are symptoms suggestive of UTI, such as dysuria and frequency, then culture of a catheterized collected urine is performed. Urine glucose and specific gravity can exclude diabetes mellitus and insipidus. An imaging evaluation is necessary in the child with voiding dysfunction and a history of UTI. Upper tract imaging is done with an ultrasound. For the bladder and urethra, we prefer a radiographic voiding cystourethrogram (VCUG). This provides additional information for evaluating the incontinent child. The “scout” or plain film of the abdomen (also known as the KUB image—kidney, ureters, and bladder) is the first image obtained with a VCUG study. It is examined for abnormalities of the spine as well as for any increased amount of stool in the colon suggestive of constipation. Bladder capacity can be measured during the filling phase of the VCUG, and the configuration of the bladder is assessed. Bladder trabeculation or cellule formation may suggest dyssynergia or a neuropathic bladder. The voiding phase of the VCUG will demonstrate the urethra as well as any vesicoureteral reflux. Finally, the postvoid film will show any retained urine within the bladder or vagina. D.

Diagnosis

The specific voiding dysfunction is typically quite evident after the voiding history or when the child returns with the elimination diary. The urinary volumes and frequencies are often under- or overestimated by the caregivers prior to obtaining this diary. Constipation is often unknown by the parent until attention is directed with the diary. As the voiding and defecation patterns are more clearly understood, a more focused therapeutic guidance for resolving each of these voiding dysfunctions can be accomplished.

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VII. OVERVIEW OF VOIDING DISORDERS Understanding the factors that contribute to each voiding disorder ensures that each is appropriately addressed in the management plan. Ongoing parental education and participation is emphasized. Significant patience is required until parents can fully grasp what is wrong with their child and what is required of them in the therapeutic process. Specific management is individualized depending on the specific disorder. The following is an overview and management of each of the voiding dysfunctions (Table 1). A. Mild Dysfunctional Disorders 1. Extraordinary Daytime Urinary Frequency Syndrome The sudden onset of daytime urinary urgency and frequency every 10–20 min without dysuria or incontinence characterizes the extraordinary daytime urinary frequency syndrome [24,25]. It is seen more commonly in 3–8 year olds. Typically, there is no nocturia or enuresis, although this may sometimes occur. A careful history, physical exam, and urinalysis should be performed to exclude other etiologies. Imaging studies and urodynamics are normal and unnecessary. Because of the striking symptomatology at presentation, the diagnosis is easily made, and one should refrain from delving into elaborate investigations because of their invasiveness, expense, and low yield. There seems to be an increased incidence of the extraordinary frequency syndrome in the spring and fall, and the etiology remains unknown. A behavioral component may sometimes be incriminated. Anticholinergics are of little help. The syndrome is self-limiting and tends to resolve almost as suddenly as it appears, anywhere from 2 days to 16 months (average 2.5 months). Although recurrences are possible, they are rare (about 3%). Reassurance is therefore the mainstay of therapy. 2. Giggle Incontinence (Enuresis Risoria) Embarrassing wetting episodes associated with giggling and laughter characterize giggle incontinence (enuresis risoria), most commonly seen in peripubertal girls [26]. The diagnosis is made mainly from the history, and in this type of incontinence, a massive unexpected detrusor contraction causes the bladder to empty completely. Giggle incontinence is an uncommon voiding disorder that is selflimiting, but may persist into adulthood. Women learn to adapt by withdrawing from activities that will bring on excessive hilarity. Other treatment options include anticholinergics, sympathomimetics [27], and stimulants [28]. The urine is normal, and the upper tracts are not affected. Urodynamics may show mild uninhibited contractions. Reinberg and Sher reported a favorable response to methylphenidate (Ritalin ) administered in varying dose schedules for 1 to 5 years [29]. Alteration of muscle tone may be precipitated by laughter and is suggestive of a functional relationship to cataplexy, a part of the narcoleptic syndrome complex that may respond to stimulant medication. Conditioning therapy has been reported as another therapeutic modality. Inhibition of the voiding reflex was conditioned after self-administration of a harmless, painless, low-voltage electric shock to the back of one hand when incontinence was induced by

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laughter. Five children received eight sessions of 45-min duration. The frequency of wetting was reduced 1 year after treatment was completed by a mean of 89% [30]. 3. Stress Incontinence Most commonly encountered in adult women, stress incontinence is not seen in childhood, but rather is encountered in teenagers. Affected adolescents are usually athletic, and running, jumping, and high-impact landing induces the incontinence. In a study of young, nulliparous, physically fit, first-year physical education students, Bo et al., using ambulatory urodynamics, reported a high prevalence of urethral sphincteric incompetence [31]. In a large study of 156 nulliparous, college varsity female athletes with a mean age of 19.9 years, the prevalence of incontinence while participating in their sport was 28% [32]. Incontinence induced by jumping, high-impact landings, and running was first noted by 40% of the young women when participating in their sport while in high school. In 17%, it was noted to have started in junior high school. The proportion of incontinent subjects participating in different sports was as follows: gymnastics 67%, basketball 66%, tennis 50%, field hockey 42%, track 29%, swimming 10%, volleyball 9%, softball 6%, and golf 0%. A relationship between stress incontinence and force absorption on impact has been implied by assessment of foot arch flexibility. Nygaard et al. measured the change in medial longitudinal arch height from the neutral gait stance to the maximally dorsiflexed ankle position and demonstrated a statistically significant association with incontinence when there was decreased foot flexibility between the two gait stances [33]. The mechanics involved in the transmission of impact forces to the pelvic floor may provide further understanding of the pathophysiology and management of stress urinary incontinence in the adolescent. In general, the degree of incontinence is quite minimal and can usually be managed by timely bladder emptying prior to exercising. In addition, sympathomimetics may also be of benefit. 4. Postvoid Dribbling (Vaginal Voiding) Postvoid dribbling (vaginal voiding) dysfunction occurs in girls after they have finished voiding due to urine accumulation in the lower vagina. When they stand up, urine trickles out of the vagina into the underwear. Patients with postvoid dribbling often present with labiovulvar erythema and/or leukorrhea, which may cause burning, itching, and skin excoriation [34]. Vaginal voiding is different from vaginal pooling of contrast commonly seen during a VCUG. Unlike vaginal voiding, these children do not exhibit any genitalia symptomatology, and the vaginal pooling is due to the recumbent position adopted during the VCUG and has little clinical significance. The problem is secondary to poor posture during micturition and is more prone to occur in either very small girls or, paradoxically, obese girls. In the former, their tiny body habitus causes them to adopt a hairpin configuration on the toilet bowl, with their feet being unsupported during micturition. As the force of the urinary stream decreases toward the end of urination, this position favors the accumulation of a small amount of urine in the introitus and lower vagina. The

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condition is often diagnosed as a fungal vulvovaginitis that does not respond well to medication as it is really secondary to a postural problem. Correction of the posture adopted during micturition will usually resolve the condition. Having the child sit astride the toilet seat facing the wall, which ensures that the back is erect and the thighs are well separated, will correct the problem. Alternatively, a toilet seat adapter or foot supports may be provided, although this may be cumbersome. In obese girls, vaginal trapping of urine occurs for a different reason. These girls often do not spread their legs sufficiently apart when they void, either because they are restricted by tight jeans or underwear. Asking them to void facing the wall will make them remove any restrictive clothing, and their stream is likely to become more realigned toward the vertical than the horizontal. Recognizing that this condition is a functional postural anomaly will probably spare the child interminable treatments with inefficient creams and ointments. B. Moderately Dysfunctional Disorders 1. Lazy Bladder Syndrome Lazy bladder syndrome was first described by DeLuca et al. in 1962 and is characterized by a large-capacity hypotonic bladder, infrequent voiding every 8 to 12 h, and incontinence between voiding [35]. The sensation of bladder fullness is diminished, incontinence is due to overflow, the urinary stream is poor, and voiding is incomplete. The child will often not urinate on awakening and will only do so in midmorning or even later. Bladder infections are frequent, and constipation is usually present. Patients must strain to void. The urinary stream is poor and unsustained, and voiding is incomplete. Upper tract dilatation is sometimes found, and the bladder is large and smooth walled. Urodynamics typically demonstrates a large-capacity, hypotonic bladder with a variable amount of postvoid residual urine. Outflow obstruction has not been demonstrated. Ruarte and Quesada studied 636 children without overt neurological disease or outflow obstruction urodynamically and established the incidence as 6.9% [36]. Treatment is oriented to reeducation of the bowel and bladder to promote efficient emptying. Management of constipation or lesser degrees of fecal retention must first be diligently addressed with a bowel regimen tailored to the patient’s degree of constipation. The management of constipation is pertinent to most forms of voiding dysfunction and is addressed below in more detail. The administration of Fleet enemas for a few days to empty the lower bowel of hard stool, followed by a stool softener and a high-fiber diet are required before specific therapy is oriented to the bladder. Bladder retraining is achieved by a timed voiding or behavioral modification program for the bladder. Voiding is done by the clock or by a schedule during the daytime. The idea is to keep the bladder empty so urine will be less likely to leak or become infected. An alarm watch may be a good way to remember, but it is critical to establish a schedule that will become routine and “second nature.” In our practice, we have recommended a voiding schedule that centers micturition on common daily events (e.g., bedtime, mealtimes, and inbetween times) (Table 3). In general, the schedule should strive for a regular voiding pattern every 2–3 h. In addition, double and triple voiding that involves voiding one to two more times a few minutes after the initial void are sometimes necessary to ensure good emptying.

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Table 3 Timed Voiding Program Void Void Void Void Void Void Void

on awakening at breakfasttime at midmorning school break at lunchtime at midafternoon or school ending at dinnertime at bedtime

Intermittent catheterization may be necessary if adequate bladder emptying cannot be accomplished with bladder retraining. After initiating a 6-h catheterization schedule, patients will usually start to void on their own without wetting. At that point, catheterization should be performed after voiding to measure residual urine, which will be found to diminish progressively. We have recently obtained encouraging results with the use of α-1-adrenergic blocking agents directed at relaxing the bladder outlet to promote bladder emptying in a variety of conditions, including the lazy bladder syndrome [37]. At the present time, we would attempt a trial with α-blockers before resorting to CIC. 2. Overactive Bladder As the most common voiding dysfunction encountered in children, the overactive bladder has a peak incidence between 5 and 7 years of age. Ruarte and Quesada found an incidence of 57.4% in a group of 383 children ranging in age from 3 to 14 years [36]. Sex prevalence was 48.9% in boys and 60.1% in girls. These children have bladder instability or hyperactivity and exhibit diurnal enuresis with urgency and small, frequent voids. In children, bladder overactivity is believed to be due to a delay in the acquisition of cortical inhibition over uninhibited detrusor contractions in the course of achieving the mature voiding pattern of adulthood. The site of maturational delay is thought to lie in the reticulospinal pathways of the spinal cord, as well as in the inhibitory center within the cerebral cortex. Cortical control over subcortical centers is normally established between 3 and 5 years of age. The subcortical centers subsequently modulate medullary automatism to achieve voluntary micturition control [38,39]. A delay in the fine-tuning of vesicosphincteric coordination during micturition will cause uninhibited detrusor contractions to be met with voluntary external urethral sphincter contractions, the control of which is acquired at an earlier age. An increase in intravesical pressure can manifest itself in an array of symptoms that include urgency, urge incontinence, and nocturnal enuresis. Disturbed voiding dynamics will favor the establishment of recurrent urinary tract infections and an acquired form of vesicoureteral reflux. Reflux occurs in 33–50% of children with overactive bladders and can be associated with significant upper tract dilatation [40,41]. Several studies have shown that addressing the overactive bladder or the associated dysfunctional elimination problems when they are present will triple the rate of reflux resolution in relation to controls [5,42,43].

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Signs and Symptoms. The overactive bladder manifests itself mainly by daytime urgency and incontinence. It may have a nocturnal component, which causes it to sometimes be confused with the symptoms of nocturnal enuresis. Some nocturnal enuretics also may have episodes of wetting during the day, and this overlap is the source of difficulties in diagnosis and management. Nocturnal bladder instability has been demonstrated in about one third of enuretics [44]. The uninhibited or overactive detrusor contraction that triggers bladder overactivity occurs early in the filling phase, causing the pelvic floor to respond by a voluntary contraction, which in turn gives rise to holding maneuvers such as leg crossing, squatting, or Vincent’s curtsey. The passive external urethral compression that is achieved in this manner may possibly cause a temporary reflex relaxation of the detrusor, affording momentary relief from the effects of an uninhibited detrusor contraction. UTIs are common due to poor emptying secondary to these holding maneuvers used to combat the bladder instability. Children with recurrent UTIs are sometimes maintained on antibiotic prophylaxis until bladder emptying is improved with treatment. A constant finding on the voiding and elimination diary is a small functional bladder capacity for the child’s age. This is due to a state of detrusor hypertonicity resulting from persistent overactivity, which resolves as the condition improves. It is therefore a good clinical indicator of response to treatment. Constipation is often present and may contribute significantly to the symptomatology of the overactive bladder; it must be diligently sought in the course of the patient/family interview. The association of constipation or various degrees of fecal retention with the overactive bladder has led to speculation that the frequent voluntary pelvic floor contractions generated to combat incontinence episodes end up favoring constipation by simultaneously contracting the external anal sphincter [45]. Treatment. Several therapeutic modalities are available for the management of overactive bladder of childhood. BEHAVIORAL THERAPY. Similar to the child with lazy bladder syndrome, behavioral modification or a timed voiding program is necessary to retrain the bladder to empty more efficiently (Table 3). The difference in this form of voiding dysfunction is that an overactive bladder is too unstable to adhere to a timed voiding program, necessitating a bladder relaxant to allow the child’s bladder to “make it” to the next scheduled void. Anticholinergics are used to suppress the bladder instability, allowing the child enough time to get to the toilet. It is imperative when using anticholinergics to resolve any constipation because these agents will also inhibit the bowel and thus promote constipation. A common scenario seen on referral is the initial improvement of bladder symptoms with anticholinergics, followed by relapse secondary to exacerbated constipation. BIOFEEDBACK—ELECTRICAL STIMULATION. Biofeedback to retrain the bladder has been used in adults for more than 20 years and has met with reasonable success [46]. This therapeutic modality has also been used in children and has had varying degrees of sustained positive results (51–83%) [47–51]. Difficulties in maintaining the child’s interest and attention are inherent to biofeedback therapy so that long-term results can be quite variable. Recently, a program was developed

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that makes use of computer games to maintain the child’s interest. Game action is controlled by patient pelvic muscle activity; the program was carried out in an outpatient setting with very encouraging results [52]. NEUROMODULATION—ELECTRICAL STIMULATION. Neuromodulation has shown some success in the management of adults with bladder instability refractory to other forms of treatment [53]. Overactive bladder results from insufficient cortical inhibition of the micturition reflex. The micturition reflex may be blocked by pudendal somatic afferent stimulation directly at the sacral cord. In children, the use of transcutaneous electrical nerve stimulation (TENS) shows promise in the management of detrusor hyperactivity [54]. Of 40 children, 27 were placed on trial therapy for 1 month and showed sufficient response to continue therapy for 6 months with stimulation delivered via surface electrodes to the level of the S3 foramen for 2 h every day. Alternatively, the surface electrodes may be placed suprapubically, in which case stimulation is increased to 150 Hz. Favorable response rates are seen in 70–75% with this mode of therapy, which still needs further evaluation.  PHARMACOLOGICAL THERAPY. Propantheline bromide (Pro-Banthine ) has long been available as a smooth muscle relaxant of the bowel. Anticholinergic effects were found to extend to the bladder, and this agent has been used to treat bladder overactivity for a number of years. Oxybutynin chloride (Ditropan ) then became available and was found to have a more specific action on the bladder while still having some effect on the bowel. Ditropan is currently the only anticholinergic approved by the Food and Drug Administration (FDA) for overactive bladder in children 5 years and older. A sustained-release preparation is now available (Ditropan XL ), which may improve patient compliance and side-effect profile. Hyoscyamine preparations are also effective in achieving detrusor relaxation, and they are available in different forms, from sublingual to sustained release (Levsin , Levsinex ). Glycopyrrolate (Robinul ) is also sometimes used. The newest addition to this group of medications is tolterodine (Detrol ). It is an antimuscarinic agent that is relatively selective for the bladder. Tolterodine has been found to have comparable efficacy to oxybutynin in adults and produces less mouth dryness [55]. In a European report, tolterodine’s safety profile, efficacy, and pharmacokinetics were recently established in children 5–10 years old with a body weight of 17–39 kg [56], but like many common medications used in adults, this is currently not FDA approved for use in the pediatric population in the United States. Similar to oxybutynin chloride, there is an extended-release form that allows once-a-day dosing (Detrol LA ). The anticholinergic effects of the medications mentioned above rely on partial blockade of the efferent parasympathetic innervation to the detrusor. Systemic side effects often preclude the use of high enough doses to combat detrusor overactivity. These include facial flushing, constipation, and dry mouth. Less common complaints are headache and palpitations. The minor side effects will often abate with prolonged usage, but the medication dosage has to be altered or stopped in 20% of our patients. Consequently, other potential medications have been investigated. The periodic intravesical instillation of capsaicin or resiniferatoxin holds promise. They are specific neurotoxins that desensitize the C fiber afferent neurons responsible for triggering detrusor overactivity. While the side-effect profile

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of capsaicin may preclude its use in children, resiniferatoxin, an ultrapotent analogue of capsaicin with fewer side effects, may be more useful [57]. 3. Dysfunctional Elimination Syndrome The common association of fecal elimination disturbances with dysfunctional voiding syndromes has led Koff and associates to coin the phrase dysfunctional elimination syndromes (DES) [5]. These syndromes comprise functional bowel and/or bladder disorders, including bladder instability, constipation, and infrequent voiding (lazy bladder). The effects of dysfunctional elimination on the upper tract are not negligible. In a group of 143 children thought to have primary vesicoureteric reflux, 66 patients (43%) manifested bowel and bladder disturbances. Of these children, 82% had breakthrough infections and required reimplantation surgery, as opposed to 18% without the syndromes. After reflux resolution, the rate of recurrent UTI remained four times higher in children with DES. Interestingly, unsuccessful surgical outcomes with reimplantation surgery only occurred in children with DES [5]. Recurrent UTI is the sounding board that should alert the clinician to screen patients for DES even in the absence of reflux. Parents have a tendency to be more observant of voiding problems in their children than of problems with defecation as the latter are more subtle in their manifestations. C. Severe Dysfunctional Disorders 1. The Hinman Syndrome The Hinman syndrome represents the extreme of the spectrum of voiding dysfunction. In this syndrome, bladders behave much like a neuropathic bladder, although these children do not have any apparent neurological deficit. To emphasize the absence of neurological disease, the term non-neurogenic neurogenic bladder was coined. As this term seemed to cause some confusion, the condition became known as the Hinman syndrome in 1986 [58]. Hinman syndrome is believed to be an acquired voiding disorder characterized by the inappropriate voluntary contraction of the striated urinary sphincter during the process of micturition. This results in a functional urinary obstruction that over time causes UTIs, myogenic bladder failure, hydronephrosis, and eventually renal insufficiency. The exact etiology of this disorder is uncertain, but it is considered a behavior that is acquired during potty training, when children learn to control their urinary tract by actively contracting the urinary sphincter. It is postulated that this behavior becomes habitual when the child fails to differentiate between voluntary and involuntary voiding. Diagnosis. Most patients will present with incontinence associated with chronic urinary retention. An intermittent voiding pattern with reduced flow rates and prolonged voiding time can be seen on uroflowmetry. Elevated postvoid residuals may or may not be present. Clinical examination will fail to reveal a neurological abnormality. Magnetic resonance imaging (MRI) should be performed to rule out cord tethering and other neurological lesions before reaching a final diagnosis.

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Renal function is often reduced, with elevations in serum creatinine and reduced clearance. Hypertension may be present. Renal/bladder sonography will show varying degrees of unilateral or bilateral hydronephrosis with or without dilatation of the ureters. Bladder wall thickening should be assessed, and the examination should be repeated after emptying the bladder. This will help to determine if ureteral dilatation is secondary to bladder dysfunction rather than an intrinsic ureterovesical junction obstruction. The presence of renal scarring should be noted and monitored by DMSA renal scans. VCUG may show varying grades of reflux, either a trabeculated or an enlarged, decompensated bladder with failure to empty completely. Careful attention to the urethra may yield clues as to the effects of sphincteric overactivity, such as a spinning top urethra with poor filling of the anterior urethra in girls. Urodynamics may show a variety of patterns depending on the severity and duration of this acquired malfunction. Uroflowmetry usually shows intermittency with reduced flow rates and prolonged voiding, as mentioned above. Cystometric findings will depend on the stage of the disease, with uninhibited contractions early on and bladder atony in advanced cases with myogenic detrusor failure. Initially, detrusor hyperreflexia is associated with sphincteric dyssynergia. The electromyographic tracing differs from that of dyssynergia associated with neurological bladder disease (as in spinal transection) in the timing of onset of sphincteric contraction [59]. With time and as the detrusor decompensates, a broad spectrum of dysfunction may be found. Some cases may show detrusor hypotonia or atony, while the sphincter may or may not be hyperactive. Griffiths and Scholtmeijer thoroughly studied 143 children with detrusor-sphincter dyssynergia and found a variety of patterns of activity both in the detrusor and in the urethra. These authors introduced the concept of consistent urethral overactivity, which they found to be significantly more common in children with upper tract changes [60]. In Hinman’s original description, psychological factors were attributed to the etiology [61], although in many cases, this seems less significant. Unemployment, alcoholism, divorce, sexual abuse, and a dominating or overprotective parent may be present in the history. Cultural problems in migrant families may be a source of social pressure to which the child is exposed. Paradoxically, in some cases the child may appear quite happy rather than withdrawn, seeming to have found a way to become articulate and to get attention through the disease [62]. Treatment. Treatment is multimodal and aimed at restoring balanced voiding and preventing upper urinary tract deterioration. CIC is often required to achieve complete bladder emptying. Drug therapy is guided by urodynamic findings and includes anticholinergics and α-blockers either alone or in combination. Dosage will need careful adjustment and will depend on patient response as determined by periodic imaging and urodynamic evaluation. Botulinum-A toxin has been used to induce striated muscle paralysis in other medical disciplines and has been used to treat vesicosphincteric dyssynergia in patients with spinal cord injury [63]. Steinhardt et al. subsequently reported this form of therapy in managing a little girl with dysfunctional voiding who was refractory to other forms of treatment [64]. As the degree of paralysis produced is dose dependent and reversible, repeated injections may be necessary every few

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months. Further studies will be needed to validate this method in the management of the Hinman syndrome. In cases when psychological factors are present, collaborative treatment with the psychologist, urology nurse/urotherapist, and pediatric urologist may be necessary. The impact of psychosocial problems with the severe voiding problems may exacerbate one another, making treatment difficult [65]. It has become clear that therapeutic strategies must be tailored to the individual. Sensate patients may not be compliant with their intermittent catheterization regimen, thus allowing renal function to deteriorate further. On the other hand, psychological management may cause delays in the initiation of specific therapy targeted to the urinary tract. Appropriate timing and close follow-up will allow assessment of the progress being achieved. If the upper tracts continue to deteriorate, then temporary urinary diversion as dictated by the child’s age and condition should be considered. 2. The Ochoa (Urofacial) Syndrome Children with Ochoa syndrome have all the clinical features of Hinman syndrome. It is also known as the urofacial syndrome (UFS) because of the unusual inversion of facial expression when smiling is attempted [66]. The face becomes contorted into a grimace that makes the subject appear to be crying. The Ochoa syndrome has an autosomal recessive pattern of inheritance, and the prevalence is rather low as only less than 200 cases have been identified [67]. The UFS gene has been mapped in families from Colombia [68], but subsequently, genetic homogeneity of the syndrome was demonstrated through mapping in American patients with Irish heritage [69]. Treatment is similar to that for Hinman syndrome. Bladder reeducation is the mainstay of therapy with a combination of anticholinergics and antibacterials and attempts at relaxing the external sphincter region. The α-blockers may play a role in this endeavor. Intermittent catheterization or temporary vesicostomy may be needed in some patients. As with the Hinman syndrome, constipation constitutes a major issue and must be vigorously addressed. 3. Myogenic Detrusor Failure Myogenic detrusor failure occurs as end-stage bladder decompensation. It is frequently seen in neurogenic bladders. Because this altered detrusor state takes time to develop, patients have typically reached early adolescence by the time it is recognized. These patients have a moderate amount of residual urine and thus are prone to develop recurrent UTIs. Hydronephrosis is the result of the earlier hyperreflexic state of the detrusor before decompensation and usually tends to remain stable. These patients may require intermittent catheterization or possibly α-blocker therapy. VIII. PROGNOSIS Most children with dysfunctional voiding can expect a successful resolution of the problem. The time course to resolution of urinary symptoms may be prolonged. Behavorial modification and timed voiding programs will cure the majority of children. Pharmacological intervention may speed this along for some patients.

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However, it is the establishment of good voiding behavior that is the key to success. If there is a history of constipation or encopresis, this should be treated with dietary measures and/or laxatives to restore regular bowel habits. Failure to identify constipation with the dysfunctional voiding disorder represents a common pitfall in treatment. For children who fail to respond to behavioral modification and pharmacological treatment, we recommend more extensive diagnostic studies, including urodynamic evaluation of bladder function. Children who have infections and reflux can have significant morbidity. Renal scarring and damage is more prevalent in children with reflux and voiding dysfunction. Therefore, aggressive treatment of these children is warranted. Children who have more significant voiding problems, such as the Hinman syndrome or myogenic failure, are most susceptible to renal damage.

IX. CONCLUSION Successful treatment of voiding dysfunction requires proper identification and an understanding of the various subtypes. Treatment plans are tailored to the individual voiding dysfunction disorders. Many of the mild and moderate forms of voiding dysfunction can be treated by the primary care provider. However, those children with more severe voiding dysfunctions that are refractory to initial management require referral to specialists.

REFERENCES 1. Norgaard JP, et al. Standardization and definitions in lower urinary tract dysfunction in children. International Children’s Continence Society. Br J Urol 1998; 81(suppl 3): 1–16. 2. Hellstrom AL, et al. Micturition habits and incontinence in 7-year-old Swedish school entrants. Eur J Pediatr 1990; 149(6):434–437. 3. Bloom DA, et al. Toilet habits and continence in children: an opportunity sampling in search of normal parameters. J Urol 1993; 149(5):1087–1090. 4. Bower WF, et al. The epidemiology of childhood enuresis in Australia. Br J Urol 1996; 78(4):602–606. 5. Koff SA, Wagner TT, Jayanthi VR. The relationship among dysfunctional elimination syndromes, primary vesicoureteral reflux and urinary tract infections in children. J Urol 1998; 160(3 pt 2):1019–1022. 6. Muellner SR. Development of urinary control in children: some aspects of the cause and treatment of primary enuresis. JAMA 1960; 172:1256–1261. 7. de Groat WC, et al. Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine. J Auton Nerv Syst 1981; 3(2–4):135–160. 8. Goellner MH, Ziegler EE, Fomon SJ. Urination during the first three years of life. Nephron 1981; 28(4):174–178. 9. Holmdahl G, et al. Four-hour voiding observation in healthy infants. J Urol 1996; 156(5):1809–1812. 10. Noto H, et al. Excitatory and inhibitory influences on bladder activity elicited by electrical stimulation in the pontine micturition center in the rat. Brain Res 1989; 492(1– 2):99–115. 11. Araki I, de Groat WC. Developmental synaptic depression underlying reorganization of visceral reflex pathways in the spinal cord. J Neurosci 1997; 17(21):8402–8407.

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12. Park JM, Bloom DA, McGuire EJ. The guarding reflex revisited. Br J Urol 1997; 80(6): 940–945. 13. Hjalmas K. Urodynamics in normal infants and children. Scand J Urol Nephrol Suppl 1988; 114:20–27. 14. Stein Z, Susser M. Social factors in the development of sphincter control. Dev Med Child Neurol 1967; 9(6):692–706. 15. Brazelton TB. A child-oriented approach to toilet training. Pediatrics 1962; (29):121– 128. 16. Rushton HG. Wetting and functional voiding disorders. Urol Clin North Am 1995; 22(1):75–93. 17. Galdston R, Perlmutter AD. The urinary manifestations of anxiety in child. Pediatrics 1973; 52(6):818–822. 18. Ellsworth PI, Merguerian PA, Copening ME. Sexual abuse: another causative factor in dysfunctional voiding. J Urol 1995; 153(3 pt 1):773–776. 19. Berger RM, et al. Bladder capacity (ounces) equals age (years) plus 2 predicts normal bladder capacity and aids in diagnosis of abnormal voiding patterns. J Urol 1983; 129(2):347–349. 20. Bors EH, Blinn KA. Bulbocavernosus reflex. J Urol 1959; 82:128–130. 21. Blaivas JG, Zayed AA, Labib KB. The bulbocavernosus reflex in urology: a prospective study of 299 patients. J Urol 1981; 126(2):197–199. 22. Leung AK, Robson WL. Labial fusion and urinary tract infection. Child Nephrol Urol 1992; 12(1):62–64. 23. Hinds A, Baskin LS. Child sexual abuse: what the urologist needs to know. J Urol 1999; 162(2):516–523. 24. Koff SA, Byard MA. The daytime urinary frequency syndrome of childhood. J Urol 1988; 140(5 pt 2):1280–1281. 25. Zoubek J, Bloom DA, Sedman AB. Extraordinary urinary frequency. Pediatrics 1990; 85(6):1112–1114. 26. Glahn BE. Giggle incontinence (enuresis risoria). A study and an aetiological hypothesis. Br J Urol 1979; 51(5):363–366. 27. Arena MG, et al. “Enuresis risoria”: evaluation and management. Funct Neurol 1987; 2(4):579–582. 28. Sher PK. Successful treatment of giggle incontinence with methylphenidate. Pediatr Neurol 1994; 10(1):81. 29. Sher PK, Reinberg Y. Successful treatment of giggle incontinence with methylphenidate. J Urol 1996; 156(2 pt 2):656–658. 30. Elzinga-Plomp A, et al. Treatment of enuresis risoria in children by self-administered electric and imaginary shock. Br J Urol 1995; 76(6):775–778. 31. Bo K, et al. Clinical and urodynamic assessment of nulliparous young women with and without stress incontinence symptoms: a case-control study. Obstet Gynecol 1994; 84(6):1028–1032. 32. Nygaard IE, et al. Urinary incontinence in elite nulliparous athletes. Obstet Gynecol 1994; 84(2):183–187. 33. Nygaard IE, Glowacki C, Saltzman CL. Relationship between foot flexibility and urinary incontinence in nulliparous varsity athletes. Obstet Gynecol 1996; 87(6):1049– 1051. 34. Davis LA, Chumley WF. The frequency of vaginal reflux during micturition—its possible importance to the interpretation of urine cultures. Pediatrics 1966; 38(2):293– 294. 35. DeLuca FG, et al. The dysfunctional “lazy” bladder syndrome in children. Arch Dis Child 1962; 37:117–120. 36. Ruarte AC, Quesada EM. Urodynamic evaluation in children. Int Perspect Urol 1987; 14:114–124.

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37. Austin PF, et al. α-Adrenergic blockade in children with neuropathic and nonneuropathic voiding dysfunction. J Urol 1999; 162(3 pt 2):1064–1067. 38. Lapides J, Diokno AC. Persistence of the infant bladder as a cause for urinary infection in girls. J Urol 1970; 103(2):243–248. 39. Buzelin JM, Lacert P, Le Normand L. [Ontogenesis of vesico-sphincter function]. J Urol 1988; 94(4):211–216. 40. Koff SA, Lapides J, Piazza DH. Association of urinary tract infection and reflux with uninhibited bladder contractions and voluntary sphincteric obstruction. J Urol 1979; 122(3):373–376. 41. Snodgrass W. Relationship of voiding dysfunction to urinary tract infection and vesicoureteral reflux in children. Urology 1991; 38(4):341–344. 42. Koff SA, Murtagh DS. The uninhibited bladder in children: effect of treatment on recurrence of urinary infection and on vesicoureteral reflux resolution. J Urol 1983; 130(6):1138–1141. 43. Homsy YL, et al. Effects of oxybutynin on vesicoureteral reflux in children. J Urol 1985; 134(6):1168–1171. 44. Watanabe H. Sleep patterns in children with nocturnal enuresis. Scand J Urol Nephrol Suppl 1995; 173:55–56. 45. Issenman RM, Filmer RB, Gorski PA. A review of bowel and bladder control development in children: how gastrointestinal and urologic conditions relate to problems in toilet training. Pediatrics 1999; 103(6 pt 2):1346–1352. 46. Cardozo LD, et al. Idiopathic bladder instability treated by biofeedback. Br J Urol 1978; 50(7):521–523. 47. Hellstrom AL, Hjalmas K, Jodal U. Rehabilitation of the dysfunctional bladder in children: method and 3-year follow-up. J Urol 1987; 138(4):847–849. 48. Jerkins GR, et al. Biofeedback training for children with bladder sphincter incoordination. J Urol 1987; 138(4 pt 2):1113–1115. 49. Hoebeke P, et al. Outpatient pelvic-floor therapy in girls with daytime incontinence and dysfunctional voiding. Urology 1996; 48(6):923–927. 50. Combs AJ, et al. Biofeedback therapy for children with dysfunctional voiding. Urology 1998; 52(2):312–315. 51. Schulman SL, et al. Comprehensive management of dysfunctional voiding. Pediatrics 1999; 103(3):E31. 52. McKenna PH, et al. Pelvic floor muscle retraining for pediatric voiding dysfunction using interactive computer games. J Urol 1999; 162(3 pt 2):1056–1062; discussion 1062–1063. 53. Bower WF, et al. A urodynamic study of surface neuromodulation versus sham in detrusor instability and sensory urgency. J Urol 1998; 160(6 pt 1):2133–2136. 54. Hoebecke P, et al. Transcutaneous neuromodulation in non-neuropathic bladder sphincter dysfunction in children: preliminary results. Paper presented at: Second Congress, International Children’s Continence Society; 1999; Denver, CO. Abstract 55, p. 102. 55. Abrams P, et al. Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder. Br J Urol 1998; 81(6): 801–810. 56. Hja¨lma˚s K, et al. Safety, efficacy and pharmacokinetics of tolterodine in pediatric patients with overactive bladder. Paper presented at: Second Congress, International Children’s Continence Society; 1999; Denver, CO. Invited Lecture: 78–79. 57. Chancellor MB, de Groat WC. Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder. J Urol 1999; 162(1):3–11. 58. Hinman F. Nonneurogenic neurogenic bladder (the Hinman syndrome)—15 years later. J Urol 1986; 136(4):769–777.

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59. Rudy DC, Woodside JR. Non-neurogenic neurogenic bladder: the relationship between intravesical pressure and the external sphincter electromyogram. Neurourol Urodyn 1991; 10:169–173. 60. Griffiths DJ, Scholtmeijer RJ. Detrusor/sphincter dyssynergia in neurologically normal children. Neurourol Urodyn 1983; 2:27. 61. Hinman F, Baumann FW. Vesical and ureteral damage from voiding dysfunction in boys without neurologic or obstructive disease. Trans Am Assoc Genitourin Surg 1972; 64:116–121. 62. Varlam DE, Dippell J. Non-neurogenic bladder and chronic renal insufficiency in childhood. Pediatr Nephrol 1995; 9(1):1–5. 63. Schurch B, et al. Botulinum-A toxin as a treatment of detrusor-sphincter dyssynergia: a prospective study in 24 spinal cord injury patients. J Urol 1996; 155(3):1023–1029. 64. Steinhardt GF, Naseer S, Cruz OA. Botulinum toxin: novel treatment for dramatic urethral dilatation associated with dysfunctional voiding. J Urol 1997; 158(1):190–191. 65. Phillips E, Uehling DT. Hinman syndrome: a vicious cycle. Urology 1993; 42(3):317– 319; discussion 319–320. 66. Ochoa B, Gorlin RJ. Urofacial (Ochoa) syndrome. Am J Med Genet 1987; 27(3):661– 667. 67. Ochoa B. The urofacial (Ochoa) syndrome revisited. J Urol 1992; 148(2 pt 2):580–583. 68. Wang CY, et al. Construction of a physical and transcript map for a 1-Mb genomic region containing the urofacial (Ochoa) syndrome gene on 10q23-q24 and localization of the disease gene within two overlapping BAC clones (⬍360 kb). Genomics 1999; 60(1):12–19. 69. Wang CY, et al. Genetic homogeneity, high-resolution mapping, and mutation analysis of the urofacial (Ochoa) syndrome and exclusion of the glutamate oxaloacetate transminase gene (GOT1) in the critical region as the disease gene. Am J Med Genet 1999; 84(5):454–459.

13 Nonsurgical Treatment of Urinary Incontinence FAH CHE LEONG St. Louis University School of Medicine St. Louis, Missouri, U.S.A.

I.

INTRODUCTION

Urinary incontinence in women is disturbingly common, with a large number of women who do not report the problem and subsequently do not get help for the problem. Incontinence is generally divided into stress incontinence, which has traditionally been treated surgically, and urge incontinence, which is usually treated with medication. As stated in AHCPR (Agency for Health Care Policy and Research) guidelines for the management of urinary incontinence, the first choice for treatment should be the least invasive with the fewest potential adverse complications that is appropriate for the patient [1]. Voiding dysfunction can occur with either overactivity or underactivity of detrusor muscles. Occasionally, with an entity such as detrusor hyperreflexia with inadequate contractility, a combination can exist. It is important to be certain that the voiding dysfunction is not a consequence of a mechanical impediment before embarking on pharmacological manipulation. As part of the initial assessment of the patient, her postvoid residual will be measured. In general, there will be no further investigation into the possibility of incomplete bladder emptying if the postvoid residual is less than 150 cc. It is important to find out if the patient has Valsalva voided, or performed a Crede maneuver to “completely empty” her bladder. If that is the case, she will still have complaints of postvoid fullness, but the evidence may not be there.

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II. INADEQUATE BLADDER EMPTYING An inadequately emptying bladder may be the first sign of a neurological disorder such as multiple sclerosis. As such, it is important to perform a complete neurological examination of the patient with voiding dysfunction. Upper motor neuron signs, or even side-to-side discrepancies, on examination may be the only findings in a patient with early disease. Appropriate imaging and neurological consultation may be necessary. A patient may also present with vague discomfort, but have recurrent bladder infections and be found to be in retention. On physical examination, it is important to rule out a physical impediment to voiding. Quite frequently, a patient may present with pelvic organ prolapse, which prevents efficient voiding. In pregnancy, as the gravid uterus expands beyond the true pelvis, it can be trapped in a retroverted position and prevent voiding. Infrequently, the position of other masses such as leiomyoma or a suburethral diverticulum may prevent voiding. On some patients, a history of prolonged overdistension of the bladder may lead to inadequate voiding and subsequent recurrent bladder infections. This is unfortunately common after gynecological surgery when a catheter has been removed and the patient has not voided for a prolonged time, or when a patient purposefully overhydrates in an attempt to void thinking that she is “not making urine,” but really just cannot void. Patients can be warned of these consequences and are encouraged to call with concerns to avoid these mishaps. Instead of a structural impediment to voiding, they may be a functional obstruction. Patients who have severe pelvic pain have difficulty relaxing the pelvic floor to void [2]. This can be further exacerbated by poor voiding habits, such as “hovering” above the commode to void in public restrooms. This is usually a lifelong habit that is difficult to break. Pessaries can be used diagnostically as well as therapeutically for problems with voiding associated with pelvic organ prolapse. When fitted correctly, the prolapse is reduced, and voiding can become more efficient. It is important to use a size and type of pessary that is comfortable and yet supports correctly. If the pessary does not correct the voiding dysfunction, and there is still an obvious impediment to voiding, it will be necessary to proceed with urodynamic testing, especially of the voiding phase. In patients who have had a bladder suspension, it is important to look for overelevation of the bladder neck. This will provide a mechanical obstruction and becomes worse over time if there is a subsequent prolapse of the bladder around the suspension, creating a kink in the urethra. The overelevation can sometimes be corrected by cutting one of the arms of the suspension, but occasionally urethrolysis must be done. These patients can also suffer from chronic overdistension, and function may not always be restored with the restoration of anatomy. In patients who have an entrapped uterus in pregnancy, restitution of the uterus is usually accomplished with the patient in knee-chest position and by repositioning the uterus. A pessary can then be fitted to avoid the same complication. Over the next few weeks of gestation, the uterus moves out of the true pelvis and will usually not become impacted on the pelvic brim. Medical management of bladder underfunction has been disappointing. A more appropriate means of managing chronic urinary retention is the use of clean

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intermittent self-catheterization. The nonsterile, but clean, procedure results in rates of infection that are lower than those with indwelling catheters. The routine use of long-term antibiotic suppression is not necessary, and treatment is reserved for patients who have symptoms of a bladder infection. Most patients are able to accomplish this, even if most are reluctant to even try this at first. The goal of catheterization is to keep the postvoid residual at a reasonable amount, 150 to 200 cc. The frequency of catheterization is tailored to the patient. Occasionally, the patient is unable to perform self-catheterization despite her greatest efforts. This can be because of her habitus, poor proprioception, or poor coordination. Although it does not work for everyone, the patient can use a device to assist herself, such as the Asta-Cath device (A⫹ Medical), which will help position the catheter above the urethra. Rarely, if the patient is impaired, and there is no alternative with caregivers, the bladder can be drained by a suprapubic catheter. Complications of a suprapubic catheter can include stone formation around the catheter tip, recurrent bladder infections, blockage of the catheter, and leakage around the catheter. A suprapubic catheter is preferable to an indwelling transurethral catheter as it eliminates urethral complications. A tragic consequence of using an indwelling catheter is the erosion of not just the urethra, but the entire bladder neck, resulting in a large hole at the bottom of the bladder. III. BLADDER OVERACTIVITY Medications are the mainstay of treatment of the overactive bladder, but there is a role for behavioral treatment. Depending on the extent of the problem and the circumstances of the patient, environmental changes can also be quite useful. A careful review of the patient’s voiding pattern and living situation can reveal some areas that can be improved. Although sometimes seen as a bother by the patient, a 24-h voiding diary listing volumes voided, oral fluids, with time and circumstance of leakage can be quite enlightening. Many patients have been told to drink “at least 8 cups of water for their health,” but then add to that numerous cups of coffee, juice, soda, and milk. Normalizing their intake can be quite effective. Limiting nighttime drinking to a few hours before sleep can be helpful. For patients who have a problem with mobility, having a bedside commode can make the difference between getting wet and staying dry. Patients who have cognitive problems may benefit from prompted voiding, especially if they have little warning of urinary leakage or have very high urinary volumes. A simple option for patients who have urinary frequency and urgency is bladder training. This is a behavioral means of reducing not only urinary urgency, but also urge incontinence. Basically, this is a variation of prompted voiding with scheduled lengthening of voiding intervals [3]. The patient is first asked to void at set voiding intervals throughout the waking hours. The initial interval is determined by the usual voiding interval that is found in the patient’s voiding diary. The patient is asked to void at this interval whether there is an urge to void. This is kept up for a week, allowing the patient to void with her normal prompts over the sleeping hours. At the end of a week, the voiding interval is increased by 15 to 30 min, and the cycle is repeated until the patient has a voiding interval of 2 to 3 h. Fantl studied 131 women with mixed incontinence, 60 women were treated with bladder training. Of these, 12% reported that they were dry, and 75% of the

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patients in that group had at least a 50% reduction in leakage episodes [4]. In a comparison of behavioral and drug treatment for urge incontinence, Burgio et al. found that, in their older population, behavioral treatment was more effective than drug treatment with an 80.7% reduction in incontinence episodes compared to a 68.5% reduction using medication [5]. A.

Pelvic Floor Strengthening

As with stress incontinence, pelvic muscular strengthening can be used for bladder overactivity. These exercises are generally called Kegel exercises and were described by Kegel in 1948. He had found an 84% cure rate for stress incontinence when women completed 300 contractions a day [6]. A major disadvantage is that nearly 30% of women cannot correctly contract their pelvic floor and may need additional instruction [7]. A pelvic floor physical therapist can be very helpful in improving the patient’s ability to do Kegel contractions. In the therapist’s armamentarium are methods and devices to improve both the strength and control of the pelvic floor. Initial efforts begin at the physician’s office, where the patient’s pelvic floor strength and control is assessed by direct examination. At this examination, a thorough assessment of function and structure is done, including looking for prolapse and pain. It is very difficult for the patient to provide pelvic contractions when she has muscular pain that produces splinting with each effort at activating the muscles. It is important to address pelvic pain first and strength later. Moderate-to-large pelvic organ prolapses can also decrease the patient’s ability to contract the pelvic floor. Restituting the pelvic floor with a pessary may help the patient achieve more control and eventually more strength. When patients are seeing a physical therapist, they are started with exercises in the supine position to provide mechanical advantage and decrease the resistance from gravity. As they progress, the patients are then taught to do the exercises in more difficult positions. This can be from supine, to sitting, to standing, and finally while walking. They may even be able to do some of the exercises while in stress situations, such as coughing or sneezing. They also tend to do better with more follow-up despite little reported differences in compliance [8]. The optimal number of contractions a patient does during a day is not known. Nygaard and Bo prescribed exercises which totaled 10 minutes a day with exercises completed 2 to 3 times [8–11]. Yalcin et al. asked patients to contract and relax 15 to 20 times for 5 s, done initially 5 times a day and progressing to 10 times a day, for a total of 200 contractions [12]. In general, patients are told that this is a program of lifelong exercise rather than a short treatment to permanently improve on incontinence. Cure rates from Kegel exercises range from 15% to 48%, with 38% to 77% subjective improvement rates [8,13,14]. Nygaard found equally high improvement rates for stress, urge, and mixed incontinence. Nygaard concluded that many women with unstable detrusor contractions can inhibit these contractions by learning to contract the pelvic floor [9]. Another option is the use of the pelvic floor electrical stimulator. The device stimulates the levator ani and external urethral and anal sphincters and causes a reflex inhibition of the detrusor muscles. This depends on an intact reflex arc through the sacral micturition center. This is done through vaginal, anal, or sur-

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face electrodes. Most devices are battery powered, limiting the strength of the stimulation. “Cure” or improvement rates ranged from 48% to 94% for studies using maximal stimulation [15,16]. Oddly, in a study of cognitively impaired patients in a nursing home, there was a trend toward increased wetness [17]. There are few side effects to treatment other than pain and discomfort during treatment. The parameters for stimulation are not standardized. Central sacral neuromodulation is a minimally invasive technique for the treatment of intractable urgency and urge incontinence. The treatment begins with a trial stimulation with a nonimplanted stimulator unit. If successful, then the patient becomes a candidate for permanent implantation. The electrodes are placed through the S3 sacral foramen, and this can be done with fluoroscopic guidance or the use of evoked responses on electromyography. The implant is placed on the lateral buttocks. The neurostimulator inhibits sensory processing in the spinal cord through the somatic afferent nerves. This in turn inhibits supraspinally mediated hyperactive voiding [18]. Peripheral sacral neuromodulation can be achieved by stimulating an afferent branch of S2 and S3, the posterior tibial nerve. At present, this is done percutaneously with a 34-gauge needle near the ankle. In initial trials by Stoller, it was found that 55% reported success, and 34% reported improvement [19]. In more recent trials, 71% of 53 patients enrolled in a multicenter trial were classified as successes, noting on average that urge incontinence was reduced by 35%. There were even some improvements noted in selective pain and quality-of-life indexes [20]. The patient undergoes 10 to 12 weekly treatments for 30 min each time. Most patients do not feel any improvement until the sixth treatment; in general, the first improvement is in decreasing nocturia. In some patients, who have had poor or negligible results with medication, the addition of this modality increases effectiveness of the medication. There were no serious adverse side effects seen in treatment trials, with only a drop of blood at the needle insertion site in about 5% of patients. B. Pharmacological Treatment The goals of treatment in the overactivity of the detrusor muscle are both the reduction of incontinence episodes and the reduction of urinary urgency events, such as frequency, urgency, and nocturia. The mechanism of sensation in the bladder is poorly understood. The bladder has multiple different subtypes of muscarinic and serotonergic receptors. Nitric oxide and adenosine triphosphate may play a role in bladder sensation [21]. C. Oral Treatment of Detrusor Overactivity Anticholinergic medications are competitive inhibitors of acetylcholine and block its muscarinic effects. These agents block contractions of the normal bladder and probably the unstable bladder as well. These medications have important and dose-limiting side effects that patients must endure. They are warned of dry mouth, constipation, blurry vision, and palpitations. Patients who have uncorrected closed-angle glaucoma cannot use these medications. Over the last few years, two new formulations have been approved by the Food and Drug Administration (FDA) in the treatment of overactive bladder.

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These include tolterodine, which is available as an immediate release form as well as a long-acting form, and a long-acting form of oxybutynin. Welcome side effects of having new medications available are renewed media interest and getting patients to speak to their physicians about this problem. Older medications that are still quite useful are oxybutynin, propantheline bromide, and hyoscyamine. Oxybutynin has both anticholinergic and direct smooth muscle relaxant properties. Tricyclic antidepressants such as imipramine are also useful. These should be used carefully in elderly patients. They may have both cardiac and anticholinergic side effects. Patients may also experience fatigue with this class of drug. The blood level must be built up over several weeks, and if they are to be discontinued, they should be tapered over several weeks to avoid rebound depression. It is also possible to combine a tricyclic antidepressant with an anticholinergic agent for additive effects, keeping in mind the possibility of urinary retention. Other classes of oral medication include prostaglandin inhibitors, calcium channel blockers, scopolamine, baclofen, and bromocriptine [22]. There are trials using intravesical instillations of medications for detrusor instability. This offers the possibility of using higher concentrations of medications while avoiding systemic side effects. Medications most commonly used include anticholinergics. Capsaicin instillations have had limited success since the drug can cause severe pain with the initial release of substance P in the bladder. In a clinical trial by Chancellor and DeGroat, 72% of patients had symptomatic improvement with capsaicin instillation [23]. Trials of resiniferatoxin (RTX) for detrusor overactivity are in the early stages, but it has the promise of being as useful as capsaicin without the painful side effects [24]. Phase II trials for urge incontinence were conducted by the Afferon Corporation, which owns the rights to RTX. Other instillants attempted include emepronium bromide, lidocaine, and verapamil, which have shown variable degrees of success. IV. STRESS INCONTINENCE The treatment options for stress incontinence range from the very conservative to complex reconstructive surgery. As stated in the clinical practice guideline for urinary incontinence published by the U.S. Department of Health and Human Services, the first choice should be the least invasive treatment with the fewest potential adverse complications that is appropriate for the patient [1]. A.

Behavioral Methods

The least invasive means of treatment uses behavioral methods to modify the patient’s circumstances so that incontinence is less of a problem. A careful history with a bladder voiding diary is helpful in finding approaches that can be tailored to the patient’s particular underlying problem. B.

Bladder Training

Although bladder training is most useful for urge incontinence, it is also useful for stress urinary incontinence. It generally consists of education about the pathophysiology of stress incontinence and scheduling voids with systematically in-

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creased delay of voiding. In Fantl’s controlled, randomized trial of women with mixed incontinence, 12% of the treated women became dry, and 75% of the treated women had at least a 50% reduction of incontinence episodes [4]. C. Pelvic Muscle Strengthening Kegel muscle exercises as described for patients with overactive bladder can be used for women with stress incontinence symptoms. The exercises strengthen the periurethral and perivaginal muscles to contribute to the closing force of the urethra, as well as contribute to the support of the pelvic visceral structures. There have been many trials of the use of pelvic muscle strengthening for stress incontinence, with subjective cure rates of between 15% and 48% and subjective improvement rates of between 38% and 77% [8,12,14,25]. Improvement is generally determined as greater than 50% reduction in urinary loss. The long-term effects of pelvic floor strengthening are not as well documented. In Bo’s follow-up of 23 women who had participated in a 1990 study, 13% of the women had continence surgery, and 30% remained continent by pad testing. Of these women, 70% were still satisfied with their level of continence [10]. Cammu and Van Nylen did a 5-year follow-up survey of their patients and found that 81% of the women who had been cured were still cured or significantly improved. The overall cure rate at 5 years was 58%, but 27% of the women had continence surgery [26]. D. Strengthening with Vaginal Cones Plevnik introduced vaginal cones in 1985. They are usually made of stainless steel coated in plastic with a nylon cord attached. They need to be placed just within the vaginal introitus, avoiding placement too high in the vagina. High placement may leave the cone on the levator plate so that no active contractions are needed to keep the cone in place. Active pelvic contractions keep the cone within the vagina, and as the cones slip outward, the patient will reflexively or voluntarily contact the pelvic floor to keep the cone in place. The cones cannot be used in patients with poor pelvic floor strength. They are quite useful in increasing strength since they provide resistance. The subjective cure rates range from 4% to 58%, with subjective improvement rates ranging from 9% to 80%. Objective cure rates, reported only in two studies, were 15% and 50%, and objective improvement rates ranged from 30% to 63% [8,27,28]. There are also reports that there may be no relationship between cone weight and the outcome. Long-term use is also variable. Wilson and Borland reassessed 34 women 12 to 24 months after study completion and found that 59% of them had undergone surgery for incontinence; only 18% continued using the vaginal cones [29]. E.

Biofeedback

Arnold Kegel introduced biofeedback for incontinence in 1948 with the use of a perineometer. It was placed in the vagina and gave feedback of the patient’s contractions. The patients are first made aware of their pelvic floor with biofeedback, and once aware of how to contract effectively, then could proceed with

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strengthening. This can be done with an internal probe or external electrode. The surface electrode records more noise from other muscle groups, but is generally more accepted by patients. This can be modified to include auditory or visual feedback to the patient. The subjective cure rate varied from 13% to 67%, with improvement rates from 11% to 70%. Objective cure rates from 29% to 72% are reported [30–32]. The treatment protocols were also very variable, so studies are difficult to compare. F.

Functional Electrical Stimulation

In patients who have poor initial pelvic floor strength, the addition of functional electrical stimulation is an option. Although available for more than 30 years, the means of stimulation has changed from implanted electrodes with long-term stimulation of 6 to 20 h to short-term stimulation with removable electrodes. The electrical stimulator is theoretically similar to pelvic floor muscle exercises, with the goal increased strength and ability to contract the correct muscles. Once the muscles are isolated and the patient can exercise independently of the stimulator, she is then asked to continue active contractions and to continue to strengthen her pelvic floor. The use of the stimulator assumes that the nervous system is intact. This is relevant as pudendal denervation is possible after childbirth when there is stretch injury to the nerve. Fortunately, the injury only results in partial denervation with some reinnervation, so an intact neural axis still exists. Technical considerations in the use of electrical stimulation include the intensity of stimulation, the frequency of the stimulation current used, and the amount of time the patient is stimulated. Richardson found that a mean intensity of 36.7 ⫾ 13.6 mA produced a contraction in women with stress incontinence [33]. Bo and Talseth found that only 6 of 12 women could increase the intensity high enough to achieve a pelvic floor contraction [34]. The second parameter used is the frequency. Fall recommends a frequency of 50 to 100 Hz for patients with stress incontinence and a frequency of 5 to 10 Hz for urge incontinence. Frequencies this low may be uncomfortable, so in general, 20 Hz is used [35]. Another method is the use of interferential frequencies. For example, using frequencies of 4010 Hz and 4000 Hz produces a frequency of 10 Hz at the pelvic floor. This is useful as higher frequencies are less irritating to the skin [36]. The major disadvantage to using the pelvic floor stimulator is poor reimbursement, if any, from third-party payers. If not reimbursed, the equipment is quite expensive if used at home [37]. In comparing the increase in women’s urethral pressure from an active pelvic floor contraction with those from electrical stimulation, the increase in pressure is greatest from active contraction [38]. The women in Bo’s study stated that the contractions felt different, and that the stimulator would cause contractions of the hip adductors and the external rotators. Comparing studies of electrical stimulation is also difficult as the parameters of stimulation are quite variable. It is also done in both the home and the clinic setting with different types of equipment. In general, if used at home, the patient uses a stimulator for 15 to 30 min twice a day, careful to avoid muscular fatigue. The most commonly used electrode is an intravaginal electrode. It is also possible to use intra-anal and perianal electrodes. The subjective cure rates vary from 9%

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to 63%, with subjective improvement rates from 19% to 79%. Objectively, the cure rates range from 12% to 45%, and improvement rates of from 22% to 89% are reported [39,40]. V.

CONCLUSION

Nonsurgical treatment of both urge and stress incontinence is possible and can be effective. The use of medications and the availability of new medications for the treatment of urge incontinence have increased our armamentarium and also brought new awareness of a common problem to the public. In the use of nonpharmacological treatment, there has been poor standardization of techniques, and thus comparing studies and outcomes is difficult. Nevertheless, many of the techniques can offer significant improvement from symptoms with minimal side effects. Enlisting the help of a pelvic floor physical therapist can improve the patient’s outcome. REFERENCES 1. Urinary Incontinence in Adults: Acute and Chronic Management. Vol. 2. Rockville, MD: U.S. Department of Health and Human Services, 1996:154. 2. External sphincter spasticity syndrome in female patients. J Urol 1976; 115:443–446. 3. Urinary incontinence: an augmented prompted void approach. J Gerontol Nurs 1992; 18:3–10. 4. Efficacy of bladder training in older women with urinary incontinence. JAMA 1991; 265:609–613. 5. Behavioral versus drug treatment for urge urinary incontinence in older women. JAMA 1998; 280:1995–2000. 6. Progressive resistance exercises in the functional restoration of the perineal muscles. Am J Obstet Gynecol 1948; 56:238–248. 7. Reeducative treatment of female genuine stress urinary incontinence. Am J Phys Med 1987; 66:155–168. 8. Single blind, randomised controlled trial of pelvic floor exercises, electrical stimulation, vaginal cones, and no treatment in management of genuine stress incontinence in women. BMJ 1999; 318:487–493. 9. Efficacy of pelvic floor muscle exercises in women with stress, urge, and mixed incontinence. Am J Obstet Gynecol 1996; 174:120–125. 10. Pelvic floor muscle for the treatment of female stress urinary incontinence: ill effects of two different degrees of pelvic floor muscle exercises. Neurol Urodyn 1990; 9. 11. The effect of post-natal exercises to strengthen the pelvic floor muscles. Acta Obstet Gynecol Scand 1996; 75:382–385. 12. Results of the anti-incontinence operations and Kegel exercises in patients with type II anatomic stress incontinence. Acta Obstet Gynecol Scand 1998; 77:341–346. 13. Pelvic muscle exercise for stress urinary incontinence in elderly women. JAGS 1991; 39:785–791. 14. Long-term results of pelvic floor training in female stress urinary incontinence. Br J Urol 1993; 72:421–427. 15. Maximal electrical stimulation of patients with frequency, urgency, and urge incontinence. Report of 38 cases. Acta Obstet Gynecol Scand 1992; 71:629–631. 16. Pelvic floor electrical stimulation in the treatment of genuine stress incontinence: a multicenter, placebo-controlled trial. Am J Obstet Gynecol 1995; 173:72–79.

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17. The treatment of urinary incontinence with electrical stimulation in nursing home patients: a pilot study. J Am Geriatr Soc 1992; 40:48–52. 18. Sacral nerve stimulation for treatment of refractory urinary urge incontinence. J Urol 1999; 162:352–357. 19. Clinical trials of the SANS afferent nerve stimulator to treat urinary incontinence: Urosurge, 1999. 20. Percutaneous afferent neuromodulation for the refractive overactive bladder: results of a multicenter study. J Urol 2001; 165:1193–1198. 21. Medical and minimally invasive treatment of urinary incontinence. Rev Urol 1999; 1: 111–120. 22. A double blind trial of bromocriptine in the treatment of idiopathic bladder instability. Br J Urol 1979; 51:24–27. 23. Intravesical capsaicin as a treatment for refractory detrusor hyperreflexia: a dual center study with long-term followup. J Urol 1997; 158:2087–2092. 24. Intravesical treatment of overactive bladder. Urology 2000; 55:60–64. 25. Pelvic muscle exercise for stress urinary incontinence in elderly women. JAGS 1991; 39:89–93. 26. Pelvic floor muscle exercises: five years later. Urology 1995; 45:113–117. 27. Pelvic floor exercise alone or with vaginal cones for the treatment of mild to moderate stress urinary incontinence in premenopausal women. Int Urogynecol J 1995; 6:14– 17. 28. The conservative management of patients with symptoms of stress incontinence: a randomized, prospective study comparing weighted vaginal cones and interferential therapy. Am J Obstet Gynecol 1990; 162:87–92. 29. Vaginal cones for the treatment of genuine stress incontinence. Aust N Z J Obstet Gynaecol 1990; 30:1157–1160. 30. Pelvic floor rehabilitation in the treatment of incontinence. J Reprod Med 1993; 38: 662–665. 31. Treatment of stress incontinence with pelvic floor exercises and biofeedback. JAGS 1990; 38:341–344. 32. Efficacy of biofeedback, when included with pelvic floor muscle exercise treatment, for genuine stress incontinence. Neurol Urodyn 1996; 15:37–52. 33. Pelvic floor electrical stimulation: a comparison of daily and every-other day therapy for genuine stress incontinence. Urology 1996; 48:110–118. 34. Change in urethral pressure during voluntary pelvic floor muscle contraction and vaginal electrical stimulation. Int Urogynecol J. 1997; 8:3–7. 35. Advantages and pitfalls of functional electrical stimulation. Acta Obstet Gynecol Scand 1998; 168:16–21. 36. Objective methods for evaluation of interferential therapy in the treatment of incontinence. IEEE Trans Biomed Eng 1990; 37:615–622. 37. Transvaginal electrical stimulation for female urinary incontinence. Am J Obstet Gynecol 1997; 177:536–540. 38. Pelvic floor rehabilitation, part 1: comparison of two surface electrode placements during stimulation of the pelvic floor musculature in women who are continent using bipolar inteferential currents. Phys Ther 1995; 75:1067–1074. 39. Intravaginal maximal electrical stimulation in the treatment of urinary incontinence. J Reprod Med 1993; 38:557–671. 40. Pelvic floor stimulation in the treatment of mixed incontinence complicated by a lowpressure urethra. Obstet Gynecol 1996; 88:757–760.

14 Sacral Nerve Root Neuromodulation/ Electrical Stimulation STEVEN W. SIEGEL and JYOTHI B. KESHA Metro Urology, St. Paul, Minnesota, U.S.A.

I.

INTRODUCTION

An estimated 13 million Americans suffer from urinary incontinence. Urge incontinence is conservatively estimated to account for the difficulties of 40% of all incontinent patients [1]. Of this population, two thirds suffer from chronic or established incontinence. Yet, patients diagnosed with urinary incontinence due to detrusor instability have had limited treatment options. Conservative interventions such as diet modification, behavioral techniques (pelvic muscle exercises, biofeedback, timed voiding), drug therapies, and containment devices are commonly used to treat the condition. If these therapies fail or are unsatisfactory to the patient, a surgical intervention may be the next step. Procedures such as bladder denervation, augmentation cystoplasty, or even urinary diversion can be considered. These alternatives have their own set of risks and consequences, making them unattractive to the majority of patients. According to the 1996 National Association for Continence (NAFC) survey of 2000 incontinent persons in the United States, although more treatments are now available to urge-incontinent patients, 62.6% of these patients reported they were “not satisfied” with their treatment outcomes. The lack of effective treatment for urge incontinence is particularly disturbing given the debilitating nature of this condition. Incontinent patients commonly experience loss of self-esteem, shame, depressive symptoms, embarrassment, anger, and a significant loss of quality of life [1]. Urge incontinence is especially difficult given the severity and unpredictable nature of leaking episodes. Consequently, patients restrict or avoid social interactions, become iso225

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lated, and have difficulties meeting daily responsibilities. Although not life threatening, the condition tends to be socially devastating. Over the past 30 years, numerous advances have been made in the treatment of urinary incontinence via electrical stimulation of neural pathways that control bladder function. New therapies have emerged, offering treatment that is reversible and does not preclude other complimentary alternatives for management. They include use of transvaginal or transanal stimulation devices, sacral nerve stimulation (SNS), and percutaneous afferent nerve stimulation. Electrical stimulation therapies involving these devices may differ in their mechanism of action, patient compliance and acceptability, efficacy, and suitability for a given underlying condition. Anatomic variations in patients may also preclude certain forms of treatment. Various forms of electrical stimulation have been used for symptoms of stress, urge, and mixed incontinence; urgency-frequency syndromes; urinary retention; and pelvic pain syndromes. Regardless of the clinical diagnosis, the goal of therapy is to alter lower urinary tract function by stimulation of pudendal or sacral nerves and to modulate pelvic visceral and striated muscle behavior. II. NORMAL URINE STORAGE AND EVACUATION Normal micturition relies on urine storage and release as inverse functions in which there is precise coordination among the detrusor musculature, the striated muscles of the pelvic floor (levator ani/sphincter), and the external urinary sphincter. Storage of urine during bladder filling requires the bladder to be compliant (viscoelastic) to distend without increased pressure and to be stable so that the detrusor does not contract, causing sudden increased pressure and possible incontinence. Coordination of these muscle systems is controlled by nervous system components located in the brain, pons, spinal cord, bladder, and urethra via reflex mechanisms. Tension (afferent) receptors in the bladder wall respond to distention, transmitting signals through the A-delta fibers when intravesical pressure approaches 5–10 cm H 2 O [2,3]. As the bladder fills, the detrusor continues to relax, and the pelvic floor tightens (guarding reflex). With continued filling, the afferent signals to the sacral cord and brain stem become stronger, and the guarding reflex increases accordingly. On initiation of normal voluntary voiding, the pelvic floor relaxes, and the detrusor contracts [4]. A positive-feedback loop between bladder afferent and pelvic efferent neurons allows for efficient bladder emptying with minimal residual. This action is facilitated by supraspinal input through the pontine micturition center. III. DISRUPTED MICTURITION BALANCE Conscious control allows voiding to occur at appropriate, socially acceptable times. Inhibitory reflexes (autonomic and somatic) coordinated by the pons are needed to keep the sacral micturition reflex in balance. If these reflexes are overly inhibited, the balance is tipped toward urgency and urge incontinence. If they are overly facilitated, the balance is shifted toward urinary retention. Viewed in this way, detrusor instability and urge incontinence may simply represent the flip side of urinary retention, with both syndromes representing a central nervous system dysfunction, which secondarily affects pelvic visceral function. It follows that

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other organs innervated by the same pelvic nerves may also show evidence of dysfunction. Bowel dysfunction (irritable bowel or chronic constipation), dyspareunia, and chronic pelvic pain may be due to the same imbalance of reflexes. It becomes clear that any therapy (i.e., anticholinergics, denervation procedures, augmentation cystoplasty) directed at the end organ is unlikely to be completely successful. IV. MECHANISM OF ACTION OF ELECTRICAL STIMULATION The exact way in which electrical stimulation improves voiding dysfunction is not well understood, but most experts agree that the therapies work by modulating sacral nerve reflexes [5–10]. Stimulation restores a balance between sacral reflexes that are either overly inhibited or overly facilitated. The site of stimulation may also alter the mechanism and potential benefit elicited. For example, transvaginal or transanal devices first stimulate skin receptors and myelinated A-delta fibers, causing the striated muscles of the pelvic floor to contract, turning off inappropriate detrusor contractions by augmenting the guarding reflex. These actions may be duplicated by conscious efforts and practiced behaviors (Kegel exercises),

Figure 1 Position points and nerve pathways for electrical stimulation devices.

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but they must be incorporated into everyday behavior to have long-term success. If effective over the long term, there is an implication that the abnormal reflex activity can be modified by consistent corrective behavior, or that the dysfunctions in the nervous system can be altered permanently. Sacral nerve stimulation may work in a similar fashion, but also affects the nervous system through direct modulation of unmyelinated C-fiber sacral nerve afferents, which have a much higher threshold of stimulation than the myelinated A-delta fibers. Recent evidence also shows that neuromodulation reduces c-fos gene expression and bladder hyperreflexia, both events occurring when afferent c-fiber activity is inhibited [11]. In addition, studies in rats show that sacral root neurostimulation attenuated the rise in neuropeptide contents of the dorsal root ganglia of L6, suggesting that blockade of c-afferent fiber activity is one of the mechanisms of action of sacral root neuromodulation [12]. It is certain that these nerves play an important role in abnormal bladder activity and in syndromes with pelvic pain [10]. Because the devices are implanted and entail the usage of a pacemaker battery, they can constantly modulate abnormal reflex activity even if the patient is incapable of conscious behavioral change, or if the changes in the central nervous system are otherwise permanent (Fig. 1). V.

ELECTRICAL STIMULATION AS A TREATMENT MODALITY

Devices for electrical stimulation therapy are the result of observations that spontaneous or artificially evoked bladder hyperactivity can be inhibited by electrical stimulation of the pelvic floor and sacral nerves [5–7]. Animal experiments and electrophysiological studies in humans have confirmed that electrical stimulation can activate spinal inhibitory reflexes capable of interrupting a detrusor contraction [13,14]. The afferent anorectal branches of the pelvic nerve, afferent nonmuscular somatic (sensory) fibers of the pudendal nerve, and muscle afferents from the limbs are all sensitive to low-frequency stimulation [6,8,15–21]. Various devices are currently on the market to utilize these nerve paths (Fig. 2). There are two main types of electrical stimulation in use, long term or chronic and acute maximal functional electrical stimulation. Chronic stimulation is usually delivered below the sensory threshold or at a low, comfortable level for more than 6 h a day over a number of months or, with implantable devices, for years. Maximal functional stimulation is used for short periods of time, such as 15 to 30 min, at varying intervals from daily to weekly, for lengths of time ranging from 10 to 20 weeks. This is the type of stimulation currently used in percutaneous afferent nerve stimulation. In both types of stimulation, electrical current is pulsed at frequencies based on clinical diagnosis. In detrusor instability, the goal of therapy is to increase inhibitory impulses to the bladder using afferent nerve pathways, as well as affecting the striated pelvic muscles responsible for inhibition of bladder contraction. Control of voiding mediated by electrical stimulation does not appear to be the result of a placebo effect, and the nature of the treatment intervention generally precludes double-blind studies. There is evidence to suggest that a significant placebo effect is not present. A study of vaginal stimulation included a period of active electrical stimulation followed by a period of mechanical stimulation of a

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Figure 2 Electrode placement at the S3 nerve root. The sacral foramina are probed with an insulated needle using bony landmarks as a guide. There is little risk of direct nerve impingement with correct orientation of the needle.

vaginal electrode without connection to a pulse generator. In the absence of electrical stimulation, there was no effect on incontinence [2]. Clinical trials of the InterStim  device also included a therapy evaluation period when electrical stimulation was turned off. Incontinence levels returned to baseline in all patients [22]. The results suggest that a placebo effect is not apparent, and that electrical stimulation is necessary for inducing incontinence control in treated patients (Table 1).

VI. TRANSVAGINAL AND TRANSANAL ELECTRICAL STIMULATION DEVICES Modulation of the pelvic floor using an externally applied electrical source offers an attractive, noninvasive way of retraining the basic physiological responses of intact muscle tissue for patients with stress, urge, or mixed incontinence. Electrical stimulation induces a Kegel-type movement of the pelvic floor muscles and there-

Stimulation of the pelvic floor muscles using a vaginal or anal probe and external power source

Stimulation of sacral nerves using a needle positioned at the posterior tibial nerve and an external power source

Stimulation of sacral nerves at the S3 level using a fully implanted device, including a lead implanted at the nerve root, an extension wire, and a pulse generator

Needle stimulation

Direct sacral nerve stimulation

Description

Low-frequency, electrical neuromodulation of unmyelinated afferent nerves at the S3 level to directly stimulate nerves responsible for voiding functions

Electrical stimulation delivered through the needle uses the posterior tibial nerve to activate the sacral nerve arc, inhibiting the sacral micturition center

Electrical stimulation delivered through the probe causes muscles to contract involuntarily (electronically induced Kegel exercise)

Mechanism

Clinical applications for urge or mixed incontinence, urgency/ frequency, and urinary retention

Urge or mixed incontinence and urgency/frequency

Dependent on stimulation frequencies: stress, urge, or mixed incontinence

Clinical application

Comparative Overview of Electrical Stimulation Therapies for Urinary Incontinence

Transvaginal and transanal stimulation of pelvic floor

Table 1

Patients use the device frequently for 15–30 min each session Improvement is dependent on patient compliance with stimulation regimen Length of trial period to assess efficacy is ≅ 12 weeks Patients use the device weekly or biweekly for 20–30 min during an outpatient visit Improvement is dependent on patient compliance with stimulation regimen Length of trial period to assess efficacy is not known Long-term implantation that does not require active patient involvement on an ongoing basis for effectiveness Assessment of efficacy is immediate based on peripheral nerve evaluation, followed by trial use of 3–7 days

Treatment regimen

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fore may be useful in patients who are unable to perform these exercises correctly using verbal, written, or other visual cues. Devices of this type have been used transvaginally in females and transanally in males. They are connected to an external power source, and the resultant stimulation causes the pelvic floor muscles to contract involuntarily. The frequency of stimulation is modified depending on the type of incontinence. A frequency of 50 Hz may be used in treatment of stress incontinence; lower frequencies, below 25 Hz, are used for the treatment of urge incontinence [23]. Typical treatment regimens involve use of the devices for 15 to 30 min twice per day, every other day, thus allowing the muscles to recover from the refractory period induced by maximal functional stimulation. Improved continence in 54–77% of patients has been demonstrated at follow-up periods from 6 weeks to 2 years [24–28], although conflicting evidence exists [29–31]. Variations in stimulation protocols make direct comparisons of the literature difficult [30]. Combination therapies have been shown to increase cure/improvement rates, and continued pelvic floor muscle exercises after treatment have also been shown to be of benefit [32]. This form of treatment is desirable because it may be effective for all types of incontinence. Another obvious advantage is its ease of use and relatively low cost. The techniques are easily taught, the cost is considerably less than a yearly prescription of tolterodine, and the therapy is completely reversible with very few side effects noted in clinical trials [24,27]. Compliance with stimulation regimens is an important issue. A study of daily versus every-other-day stimulation for a treatment period of 20 weeks found that either regimen was equally effective in treating stress, urge, and mixed incontinence [24,27]. It was also demonstrated that a period of up to 12 weeks was needed to determine if a patient would obtain any benefit from the stimulation. The every-other-day protocol had significantly higher compliance (up to 93% during the 20-week evaluation period) compared to the daily regimen. Compliance over longer periods of use has not been assessed to date, but to maintain improvement, long-term attention must be paid to pelvic floor behavior, making the issue of compliance critical to the ultimate success of this therapy [24].

VII. ELECTROMAGNETIC STIMULATION Extracorporal magnetic innervation (ExMI) offers a new approach for pelvic floor stimulation. Therapy utilizes a special chair containing an electromagnet in the seat controlled by an external power source. The resulting resonating magnetic flux induces electrical depolarization of nerves and muscles within the magnetic field. An ongoing, prospective, multicenter study shows promising data. Patients utilized the chair for treatments lasting 20 min twice a week for 6 weeks. Results at 8 weeks showed 77% improvement overall, with 56% reporting no leakage. Pad weight was reduced from 4.5 ounces to 0.5 ounces. Pad use was reduced from 2.3 pads a day to 0.5, and leakage episodes fell from 2.3 per day to 0.8. Quality-of-life scores also improved significantly. Longer follow-up will be required to determine how long the benefits of treatment will last and whether retreatment is necessary [33].

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VIII. NEEDLE STIMULATION DEVICES Needle stimulation for the treatment of urinary incontinence is an adaptation of transcutaneous electrical nerve stimulation (TENS). A stainless steel 34-gauge needle is inserted approximately 5 cm cephalad from the medial malleolus just posterior to the margin of the tibia and then advanced to the medial edge of the fibula. Maximal functional electrical stimulation is applied using the posterior tibial nerve to inhibit the sacral micturition center. Stimulation via this route has been proposed as the optimal choice for patients with neurological lesions, for whom complete pelvic floor rehabilitation is not a clinical goal [34]. Results from a study of 90 patients using needle electrical stimulation have also been reported [35]. Patients with various voiding disturbances were treated once weekly for 20–30 min per session for 10 consecutive weeks. Successful outcomes (at least 50% improvement in symptoms documented by voiding diaries) were reported for 81% of treated patients. More recent data from a 12-week, multicenter prospective clinical trial using the above described technique and the SANS  device (percutaneous afferent nerve stimulator, Urosurge, Coralville, IA) had successful outcomes in 71% of patients. On average, patients noted a 25% reduction in mean daytime and 21% reduction in mean nighttime voiding frequencies (P ⬍ .05). Urge incontinence was reduced by an average of 35% (P ⬍ .05). Statistically significant improvements were noted in selective pain and quality-of-life indices as well. This study was designed to determine the safety and efficacy of the device, and patients with successful outcomes have subsequently moved on to a long-term treatment phase [36]. The length of the trial period to assess efficacy of treatment is currently not known. As with transvaginal/transanal stimulation, compliance is an issue of critical concern. In the case of percutaneous needle stimulation as described above, treatment necessitates outpatient office visits one to two times per week. To be a desirable long-term therapy, it must be shown that a benefit can be sustained without ongoing office-based treatment.

IX. SACRAL NERVE STIMULATION Sacral nerve stimulation therapy (SNS) acts on the neural reflexes of the bladder at the level of the S3 sacral nerves. The therapy is based on conclusions from animal experimentation and electrophysiological studies that electrical stimulation of sacral nerves can modulate neural reflexes that influence bladder, sphincter, and pelvic floor behavior [8,16,17,20,37]. The effects of SNS depend on the electrical stimulation of afferent axons in the spinal roots, which in turn modulate voiding and continence reflex pathways in the CNS [10]. Electrical stimulation of the S3 nerve ramus is optimal because it contains the sensory fibers from the genitals and perineum, afferent and efferent fibers from the anterior part of the levator ani and urethral sphincter, and autonomic fibers from the detrusor [17,38]. Neuromodulation at this level involves unmyelinated fibers, so that very low frequencies, around 10–25 Hz, can be utilized. A sacral nerve stimulation device consists of a lead implanted adjacent to a targeted sacral nerve, a pulse generator (IPG) implanted in the lower abdomen

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or upper buttocks, and an extension that connects the lead to the IPG. Electrical pulses from the IPG are transmitted through the extension and lead to the targeted sacral nerve via electrodes located at the distal end of the lead. A. Test Stimulation The first stage in the implantation of the device is test stimulation using a temporary electrode. Unlike other electrical stimulation modalities, sacral nerve stimulation provides the opportunity to test potential candidates and to select the patients most suitable for long-term therapy. During acute stimulation, a temporary electrode is used to determine the functional integrity of the sacral nerves. A successful response to subchronic test stimulation indicates that the patient’s symptoms are due to central nervous system dysfunction and are treatable with neuromodulation. Studies have reported constant reproducibility of the results of the subchronic test stimulation compared to those of the permanent lead implant [40]. B. Temporary Electrode Implantation Patients are placed in the prone position with pillows under the chest and abdomen to flatten the back and are draped in a sterile manner. Bony landmarks are used to define the level of the sacral foramina on either side. The S3 is located at the level of the greater sciatic notch, one fingerbreadth lateral to the midline spinous process. One can also look for the point at which the curve of the lower back (sacrum) lays flattest or, alternatively, one hand’s breadth cephalad from the tip of the coccyx. After infiltration of the skin and subcutaneous tissue with 1% lidocaine, the posterior surface of the bony sacrum is probed with an insulated needle. Each plane of resistance, including the subcutaneous tissue, fascia, and posterior sacral periosteum, is flooded with local anesthetic. Care should be taken not to infiltrate the foramen with lidocaine as this may make the results of stimulation unreliable if the nerve is infiltrated. The probing needle is oriented to follow the natural course of the sacral ramus through the bone table. The sacral nerve root usually lies in an inferomedial position in the foramen. When the foramen is localized, the spinal needle will drop off the posterior surface of the sacrum into the sacral foramen. (Fig. 3). Once the electrically insulated needle has been positioned, a graduated current amplitude is applied to the nerve, looking for responses from the third sacral nerve root. Because S3 is primarily responsible for levator function and has less contribution to the motor function of the lower extremity, stimulation at this level is preferable. The S3 responses are deepening of the buttocks groove (“bellows” response) and plantar flexion of the great toe only. When these responses are obtained, a test stimulation lead is threaded through the needle lumen, and the needle is withdrawn, leaving the lead in place. The portion of the test stimulation lead above the skin level is secured using a breathable membrane dressing, and position of the electrode is confirmed by anteroposterior and lateral sacral radiography. If the positioning of the temporary lead is appropriate and S3 responses are obtained, a subchronic test is performed. The proximal end of the lead is connected to an external stimulator, and a test period of 3 to 7 days follows. Patient responses to stimulation sensations aid in determining the electrical stimulus pat-

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Figure 3 The sacral foramina are probed with an insulated needle using bony landmarks as a guide. There is little risk of direct nerve impingement with correct orientation of the needle. Because of the long extradural course of S3 in the foramen, a potential theoretical risk of nerve lesions exists, although this has never been reported [41].

terns that meet their individual needs, and changes in incontinent symptoms are quantified in the voiding diary. Patients are contraindicated for implant if, during the test period, sacral nerve stimulation is not found satisfactory in alleviating target symptoms, if the patient is unable to operate the device, or if the treatment is not acceptable to the patient. The test stimulation lead is removed, and the patient is free to explore other treatment options. Patients who experience a 50% reduction of symptoms in at least one key symptom variable, such as number of incontinence episodes, pads, or severity scores, are considered candidates for long-term therapy [3]. C.

Surgical Implantation

The second stage, surgical implantation, is performed under general anesthesia. The patient receives prophylactic intravenous antibiotics and is then placed in a prone position supported by a laminectomy frame. The feet need to remain exposed so that great toe flexion may be assessed. A 6–12-cm paramedian incision is made overlying the site of likely nerve root exit (based on the site of test stimulation lead placement) to the level of the underlying lumbodorsal fascia, which is then exposed and incised longitudinally. The presence of gluteal muscle fibers

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adjacent (inferior) to the lumbodorsal fascia can be used as an anatomic landmark for the third sacral foramen. The underlying paraspinous muscle is split in the direction of its fibers, and with blunt dissection, the posterior surface of the sacrum is exposed. An insulated needle is inserted into the foramen in the direction of the course of the nerve, and proper S3 responses are again identified as in the test stimulation. If necessary, the position of the needle may be changed to obtain appropriate responses and, when determined, removed to allow insertion of a surgically implanted lead into the needle puncture site to a depth limited by a preattached fixation cuff. The distal end of the lead contains four electrical contact points, which are tested intraoperatively to confirm the response obtained during prior test stimulation procedures. The perineum and foot are observed carefully for typical motor responses, and if necessary, the electrode may be removed and reinserted to improve the response. If any uncertainty exists about the position of the lead, intraoperative fluoroscopy can be used to determine its position based on bony landmarks. Ideally, the response at the perineum should be greater than that at the great toe. When satisfactory responses are obtained, the position of the lead is maintained by securing a preattached fixation cuff to the posterior sacral periosteum. The proximal portion of the electrode is routed toward the flank or upper buttock. A subcutaneous pouch approximately 2 cm below the skin’s surface is created for the IPG in the upper buttock, lateral to the edge of the sacrum, and below the posterior superior iliac crest. The pouch is created in a position such that belts or clothing will not put pressure on the area. The IPG and the electrode are connected by an extension lead tunneled in the subcutaneous tissue between the midline and upper buttock incisions. D. Clinical Efficacy A randomized, multicenter clinical trial conducted in the United States, Canada, and Europe evaluated the safety and efficacy of SNS therapy in three different patient populations: those with urge incontinence (155 patients), urgencyfrequency (220 patients), and urinary retention (177 patients). Study inclusion criteria required that patients be refractory to conservative forms of medical treatment. After a successful test stimulation procedure, qualified patients were randomly placed in one of two treatment groups: a stimulation group (treatment) and a delay group (control). The delay group served as the control arm of the study and continued to use conservative treatments to manage symptoms for a period of 6 months. Control patients were then allowed to cross over to the treatment arm of the study on conclusion of the delay period. Voiding diaries were used to collect efficacy outcome information on accepted measures for each of the three patient populations. Health-related quality of life was also examined. Efficacy was evaluated by comparing outcomes of the treatment and control groups at 6 months. 1. Urge Incontinence Of the 155 patients diagnosed with urge incontinence who underwent test stimulation, 98 qualified for implantation; 58 patients were implanted and had data at 6 months. Results demonstrated that, compared to the control group, patients in the treatment group demonstrated clinically and statistically significant reduc-

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tions in the frequency of urge-incontinent episodes, the severity of leaking episodes, and the use of absorbent pads/diapers. At 6 months, 74% of the treatment group patients reduced the frequency of incontinent episodes by more than 50%; of these patients, 47% were completely dry. Of the treatment group patients who experienced heavy leaking at baseline, 77% had eliminated these types of leaks at 6 months postimplant. The results were sustained at 12 months and 18 months postimplantation. Analysis of SF36 results indicated statistically significant improvements in the domains of Physical Functioning, Vitality, and General Health [22]. 2. Urgency/Frequency Of the 220 patients with urgency-frequency, 80 patients qualified for surgical implantation following a successful test stimulation procedure; 47 were randomly placed in the treatment group and 33 in the control group. At 6 months postimplantation, statistically significant reductions were documented in the treatment group with respect to the three primary diary variables: number voids/day, the volume/void, and the degree of urgency ranking. Of the treatment group patients, 88% documented clinical success on these measures compared with 32% of patients in the control group. Patients in the treatment group demonstrated a significant reduction in pelvic/bladder discomfort at 6 months and also documented clinically and statistically significant changes in the ability to store urine and the ability to empty urine and a decrease in incontinent episodes per day; control group patients documented no statistically significant changes in these parameters. Sustained clinical benefit was documented at 12 months and at 18 months postimplantation. The treatment group patients demonstrated significant improvements at 6 months postimplantation in 7 of the 10 health-related quality-of-life domains measured by the SF36 (Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, and Mental Health). Implant patients also had more favorable perceptions of their general health status over time compared to control patients [20]. 3. Retention Of the 177 patients presenting with urinary retention, 68 patients qualified for surgical implantation following a successful test stimulation procedure; 37 were randomly place in the treatment group and 31 into the control group. Treated patients documented significant reductions in catheter volumes at 6 months postimplantation; 69% of the treated patients completely eliminated catheterization, with an additional 14% demonstrating 50% reduction in catheter volumes. Successful results were therefore achieved by 83% of the treated patients. Patients in the control group remained clinically unchanged, with only 9% demonstrating a clinically meaningful change in retention symptoms. There were also significant improvements in the ability to empty urine (decreased number of catheterizations per day, decreased total catheter volume per day, decreased maximum catheter volume), the ability to void urine (increased number of voids per day, increased total volume voided per day, increased average volume voided per void, increased maximum voided volume, improved urine stream force), and increased patient comfort among implanted patients. At 6 months postimplantation, 69% of

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the treatment group retention patients had eliminated catheterization completely. Evidence of improved bladder function was further demonstrated by the statistically significant reduction in urinary tract infections for the treatment group at 12 months postimplantation. Sustained clinical benefit was documented at 12 months and at 18 months postimplantation [43]. At the 6-month follow-up analysis, implant patients demonstrated significant improvements in Bodily Pain as measured by the SF36 and had more favorable perceptions of their general health transition compared to control patients [22]. Another recently published prospective multicenter study with longer follow-up reported 59% of 41 urinary urge-incontinent patients showed greater than 50% reduction in leaking episodes per day, with 46% of patients being completely dry at 3 years. After 2 years, 56% of the urgency-frequency patients showed greater than 50% reduction in voids per day. After 1.5 years, 70% of 42 retention patients showed a greater than 50% reduction in catheter volume per catheterization [44]. The efficacy of SNS in the treatment of voiding dysfunction has been demonstrated and was reported in earlier literature [15,37]. Published results of clinical trials using the InterStim device suggest that SNS is a safe and effective treatment alternative for a variety of urinary incontinence problems [10,17,20,40,45]. The Food and Drug Administration (FDA) approved the use of the InterStim continence control system for the indication of refractory urge incontinence in 1997 and for indications of urgency-frequency and urinary retention in 1998. The device has been available for these indications in Canada, Europe, and Australia since 1994. Adverse events related to the therapy, the device, or implant procedure have been comprehensively recorded in the multicenter trial and include pain at the lead implant site (21%) or at the IPG site (17%); these events may require surgical revision, but are resolvable. The probability of surgical revision, computed from survival analysis of clinical trial data, was 29% within the first 6 months and 12% in the second 6 months, suggesting that the potential for surgical revision declines over time. It is likely that further refinements in technique, such as positioning of the IPG in the upper buttocks instead of the lower abdomen, monitoring of sacral evoked-response potentials during lead placement, and potentially doing all lead placements in a staged fashion (with the test stimulation being the first stage) will reduce the need for surgical revision in the future. Other adverse events associated with use include infection/skin irritation (7%), technical problems (7%), and transient increases in electrical sensation (6%). Changes in bowel function (5%), numbness (1.3%), and suspected nerve injury (⬍0.5%) may result during chronic treatment [20]. SNS therapy has not been associated with deterioration of bladder function with continued use [22]. The incidence of adverse events using SNS is significant, but must be considered against the nature of the underlying complaint. Patients who suffer the debility of chronic, intractable voiding dysfunction are otherwise subjected to ongoing symptoms, drug side effects, and/or the acute and chronic risks of more major, irreversible surgical interventions, such as augmentation cystoplasty. Patients undergoing test stimulation are able to make an informed decision about the potential benefit of surgical implantation. Once implanted, there is high likelihood of significant and prolonged relief of the underlying voiding complaint. Even if an

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adverse event occurs, almost all are resolvable to the point at which the benefit of the therapy is reestablished. If not, SNS is completely reversible. On cessation of therapy or removal of the implanted devices, the patients are free to use alternate therapies or proceed to surgical intervention if necessary. X.

CONCLUSIONS

The goal of any treatment for incontinence is restoration of normal bladder function, prevention of secondary health consequences, and improvement of quality of life of individual patients. The various electrical stimulation techniques offer alternatives to more conservative therapies and surgery. While it is reasonable to attempt other conservative treatments first, when these options fail or are otherwise not indicated, electrical stimulation should be considered before offering surgical treatment. Therapies involving electrical stimulation are based on the concept that urge incontinence due to detrusor instability is not an end organ problem, but that the condition represents a central nervous system dysfunction. The problem, in turn, may be manifest as symptoms of urge incontinence, urgency-frequency syndromes, urinary retention, or bowel dysfunction [46]. Stimulation therapies are able to modulate abnormal reflexes among the bladder, pelvic floor, and external sphincter. Unlike other electrical stimulation techniques with more limited applications, sacral nerve stimulation holds great promise for a large number of patients who suffer a spectrum of lower urinary tract dysfunction. Implantation of a sacral nerve stimulation device in properly selected patients is likely to provide significant and sustained relief from debilitating urologic symptoms, is totally reversible, and does not preclude the use of other standard treatments. REFERENCES 1. Fantl JA, Newman DK, Colling J, et al. Urinary Incontinence in Adults: Acute and Chronic Management. Clinical Practice Guideline No. 2. 1996 Update. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, March 1996. AHCPR Publication 96–0682. 2. Fall M. Electrical pelvic floor stimulation for the control of detrusor instability. Neurourol Urodyn 1985; 4:329–335. 3. Fall M, Lindstrom S. Electrical stimulation: a physiologic approach to the treatment of urinary incontinence. Urol Clin N Am 1991; 18(2):393–407. 4. Wein AJ, Barret DM. Voiding Function and Dysfunction: A Logical and Practical Approach. Chicago: Yearbook Medical Publishers, 1988. 5. Schmidt RA, Senn E, Tanagho EA. Functional evaluation of sacral nerve root integrity: report of a technique. Urol 1990; 35(5):388–392. 6. Schmidt RA. Applications of neurostimulation. Neurourol Urodyn 1988; 7:585. 7. Tanagho EA, Schmidt RA. Electrical stimulation in the management of the neurogenic bladder. J Urol 1988; 140:1331. 8. Thon W, Baskin L, Jonas U, et al. Neuromodulation of voiding dysfunction and pelvic pain. World J Urol 1991; 9:138–141. 9. Mersdorf A, Schmidt RA, Tanagho EA. Topographic-anatomical basis of sacral neurostimulation: neuroanatomical variations. J Urol 1993; 149:345–349. 10. Chancellor MB, deGroat WC. Hypotheses on how sacral nerve stimulation works for the treatment of detrusor overactivity and urinary retention. Submitted.

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11. Wang Y, Hassouna MM. Neuromodulation reduces c-fos gene expression in spinalized rats: a double-blind randomized study. J Urol 2000; 163(6):1966–1970. 12. Shaker H, Wang Y, Loung D, Balbaa L, Fehlings MG, Hassouna MM. Role of C-afferent fibres in the mechanism of action of sacral nerve root neuromodulation in chronic spinal cord injury. BJU Int 2000; 85(7):905–910. 13. Blok BFM, van Maarseveen JTPW, Holstege G. Electrical stimulation of the sacral dorsal gray commissure evokes relaxation of the external urethral sphincter in the cat. Neurosci Lett 1998; 249:68–70. 14. Schultz-Lampel D; Jiang C, Lindstrom S, Thuroff, JW. Experimental results on mechanisms of action of electrical neuromodulation in chronic urinary retention. World J Urol 1998; 16:301–304. 15. Vapnek JM, Schmidt RA. Restoration of voiding in chronic urinary retention using the neuroprosthesis. World J Urol 1991; 9:142–144. 16. Siegel SW. Management of voiding dysfunction with an implantable neuroprosthesis. Urol Clin N Am. 1992; 19(1):163–170. 17. Diijkema H, Weil EHJ, Mijs P, Janknegt RA. Neuromodulation of sacral nerves for incontinence and voiding dysfunctions. Eur Urol. 1993; 24:72–77. 18. Hassouna M. Neural stimulation for chronic voiding dysfunctions. J Urol 1994; 153: 2078–2080. 19. Koldewijn EL, et al. Predictors of success with neuromodulation in lower urinary tract dysfunction: results of trial stimulation in 100 patients. J Urol 1994; 152:2071–2075. 20. Bosch J, Groen J. Sacral (S3) segmental nerve stimulation as a treatment for urge incontinence in patients with detrusor instability: results of chronic electrical stimulation using an implantable neural prosthesis. J Urol. 1995; 154:504–507. 21. Bosch J, Groen J. Treatment of refractory urge urinary incontinence with sacral spinal nerve stimulation in multiple sclerosis patients. Lancet 1996; 348:717–719. 22. Medtronic data on file; MDT-103. 23. Empi. The Fundamentals of Pelvic Floor Stimulation: Innovative Treatments for Urinary Incontinence. St. Paul, MN: Empi, 1994. 24. Siegel SW, Richardson DA, Miller KL, et al. Pelvic floor electrical stimulation for the treatment of urge and mixed urinary incontinence in women. Urol 1997; 50(6):934– 940. 25. Bent AE, Sand PK, Ostegard DR, Brubaker L. Transvaginal electrical stimulation in the treatment of genuine stress incontinence and detrusor instability. Int Urogynecol J 1993; 4:9–13. 26. Sand PK, Richardson DA, Staskin DR, et al. Pelvic floor electrical stimulation in the treatment of genuine stress incontinence: a multicenter, placebo-controlled trial. Am J Obstet Gynecol 1995; 183:72–79. 27. Richardson DA, Miller KL, Siegel SW, et al. Pelvic floor electrical stimulation: a comparison of daily and every-other-day therapy for genuine stress incontinence. Urol 1996; 48(1):110–118. 28. Elgamasy AN, Lewis V, Hassouna ME, Ghoniem GM. Effect of transvaginal stimulation in the treatment of detrusor instability. Urol Nurs 1996; 16(4):127–130. 29. Brubaker L, Benson JT, Bent A, et al. Transvaginal electrical stimulation for female urinary incontinence. Am J Obstet Gynecol 1997; 177:536–540. 30. Luber KM, Wolde-Tsadik G. Efficacy of functional electrical stimulation in treating genuine stress incontinence: a randomized clinical trial. Neurourol Urodyn 1997; 16: 543–551. 31. Kulseng-Hanssen S, Kristoffersen M, Larsen E. Evaluation of the subjective and objective effect of maximal electrical stimulation in patients complaining of urge incontinence. Acta Obstet Gynecol Scand 1998; 168(suppl):12–15. 32. Davila GW, Bernier F. Multimodality pelvic physiotherapy treatment of urinary incontinence in adult women. Int Urogynecol J 1995; 6:187–194.

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33. Galloway N, El-Galley R, Appell R, Russell H, Carlan S. Multicenter trial: extracorporeal magnetic innervation (ExMI) for the treatment of stress urinary incontinence. Presented at June 1998 meeting of the International Continence Society. Abstract. 34. McGuire EJ, Shi-Chun Z, Horwinski ER, et al. Treatment of motor and sensory detrusor instability by electrical stimulation. J Urol 1983; 129:78–79. 35. Stoller ML. Afferent nerve stimulation for pelvic floor dysfunction [abstract F2–6]. J Endourol 1998; 12(1):S108. 36. Govier F, Nitti V, Kreder K, Rosenblatt P. Percutaneous afferent neuromodulation: a novel treatment for the refractory overactive bladder: results of a multicenter study. Submitted. 37. Elabbady AA, Hassouna MM, Elhilali MM. Neural stimulation for chronic voiding dysfunctions. J Urol 1994; 152:2076–2080. 38. Appell RA. Electrical stimulation for the treatment of urinary incontinence. Urol 1998; 51(2A suppl):24–26. 39. Goldberg RP, Sand PK. Electromagnetic pelvic floor stimulation: applications for the gynecologist. Obstet Gynecol Surv 2000; 55(11):715–720. 40. Shaker HS, Hassouna M. Sacral nerve root neuromodulation: an effective treatment for refractory urge incontinence. J Urol 1998; 159:1516–1519. 41. Liguoro D, Viejo-Fuertes D, Midy D, Guerin J. The posterior sacral foramina: an anatomical study. J Anat 1999; 195 (pt 2):301–304. 42. Weil EH, Ruiz-Cerda JL, van den Bogaard AE, van Kerrebroeck PE. Novel test lead designs for sacral nerve stimulation: improved passive fixation in an animal model. J Urol 2000; 164(2):551–555. 43. Jonas U, Fowler CJ, Chancellor MB, et al. Efficacy of sacral nerve stimulation for urinary retention: results 18 months after implantation. J Urol 2001; 165(1):15–19. 44. Siegel SW, Catanzaro F, Dijkema HE, et al. Long-term results of a multicenter study on sacral nerve stimulation for treatment of urinary urge incontinence, urgency-frequency, and retention. Urology 2000; 56(6 suppl 1):87–91. 45. Shaker HS, Hassouna M. Sacral root neuromodulation in idiopathic nonobstructive chronic urinary retention. J Urol 1998; 159:1476–1478. 46. Stadelmaier MKE, Hohenfellner M, Gall FP. Electrical stimulation of sacral spinal nerves for treatment of faecal incontinence. Lancet 1995; 346(8983):1124–1127.

15 Musculoskeletal Evaluation for Pelvic Pain HEIDI PRATHER Washington University School of Medicine St. Louis, Missouri, U.S.A.

I.

INTRODUCTION

Evaluating pelvic pain can be challenging for both the patient and the health care provider. The general term pelvic injury has a wide variety of meanings. First, the interaction between patient and provider is very dependent on the patient’s ability to report the history. A thorough history reveals if there may be a visceral, neurogenic, mechanical, or hormonal component contributing to pain. Second, the interaction is dependent on the health care provider’s ability to interpret the information. This is often dependent on the professional’s specialty background. In addition to primary care physicians, several medical specialists, including obstetricians/gynecologists, orthopedic surgeons, urologists, physiatrists, and colorectal surgeons, evaluate and treat women with pelvic pain. If the problem lies outside the parameters of the specialty and additional referrals are not made, appropriate evaluation and treatment may not be completed. This chapter focuses on the musculoskeletal perspective of the evaluation of pelvic pain. The general musculoskeletal practitioner will often focus attention on bony, ligamentous, joint, and muscle injury. Considerable overlap exists regarding referral of pain to the pelvic region from the spine, hip, and lower extremity. Likewise, the pelvis also holds important visceral structures that are gender specific and are supported by the muscular complex comprising the pelvic floor. Trauma or overuse injuries to remote sites can cause adaptive changes in the pelvic floor, which can produce pain and bowel and bladder dysfunction. The female pelvis acquires changes with aging. These occur as a result of hormonal changes, pregnancy, childbirth, and menopause. To provide comprehensive management of 241

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pelvic and hip problems in women, the health care provider must take into account these changes and adapt the therapeutic approach accordingly.

II. ANATOMY AND FUNCTION An understanding of the anatomy and function of the spine, hip, and pelvis is essential to evaluate and treat a woman presenting with pelvic pain. The pelvis serves as the central base through which forces are transmitted both directly and indirectly. The joints of the pelvis are inherently stable joints. Repetitive loads or high-injury loads can lead to ligamentous, bony, and muscle overuse syndromes. Adaptive patterns may occur in the pelvis as a result of spine or lower extremity injuries. Asymmetrical force transmission can then lead to dysfunction at the pelvis. The natural degenerative changes that take place must also be considered in the aging female. Women have further physiological changes during their life cycle that put them at risk for injury. These changes should be considered during the discussion of mechanics. Further awareness of the physiological changes that occur during the female life cycle is important and should be incorporated in the evaluation. The bony pelvis includes three bones that articulate at three joints. The ilium articulates with the sacrum at the sacroiliac joint. The lumbar spine articulates with the sacrum anteriorly via the lumbar disc and posteriorly via the L5-S1 facets. The lower extremity extends from the pelvis, including the femur articulating with the acetabulum at the hip joint. In general, the shape of the bony pelvis of the female is broader than that of the male. The combination of greater femoral neck anteversion and shorter lower extremity limb length leads to a lower center of gravity for women compared to men [1]. This alignment suggests different adaptive or firing patterns in women versus men, but not necessarily increased risk for injury [2]. For both genders, the pelvis is inherently a stable ring. Proper functioning of the joints surrounding the pelvis is key for cohesive mechanics at the pelvis. The sacroiliac joint (SIJ) meets the definition of a synovial joint, synarthrosis, and amphiarthrosis. The joint is “L” or “C” shape with two lever arms that meet at the second sacral level, where it interlocks (Fig. 1). The sacral side is lined by thick hyaline cartilage, and the ilial side is lined with fibrocartilage. There are intra- and interindividual differences in the shape of the joint. The anterior fibrous capsule is well formed, but the posterior capsule is thinner and may have multiple plications. Accessory articulations may occur in up to 35% of the population. These are thought to occur secondary to degenerative changes over time [3]. Ligaments that affect the stability of the joint include the intraarticular, periarticular, and accessory ligaments. The interosseous ligaments are the strongest ligaments that support the joint and resist motion between the sacrum and ilium. The thin anterior ligaments pass between the psoas major and the obturator internus and provide a sling for the ilium and sacrum. The posterior ligament has three layers, from deep to superficial. The most superficial layer becomes continuous with the sacrotuberous and sacrospinous ligaments. As an accessory ligament, the sacrotuberous ligament influences the joint through load and tension forces from the lower extremity and pelvis (Fig. 2). Laxity or tautness in this ligament influences

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Figure 1 The lateral aspect of the sacrum. motion at both the sacrum and ilium. The iliolumbar ligament also affects the joint by preventing anterior translation and rotation of L5. Vleeming et al. best described the subtle motion changes that occur at the SIJ as a “self-locking mechanism” [4,5]. They described that stability of the interlocking mechanism is related to form and force closure. Form closure refers to joint surfaces that congruently fit together and require no extra forces to maintain

Figure 2 The ligaments of the pelvic girdle viewed from the anterior aspect.

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stability. Force closure refers to a joint that requires outside force, provided by muscles and ligaments, to withstand load. If opposing forces do not have the appropriate form and/or force closure, the joint is less stable and more subjective to shear force. In side-to-side comparisons, the shape of the SIJ can vary in individuals. As a result, provision of stability by form and force closure may differ as well. Asymmetrical force transmissions can lead to breakdown or secondary adaptive patterns that facilitate dysfunction or injury. The form closure in women is less congruent because of a wider pelvis and decreased joint space surface area compared to men. Force closure in women is susceptible to hormonal changes that occur during pregnancy. Increased joint laxity occurs related to elevated levels of relaxin and estrogen. These hormones return to baseline in the weeks and months postpartum, but less predictably so in women who breastfeed. Muscle groups that operate at a biomechanical disadvantage during pregnancy and in the postpartum period because of increasing abdominal girth, changes in load transfer, and deconditioning may also alter force closure. The thoracolumbar fascia is also important in load transfer from the lower extremity through the pelvis, lumbar spine, and abdominals. The superficial lamina of the thoracolumbar fascia facilitates transmission of forces from the lower extremity to the contralateral latissimus dorsi. These forces cross at the level of the pelvis. This transitional region may be a potential area of breakdown [6] (Fig. 3). Muscles at the hip, pelvis, and lumbar spine provide indirect motion at the SIJ. Abdominal muscles affect motion at the ilium, pubis, and lumbar spine. The psoas connects the thoracolumbar fascia with the lower extremity and may restrict lumbopelvic rhythm. The hamstring and gluteals directly affect the position of the ilium. They contract to posteriorly rotate the ilium. An inhibited or weak gluteal muscle can facilitate anterior iliac rotation. Hamstrings that fire in a shortened position facilitate a posteriorly rotated ilium. Likewise, inhibited hamstrings promote an anteriorly rotated ilium. An anteriorly rotated ilium facilitates contraction of the psoas in a shortened position. This furthers the anterior rotation of the ilium while increasing lumbar lordosis. The anteriorly rotated ilium also forces the abdominals to fire in an inefficient lengthened position. Muscles that function in a lengthened position are not able to provide maximal force absorption. Abdominals that fire in a lengthened position do not efficiently absorb forces that affect stability at the lumbar spine and pubic symphysis. Often forgotten pain generators are the muscles of the pelvic diaphragm. A clear understanding of the anatomy, physiology, and neurological supply of the entire pelvic cavity is essential for appropriate assessment and examination. These are discussed below. Specific muscles in the pelvic diaphragm to focus on during the examination are listed in Table 1. The levator ani group is the deepest layer of striated muscle. The group shares borders laterally by the tendonous arch of the obturator internus muscle fascia and the obturator internus and piriformis muscles. The levator ani group is divided into anterior and posterior portions. In the anterior portion, the pubococcygeus works to support the pelvic viscera and pulls the rectum toward the pubis. The pubovaginalis works as a sphincter for the vagina and urethra. The

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Figure 3 The posterior oblique system of the outer unit includes the latissimus dorsi, gluteus maximus and the intervening thoracodorsal fascia. (Redrawn from Vleeming et al 1995a.)

puborectalis surrounds the rectum and works to elevate and constrict the canal. The iliococcygeus comprises the posterior portion of the levator ani group. It functions to support the pelvic viscera and pulls the rectum and vagina anteriorly toward the pubis. As a group, the levator ani muscles supply constant resting tone to support the floor and provide a shelf for the viscera. This is a separate function from when it is in a contracted state. During increases in abdominal

Table 1 Pelvic Diaphragm Muscles Levator ani group Anterior portion Pubococcygeus Pubovaginalis Puborectalis Posterior portion Iliococcygeus Coccygeus Obturator internus Piriformis

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pressure, the levator ani group contracts to increase pelvic floor closure. The group also assists the anterior abdominal muscles in compression of the abdominal and pelvic contents during forced expiration, coughing, vomiting, and urination. Several other muscles of the pelvic diaphragm function as support structures to the floor, but also have important roles regarding function and stability of the joints of the pelvis. The coccygeus muscle functions to flex the coccyx, support the pelvic viscera, and stabilize the sacroiliac joint. The obturator internus functions primarily as a hip external rotator, but originates within the pelvic floor. The piriformis also arises from the pelvic floor and serves to pad the posterior wall of the pelvis where the sacral and coccygeal nerve plexus lie. It facilitates different motions at the hip based on the position of the hip. In hip extension, the piriformis is an external rotator of the hip. In 60° of hip flexion, the piriformis is an abductor. With the hip positioned at 90° of flexion, the piriformis internally rotates the hip [7]. Altered lower extremity and pelvic mechanics can then alter pelvic floor function. In women, this may lead to secondary pain and potential incontinence. In particular, the obturator internus may be susceptible to overload (Fig. 4). This muscle is a primary hip external rotator and secondary abductor. If the gluteus medius is inhibited, the obturator internus is recruited as a hip abductor. It may not be strong enough to respond to the load demand or repetition. As a result, an overuse syndrome may develop. Pain in the groin and pelvic floor may be the primary symptom. Other pelvic floor muscles, such as the levator ani group, must transfer load forces directly and indirectly across the SIJ and pubic symphysis. Again, breakdown in symmetric load transfer can lead to pain syndromes. Muscle pain may result from inadequate nerve supply due to nerve-to-nerve injury or dysfunction. The innervation of the pelvic floor musculature is listed in Table 2. There is a noticeable overlap of innervation within the joints, exterior muscles of the hip, pelvis, and lumbar spine (Table 3). Recognizing the common neurogenic origin of these somatic structures is important as pain syndromes can present in nonclassical forms. The sacroiliac joint innervation is also important to be familiar with as referral patterns of pain can vary greatly. The innervation of the sacral iliac joint is from multiple root levels of the lumbosacral pelvis. The posterior joint receives innervation from L3-S3, while the anterior joint receives innervation from L2-S2. The primary innervation is thought to be from the S1 root level [8,9]. Because of the various levels of innervation, SIJ pain may present with a variety of pain locations. Similar to its primary level of innervation, SIJ pain often presents with S1 distribution symptoms in the form of pain and/or numbness. The biomechanics regarding the SIJ are complex. Most research has looked at one or two components of force and movement. Motion at the SIJ occurs indirectly. Body weight and postural changes may create or inhibit motion at the SIJ. Muscle groups surrounding the joint also cause indirect motion. These include gluteals, hamstrings, hip external rotators, psoas, abdominals, latissimus dorsi, quadratus lumborum, and erector spinae. Myofascial changes associated with these muscle groups will also alter mechanics. The SIJ forms the base of support for the spine. The joint receives and transmits forces from the trunk and lower and upper extremities. Forces absorbed through the SIJ allow changes in body

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Figure 4 Nerves (white) and arteries (black) of the buttock.

Table 2 Pelvic Diaphragm Innervation Muscle Levator ani Coccygeus Obturator internus Piriformis

Peripheral nerve Inferior rectal/pudendal Ventral rami Obturator internus nerve Ventral rami

Root level S4 S4, S5 L5, S1 S1, S2

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Table 3 Innervation of Hip, Pelvis, and Trunk Muscles Muscle Abdominals Gluteus medius Gluteus maximus Superior gemellus Inferior gemellus Obturator externus Quadratus femoris Semimembranosus Semitendinosus Biceps femoris Tensor fascia lata Quadratus lumborum Iliacus Psoas major Psoas minor Erector spinae Multifidus

Peripheral nerve

Roots

Ventral rami Superior gluteal nerve Inferior gluteal nerve Nerve to obturator internus Nerve to quadratus femoris Obturator Nerve to quadratus femoris Tibial Tibial Tibial, common peroneal Superior gluteal Ventral rami Femoral Ventral rami Ventral rami Segmental dorsal rami Segmental dorsal rami

T12, L1 L5, S1 L5, S1, S2 L5, S1 L5, S1 L3, L4 L5, S1 L5, S1, S2 L5, S1, S2 L5, S1, S2 L4, L5 T12-L4 L2, L3, L4 L1, L2, L3 L1

weight transmission to occur while providing stability. SIJ motion is affected by motion at the spine, ilium, pubic symphysis, and hip. Studies have shown various ranges of motion, but most agree that approximately 4° of rotation and 1.6 mm of translation occur [10]. The amount of joint motion decreases with age. Women develop degenerative changes that restrict motion at age 50, while men develop them around age 40. It is not clear that change in motion at one joint is the source of pain at that joint. Gender differences in flexibility and range of motion that may affect performance have been well documented. Reports indicate that women have greater range of motion and flexibility [11]. This further suggests that relative imbalances in muscle length and strength may place the female athlete at risk for SIJ dysfunction. Acquired hyper- or hypomobility results in altered load transmission, which may lead to muscle and other joint dysfunction secondary to adaptations. Women develop relative changes in motion based on hormonal fluctuations as well. During pregnancy, estrogen and relaxin play a key role in promoting increased ligamentous laxity. If the secondary stabilizers (musculature of the hip, spine, and pelvis) do not provide the stability needed, the joint may enter a relatively hypermobile state. Estrogen level changes continue in the postpartum period. This is also the time when the supporting musculature are developing new adaptive patterns as a result of the pregnancy and delivery. Again, these circumstances may place the female athlete at greater risk for injury. With aging, degenerative changes direct the joint into a relative hypomobile state. Often there is an attempt to regain motion lost at the SIJ at another joint. Examples include the hip, lumbosacral segments, and pubic symphysis. So, while changes in motion at the SIJ may not cause direct injury to the joint, they place peripheral joints at risk for altered

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adaptive patterns. Changes in adaptive patterns and mechanics may make these joints more susceptible to injury. III. BONY INJURIES Weight-bearing exercise is protective because it helps build bone mass. However, excessive activity increases the risk of stress fracture. Determining what is excessive is specific to the individual’s circumstances. Athletes or individuals participating in endurance-type exercise or sports are at increased risk for these fractures. Bony injuries involving the hip and pelvis may occur because of overuse and/or trauma. Stress fractures may occur at various sites, including the ilium, lesser trochanter, femoral neck, pubis, and sacrum. Early diagnosis is important to prevent further injury or complete fracture. Recurrent stress fractures may be a sign of an underlying systemic problem. The health care provider needs to investigate reasons other than exercise or sports participation for repeated injury. The adolescent or young adult athlete should be questioned regarding other symptoms of the female triad. For the older female athlete or exerciser, osteopenia or osteoporosis should be ruled out. Early intervention will decrease the risk of repeated injury. Other bony injuries to the hip and pelvis are often sustained as a result of high impact or trauma. These include avulsion injuries, acetabular labral tears, and complete fractures. Avulsion injuries occur at the attachment of a tendon or ligament to bone. They occur as a result of a strong and rapid muscle contraction and are seen most commonly in adolescents participating in sports. The most common sites for avulsion injuries include the anterior superior and inferior iliac spines, ischial tuberosity, and iliac crest. Clinically, avulsion injuries present with tenderness at the site of muscle origin and demonstrate weakness of the isolated muscle. Apophysitis has a similar clinical presentation; this is an inflammation at the tendon-periosteal junction, but with no avulsion of bone. In contrast, apophysitis results from an overuse injury. Radiographs can differentiate the two injuries because a fracture will be identified in avulsion injuries. Apophysitis may be noted on imaging (such as a bone scan or magnetic resonance imaging [MRI]) edema at the site of injury. Acetabular labrum tears often result from trauma or repetitive twisting injury. They can also occur from irregular wear-and-tear patterns associated with mild hip dysplasia, found more commonly in women than men. Presenting symptoms include a catching and giveaway sensation in the anterior hip and groin. Pain may occur with pivoting or transitional movements as when arising from a chair. Clicking may be noted when the hip is passively extended, internally rotated, and adducted [12]. Once x-rays have been completed and show no fracture, an MRI arthrogram has high sensitivity and specificity in identifying labral tears. Laparoscopic hip procedures now provide a minimally invasive definitive treatment in cases that have failed conservative management. Avascular necrosis of the femoral head may occur as the result of repetitive trauma and may present as groin or pelvic pain with a change in gait pattern. Individuals at increased risk may have a history of alcohol use/abuse and corticosteroid use. It most commonly occurs in men between 30 and 70 years of age.

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Again, early diagnosis is important in improving long-term outcome. X-rays may not show the early changes of avascular necrosis, and an MRI should be obtained in suspected cases. Osteoarthritis is the most common hip disorder in the general population. The etiology is multifactorial, including familial factors, obesity, and history of hip injury or disease. Men and women are equally prone to hip pathology. Recent studies outlined concern for the development of an increased risk of hip osteoarthritis in women who participate in sports and exercise. Lane and colleagues compared self-reported activity levels and hip x-rays and pain in elderly women [13]. Women who exercised more than four times per week had a marginally increased risk of hip osteoarthritis. Vingard et al. compared self-reported sports activities in women who underwent total hip replacement for osteoarthritis to control without hip problems [14]. Those with high sports exposure were 2.3 times more likely to develop hip osteoarthritis leading to total hip replacement. Both of these studies were retrospective and relied on the subject to recall activity level over a lifetime. Caution should be used in counseling women to abstain from physical activity because of the risk of osteoarthritis. Though activity may increase the risk of osteoarthritis, better skill training and prehabilitation for women in the future may show a plateau in the incidence of activity-associated osteoarthritis. Osteitis pubis is a syndrome that involves bony change that often occurs as a result of an overuse injury. Pubic symphysitis and recurrent groin injuries may in fact be precursors to the degenerative changes described as osteitis pubis. Risks for osteitis pubis include activities that require repetitive kicking, pivoting, and running. Also, nonathletic risks include previous bladder, prostate, or colon surgery or pelvic floor trauma. Symptoms at presentation include groin, anterior hip, and lower abdominal pain. Often, a recurrent “groin strain” has been diagnosed. Antalgic gait, pain on palpation of the pubic symphysis that increases with resisted hip motion, is often noted on physical examination. X-rays may show sclerotic changes, but oftentimes are normal. A bone scan may show asymmetric uptake at the pubic symphysis. MRI is helpful in delineating stress fracture from stress reaction. Arriving at the diagnosis of osteitis pubis takes coordination of history and physical examination because adjunct testing is limited. Addressing the pain complaints prior to x-ray changes is essential. IV. SOFT-TISSUE, NERVE, AND MUSCLE INJURY Tendonitis, muscle strains, and muscle imbalances are common types of injuries that present as pelvic pain. Muscle and tendon dysfunctions can lead to friction and, at specific sites, cause bursitis. There are several theories regarding the concept of muscle imbalance. These are listed in Table 4 [15]. Therefore, trauma or injury is not the only way muscle imbalances develop. Jull and Janda have studied muscle imbalance and adaptations in children and adolescents. They found a 21% incidence of short muscles in 115 school-aged children. Follow-ups at ages 12 and 16 years showed that muscle tightness increased and then plateaued. These muscle imbalances did not correct without intervention [16]. Muscles involving the hip and pelvis that are prone to tightness include the iliopsoas, rectus femoris, tensor fascia lata, short adductors, hamstrings, quadratus lumborum, and piriformis. Strains and muscle tears often occur in muscles that are prone to tightness.

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Table 4 Theoretical Causes of Muscle Imbalances Postural adaptation to gravity Neuroreflexive response due to joint blockage Central nervous system malregulation (impaired programming) Response to painful stimuli Response to physical demands Lack of variety of movement patterns Psychological influences Histochemical differences Source: Ref. 15.

Tendonitis often occurs in weak, inhibited muscle groups. Examples at the hip and pelvis include the gluteus medius, gluteus maximus, abdominals, and quadriceps [7]. Identifying muscles functioning in a shortened position or those that are inhibited is key to devising a treatment program. Bursitis can also accompany a primary muscle or tendon dysfunction. A bursa becomes fluid filled as a result of inflammation that develops because of friction. This friction occurs because a tendon is not able to glide efficiently across a region. This inefficiency may be because of bony protrusions or primary muscle or tendon injury. Common sites for bursitis involving the hip and pelvis include iliopsoas at the ischial pectineal line, greater trochanter of the hip, ischiogluteal area, and origin of the obturator internus. Determining the primary mechanism of injury will facilitate a treatment program and prevent reinjury. Several specific muscle imbalance syndromes occur at the hip and pelvis. They may present with a wide range of symptoms, including pain in the buttocks, groin, lumbar spine, and knee. Piriformis syndrome may present with a variety of complaints. These include back and/or buttocks pain and lower extremity pain and/or numbness. The true syndrome by definition includes electrophysiological changes along the distribution of the sciatic nerve as a result of compression by the piriformis. The sciatic nerve travels through the sciatic notch and passes anterior to the piriformis 85% of the time. Variations of this relationship exist. In 10% of the population, the sciatic nerve divides before passing through the gluteal region. The common peroneal portion passes through the piriformis, and the tibial portion passes anterior to the piriformis. In 2–3% of cadavers, the peroneal portion loops superior and posterior to the piriformis, and the tibial portion travels anterior to the muscle. Another variation found in less than 1% of the cadavers is an undivided nerve that passes through the piriformis. Regardless of its position, the sciatic nerve is vulnerable to compression or irritation at the site of the piriformis. Because the muscle performs different motions in different hip positions, the examiner must include different positions to fully exam the muscle (Fig. 5). Again, an imbalance in muscle length and strength may create a dysfunction that results in pain. The author postulates that there are a number of patients that present with a symptom complex related to piriformis dysfunction and pain without electrophysiological changes on electromyography. This may be a result of inherent muscle weakness or because neurogenic compression is only intermittent. Yet, piriformis irritability and dysfunction may still occur even though elec-

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Figure 5 It is important to test strength and flexibility of the piriformis muscle with the hip positioned in different angles. (A) Hip flexed at 90° with examiner testing flexibility by externally rotating hip. (B) Examiner testing flexibility with the hip flexed at less than 90°.

trodiagnostic testing does not fulfill the criteria for piriformis syndrome. Even if this does not meet the definition of piriformis syndrome, the area needs to be treated to prevent further regional breakdown in mechanics. A painful piriformis by history and on physical examination may be part of a symptom complex of another regional diagnosis. Examples include L5-S4 radiculopathy, intrinsic hip pathology, and sacroiliac joint (SIJ) dysfunction. These need to be further investigated so as not to treat the problem incompletely. Activities that require singleleg stance or shifting from one extremity to the other may place the individual at risk for pain associated with the piriformis muscle. Clinically, the woman may present with low back, buttocks, and lower extremity pain and/or numbness. Lower extremity symptoms may not pass far beyond the gluteal fold or may involve the foot. On examination, pain with palpation of the muscle may be noted and further exacerbated with stretch or with

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resisted activation. The examiner must be careful to stretch and activate the muscle according to the function it performs in different hip positions. Specific positioning for testing relative muscle strength and length is essential to formulate a specific rehabilitation plan. Positioning may also bring out symptoms other than pain such as numbness or tingling. Further internal palpation via rectal examination can help clarify the clinical diagnosis in questionable cases. Muscle stretch reflexes may be reduced, as may sensory deficits in the tibial and/or peroneal distribution. Snapping hip syndrome is another common symptom complex that presents with lateral hip or anterior groin pain. A snapping or clicking sensation during activity may be associated with pain. The cause of the click is site specific. The most common etiology is the hip suction phenomenon. Other intra-articular causes that should be carefully ruled out include subluxation, acetabular labral tear, loose body, and osteochondromatosis. Other common tendon causes include the iliopsoas snapping over the iliopectineal eminence and the iliotibial band (ITB) moving over the greater trochanter. Pubic symphysis instability may present with clicking in the groin region as well. The instability may be related to trauma such as that experienced with childbirth or generalized ligamentous laxity. Determining the site of the clicking is important, but can be difficult. The examiner should palpate the area of the snapping during active and passive hip range of motion to distinguish the structure [18]. Again, regional muscle imbalance should be considered once the source of snapping has been determined. The ITB may tighten because the muscle is serving as a hip abductor as the result of an inhibited gluteus medius. The health care provider should not expect the snapping hip syndrome to remain resolved solely with ITB stretching. Gluteus medius strengthening in the appropriate hip position will allow the ITB to remain in its new lengthened position. Neurogenic pain should be considered in the differential for pelvic and groin pain. Meralgia paresthetica is one common nerve entrapment at the pelvis. The lateral femoral cutaneous nerve is entrapped in the pelvis as it crosses the groin medial to the anterosuperior iliac spine. Fibrous tunnels may exist that the nerve or branches may cross through. Overweight and pregnant exercisers are at increased risk for developing an entrapment. Nerve conduction studies are helpful in confirming the diagnosis. Reducing equipment or clothing restrictions at the hip and groin can be helpful in reducing symptoms. Other neurogenic etiologies for pain at the groin and pelvis include high lumbar radiculopathy, entrapment of the genital branch of the genitalfemoral cutaneous nerve, obturator nerve entrapment at the pelvis, and pudendal nerve injury should be excluded. Previous trauma or spine or pelvic surgery may place the individual at increased risk for these problems. Pudendal nerve injury in particular can lead to a number of pelvic floor dysfunctions, described separately below. V.

SACROILIAC JOINT DYSFUNCTION

The sacroiliac joint (SIJ) is a controversial instigator of pain and dysfunction. Reasons for controversy are multifactorial. The joint is narrow, with only a few degrees of motion, and degenerates with aging, losing further motion [19]. The biomechanics regarding the joint are complex. Research is ongoing regarding joint

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mechanics and load transmission. There are no specific standards for evaluation of SIJ dysfunction, and often it is a diagnosis of exclusion. Imaging of the joint commonly reveals changes associated with aging, but does not distinguish asymptomatic from symptomatic individuals. For women, SIJ pain and dysfunction may be underdiagnosed because of coexisting gynecological problems or because of pelvic changes that occur during and after pregnancy. The prevalence of SIJ pain is unknown. Bernard et al. reported that, of 1293 patients with low back pain, SIJ dysfunction was thought to be the pain source in 22.5% based on history and physical examination [20]. Another study showed that 58% of those with SIJ dysfunction by history and physical examination had a history of trauma [3]. Sports and training equipment that require repetitive unidirectional pelvic shear and torsional forces may be an important risk factor for SIJ dysfunction. These sports include skating, gymnastics, golfing, and bowling. Asymmetric shear forces can be distributed through the SIJ during the use of a stairstepper, elliptical trainer, or workouts that include step aerobics. SIJ dysfunction may present in various patterns. Commonly, the woman may complain of pain in the low back, posterior pelvis, or buttock near the posterior superior iliac spine. Pain may radiate down the posterior leg or anterior groin. Pain may be exacerbated with repetitive overload activity, transitional movements, and unsupported sitting. There are no specific exam techniques or diagnostic tests that consistently or accurately identify SIJ pain. SIJ dysfunction is often determined by exclusion. Physical exam should include the usual gait analysis; neurological, postural, and joint range of motion; and flexibility and strength evaluation. Gillet’s test assesses side-to-side ilial-sacral motion. Lack of posterior rotation of the ilium on single-leg stance indicates an alteration in range of motion. This is not necessarily indicative of the site of pain or dysfunction. Observation and palpation of bony landmarks in weight-bearing and non-weight-bearing positions is important. Asymmetric lumbopelvic rhythm in standing and/or sitting can help identify problem areas to address. Determination of a functional or anatomical leg length discrepancy exists is necessary. Patients often have pain on palpation along the PSIS and sacral sulci. Provocative testing, such as Gaenselen’s test, Patrick’s test, or pelvic compression may help direct the diagnosis, but a negative test does not exclude SIJ dysfunction (Figs. 6 and 7). The differential diagnosis of SIJ pain includes many diagnosis. Inflammation of the SIJ may occur as a result of metabolic changes, arthritis, trauma, or infection. Primary tumors of the SIJ are rare. Iatrogenic instability may result from graft harvesting. Osteitis condensans, increased density on the ilial side of the inferior SIJ, occurs in 2.2% of the multiparous female population and is usually selflimiting. Sacroiliitis may develop as a part of pelvic inflammatory disease. Changes that occur during pregnancy must be considered. Pain may be referred from other sites of dysfunction, including lumbar radiculopathy, lumbar facet joint pain, lumbar central or lateral recess stenosis, lumbar discogenic pain, hip disease, and Maigne’s syndrome. Obtaining x-rays of the SIJ is important to rule out infection, metabolic changes, fracture, or tumor. Computerized tomography (CT), MRI, bone scan, or single photon emission computed tomography provides more detailed information regarding the joint. Rarely will imaging clearly define SIJ dysfunction.

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Figure 6 (A) Gaenselen’s sign. (B) Pain upon the execution of this maneuver indicates pathology in the area of the sacroiliac joint.

Figure 7 The Patrick or Fabere test.

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The health care provider must consider the information gained from the history and correlate it with clinical observation to arrive at the diagnosis. The physical exam includes noting subtle changes in flexibility and strength and rules out neurogenic etiology. When clarification is necessary, diagnostic fluoroscopically guided SIJ injection can be helpful in confirming the diagnosis. Caution should be upheld in interpreting the results of an injection as all pain associated with this syndrome may not be intra-articular. Periarticular ligaments, muscles, and fascia are also sources of pain. VI. PELVIC FLOOR DYSFUNCTION Pelvic floor pain and dysfunction can cause considerable impairment for women. The pelvic floor is a group of muscles that must act in coordination with their surrounding joints, including the lumbar spine, SIJ hip joint, and pubic symphysis. In addition, the pelvic floor must function in coordination with visceral structures such as the bladder, vagina, uterus, ovaries, and colon. The muscles of the pelvic floor may respond adaptively to a primary visceral problem. An example includes increased muscle tone that may occur in the levator ani on the ipsilateral side of an ovarian cyst. The woman may present with primary complaints of pelvic pain with urination, defecation, intercourse, and around the time of menstruation. Primary hormonal dysfunction, a visceral problem, and infection should be ruled out. When excluded, determining the musculoskeletal dysfunction will facilitate the recovery and treatment program. The following focuses on primary musculoskeletal problems or pain syndromes involving the pelvic floor. A.

Pelvic Floor Pain

Adaptive patterns in the pelvic floor can also develop as a result of a primary joint injury. A hip with osteoarthritic changes and loss of range of motion may refer pain to the groin and pelvic floor. Muscle guarding may occur, causing increased tone within the pelvic floor. Increased muscle tone within the pelvic floor may lead to pain and dyssynergic problems. Primary muscle imbalances can also refer or cause subsequent pelvic floor muscle imbalance. A woman with piriformis syndrome with an inhibited gluteus medius may develop obturator internus pain noted in the pelvic floor. The obturator internus acts as a secondary hip abductor. Overload may occur because of the inhibited gluteus medius, with resultant obturator internus pain. Pelvic floor myofascial pain is often associated with asymmetrical tautness in the sacrotuberous ligament and the surrounding muscles and fascia. Facilitating muscle tone symmetry is key for appropriate treatment. Because overlap exists in hip, back, and pelvic injuries and dysfunction, the biomechanics of the pelvic floor should be addressed just as they are addressed for an external pelvic dysfunction. Tension myalgia is another label often given to general pelvic floor pain. Diagnoses also included under this heading are piriformis syndrome, levator ani syndrome, coccydynia, and vagismus. Dysfunctions involving increased muscle tone of the musculoskeletal and urogynecological systems are often referred to as levator ani syndrome. Increased pelvic floor muscle tone may be an adaptive component to other primary dysfunctions. These include individuals with low

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Table 5 Pelvic Floor Muscles Susceptible to Trigger Point Formation Coccygeus Levator ani Obturator internus Adductor magnus Piriformis Oblique abdominals

back pain, chronic pelvic pain with negative laparoscopy, endometriosis, interstitial cystitis, urethral syndrome, and sphincter dyssynergia. Women often present with pain in the general region of the vagina, rectum, lower abdominal quadrants, and posterior pelvis. Other areas of discomfort can include the coccyx, pubic symphysis, and posterior thigh. Functional limitations because of pain are often reported. These limitations include dyspareunia, sexual dysfunction, difficulty with voiding, and constipation. Urinary frequency and urgency may also be present. Increased muscle tone in the pelvic floor may occur for several reasons, such as direct trauma to the pelvis as with fractures or joint injuries involving the hip, ilium, and sacrum. Abnormal use or adaptive muscle imbalance syndromes described above can contribute to increased pelvic floor muscle tone. Myofascial pain syndromes may develop primarily or secondary to trauma or muscle imbalance. Travell and Simons have identified specific pelvic floor muscles that may cause symptoms [21]. Trigger points within these muscle groups can refer pain. These muscles are listed in Table 5. A history of sexual abuse, anxiety, depression, and general lifestyle stress can cause muscle tension [22]. Concomitant evaluation of psychosocial factors is imperative to evaluate and treat the pain syndrome comprehensively. Pelvic floor muscle dyssynergia is another cause of pelvic floor pain. Muscles must fire at the appropriate place, time, and intensity. If muscles are unable to coordinate contraction and relaxation, dysfunctions in micturition and defecation may occur. This complex of symptoms is referred to as pelvic floor dyssynergia. Several etiologies for pelvic floor dyssynergia exist. Pudendal nerve injury can result in sensory and motor deficits that inhibit appropriate muscle functioning. Improper technique during exercise that causes a bearing down on the pelvic floor rather than lifting of the pelvic floor can facilitate dyssynergia. Other neurological diseases or injury and inability to isolate pelvic floor muscle contractions from abdominal or gluteal muscle contractions can lead to muscle incoordination and dyssynergia [23]. B. Pelvic Floor Evaluation Examination of the perineum and pelvic floor musculature is essential to arrive at a specific diagnosis and thereby outline a specific treatment plan. This examination is different from the standard pelvic examination performed by the primary care physician, gynecologist, or urologist and should be completed once the patient has been evaluated via speculum by one of the above practitioners.

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Taking an accurate history to help guide the examination is essential. Topics to be covered include number of previous pregnancies and births, length of labor, position of delivery, episiotomy or tearing, past gynecological/urological and medical history, and medications. It is important to ask about symptoms with voiding, defecation, menstruation, intercourse, sexual activity, and exercise. Also, determine if symptoms are brought on or relieved by general activities of daily living, such as sitting, walking, and driving. Reviewing a voiding diary or pain diary can be very helpful. For suspected cases of abuse, follow the guidelines set forth by the individual state. Carefully explain to the patient the purpose and specific steps of the palpatory examination. Educating the woman early in the examination as to the importance of assessing muscle tone, strength, and sensation will assist in better understanding of the forthcoming treatment plan. Always inform the patient that the examination can be terminated at her request. The external examination involves observing the perineum for skin color, scars, symmetry, swelling, gland enlargement, rash, and location of the structures. It is often helpful to ask the patient to point to the greatest area of pain if she is able. Next, observe the motion of the perineum from the resting position, contracted position, and Valsalva and with coughing. Inspect for excursion of tissues while asking the patient to “lift the perineum” and then “bear down.” Observe for isolation of the pelvic floor muscles with contraction versus substitution with the gluteal, abdominal, or adductor muscles. Assess the ability to “lift” the tissues, amount and symmetry of tissue recruited, evidence of breath holding, pain complaints with contractions, and a pelvic tilt performed instead of a perineal contraction. Palpate the perineum to assess tissue texture, hypo/hypertonicity, and trigger points. Assessing dermatomal sensation, light touch, deep pressure, hypersensitivity, or allodynia should be completed at this time. Reflexes can be assessed at this time as indicated. These include the anal sphincter reflex, bulbocavernosus reflex, and cough reflex. With lubrication, palpate the distal introitus in a circular manner and note if the introitus feels normal, loose, asymmetrical, or tight. Also, determine if pain or changes in sensation are present. Ask the patient to then “squeeze around the finger” inserted in the introitus and grade the strength of the contraction on a scale of 0 to 5 of 5. Assess for accessory muscle contractions in the gluteals, adductors, abdominals, and lower extremities. Advance the finger to the level of the levator ani muscles, which should be approximately 5 cm or to the level of the MCP joint. Assess sensation to the right, left, anterior, and posterior vaginal walls. Patients may report pressure and the urge to void or defecate. Describe the muscle tone in the same four areas of the vaginal wall as normal, hypotonic, or hypertonic. Manual muscle testing at the level of the levator ani should then be performed. Cue the patient to “squeeze around the finger and lift up and in.” Complete muscle relaxation between contractions is important; again, cueing may be necessary. Assess for contraction symmetry in all four areas of the vaginal wall. There are several manual muscle-testing scales, and the examiner should use the one of his/her choice. Examples of grading systems are listed in Table 6 [24,25]. Surface electromyographic (EMG) biofeedback evaluation can also be performed with internal and external electrodes and is helpful in determining baseline resting muscle activity. Tone changes that occur with position changes,

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Table 6 Pelvic Floor Muscle Strength Grading Grading scale of Laycock [24] 0–none 1–flicker 2–weak 3–moderate 4–good 5–strong Grading scale of Chirarelli [25] 0–no contraction 1–flicker, only with the muscle stretched 2–a weak squeeze, 2-s hold 3–a fair squeeze, definite “lift” 4–a good squeeze, good hold with “lift,” repeatable 5–a strong squeeze, good lift, repeatable

exercise, or functional activities can also be identified. This muscle examination helps to determine if the woman will be a good candidate for pelvic floor exercises. A specific physical therapy prescription can then be written to indicate if too much or too little muscle tone, strength, or coordination is the problem. If the woman reports urgency, frequency, or dysuria in the absence of infection, referral for urethrocystoscopy may be indicated. Other indications for referral include if the woman has a history of smoking or has microscopic hematuria. Full urodynamic testing is indicated when conservative treatment fails, voiding dysfunction is found, or if there is a history of pelvic surgery or radiation therapy. VII. SUMMARY The musculoskeletal evaluation of the woman with pelvic pain can be difficult because of the variety of clinical presentations and complexity of the anatomy and function; social implications make it difficult for some women to describe their problem. Multiple specialty groups receive some training regarding pelvic pain, but this is often limited to a specific organ site. As a result, women with pelvic pain find themselves being referred from physician to physician searching for the cause and solutions. Women in particular have life cycle changes that affect musculoskeletal function. As an adolescent, some girls are prone to joint hypermobility and laxity, which places them at increased risk for injury. During the early adult years, trauma to the pelvic floor as a result of childbirth can place the woman at increased risk for pelvic floor pain, pelvic pain, and urinary incontinence. Some of these dysfunctions may be subtle and become clinically relevant when the woman returns to increased activities, exercise, or sport. With middle age, hormonal changes may facilitate soft-tissue atrophy and soften bones, placing the woman at increased risk for overuse injuries. Surgeries involving the pelvis, such as hysterectomies and bladder suspensions, place the woman at risk for developing pelvic floor pain dysfunctions. Degenerative changes begin and may limit joint motion, with subsequent loss in muscle flexibility. Again, some of these changes may

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cause symptoms only when the woman increases or changes her activity level. Adapting training and exercise prescriptions to the individual is important. Taking into account her point in the life cycle of aging and hormonal changes is vital. As with many pain syndromes that become chronic, causes are not always determined. A comprehensive approach to evaluation and treatment is often necessary to address structural, hormonal, and visceral problems. This may require coordination of services among physicians, physical therapists, and pain psychologists. A detailed history with a specific musculoskeletal examination can lead to a specific treatment plan. REFERENCES 1. Sady SP, Freedson PS. Body composition and structural compositions of female and male athletes. Clin Sports Med 1984; 3:755–777. 2. Ciullo JV. Lower extremity injuries. In: The Athletic Female; American Orthopaedic Society for Sports Medicine. Human Kinetics, 1993:267–298. 3. Bernard TN, Cassidy, JD. The sacroiliac joint syndrome: pathophysiology, diagnosis, and management. In: Frymoyer JW, ed. The Adult Spine: Principles and Practice. New York: Raven Press, 1991:2107–2130. 4. Vleeming A, Stoeckart R, Volkers ACW, Snijders CJ. Relation between form and function on the sacroiliac joint, part I. Spine 1990; 15:133–135. 5. Vleeming A, Stoeckart R, Volkers ACW, Snijders CJ. Relation between form and function on the sacroiliac joint, part II. Spine 1990; 15:133–135. 6. Vleeming A, Pool-Goudzwaard AL, Stoeckart R, Van Wingerden J, Snijders CJ. The posterior layer of the thoracolumbar fascia. Spine 1995; 20:753–758. 7. Geraci MC. Rehabilitation of the hip and pelvis. In: Kibler WB, Herring SA, Press JM, eds. Functional Rehabilitation of Sports and Musculoskeletal Medicine. Maryland: Aspen Publishers, 1998:216–243. 8. Greenman PE. Clinical aspects of sacroiliac function during walking. J Man Med 1990; 5:125–130. 9. Fortin JD, Kissling RO, O’Connor BL, Vilensky JA. Sacroiliac joint innervation and pain. Am J Orthop 1999; 28(12):687–690. 10. Vleeming A, VanWindergan JP, Dijkstra PF. Mobility of the sacroiliac joint in the elderly: a kinematic and radiology study. Clin Biomech 1991; 6:161–168. 11. Kibler WB, Chandler TJ, Uhl T, Maddux RE. A musculoskeletal approach to the preparticipation physical examination. Am J Sports Med 1989; 17:525–531. 12. Sim F, Scott S. Injuries of the pelvis and hip in athletes: anatomy and function. In: Nichols JA, ed. The Lower Extremity and Spine in Sports Medicine. St. Louis, MO: C. V. Mosby, 1986:1119–1169. 13. Lane NE, Hochberg MC, Pressman A, Scott JC, Nevitt MC. Recreational physical activity and the risk of osteoarthritis of the hip in elderly women. J Rheumatol 1999; 26:849–854. 14. Vingard E, Alfredsson L, Malchau H. Osteoarthritis of the hip in women and its relationship to physical load from sports activities. Am J Sports Med 1998; 26:78–82. 15. Syllabus-exercise prescription as an adjunct to manual medicine. In: Bookout MR, Greenman PE, eds. Continuing Medical Education Course. East Lansing, MI: Michigan State University, College of Osteopathic Medicine, September 30–October 2, 1994. 16. Jull GA, Janda V. Muscles and motor control in low back pain: assessment and management. In: Twomey LT, Taylor JR, eds. Physical Therapy of the Low Back: Clinics in Physical Therapy. New York: Churchill Livingstone, 1987:253–278.

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18. Fagerson TL. Diseases and disorders of the hip. In: Fagerson TL, eds. The Hip Handbook. Woburn, MA: Butter-Heinemann, 1998:39–95. 19. Vleeming A, Van Windergan JP, Dijkstra PF. Mobility of the sacroiliac joint in the elderly: a kinetic and radiology study. Clin Biomech 1991; 6:161–168. 20. Bernard TN, Kirkaldy-Willis WH. Recognizing specific characteristics of nonspecific low back pain. Orthopedics 1987; 217:266–280. 21. Travell J, Simons D. Myofascial Pain and Dysfunction: The Trigger Point Manual. Vol. 2. The Lower Extremities. Baltimore, MD: Williams and Wilkins, 1992. 22. Walker E, Katon W, Harrop-Griffiths J, Holm L, Russo A, Hickok LR. Relationship of chronic pelvic pain to psychiatric diagnoses and childhood sexual abuse. Am J Psychiatry 1988; 145:75–80. 23. Wallace K. Female pelvic floor functions, dysfunctions, and behavioral approaches to treatment. Clin Sports Med 1994; 13:459–481. 24. Laycock J. Incontinence. Pelvic floor re-education. Nursing 1991; 4(39):15–17. 25. Chiarelli PE. Incontinence. The pelvic floor function. Aust Fam Physician 1989; 18(8): 949–957.

16 Diagnosis and Management of Interstitial Cystitis TOMAS L. GRIEBLING University of Kansas Kansas City, Kansas, U.S.A.

I.

INTRODUCTION AND HISTORICAL PERSPECTIVE

Interstitial cystitis (IC) is a chronic inflammatory condition of the urinary bladder that causes a constellation of irritative voiding symptoms and pelvic pain in the setting of negative urine cultures. Once considered a rare disorder, interstitial cystitis represents one of the major causes of pelvic floor dysfunction for many women. Diagnosis and management can be challenging even for the experienced clinician. A significant problem in establishing the diagnosis of IC is that the symptoms associated with the disorder represent an exaggeration of normal physiological sensations. This chapter reviews historical concepts of the disease, current etiological theories and associated disorders, techniques for diagnosis, and options for management. The term interstitial cystitis was first used in 1887 when Skene described an inflammatory condition of the bladder that had “destroyed the mucous membrane partly or wholly and extended to the muscular parietes” [1]. In 1915, Hunner described the cystoscopic appearance of mucosal ulcerations in a group of women with clinical symptoms of the disorder [2]. This finding is seen in some patients after hydraulic distension of the bladder under anesthesia and has since come to be referred to as Hunner’s ulcer. In 1987, the National Institute of Arthritis, Diabetes, Digestive, and Kidney Diseases (NIADDK) of the National Institutes of Health (NIH) organized a consensus conference to develop a working definition of IC for research purposes [3]. The committee developed a definition that required patients to fulfill two inclusion criteria: pain associated with the bladder or urinary urgency and demon263

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stration of either a Hunner’s ulcer or mucosal glomerulations on cystoscopic examination of the bladder following hydraulic distension under anesthesia. In addition, a list of 18 exclusion criteria was developed to help separate the diagnosis from other disorders with similar clinical symptoms. The list includes a wide variety of pelvic floor disorders, such as genitourinary malignancies, active bacterial or herpes infection, detrusor instability, and stone disease. Although developed primarily as a working definition for research purposes and creation of structured clinical trials, these criteria have been used by many clinicians for making the diagnosis of IC [4]. There is some controversy about using these exclusion criteria in a strict fashion [5]. In some cases, one or more of these diagnoses may occur concurrently in patients with IC. For example, patients can develop an acute bacterial urinary tract infection superimposed on their regular IC symptoms. However, IC is still generally considered a diagnosis of exclusion. Most authors agree that symptoms must be chronic in nature, not relieved by antibiotic therapy, and not attributable to other significant uncorrected pathology. The age restriction in the NIADDK criteria is also somewhat controversial. A requirement that patients be at least 18 years of age to be diagnosed with IC was placed primarily because potential subjects must be of legal age to consent for participation in clinical research trials. Although it is still considered an extremely rare diagnosis in children, some authors have postulated that interstitial cystitis may occur in children and adolescents with chronic irritative voiding symptoms [6]. However, to date, no studies have definitively supported evidence of progression from symptomatic childhood voiding dysfunction to an adult diagnosis of IC. II. CLINICAL PRESENTATION Patients with IC often present with symptoms that mimic an acute or chronic urinary tract infection. These include significant urinary urgency, frequency, nocturia, and pelvic or genital pain. Suprapubic pain associated with bladder filling that is relieved by voiding is one of the hallmark symptoms of the disorder. The urgency and frequency associated with this condition may be severe. Many patients report voiding at least every hour while awake, and some may void every 10 or 15 min. Nocturia may also be profound and may lead to significant sleep disruption. Delay in correct diagnosis is a common clinical problem. Many patients are treated with antibiotics for symptoms of a urinary tract infection without improvement in their clinical picture. Urine cultures are usually negative, and because the disorder is not caused by a typical bacterial infection, patients do not respond to antibiotic therapy. It is not uncommon to see patients who have been unsuccessfully treated with multiple courses of different antibiotics by various practitioners. The delay in diagnosis may range from months to even years. Although IC may occur in all types of patients, there are some general epidemiological characteristics of the disorder. Several population-based studies have demonstrated a significant predilection for the disorder in women [7–9]. The quoted ratio is generally 9 to 10 women for each man diagnosed with IC. However, some recent data suggest that some men previously diagnosed with chronic

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Table 1 Etiological Theories of Interstitial Cystitis Disruption of epithelial glycosaminoglycan (GAG) layer Mast cell deposition and degranulation Upregulation of neural pain pathways Autoimmunity Urinary chemical mediators Infection (atypical organisms)

prostatitis may in actuality suffer from IC [10]. The disease appears to be more prevalent in Caucasians, particularly those with light hair and skin complexion, although it can be seen in any ethnic group. III. ETIOLOGICAL THEORIES Despite extensive clinical and basic science research, the exact etiology of IC remains unknown. No single pathognomonic finding has been identified that can explain all cases of the disorder; however, a variety of etiologic theories has been proposed (Table 1). There appears to be a strong association between IC and other chronic pain syndromes, such as fibromyalgia, irritable bowel syndrome, vulvodynia, vulvovestibulitis, and migraine headache [11–13]. Over 40% of IC patients report a history of allergies or allergic symptoms [14]. There is a growing body of evidence that suggests that IC may actually represent a syndrome of the final symptom pathway for a variety of disorders rather than a single specific disease entity. A number of plausible etiological theories for the development of IC have been proposed, and it is most likely that the disorder is multifactorial. A. Increased Bladder Epithelial Permeability Disruption of the bladder epithelium with loss of the normal cytoprotective barrier is one popular theory. Scanning electron microscopy and other techniques have demonstrated that the transitional epithelium in the normal bladder is covered with a hydrophilic glycosaminoglycan (GAG) layer [15–17]. This acts to coat the underlying bladder mucosa and serves as a protective barrier. Disruption of the GAG layer may allow chemical irritants in the urine to contact underlying tissue, causing inflammation and associated symptoms. The potassium permeability test described in the section on diagnostic techniques was developed based on this theory. Some clinicians now differentiate between the ulcerative and nonulcerative forms of the disorder [18]. This may have implications for selecting therapeutic options, although specific data regarding predictive value have yet to be elucidated [19]. B. Mast Cells Increased mast cell deposition has also been a popular theory regarding development of IC. During the degranulation process, mast cells release histamine. It is hypothesized that increased urinary histamine may cause a local inflammatory response in the bladder, which leads to pain and irritative voiding symptoms [20–

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22]. However, there are conflicting data in the literature regarding mast cells. Some studies have shown an increased concentration of mast cells in patients with IC compared to age-matched controls on bladder biopsy [23]. However, other studies have not shown a significant difference [24]. Similarly, some patients report improvement in their symptoms with antihistamines, while others obtain no relief. C.

Infection

Although infection has long been a popular theory for the development of IC, no studies have conclusively documented a clear relationship [25]. It is possible that an as-yet-undiscovered organism may be responsible. Infections with fastidious organisms such as Ureaplasma or Borrealis have been suggested, but remain unproven [26,27]. It is also possible that an infectious agent could lead to other possible causative mechanisms, such as increased autoimmunity or upregulation of neural pain pathways. D.

Autoimmunity

Autoimmunity has been considered as a potential etiological factor for many years [28,29]. The epidemiology of IC matches that of many autoimmune disorders with a large percentage of female patients and a chronic course. Some studies have suggested a relationship between antibodies to various bladder components and IC [30]. Other studies have demonstrated a high prevalence of positive antinuclear antibody (ANA) titers in patients with IC compared to controls [31]. However, this finding is nonspecific and can be demonstrated in a variety of associated clinical conditions common in IC patients. E.

Hormonal Factors

Many women with IC describe an increase in their symptoms around the time of their menstrual cycles. Estrogen may play a role in these patients, and the female preponderance of the disease would support this theory. There is evidence that bladder mast cells show a high degree of affinity for estrogen receptors [81,32]. Estradiol has been shown to exacerbate symptoms in some patients, while tamoxifen may decrease symptoms [33]. Some patients anecdotally describe that their symptoms are significantly improved during pregnancy. F.

Urinary Factors

Inflammatory mediators and other chemical factors in the urine have been examined as a potential cause of IC [34–36]. As with the other theories, results have been contradictory. Many patients anecdotally report an increase in symptoms during periods of significant emotional or psychological stress. Several recent studies have demonstrated an increase in various inflammatory mediators in the urine of IC patients in response to emotional stress [37–39]. G.

Neurological Sources

Recent attention has focused on the possibility that a neurogenic mechanism may be responsible for the development of symptoms in some IC patients [40]. Stimula-

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tion of C-afferent fibers leads to release of neuropeptides, which can cause pain response by an increase in local inflammation. This increased inflammation may be associated with other local responses, including increased vascular and epithelial permeability, mast cell degranulation, and smooth muscle contraction. IV. DIAGNOSTIC EVALUATION A thorough history and examination are critical to establishing the correct diagnosis of IC. In many cases, the history alone will be highly suggestive; however, additional diagnostic tests are usually required to confirm the diagnosis (Table 2). IC should be suspected in women who present with a history of chronic irritative voiding symptoms unresponsive to antibiotic therapy. Often, the urologist or gynecologist will be asked to evaluate a patient for recurrent urinary tract infections or endometriosis even though previous clinical evaluations do not necessarily support these diagnoses. As previously discussed, IC is still generally considered a diagnosis of exclusion. Care must be taken to verify that the patient does not have another condition that could explain her symptoms [41]. It is particularly important to rule out the presence of carcinoma in situ or other genitourinary malignancies, especially in middle-aged or older women or patients who have any degree of hematuria. Urodynamic studies may be performed in select patients and are particularly helpful in patients with urinary incontinence or a possible diagnosis of detrusor instability. The most common urodynamic findings in patients with IC include a hypersensate bladder with early sensation of filling and urgency and reduced bladder capacity. Some patients may experience pain with bladder filling on urodynamics that simulates their daily symptoms, but this finding alone is nonspecific. Two specific techniques have been used to help clinically establish the diagnosis of IC: cystoscopy with bladder hydrodistension and potassium permeability testing. A. Cystoscopy with Hydrodistension Cystoscopic examination of the bladder with hydraulic distension under anesthesia has long been considered the gold standard technique to establish the diagno-

Table 2 Diagnostic Tests for Interstitial Cystitis History and physical examination Cystoscopy and bladder hydrodistension under anesthesia Reduced bladder capacity Terminal hematuria Mucosal changes (glomerulations, ulcerations) Potassium permeability test Sterile water or saline (40 cc)—no increase in urgency or pain Potassium chloride (40 cc of 0.4 M KCl)—increased urgency or pain Urodynamic testing Evaluate for detrusor instability Hypersensate bladder Reduced cystometric capacity

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sis of IC. After induction of either general or spinal anesthesia, routine cystoscopy is performed. A barbotage cytology specimen is useful to screen for malignancies such as carcinoma in situ. Hydrodistension is then performed with the cystoscopic irrigant approximately 60 cm above the patient’s symphysis pubis. The bladder is filled to capacity and left distended for 1 to 2 min. Two distensions are typically performed. The volume of irrigant is measured, and the fluid is examined for gross evidence of terminal hematuria. Reinspection of the bladder mucosa is then performed to identify mucosal abnormalities. Classic Hunner’s ulcerations are rare, occurring in less than 20% of patients in most studies. The more common finding includes diffuse petechial hemorrhages or glomerulations (Fig. 1). The three characteristics classically seen in IC after hydrodistension include diminished bladder capacity, terminal hematuria with bladder drainage, and mucosal ulcerations or glomerulations. To establish the diagnosis, the mucosal lesions should be present diffusely throughout the bladder. Some patients do not have all of these classical findings. Preservation of normal bladder capacity may represent an earlier stage of IC compared to the small bladder often seen in later stages of the disorder. Histopathology may be variable, and no specific findings are diagnostic of the disorder. Bladder biopsies may be obtained after hydrodistension and are particularly useful to help rule out a diagnosis of carcinoma in situ or other urothelial malignancy. Giemsa staining may reveal increased mast cell deposition in the mucosa and submucosa. This finding is suggestive, but not pathognomonic, of IC. Although IC is generally considered to be an inflammatory disorder, the observed degree of cellular inflammation may be highly variable. One recent

Figure 1 Cystoscopic appearance of bladder mucosa in a patient with interstitial cystitis after hydrodistension. Note the petechial hemorrhages and glomerulations.

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study revealed no significant correlation between the severity of cystoscopic findings in patients with IC and the histologic degree of inflammation observed on biopsies [42]. The need for general or spinal anesthesia to perform the procedure is certainly one disadvantage to this diagnostic technique. Although hydrodistension of the bladder is considered a relatively straightforward and safe procedure, several potential complications have been recognized. Perioperative antibiotics are usually administered to prevent postoperative urinary tract infections. If biopsies are performed, they should only be taken after hydrodistension is completed to prevent bladder perforation. Such perforations are usually small and can generally be managed conservatively with a short course of indwelling catheter drainage. Bladder rupture may occur if the irrigant is too high or if the bladder is overdistended [43]. Ruptures typically occur at the bladder dome and usually require immediate open surgical exploration and repair. Rarely, patients may experience significant hematuria after the procedure and can develop clot retention. Hydrodistension is typically performed on an outpatient basis. Patients should be counseled that they may experience an increase in irritative voiding symptoms, but that this will typically resolve within a few days. In fact, hydrodistension may be therapeutic as well as diagnostic. Many patients report a significant improvement in their voiding symptoms, although this is usually temporary and often lasts only a few weeks. In rare patients, the results may be more sustained, and these individuals may be successfully treated with periodic hydrodistension procedures. Although relatively sensitive, mucosal changes on hydrodistension are not absolutely specific for IC. Waxman and colleagues demonstrated in a case-control study that mucosal glomerulations may occur following bladder hydrodistension in some control patients with no existing urinary symptoms [44]. It is the combination of subjective irritative voiding symptoms and classic cystoscopic findings that is used to establish the diagnosis. B. Potassium Permeability Testing Several recent studies have documented alterations in epithelial permeability in patients with IC. In a number of trials, potassium permeability has been shown to be significantly increased in patients with IC compared to asymptomatic controls [45–48]. This finding has been used to develop a new office-based diagnostic test for IC. The patient is initially catheterized, and the bladder is drained. Then, 40 mL of sterile saline is placed in the bladder, and the patient is asked to rate her urinary urgency and pain after 5 min. This should not provoke a pain response even in subjects with chronic IC. The bladder is then drained and refilled with 40 mL of 0.4 mol/L potassium chloride solution. Patients with IC caused by increased urothelial permeability will typically experience immediate onset of significant urinary urgency and pain. The bladder is drained, and transurethral viscous lidocaine gel may be administered if necessary. The test is considered negative if the subject can hold the concentrated potassium solution for 5 min without a significant increase in urgency or pain. The potassium permeability test offers several potential advantages over traditional cystoscopy and hydrodistension. It is relatively quick and easy to per-

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form. It obviates the need for anesthesia and certainly costs less than hydrodistension. However, the test may be uncomfortable for patients and carries a reported false negative rate of 12–25%. It is possible that these individuals represent a subset of patients with IC who actually have the disorder, but do not demonstrate alterations in epithelial permeability. In addition, other diagnoses, such as carcinoma in situ, could be missed if additional tests (e.g., bladder wash cytology or routine office cystoscopy) are not performed. Erickson and colleagues have recently described a similar diagnostic test using intravesical administration of rhamnose, a natural sugar not found in humans [49]. In a case-control study, patients with IC demonstrated increased serum levels of rhamnose after intravesical instillation. The test does not cause discomfort and may prove clinically useful in future trials. Additional clinical research will help to clarify the role of permeability testing with potassium or other agents in the routine diagnostic evaluation of IC. V.

MANAGEMENT

Successful management of IC is frequently as challenging as establishing the diagnosis. Because the exact cause of the disease is unknown, current treatment options are empirical and are based on the etiological theories previously described (Table 3). It is important to explain to patients that no two cases of IC are exactly the same, and effective treatment often differs between patients. Therapy for a given individual may also need to change over time based on her clinical response. The overall goals of treatment should be to relieve symptoms, permit the resumption of regular activities, and maintain an acceptable quality of life. Therapy should be tailored to each patient to achieve these goals while minimizing the number of medications, invasive therapeutic procedures, and potential treatmentrelated complications. Conversely, it must also be recognized that many patients will require combination therapy. In the majority of patients, symptoms can be brought under control with occasional flare episodes. It is helpful to envision a “ladder” approach to the treatment of interstitial cystitis. The most conservative options, such as behavioral therapy and oral medications, are attempted first. Additional treatments are added and others discontinued based on symptomatic response. Multidrug oral therapy with agents targeted at different potential causative factors may be beneficial in some patients. More involved therapies, including intravesical treatments, are added as needed based on patient response. Extirpative surgical therapy is very controversial, and it is generally reserved only for the most refractory patients. The utility of multimodal approaches likely reflects the multifactorial nature of the disorder. A.

Multimodal Therapy

1. Patient Education Education and active patient participation are crucial to the successful management of interstitial cystitis [50,51]. Founded by affected patients, the Interstitial Cystitis Association (ICA) is a leading resource for education, patient advocacy, and clinical research regarding the disorder. Local support group chapters offer a forum for patients to meet and discuss their diagnosis and treatments. Patients

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Table 3 Treatment Options Behavioral therapies Diet modification—foods commonly identified as symptom triggers Caffeine (including chocolate) Carbonated beverages Potassium-rich foods (bananas, avocados, apricots) Acidic foods and beverages (citrus fruits, tomatoes) Spicy foods Alcoholic beverages Pelvic floor retraining/exercise Sitz baths Complimentary therapies (hypnosis, acupuncture, pelvic massage) Oral medications (typical doses) Amitriptyline (Elavil), 10–75 mg PO q HS Hydroxyzine (Atarax), 10–25 mg PO qd or bid Pentosan polysulfate sodium (Elmiron), 100 mg PO tid Cromolyn sodium (Gastrocrom), 200 mg PO tid Gabapentan (Neurontin), 100–400 mg PO tid Hyocyamine (Levsin), 0.125 mg PO bid (helpful with dyspareunia) Intravesical therapies Dimethyl sulfoxide (DMSO) Heparin sulfate Oxychlorosene (Clorpactin) Lidocaine gel Capsaicin Resiniferatoxin Bacillus Calmette-Guerin (BCG) Surgical therapy Hydraulic bladder distention Laser ablation of bladder trigone Sacral neuromodulation (S3 nerve root) (Medtronic Interstim ) Cystourethrectomy with urinary diversion

often welcome this opportunity to meet with others who have shared their experiences. Such groups are also a valuable resource for increased community education and awareness about IC. 2. The Multidisciplinary Care Team Care of patients with IC often requires a multidisciplinary approach [52]. The value of concerned practitioners who approach treatment of IC with understanding and compassion cannot be overemphasized. Each member of the care team brings unique expertise to the treatment of the disorder. Most direct care for these patients is provided by urologists and urologic nurses. Consultation with a gynecologist who has a specific interest in pelvic floor dysfunction can be quite helpful for women who experience vulvodynia or dyspareunia [53]. Patients with a significant pain component can often benefit from referral to a formal pain management clinic or anesthesiologist. Nutritionists can help with dietary management, and physiotherapists can help with pelvic floor retraining. Consultation with a psychiatrist or psychotherapist may help patients to cope with the emotional and

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psychological effects of the disorder. In cases of severe disability, consultation with an occupational medicine or rehabilitation specialist may be warranted. B.

Behavioral Therapies

Several behavioral therapies may offer relief for patients with IC. Diet modification is one of the cornerstones of therapy. Many patients describe an exacerbation of their symptoms with various food triggers [54]. Specific items that tend to cause problems for patients with IC are listed in Table 3. Patients who notice food or beverage triggers are placed on dietary restriction. They should be counseled to try the modified diet for several weeks until their symptoms are stable. Once this has occurred, patients should be encouraged to experiment with different foods and beverages on the restricted list to see which ones they will be able to tolerate. Most patients are able to identify a few specific items that tend to cause problems and can ultimately broaden their diet. Referral to a registered dietitian may be beneficial. Some patients have anecdotally described that prophylactic use of antacids prior to indulging in known food triggers may reduce or prevent subsequent symptoms. Alternative and complementary forms of therapy are gaining increased attention in all areas of health care, including pain and chronic disease management. Although none of these treatment modalities has definitively been shown to significantly improve symptoms in randomized controlled trials, many patients anecdotally describe improvement in symptoms with some of these techniques. Pelvic floor muscle exercises may help some patients, particularly with symptoms of urgency, and this may be augmented by biofeedback training if available. Warm sitz baths and either a warm or a cool pack placed on the perineum may provide temporal relief of pelvic pain. Some patients in my practice have described relief or improvement of IC symptoms from diverse therapies such as acupuncture, hypnosis, yoga, meditation, and massage. Early studies have suggested therapeutic benefits from some of these techniques, and additional welldesigned scientific research will help to elucidate whether they may have broader potential utility [55–57]. C.

Oral Medications

A wide variety of oral medications have shown empiric utility in the symptomatic treatment of IC. Each option has associated risks and potential benefits that should be reviewed with the patient in detail prior to use. 1. Amitriptyline Amitriptyline, a tricyclic antidepressant, is often used as one of the first-line agents for the treatment of IC [58]. In low doses, it has been successfully used for treatment of various forms of neuropathic pain. It has anticholinergic properties and also prevents the active transport reuptake of serotonin and noradrenaline at the presynaptic level. Typical doses range from 10 to 50 mg taken orally at bedtime. Many patients report an improvement in nocturia due to the sedating effects of the medication. Care should be taken to titrate the dose to prevent morning somnolence. Most potential side effects are anticholinergic in nature and include dry mouth, constipation, drowsiness, and confusion. Like other medications with anti-

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cholinergic properties, amitriptyline is contraindicated in patients with uncorrected narrow-angle glaucoma. 2. Antihistamines Antihistamines have had variable results in clinical trials. Hydroxyzine is the most promising medication in this class [59]. It has been shown to relieve irritative symptoms, including urgency and frequency in some patients. These medications may be particularly useful in individuals found to have increased bladder mast cell deposition on biopsy. Typical doses range from 10 to 50 mg at bedtime. Like many other antihistamines, hydroxyzine has the potential to induce drowsiness, although this may help nocturia. Patients with daytime urgency and frequency who do not experience significant drowsiness from hydroxyzine may benefit from a twice daily dosing schedule. Mast cell stabilizers such as cromolyn sodium (Gastrocrom ) have also been tested with variable success [60]. The typical oral dose is 100–200 mg PO three or four times daily. 3. Pentosan Polysulfate Sodium Pentosan polysulfate sodium (Elmiron ) is a low molecular weight heparinlike medication that was designed specifically for the treatment of IC [61–63]. It acts to decrease bladder permeability by rebuilding the cytoprotective GAG layer of the bladder mucosa. The recommended dose is 100 mg PO tid. Potential side effects include thinning of hair and mild alopecia, a sensation of bloating, and transient elevation of hepatic enzymes. Liver function tests should be monitored periodically while on therapy. It may take several months for patients to notice symptomatic relief. If tolerated, therapy with pentosan polysulfate should be continued for at least 4 to 6 months before a conclusion about efficacy is made for an individual patient. 4. Gabapentin Gabapentin (Neurontin ), a neurologic agent often used as an antiseizure medication, has recently been shown to have symptomatic benefits for some IC patients [64]. The exact mechanism of action is unknown. It may be of particular use in women with vulvodynia and perineal pain. Doses are typically titrated from 300 mg PO tid up to a maximum of 1200 mg PO tid as tolerated. Leukopenia may occur at high doses, and white blood cell counts should be monitored periodically. 5. Anticholinergics Anticholinergics and other antispasmodics have not shown much efficacy for the chronic symptoms of IC. However, some women with dyspareunia report anecdotal improvement in this symptom with use of hyoscyamine 0.125 mg PO bid around the time of sexual activity. This may be due to smooth muscle relaxation in the bladder and pelvic floor associated with use of this medication. 6. Other Oral Medications Effective pain management may present a significant challenge for some patients with IC. Phenazopyridine (Pyridium ) is an oral agent that is excreted in the urine and acts as a mild topical anesthetic in the bladder. Patients should be warned that it will cause a fluorescent orange discoloration of the urine. It may be useful

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for acute flare-ups and for postoperative pain management. Phenazopyridine use should be limited to short courses due to the potential for methemoglobinemia associated with prolonged administration. Short courses of nonsteroidal antiinflammatory agents such as tramadol (Ultram ) may be useful for some patients with significant suprapubic pain. Opioid analgesics are generally avoided in the routine care of patients with IC due to the high potential for tolerance and dependence and potential side effects, including constipation. However, some patients may require opioids to control severe episodes of symptom exacerbation. These drugs are commonly prescribed in short courses after surgical procedures such as bladder hydrodistension or after intravesical treatment administration. D.

Intravesical Therapies

Numerous forms of intravesical therapy for IC have been attempted with variable results. This section reviews the most commonly used intravesical therapies. 1. Dimethyl Sulfoxide Dimethyl sulfoxide (DMSO) is a powerful antiinflammatory agent that has also been used for treatment of arthritis. It is often used as a compounding agent for transdermal medications, particularly in veterinary medicine. When used as an intravesical agent, it acts as a direct antiinflammatory for the bladder epithelium [65]. Treatments are generally well tolerated and administration can be performed in the outpatient clinic. Patients are catheterized and a solution of 50 cc of 50% DMSO is placed in the bladder. The patient should ideally hold the solution for 20 to 30 min or as long as tolerated. Treatments are usually administered weekly for an initial 6-week course. Patients are then reassessed after several weeks to determine response. If necessary, the treatment cycle can be repeated. In patients that demonstrate good response, the frequency of treatments can generally be decreased. Some patients continue to have sustained improvements with an occasional treatment every few months or when symptoms acutely flare. A garliclike or metallic taste may occur transiently during treatment sessions. 2. Heparin Heparin sulfate can be a useful intravesical treatment for some patients [66]. Like oral pentosan polysulfate, it acts to rebuild the natural protective GAG layer of the bladder. Some clinicians combine DMSO with heparin and/or steroids as an intravesical “cocktail.” The administration cycle is similar to that described above for DMSO. 3. Clorpactin Clorpactin (oxychlorosene) is another intravesical agent that has been used to treat IC [67]. It is essentially a dilute bleach solution that is instilled into the bladder at a concentration of 0.1–0.4%. The exact mechanism of action is unknown, but it is theorized that the medication leads to diffuse sloughing of the GAG layer with subsequent regeneration or an inhibition of the C-afferent pain fibers in the bladder. At higher concentrations, instillation can be quite painful and is usually performed under anesthesia. Patients typically report a temporal increase in suprapubic pain that subsides several days after instillation. A cystogram is

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indicated prior to initial administration to verify that the patient does not have vesicoureteral reflux. A six-treatment cycle is commonly used. Prolonged administrations should be avoided due to the potential for fibrotic changes in the bladder. 4. Other Agents Several other agents have recently shown promise in early clinical trials for intravesical administration in patients with IC. Bacillus Calmette-Guerin (BCG) is attenuated mycobacterium preparation that is commonly used in the management of patients with carcinoma in situ or recurrent transitional cell carcinoma of the bladder [68]. It is thought to induce an immune response at the level of the bladder epithelium. Capsaicin is the chemical that imparts the hot nature to chili peppers and may act to desensitize the C-afferent pain fibers in the bladder [69,70]. Resiniferatoxin is a plant by-product that may act by a similar mechanism [70,71]. E.

Surgical Therapies

The role of surgical therapy in the treatment of IC has traditionally been limited. Hydraulic bladder distention was previously discussed in the context of diagnostic evaluation. The procedure may be therapeutic for some patients, although the improvements are typically temporary, with relief provided for several weeks at most. In very select patients, the procedure can have longer effects and may be justified on a periodic basis. Laser ablation of the epithelium at the trigone has been reported anecdotally to improve symptoms in some patients [72]. Neodynium-yag (Nd-Yag) laser energy is typically used, and the procedure is combined with hydrodistension. The theory behind this procedure is that the laser ablation of the epithelium leads to desensitization of the pain receptors in the bladder trigone. Care must be taken during this procedure to avoid deep tissue penetration and potential perforation. Neuromodulation is one of the newest surgical techniques that may offer relief to some patients with IC [73]. Although not currently approved by the Food and Drug Administration (FDA) specifically for treatment of IC, it is indicated for urinary urgency and frequency, which are symptomatic components for most patients. Direct electrical stimulation of the S3 nerve root is accomplished with surgical implantation of a quadripolar electrode in the sacral foramen. The technology is similar to a cardiac pacemaker. The device can be programmed and adjusted to the individual patient’s symptoms. A percutaneous test is performed prior to implantation to determine if the patient will respond to therapy. Additional research with this device in the treatment of IC is currently ongoing. Analgesic injections may be used in select patients [74]. Epidural injections of long-acting analgesic agents or specific trigger point injections of regional nerves may provide symptomatic relief. Injections may be repeated periodically if patients obtain clinical improvement. Cystectomy and urinary diversion have been used to treat severe cases of IC refractory to all other forms of therapy [75–77]. This is to be considered a last resort for most patients as overall clinical results have traditionally been disappointing. Some studies show an improvement in symptoms; however, many patients develop recurrent pelvic pain even after the bladder is removed [78]. This

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supports the hypothesis that, at least in some patients, the mechanism of IC is related to a neurological alteration in pain perception rather than a primary bladder factor.

VI. CONCLUSION Interstitial cystitis is one of the most enigmatic diagnoses for urologists, gynecologists, and other clinicians interested in female pelvic floor dysfunction. Management of these patients can be challenging, but rewarding. Future research in the fields of neurophysiology, molecular biology, genetics, clinical pharmacology, and health-related quality of life may help to elucidate important information about this unique disorder.

REFERENCES 1. Skene AJC. Diseases of the Bladder and Urethra in Women. New York: William Wood, 1887. 2. Hunner GL. A rare type of bladder ulcer in women: report of cases. Boston Med Surg J 1915; 172:660–664. 3. Gillenwater JY, Wein AJ. Summary of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases workshop on interstitial cystitis. NIH, Bethesda, Maryland, August 28–29, 1987. J Urol 1988; 140:203–206. 4. Hanno PM, Landis JR, Matthews-Cook Y, Kusek J, Nyberg L Jr. The diagnosis of interstitial cystitis revisited: lessons from the National Institutes of Health Interstitial Cystitis Database study. J Urol 1999; 161:553–557. 5. Batra AK, Hanno PM, Wein AJ. Interstitial cystitis. In: Ball TP, Novicki DE, eds. AUA Update Series. Vol. 19, Lesson 2. Houston, TX: American Urological Association, 1999: 9–15. 6. Close CE, Carr MC, Burns MW, et al. Interstitial cystitis in children. J Urol 1996; 156: 860–862. 7. Oravisto KJ. Epidemiology of interstitial cystitis. Ann Chir Gynaecol Fenn 1975; 64: 57–77. 8. Curhan GC, Speizer FE, Hunter DJ, Curhan SG, Stampfer MJ. Epidemiology of interstitial cystitis: a population based study. J Urol 1999; 161:549–552. 9. Jones CA, Nyberg L. Epidemiology of interstitial cystitis. Urology 1997; 49(suppl 5A): 2–9. 10. Nickel JC. Prostatitis: myths and realities. Urology 1998; 51:362–366. 11. Griebling TL, Broghammer EL, Kreder KJ. Urodynamic findings in patients with a diagnosis of fibromyalgia. International Continence Society 29th Annual Meeting, Denver, CO, August 23–30, 1999. 12. Clauw DJ, Schmidt M, Radulovic D, Singer A, Katz P, Bresette J. The relationship between fibromyalgia and interstitial cystitis. J Psychiatr Res 1997; 31:125–131. 13. Stewart EG, Berger BM. Parallel pathologies? Vulvar vestibulitis and interstitial cystitis. J Reprod Med 1997; 42:131–134. 14. Alagiri M, Chottiner S, Ratner V, Slade D, Hanno PM. Interstitial cystitis: unexplained associations with other chronic disease and pain syndromes. Urology 1997; 49(suppl 5A):52–57. 15. Hurst RE, Roy JB, Min KW, et al. A deficit of chondroitin sulfate proteoglycans on the bladder uroepithelium in interstitial cystitis. Urology 1996; 48:817–821.

Interstitial Cystitis

277

16. Keay S, Warren JW. A hypothesis for the etiology of interstitial cystitis based upon inhibition of bladder epithelial repair. Med Hypotheses 1998; 51:79–83. 17. Nickel JC, Emerson L, Cornish J. The bladder mucus (glycosaminoglycan) layer in interstitial cystitis. J Urol 1993; 149:716–718. 18. Koziol JA, Adams HP, Frutos A. Discrimination between the ulcerous and the nonulcerous forms of interstitial cystitis by noninvasive findings. J Urol 1996; 155:87– 90. 19. Peeker R, Fall M. Treatment guidelines for classic and non-ulcer interstitial cystitis. Int Urogynecol J Pelvic Floor Dysfunct 2000; 11:23–32. 20. Spanos C, el Mansoury M, Letourneau R, et al. Carbachol-induced bladder mast cell activation: augmentation by estradiol and implications for interstitial cystitis. Urology 1996; 48:809–816. 21. Letourneau R, Pang X, Sant GR, Theoharides TC. Intragranular activation of bladder mast cells and their association with nerve processes in interstitial cystitis. Br J Urol 1996; 77:41–54. 22. el Mansoury M, Boucher W, Sant GR, Theoharides TC. Increased urine histamine and methylhistamine in interstitial cystitis. J Urol 1994; 152:350–353. 23. Peeker R, Enerback L, Fall M, Aldenborg F. Recruitment, distribution and phenotypes of mast cells in interstitial cystitis. J Urol 2000; 163:1009–1015. 24. Dundore PA, Schwartz AM, Semerjian H. Mast cell counts are not useful in the diagnosis of nonulcerative interstitial cystitis. J Urol 1996; 155:885–887. 25. Haarala M, Liilholma P, Lehtonen OP. Urinary bacterial flora of women with urethral syndrome and interstitial cystitis. Gynecol Obstet Invest 1999; 47:42–44. 26. Haarala M, Kiiholma P, Nurmi M, Uksila J, Alanen A. The role of Borrelia burgdorferi in interstitial cystitis. Eur Urol 2000; 37:395–399. 27. Potts JM, Ward AM, Rackley RR. Association of chronic urinary symptoms in women and Ureaplasma urealyticum. Urology 2000; 55:486–489. 28. Keay S, Zhang CO, Trifillis AL, Hebel JR, Jacobs SC, Warren JW. Urine autoantibodies in interstitial cystitis. J Urol 1997; 157:1083–1087. 29. Ochs RL. Autoantibodies and interstitial cystitis. Clin Lab Med 1997; 17:571–579. 30. Mattila J, Linder E. Immunoglobulin deposits in bladder epithelium and vessels in interstitial cystitis: possible relationship to circulating antiintermediate filament autoantibodies. Clin Immunol Immunopathol 1984; 32:81–89. 31. Oravisto KJ. Interstitial cystitis as an autoimmune disease. Eur Urol 1980; 6:10–13. 32. Pang X, Cotreau-Bibbo MM, Sant GR, Theoharides TC. Bladder mast cell expression of high affinity oestrogen receptors in patients with interstitial cystitis. Br J Urol 1995; 75:154–161. 33. Vliagoftis H, Dimitriadou V, Boucher W, et al. Estradiol augments while tamoxifen inhibits rat mast cell secretion. Int Arch Allergy Immunol 1992; 98:398–409. 34. Felsen D, Frye S, Trimble LA, et al. Inflammatory mediator profile in urine and bladder wash fluid of patients with interstitial cystitis. J Urol 1994; 152:355–361. 35. Erickson DR, Belchis DA, Dabbs DJ. Inflammatory cell types and clinical features of interstitial cystitis. J Urol 1997; 158:790–793. 36. Parsons CL, Bautista SL, Stein PC, Zupkas P. Cyto-injury factors in urine: a possible mechanism for the development of interstitial cystitis. J Urol 2000; 164:1381–1384. 37. Lutgendorf SK, Kreder KJ, Rothrock NE, Ratliff TL, Zimmerman B. Stress and symptomatology in patients with interstitial cystitis: a laboratory stress model. J Urol 2000; 164:1265–1269. 38. Spanos C, Pang X, Ligris K, et al. Stress-induced bladder mast cell activation: implications for interstitial cystitis. J Urol 1997; 157:669–672. 39. Ito T, Stein PC, Parsons CL, Schmidt JD. Elevated stress protein in transitional cells exposed to urine from interstitial cystitis patients. Int J Urol 1998; 5:444–448.

278

Griebling

40. Theoharides TC, Pang X, Letourneau R, Sant GR. Interstitial cystitis: a neuroimmunoendocrine disorder. Ann NY Acad Sci 1998; 840:619–634. 41. Pontari MA, Hanno PM, Wein AJ. Logical and systematic approach to the evaluation and management of patients suspected of having interstitial cystitis. Urology 1997; 49(suppl 5A):114–120. 42. Denson MA, Griebling TL, Cohen MB, Kreder KJ. Comparison of cystoscopic and histological findings in patients with suspected interstitial cystitis. J Urol 2000; 164: 1908–1911. 43. Higson RH, Smith JC, Whelan P. Bladder rupture: an acceptable complication of distension therapy? Br J Urol 1978; 50:529–534. 44. Waxman JA, Sulak PJ, Keuhl TJ. Cystoscopic findings consisitent with interstitial cystitis in normal women undergoing tubal ligation. J Urol 1998; 160:1663–1667. 45. Chambers GK, Fenster HN, Cripps S, Jens M, Taylor D. An assessment of the use of intravesical potassium in the diagnosis of interstitial cystitis. J Urol 1999; 162:699– 701. 46. Parsons CL. Potassium sensitivity test. Tech Urol 1996; 2:171–173. 47. Teichman JM, Nielsen-Omeis BJ. Potassium leak test predicts outcome in interstitial cystitis. J Urol 1999; 161:1791–1794; discussion 1794–1796. 48. Parsons CL, Greenberger M, Gabal L, Bidair M, Barme G. The role of urinary potassium in the pathogenesis and diagnosis of interstitial cystitis. J Urol 1998; 159:1862– 1866; discussion 1866–1867. 49. Erickson DR, Herb N, Ordille S, Harmon N, Bhavanandan VP. A new direct test of bladder permeability. J Urol 2000; 164:419–422. 50. Whitmore KE. Self-care regimens for patients with interstitial cystitis. Urol Clin North Am 1994; 21:121–130. 51. Webster DC, Brennan T. Use and effectiveness of psychological self-care strategies for interstitial cystitis. Health Care Women Int 1995; 16:463–475. 52. Slade D, Ratner V, Chalker R. A collaborative approach to managing interstitial cystitis. Urology 1997; 49(suppl 5A):10–13. 53. Webster DC. Recontextualizing sexuality in chronic illness: women and interstitial cystitis. Health Care Women Int 1997; 18:575–589. 54. Bade JJ, Peeters JM, Mensink HJ. Is the diet of patients with interstitial cystitis related to their disease? Eur Urol 1997; 32:179–183. 55. Chang PL. Urodynamic studies in acupuncture for women with frequency, urgency and dysuria. J Urol 1988; 140:563–566. 56. Geirsson G, Wang YH, Lindstrom S, Fall M. Traditional acupuncture and electrical stimulation of the posterior tibial nerve. A trial in chronic interstitial cystitis. Scand J Urol Nephrol 1993; 27:67–70. 57. Lynch DF Jr. Empowering the patient: hypnosis in the management of cancer, surgical disease and chronic pain. Am J Clin Hypn 1999; 42:122–130. 58. Hanno PM. Amitriptyline in the treatment of interstitial cystitis. Urol Clin North Am 1994; 21:89–91. 59. Theoharides TC, Sant GR. Hydroxyzine therapy for interstitial cystitis. Urology 1997; 49(suppl 5A):108–110. 60. Edwards L, Bucknall TE, Makin C. Interstitial cystitis: possible cause and clinical study of sodium cromoglycate. Br J Urol 1986; 58:95–96. 61. Jepsen JV, Sall M, Rhodes PR, Schmidt D, Messing E, Bruskewitz RC. Long-term experience with pentosanpolysulfate in interstitial cystitis. Urology 1998; 51:381–387. 62. Hwang P, Auclair B, Beechinor D, Diment M, Einarson TR. Efficacy of pentosan polysulfate in the treatment of interstitial cystitis: a meta-analysis. Urology 1997; 50:39– 43.

Interstitial Cystitis

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63. Hanno PM. Analysis of long-term Elmiron therapy for interstitial cystitis. Urology 1997; 49(suppl 5A):93–99. 64. Hansen HC. Interstitial cystitis and the potential role of gabapentin. South Med J 2000; 93:238–242. 65. Parkin J, Shea C, Sant GR. Intravesical dimethyl sulfoxide (DMSO) for interstitial cystitis: a practical approach. Urology 1997; 49(suppl 5A):105–107. 66. Parsons CL, Housley T, Schmidt JD, Lebow D. Treatment of interstitial cystitis with intravesical heparin. Br J Urol 1994; 73:504–507. 67. Sant GR, LaRock DR. Standard intravesical therapies for interstitial cystitis. Urol Clin North Am 1994; 21:73–83. 68. Peters KM, Diokno AC, Steinert BW, Gonzalez JA. The efficacy of intravesical bacillus Calmette-Guerin in the treatment of interstitial cystitis: long-term followup. J Urol 1998; 159:1483–1486; discussion 1486–1487. 69. deSeze M, Wiart L, Ferriere J, deSeze MP, Joseph P, Barat M. Intravesical instillation of capsaicin in urology: a review of the literature. Eur Urol 1999; 36:267–277. 70. Chancellor MB, deGroat WC. Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder. J Urol 1999; 162:3–11. 71. Lazzeri M, Benefoti P, Spinelli M, Zanollo A, Barbagli G, Turini D. Intravesical resiniferatoxin for the treatment of hypersensitive disorder: a randomized placebo controlled study. J Urol 2000; 164:676–679. 72. Malloy TR, Shanberg AM. Laser therapy for interstitial cystitis. Urol Clin North Am 1994; 21:141–144. 73. Chai TC, Zhang C, Warren JW, Keay S. Percutaneous sacral third nerve root neurostimulation improves symptoms and normalizes urinary HG-EGF levels and antiproliferative activity in patients with interstitial cystitis. Urology 2000; 55:643–646. 74. Irwin PP, Hammonds WD, Galloway NTM. Lumbar epidural blockade for management of pain in interstitial cystitis. Br J Urol 1993; 71:413–416. 75. Hohenfellner M, Black P, Linn JF, Dahms SE, Thuroff JW. Surgical treatment of interstitial cystitis in women. Int Urogynecol J Pelvic Floor Dysfunct 2000; 11:113–119. 76. Linn JF, Hohenfellner M, Roth S, et al. Treatment of interstitial cystitis: comparison of subtrigonal and supratrigonal cystectomy combined with orthotopic bladder substitution. J Urol 1998; 159:774–778. 77. Rupp BW, Perry BB, Griebling TL, Weigel JW, Titler MG. Quality of life in women with interstitial cystitis following cystourethrectomy and continent urinary diversion using the Indiana pouch [abstract]. J Urol 2000; 163(suppl):62A. 78. Baskin LS, Tanagho EA. Pelvic pain without pelvic organs. J Urol 1992; 147:683–686.

17 Abdominal Approach to Apical Prolapse JENNY JO and CHERYL B. IGLESIA Washington Hospital Center Washington, D.C., U.S.A.

I.

INTRODUCTION

The true prevalence of pelvic floor prolapse is unknown. It is estimated that 500,000 surgical procedures for prolapse are performed annually in the United States. Vaginal vault prolapse comprises 18.2% [1,2] of all the different types of pelvic organ prolapse, with an estimated occurrence of 0.2–4.4% following a hysterectomy [3,4]. Marchionni et al. prospectively evaluated 448 of 2670 patients who underwent either a total vaginal or abdominal hysterectomy for nonmalignant disease [5]. Of the 448 patients, 20 (4.5%) developed vault prolapse at a mean follow-up of 11 years (range 9–13 years). Prolapse was the primary indication for hysterectomy in 14 of the 20 patients who developed recurrent vaginal vault prolapse. II. ANATOMY, ETIOLOGY, AND PATHOPHYSIOLOGY The support system of the pelvis is made up of three major components: muscles, nerves, and connective tissue or endopelvic fascia. Both direct trauma (e.g., vaginal birth) and indirect trauma (e.g., chronic lung disease) to these important structures can disrupt the integrity of the pelvic floor and predispose a patient to pelvic organ prolapse. Connective tissue abnormalities and certain neurological disorders may also place certain patients at higher risk for development of pelvic organ prolapse [6]. The majority of the support for the pelvic organs comes from the muscles of the pelvic diaphragm, consisting of the coccygeus muscle and the leva281

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tor ani muscle. The levator ani muscle exists in a baseline tonic contractile state and has the ability to contract voluntarily as needed; it derives its primary innervation from the anterior roots of sacral nerves 2–4. The connective tissue or endopelvic fascia of the pelvis augments this support from the pelvic musculature by stabilizing the organs in their correct anatomical position [7,8]. In its normal state, the vagina is extremely well supported and, in turn, offers support to its surrounding structures, such as the urethra, bladder, cervix, and rectum. If the vagina is not well supported, the weakened areas will manifest itself as either cystocele (anterior prolapse), rectocele (posterior prolapse), enterocele (small bowel prolapse), or uterine and vaginal vault prolapse (apical prolapse). The connective tissue supporting the vagina is at three levels: level I consists of the endopelvic fascia and ligaments at the cervix and upper vagina, level II support comes from the lateral attachment of the vagina to the arcus tendineus fasciae pelvis along the middle portion of the vagina, and level III support describes the lower third of the vagina that is supported by the perineal membrane and body [7,9,10]. Furthermore, the anterior and posterior vagina are supported by the pubocervical and rectovaginal fascia, respectively. After the uterus and cervix are removed, vaginal vault prolapse can occur if the vault is not properly anchored to the cardinal and uterosacral ligaments. However, if the patient has preexisting prolapse or if the supporting ligaments are noted to be attenuated, additional surgeries or modifications may be indicated if there is a higher risk of subsequent vault prolapse. A full evaluation of all the pelvic floor defects is necessary since 72% of vault prolapse cases are associated with other pelvic floor defects [2,11]. In addition to anatomical correction of prolapse, the pelvic floor surgeon should also consider correction of urinary and/or fecal incontinence.

III. SURGICAL APPROACH TO APICAL PROLAPSE A.

Technique of Abdominal Sacrocolpopexy

First described in 1962 by Lane [12], the abdominal sacrocolpopexy is an operation that has withstood the test of time and has one of the best long-term success rates for the treatment of vaginal vault prolapse. In this operation, the abdominal cavity is entered, and the vagina is attached to the sacrum with an intervening piece of mesh, which acts as a connecting bridge for support. The operation is often performed in conjunction with other procedures to correct pelvic organ prolapse, such as a retropubic urethropexy for management of stress incontinence, paravaginal repair, cul-de-sac obliteration, and posterior colpoperineorrhaphy. Patients undergoing this operation should have an adequate preoperative bowel prep. A history of diverticulitis is a relative contraindication to this procedure, particularly with the use of synthetic mesh. The operation is approached through a vertical midline or transverse incision. If a concomitant retropubic procedure is planned, a Cherney incision, by which the rectus muscles are bisected at their tendinous insertion to the pubis, is ideal for this procedure. With an adequate retractor in place, the small intestine is packed out of the pelvis. The procedure begins with the presacral dissection. The sacral promontory is palpated, the bifurcation of the aorta is identified, and

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both ureters are identified and dissected if not readily visualized. It is often useful to retract the sigmoid colon to the left laterally with either a St. Mark’s or Sweetheart-type retractor. The peritoneum overlying the sacrum is grasped with long forceps and incised using a long-handled electrosurgical tip. The dissection is carried inferiorly for 4–5 cm to the level of the second or third sacral vertebra. A fine network of areolar tissue is encountered through which hydrodissection with a Vital-Vue suction-irrigation device (Davis and Geck, Danbury, CT) is extremely helpful for visualization. The middle sacral vessels are encountered and should be avoided. The anterior longitudinal ligament of the sacrum is visualized as a glistening white sheath. Two or three nonabsorbable sutures should be sewn to this ligament and are usually placed to the right of the middle sacral vessels. We prefer double-armed CV 2-0 Gore-tex (W. L. Gore and Associates, Flagstaff, AZ) sutures, but comparable stitches can be used. If bleeding in the presacral space is encountered, then vascular clips, pressure, bone wax, or in extreme cases, sterile titanium thumbtacks may be necessary to control hemorrhage. Profuse bleeding can be encountered from the presacral veins as they enter the bony foraminae of the sacrum. The risk of significant hemorrhage from laceration of the presacral vessels has been estimated to be between 1.2% and 2.6% [13,14]. Once the presacral sutures have been placed, then these sutures should be tagged and held for later attachment to the graft. Attention is then turned to the vaginal portion of the procedure. A doublegloved hand is place in the vagina, and the vagina is uplifted and grasped with Allis clamps at the corners of its apex. A lucite rod or an appropriately gauged EEA (end-to-end anastomosis) sizer may also substitute as an excellent vaginal stent. The peritoneum overlying the vagina is then incised with Metzenbaum scissors, and the dissection is taken posteriorly down to the level of the detached rectovaginal septum or as far as possible down the posterior vagina. Dissection anteriorly is carried out to the level of the pubocervical fascial and its detachment above the bladder. Three or four pairs of permanent sutures are placed anteriorly and posteriorly as well. Occasionally, due to the redundancy of excess vaginal length, a wedge of vaginal mucosa must be excised from the apex to shorten its length, and the cuff is then closed prior to placement of the graft-anchoring sutures. If indicated, a hysterectomy is performed prior to the vaginal dissection unless the decision has been made to maintain the cervix as in the abdominal sacrocervicopexy procedure. Once the parallel pairs of permanent sutures are placed almost full thickness through the vagina and endopelvic fascial connective tissue, then the graft material is ready to be attached. Choice of graft material has been described in numerous case series without any clear consensus on the ideal graft for sacrocolpopexy. Graft material may consist of synthetic meshes, autologous rectus fascia or fascia lata graft, or a variety of new allogenic graft materials. Two pieces of appropriate size mesh (usually 2–4 cm wide by 4–8 cm long) are fashioned and attached to the vagina, both anteriorly and posteriorly. The previously placed vaginal sutures are then sutured through the chosen graft material and tied so that the knots are on the peritoneal side of the graft. Others have described placing a circumferential ring of mesh around the vaginal apex instead of using strips for even distribution [15–17]. Before the mesh is attached to the sacrum, a cul-de-sac obliteration utilizing either the concentric Moschowitz technique or the linear Halban technique is

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performed. In this procedure, peritoneum overlying the sigmoid colon and pelvic side walls is obliterated utilizing permanent sutures. The most inferior stitch is passed through the distal end of the posterior graft. Once the cul-de-sac is copiously irrigated and drained, then the previously placed presacral stitches are passed through the superior margins of both grafts and tied down, supporting the vagina with no significant tension placed on either the graft or vagina. Several permanent sutures are usually required between anterior and posterior meshes to prevent any small bowel from herniating between the two grafts. The mesh is re-peritonealized as much as possible, and the rest of the operation, including any retropubic or vaginal procedures, is completed. Patients are placed on broadspectrum antibiotics preoperatively and for 48–72 h postoperatively. B.

Choice of Graft Material

When deciding which graft material will be used for vaginal vault suspension, the patient must be counseled on the options, risks, and benefits of the different types of material available. Autologous fascia may be used, but is associated with a higher risk of recurrence by some authors but not others [18–24]. The benefit of using autologous fascia is that it is natural and may have a lower infection and rejection rate. A distinct disadvantage is that additional surgery is required for harvesting of the graft. If rectus fascia is used, the patient may be predisposed to future incisional hernia formation. Donor (allogenic) cadaver fascia is also an option if the patient’s own fascia is weak. Complications with mesh materials include rejection, erosion, and infection [21–23]. A review of 15 articles on sacrocolpopexies reported up to a 9% mesh erosion rate. Fortunately, the majority of patients who have had their mesh removed for erosion or rejection do not prolapse afterward [25,28]. Table 1 lists potential complications associated with this procedure. The risk of recurrent prolapse following a sacrocolpopexy ranges from 0% to 32% in patients followed up to 18 years postoperatively [18–21,25,26]. Failure may be attributable to mesh choice, tissue integrity, or technique, including inadequate cul-de-plasty [18,24]. Few comparative studies have been written on the vaginal versus abdominal approach to prolapse. Sze et al. [26] and Benson et al.

Table 1 Operative Complications Associated with Abdominal Sacrocolpopexy Reference

Number of patients

2 25 26 18 20

20 15 56 9 163

19

8

Complications 1 DVT, 1 wound infection, 1 ileus No complications reported 2 ileus, 1 phlebitis, 7 fevers No complications reported 2 severe hemorrhages (precluding 1 from completing surgery), 1 enterotomy, 5 cystomies, 1 proctotomy, 1 wound dehiscence, 2 partial ureteral obstructions, 1 small bowel obstruction requiring reoperation and resection, 2 transient femoral nerve palsies, 2 ileus 1 EBL of 650 cc, 1 small bowel obstruction

DVT, deep venous thrombosis; EBL, estimated blood loss.

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Table 2 Vaginal Sacrospinous Fixation Versus Abdominal Sacrocolpopexy Route of surgery

Number of patients

Mean follow-up

Recurrent prolapse 18 (33%)

Vaginal

54

24 months

Abdominal

47

23.1 months

9 (19%)

Complications 2 transfusions, 5 incidents of transient gluteal pain, 5 fevers 2 ileus, 1 phlebitis, 7 fevers

Source: Data from Ref. 26.

[32] have found abdominal sacrocolpopexy to be superior to sacrospinous ligament fixation. The abdominal route was also found to be superior in maintaining vaginal length when compared to vaginal sacrospinous ligament suspension. Tables 2 and 3 summarize findings from both of these studies. Lienemann et al. evaluated 25 patients after sacrocolpopexies using functional cinemagnetic resonance imaging (MRI) 12 months postoperatively [28]. The exact point of vaginal fixation to the sacrum could be identified in 15 patients, and the mesh was fully identified in 13 patients and partially in 9. In all 3 patients with recurrent vaginal vault prolapse, the mesh could not be identified on MRI. IV. LAPAROSCOPIC PROCEDURES Currently, there are limited, but growing, data on the efficacy of the laparoscopic approach to vaginal vault repair [29,32,33]. Two types of laparoscopic approaches to vault repair have been described: laparoscopic sacrocolpopexy and laparoscopic uterosacral ligament suspension. Nezhat et al. reported on 15 patients who underwent a laparoscopic sacrocolpopexy with culdeplasty; they had a 0% failure rate at 3–40 months postoperatively [30]. There was one conversion to laparotomy due to presacral hemorrhage that could not be controlled laparoscopically. The mean operating time was 170 min with an estimated mean blood loss of 226 cc, excluding the one hemorrhage. Similar findings were reported in 1997 by Ross [31]. Ross also reported a 100% success rate with no recurrent vault prolapse. Both studies reported normal return to sexual function for women who were sexually active (Table 4). Since only a few limited case series have been reported, further prospective studies are necessary to compare long-term results of laparoscopic versus abdominal sacrocolpopexies in terms of objective cure of prolapse and complication rate. Table 3 Vaginal Bilateral Sacrospinous Fixation Versus Abdominal Sacrocolpexy Route of surgery Vaginal Abdominal

Number of patients

Success rate

Need for reoperation

42 38

29% 58%

33% 16%

Source: Data from Ref. 27. Patients were followed for up to 5 years postoperatively.

31

30

Ref.

Mesh material

19

15

Number of patients

41–83

48–76

Age range (years)

Laparoscopic Sacrocolpopexy

Gortex or Mersilene Polypropylene

Table 4

20–33 months

3–40 months

Follow-up

100%

100%

Cure rate

1 conversion to laparotomy due to hemorrhage 3 cystotomies, 1 seroma, 1 inferior epigastric artery laceration

Operative complications

Normal return to sexual function, 1 paravaginal defect, 3 rectoceles, 1 stress incontinence, 3 cystitis

Normal return to sexual function

Sequelae

286 Jo and Iglesia

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Ostrzenski reported on 27 women who underwent a laparoscopic uterosacral-cardinal ligament suspension repair [32]. Of these 27 women, 11 also had an additional paravaginal repair at the time of vault suspension. The modified procedure (paravaginal plus uterosacral ligament suspension) had excellent results for the period reported (up to 42 months). Only 1 patient in the modified technique group had recurrent vault prolapse at 36 months postoperatively. VII. OTHER ABDOMINAL SURGERIES A. Technique of Abdominal Sacrocolpoperineopexy An abdominal sacrocolpoperineopexy has been described for patients with significant vault prolapse and perineal descent below the ischial tuberosities. This diagnosis is made preoperatively on either physical examination or with the aid of radiographic studies, such as a dynamic cystoproctogram or dynamic pelvic floor MRI. The technique of abdominal sacrocolpoperineopexy has been described in which the posterior mesh is attached from the sacrum and distally down to the level of the perineal body [34]. In doing this operation, two separate incisions, abdominal and perineal, are utilized. The transperineal incision is carried out within the rectovaginal space between the posterior vaginal mucosa and rectum. The cul-de-sac of Douglas is entered under direct visualization so as not to cause any rectal injury. Vaginal or rectal stents again may aid dissection. The graft is then brought down from the cul-de-sac and reattached with small-caliber permanent suture to the perineal body after perineorrhaphy has been performed. Cundiff et al. reported some preliminary data on 19 women who had undergone an abdominal sacralcolpoperineopexy for vault prolapse [35]. Of the patients, 14 had stage III or IV prolapse, and all had enteroceles and perineal descent. Although the results were short term (4–24 weeks postoperative follow-up), all patients had shown improvement in their prolapse by at least one level. B. Abominal Sacrospinous Ligament Suspension In 1999, Hale and Rogers reported on 55 women who had an abdominal sacrospinous ligament colpopexy for vaginal vault prolapse [36]. There were 39 who had bilateral sacrospinous colpopexy, and 16 had the unilateral procedure. These women were followed for an average of 23 months postoperatively, and there were no reports of recurrence to date. In 25 of the 55 women, optimal support of the anterior apical vaginal wall, as evidenced by complete and clear fixation of the vault to the unilateral or bilateral sacrospinous ligment, could not be obtained through the abdominal sacrospinous approach only; thus, they required an additional sacrocolpopexy at the same time for these large apical defects. We do not recommend this procedure to be used as the primary technique for the correction of isolated vault prolapse. VIII. CONCLUSION Management of vaginal vault prolapse includes a variety of vaginal, transabdominal, and laparoscopic techniques. As the population continues to age, the prevalence of this disorder is expected to increase dramatically, and pelvic recon-

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structive surgeons must learn a variety of techniques to deal with disorders of vaginal support. Sound knowledge of anatomy and surgical judgment, including correct identification of all perceivable pelvic floor defects, is necessary for optimal outcome.

REFERENCES 1. Duton CJ, Mikuta JJ. Posthysterectomy vaginal vault prolapse. Postgrad Obstet Gynecol 1988; 8:1–6. 2. Winters JC, Cespedes RD, VanLangendonck R. Abdominal sacral colpopexy and abdominal enterocele repair in the management of vaginal vault prolapse. Urology 2000; 56(suppl 6A):55–63. 3. Cruikshank SH. Sacrospinous fixation: should this be performed at time of vaginal hysterectomy? Am J Obstet Gynecol 1991; 164:1072–1076. 4. Hardiman P, Drutz H. Sacrospinous vault suspension and abdominal colposacropexy: success rates and complications. Am J Obstet Gynecol 1996; 175:612–615. 5. Marchionni M, Bracco GL, Checcucci V, et al. True incidence of vaginal vault prolapse. J Repro Med 1999; 44(8):679–684. 6. McIntosh LJ, Mallett VT, Frahm JD, Richardson DA, Evans MI. Gynecologic disorders in women with Ehlers-Danlos syndrome. J Soc Gynecol Invest 1995; 2(3):559–564. 7. Walters MD. Description and classification of lower urinary tract dysfunction and pelvic organ prolapse. In: Walters MD, Karram MM, eds. Urogynecology and Reconstructive Pelvic Surgery. 2nd ed. St. Louis, MO: C.V. Mosby, 1999. 8. Walters MD, Weber AM. Anatomy of the lower urinary tract, rectum, and pelvic floor. In: Walters MD, Karram MM, eds. Urogynecology and Reconstructive Pelvic Surgery. 2nd ed. St. Louis, MO: C.V. Mosby, 1999. 9. DeLancey JOL. Anatomic aspects of vaginal eversion after hysterectemy. Am J Obstet Gynecol 1992; 166:1717. 10. DeLancey JOL. Surgical anatomy of the female pelvis. In: Rock JA, Thompson JD, eds. Te Linde’s Operative Gynecology. 8th ed. Philadelphia, PA: Lippincott-Raven Publishers, 1997. 11. Richter K. Massive eversion of the vagina: pathogenesis, diagnosis and therapy of the true prolapse of the vaginal stump. Clin Obstet Gynecol 1982; 25:897–912. 12. Lane FE. Repair of post-hysterectemy vaginal vault prolapse. Obstet Gynecol 1962; 20:72–77. 13. Sutton GP, Addison WA, Livengood CH III, Hammond CB. Life-threatening hemorrhagecomplicating sacral colpopexy. Am J Obstet Gynecol 1985; 140(7):836–837. 14. Timmons MC, Kohler MF, Addison WA. Thumbtack use for control of presacral bleeding with description of an instrument for thumbtack application. Obstet Gynecol 1991; 78:313–315. 15. Addison WA, Livengood CH, Parker RT. Vaginal vault prolapse with emphasis on management by transabdominal sacral colpopexy. Postgrad Obstet Gynecol 1998; 8: 1–7. 16. Addison WA, Timmons MC, Wall LL, Livengood CH III. Failed abdominal sacral colpopexy: observations and recommendations. Obstet Gynecol 1989; 74(3 pt 2):480– 483. 17. Karram MM, Sze EHM, Walters MD. Surgical treatment of vaginal vault prolapse. In: Walters MD, Karram MM, eds. Urogynecology and Reconstructive Pelvic Surgery. 2nd ed. St. Louis, MO: C. V. Mosby, 1999. 18. Kulkarni S. Surgery for post-hysterectomy vaginal prolapse. West Indian Med J 1993; 42(2):65–67.

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19. Lansman HH. Posthysterectomy vault prolapse: sacral colpopexy with dura mater graft. Obstet Gynecol 1984; 63(4):577–582. 20. Timmons MC, Addison WA, Addison SB, Cavenar MG. Abdominal sacral colpopexy in 163 women with posthysterectomy vaginal vault prolapse and enterocele. J Reprod Med 1992; 37(4):323–327. 21. Iglesia CB, Fenner DE, Brubaker L. The use of mesh in gynecologic surgery. Int Urogynecol J 1997; 8:105–115. 22. Patsner B. Mesh erosion into the bladder after abdominal sacral colpopexy. Obstet Gynecol 2000; 95(6, p 2):1029. 23. Unger JB. A persistent sinus tract from the vagina to the sacrum after treatment of mesh erosion by partial removal of a Gore-tex soft tissue patch. Am J Obstet Gynecol 1999; 181(3):762–763. 24. Podratz K, Ferguson L, Hoverman V, et al. Abdominal sacral colpopexy for posthysterectomy vaginal vault descensus. J Pelvic Surg 1995; 1:18–23. 25. Schettini M, Fortunato P, Gallucci M. Abdominal sacral colpopexy with prolene mesh. Int Urogynecol J 1999; 10:295–299. 26. Sze EHM, Kohli N, Miklos JR, Roat T, Karram MM. A retrospective comparison of abdominal sacrocolpopexy with Burch colposuspension versus sacrospinous fixation with transvaginal needle suspension for the management of vaginal vault prolapse and coexisting stress incontinence. Int Urogynecol J 1999; 10:390–393. 27. Benson J, Lucente V, McClellan E. Vaginal versus abdominal reconstructive surgery for the treatment of pelvic support defects: a prospective randomized study with longterm outcome evaluation. Am J Obstet Gynecol 1996; 175:1419–1422. 28. Lienemann A, Sprenger D, Anthuber C, Baron A, Reiser M. Functional cine magnetic resonance imaging in women after abdominal sacrocolpopexy. Obstet Gynecol 2001; 97(1):81–85. 29. Paraiso MFR, Falcone T, Walters MD. Laparoscopic surgery for enterocele, vaginal apex prolapse and rectocele. Int Urogynecol J 1999; 10(4):223–229. 30. Nezhat CH, Nezhat F, Nezhat C. Laparoscopic sacral colpopexy for vaginal vault prolapse. Obstet Gynecol 1994; 84(5):885–888. 31. Ross JW. Techniques of laparoscopic repair of total vault eversion after hysterectomy. J Am Assoc Gynecol Laparosc 1997; 4(2):173–183. 32. Ostrzenski A. Laparoscopic colposuspension for total vaginal prolapse. Int J Gynecol Obstet 1996; 55:147–152. 33. Fedele L, Garsia S, Bianch S, Albiero A, Dorta M. A new laparoscopic procedure for the correction of vaginal vault prolapse. J Urol 1998; 159(4):1179–1182. 34. Hale D. Surgery for pelvic organ prolapse. In: Gershenson DC, DeCherney AH, Curry SL, Brubaker L, eds. Operative Gynecology. 2nd ed. Philadelphia, PA: W. B. Saunders, 2001. 35. Cundiff GW, Harris RL, Coates K, Low VHS, Bump RC, Addison WA. Abdominal sacral colpoperineopexy: a new approach for correction of posterior compartment defects and perineal descent associated with vaginal vault prolapse. Am J Obstet Gynecol 1997; 177(6):1345–1355. 36. Hale DS, Rogers RM Jr. Abdominal sacrospinous ligament colposuspension. Obstet Gynecol 1999; 94(6):1039–1041.

18 Vaginal Prolapse: Types and Choice of Operation for Repair DIONYSIOS K. VERONIKIS St. John’s Mercy Medical Center St. Louis, Missouri, U.S.A.

I.

INTRODUCTION

Vaginal reconstructive surgery is concerned with returning defective vaginal anatomy to a normal state. One must clearly understand the objective desired (i.e., what is the “normal” state) if normal relationships are to be restored. Various forces that act on inherent weaknesses of the birth canal supports cause genital prolapse and may virtually turn the vagina inside out. In evaluating the patient’s problem, the physician must determine the primary weakness because the most important single step in treatment is to correct, and at times overcorrect, the primary site of damage. Unless this is done, progression is not arrested, and recurrence must be expected despite surgical repair of secondary damages. The pelvic connective tissue spaces and septa are relatively constant in existence, but are subject to individual variation in location. Finding them promptly and safely at surgery permits careful hemostatic dissection. Since the spaces and septa have a physiological function, enabling the pelvic organs to function independently, they should be restored and carefully preserved at the time of surgery. Colpography demonstrates an almost horizontal axis to the normal upper vagina of the patient in the standing position, which is accentuated by straining. The upper vagina and the rectum lie on the similarly horizontal levator plate, formed posterior to the rectum by the fused levator ani muscles. The cervix and upper vagina, though movable, are held over the levator plate posterior to the genital hiatus by the cardinal and uterosacral ligaments. Pathological elongation 291

292

Veronikis

of these ligaments may permit the vagina to evert. If, in addition, the axis of the levator plate is defective, prolapse is even more likely to develop. Postoperative recurrent prolapse is less likely to develop when the goal of the vaginal reconstructive operation is to maintain depth and reconstitute the horizontal upper axis. Basically, genital prolapse is caused by eversion of the upper vagina, eversion of the lower vagina, or both. These conditions may occur separately or together at different times of life, and the etiological factors involved are quite different. The objective of vaginal reconstruction should result in an operation designed to restore normal anatomical relationships, particularly to provide depth and adequate support of the vaginal axis. This axis normally should incorporate a perineal superior convexity in its lower half when the patient is standing. Restoration and strengthening of the levator plate will minimize any persistent tendency toward subsequent eversion of prolapse of the vagina because intra-abdominal pressure will then serve to press the upper portion of the vagina posteriorly toward the hollow of the sacrum and more firmly against an adequately reconstructed levator plate. Massive eversion of the vagina can occur with or without the presence of the uterus, and can be of varying degrees (Figs. 1 and 2) . The vault of the vagina can descend to the midportion of the vagina, a partial inversion, or all the way to the introitus or beyond, a massive eversion. It is usually accompanied by coincident cystocele (Fig. 3) and rectocele and invariably by coincident enterocele. It is my strong conviction that all elements of pelvic weakness should be identified, and if one is to be repaired, all should be repaired to lessen the necessity for future reoperation. Although the diagnosis can be established by examination in the supine position on the examining table, the effective influence of gravity often adds

Figure 1 Neglected uterine procidentia with enterocele, displacement and distention cystocele, and complete eversion of the vagina. Note erosion of vagina.

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Figure 2 Uterine procidentia with enterocele, displacement and distention cystocele, and complete eversion of the vagina. Note absence of vaginal erosion.

considerable information, and coincident examination of the patient in the standing position with Valsalva is very beneficial. With massive prolapse, there is usually a lack of any urinary stress incontinence symptoms (Fig. 4). At times, following surgery for prolapse with restoration of normal pelvic anatomy, there may be new onset incontinence by relieving the “kink” at the bladder neck and straightening the urethra from the prolapse back

Figure 3 Relationship of the anterior vaginal wall to the bladder and the uterine fundus. Note incomplete bladder emptying.

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Veronikis

Figure 4 How the prolapse kinks and obstructs the bladder neck, preventing bladder emptying and urinary incontinence. into the pelvis. Therefore, it is imperative that the surgeon be aware of this possibility and take adequate diagnostic steps within the planned surgical procedure to recognize and treat a particular patient’s tendency toward postoperative incontinence. An ideal operation to correct the problem of symptomatic eversion of the vaginal vault is one in which all of the necessary surgery can be done through the same operative exposure. For transvaginal sacrospinous colpopexy with colporrhaphy, precise and exact knowledge of the particular patient’s individual structural weaknesses and of her particular anatomy, including the tissue planes and spaces and connective tissue septa, is essential as it provides the opportunity for careful hemostatic dissection, virtually eliminating blood loss and the need for transfusion. In a patient with uterine procidentia, usually of long-standing duration (Fig. 1), and in whom surgically usable strength of the cardinal-uterosacral ligament complex cannot be demonstrated, sacrospinous colpopexy, enterocele repair with anterior and posterior colporrhaphies, as well as indicated bladder neck surgery should be performed to eliminate operative failure and recurrence of prolapse symptoms and/ or new onset of incontinence (Figs. 5–8). The sacrospinous ligaments, although not peculiarly gynecological supporting structures, are strong and are very useful substitutes for a weakened and atrophic cardinal-uterosacral ligament complex in supporting such a vaginal vault. Reconstructive gynecological surgical philosophy and the surgical execution of reconstructive procedures ought to embrace techniques that are exacting and must meet the specific needs of a particular patient. Perhaps a hallmark of vaginal surgery is the development of vaginal wall flaps, utilizing the avascular planes between organs to reduce blood loss, minimize tissue trauma, and gain access to potential pelvic spaces that provide exposure and facilitate the operative proce-

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Figure 5 Posthysterectomy prolapse 9 months after hysterectomy for uterine procidentia. Note developing erosion and pressure from enterocele. dure. This surgical attitude and exposure permits an entire array of surgical therapy to the underlying structures and organs as well as to the vagina, including excision of traumatized overdistended vaginal wall, excision of enterocele, repair of cystocele and rectocele, repositioning of the vagina over the levator plate, and reconstruction of the perineum and introitus. It is this basic philosophy of exposure and flap generation that bridges plastic surgery with gynecological recon-

Figure 6 Posthysterectomy prolapse 3 years after hysterectomy for prolapse. Note wrinkling from severe distention.

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Figure 7 Shown is a patient with posthysterectomy prolapse and no history of urinary incontinence. Note kink at the bladder neck. structive surgery. It is imperative that a gynecological reconstructive surgeon be versatile, able to apply and choose from several surgical techniques to remedy one and the same clinical situation to be able to choose the operation that best achieves the desired surgical goal for a particular patient. When the vagina is used for surgical exposure during vaginal reconstructive surgery, the goal is resolutely to reconstruct a functional, pain-free, pliable, disten-

Figure 8 Shown is a patient with urinary retention 4 months after bladder neck surgery. Note location of vaginal apex.

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sible, and well-supported structure. Vaginal reconstructive surgery is similar to plastic surgery in that it involves the development of flaps. These are essentially full-thickness vaginal wall advancement flaps. The anterior and posterior vaginal walls are mobilized by careful dissection within the vesicovaginal and rectovaginal spaces, avoiding splitting the full thickness. Splitting the vaginal wall can be correlated to harvesting split-thickness skin grafts. The amount of full-thickness vaginal wall that is removed from the herniated damaged areas, the overall dimensions of the vaginal caliber and length, and the reconstruction of the perineum and introital aperture are many times guided by the indications for surgery and the surgical judgment of the surgeon, which must also take into account repair of all defective vaginal sites. By far the most frequent damage is that occurring in the midline structures, that is, the urethra and anterior vaginal wall, so that most of the reconstructive surgical repair work is concentrated in the midline. Emphasis must be placed on identifying all the sites of weakness and performing a reconstruction literally “tailor made” for each patient. A systematic method for evaluating all the sites of damage is essential for surgical success. Preoperative and intraoperative reassessment of damage must be performed, confirming the defects and perhaps identifying new defective sites in light of better exposure and anesthesia. The pelvic connective tissue spaces are almost constant in existence, but are subject to individual variation. Identifying them at surgery should permit precise dissection and is the cornerstone of reconstructive surgery. The goals of reconstructive surgery are to restore anatomy, restore function and relieve the symptoms. The objective of vaginal reconstruction should be an operation designed to restore normal anatomical relationships, particularly to provide vaginal depth and adequate support of the vaginal caliber and axis. The massively everted vagina constitutes a completely decompensated vaginal organ with multiple defects in the midline, at the vaginal apex/vault of the vagina, and laterally. It is in essence a massive pelvic floor hernia composed of bladder, small bowel, rectum, vagina, and at times sigmoid colon. When all the areas of pelvic floor prolapse and anterior vaginal segment damage have been identified and evaluated, the surgeon must correlate the observations with the patient’s symptoms. In addition, any other laboratory tests that may further explain any additional causes of urinary incontinence, such as detrusor dysfunction or other factors, must be figured into the surgical plan, and attempts must be made to correct these before a surgical repair of the cystocele is untertaken. Mindful that it is hard to make a patient feel better by operating on something that is asymptomatic, the goals of surgical therapy must be clear. These are (1) relief of symptoms, (2) restoration of anatomy to normal, and (3) restoration of function to normal. However, when a patient is to undergo a pelvic reconstructive operation for other indications, such as symptomatic prolapse of the uterus, a rectocele, or an enterocele, any cystocele, even one that is asymptomatic, should be repaired. Other than that, there is little indication for operating on an asymptomatic cystocele except in the case of a demonstrated and sustained progression from year to year with additional areas of developing prolapse and symptoms. Conversely, when a patient demonstrates coincident weakness of the posterior vaginal wall, perineum, or both, a posterior colporrhaphy and perineorrhaphy as

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needed help support the anterior vaginal wall and aid the long-term effectiveness of anterior colporrhaphy. When there is an obvious coincident prolapse of the vaginal vault and/or uterus, vaginal hysterectomy and vaginal vault fixation must be addressed and properly repaired to best achieve a long-term reconstructive result. An enterocele is an intestine-filled deepening of the cul-de-sac of Douglas between the rectum and vagina; it represents a reopening or failure of fusion of the layers of the fascia of Denonvilliers. When the same peritoneal-lined sac is present but unfilled with intestine, it represents a deep cul-de-sac of potential enterocele, and when found at surgery, it should be obliterated. Removal of an enterocele transvaginally can be effectively accomplished by resecting the sac and closing the neck by two concentric purse-string sutures of a nonabsorbable suture material such as polybutester (Novafil) because of its permanence and elasticity and the ease with which it can be handled. The goal of treatment is to identify, open, and excise the sac as well as obliterate the enterocele sac with a high ligation of its neck, incorporating and approximating the uterosacral ligmaments in the repair. Concomitantly, there should be correction of any associated pelvic weakness and thus reduction of the potential for reoccurrence. If the vaginal vault is everted, a coincident colpopexy should be performed. Previous surgery, such as retropubic urethropexy (MarshallMarchetti-Krantz, Burch, or needle suspensions-Pereyra), that changes the normal horizontal vaginal axis exposes the vulnerable cul-de-sac to the full range of changes in intra-abdominal pressure. When such surgery is performed in the presence of a deep cul-de-sac of Douglas or a poorly supported vaginal vault, the latter should be surgically corrected at the initial surgical experience for there will be a predictable incidence of subsequent enterocele requiring reoperation. Rectocele and perineal defects are separate and distinct lesions that occur in entirely different structures; however, frequently these defects coexist. A rectocele is a defect in the posterior vaginal wall that permits the rectum to herniate into the vagina. It may occur with or without a perineal defect and may be seen low within the vagina, at its midpoint, in the upper vagina, or in any combination. Rectocele is more common in multiparous patients and is in fact the most frequent weakness of the pelvis and its supporting tissue. It may be the consequence of various causes, as is a cystocele. It may be caused by damage to the posterior vaginal wall consequent to overdistention during labor and delivery (distention rectocele), or it may be seen when the posterior vaginal wall follows the descent of the vaginal vault with or without the cervix and uterus (displacement rectocele). Some women have a combination of distention and displacement, with or without a perineal defect. Rectocele is often coincident with a widened genital hiatus, with increased distance between the medial borders of the pubococcygei as a consequence of multiparity. The perineal body is a pyramidal fibroelastic structure found in the midline between the rectum and the vagina on a line between the ischial tuberosities. Its tone, thickness, and composition vary in different individuals. It serves as the central attachment point of various muscles, the superficial and deep transverse muscles of the perineum, the bulbocavernosus, the esternal anal sphincter, and some fibers of the levator ani. Chronic lacerations and relaxation of the perineum

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299

cause an enlarged genital hiatus and loss of support to the urethra and anterior vaginal wall. II. TECHNIQUE OF SACROSPINOUS COLPOPEXY AND COLPORRHAPHIES A careful examination under anesthesia is performed to reidentify the extent of the prolapse; the location of the everted vaginal vault; the presence of any enterocele, rectocele, cystocele, and possible paravaginal defect. For posthysterectomy vaginal vault prolapse, the prolapse is replaced within the pelvis, and a Kocher hemostat, with only one click of the locking ratchet, is applied to the hymenal margin on each side of the perineum. If a hysterectomy is to be performed prior to sacrospinous colpopexy, the hysterectomy is completed, and the sequence of surgical steps begins with the placement of the Kocher hemostat on the hymenal margin. Thus, a V-shaped incision (Fig. 9) is made through the skin of the perineum, with the top of the V wide enough that when the tissues are approximated at the conclusion of the operation, there will be an adequate introitus to assure coital comfort. The perineal skin is dissected from the underlying scar tissue and perineal body, and at the hymenal margin, the dissection proceeds under the posterior vaginal wall, carefully separating vagina from rectum by sharp dissection until the rectovaginal space is identified (Fig. 10). The dissection then proceeds to the vaginal vault. All scar tissue at the sites of the vagina from previous colporrhaphy or episiotomy is incised, and a careful search is made for any enterocele sac that will usually be present (Figs. 11–13). In posthysterectomy prolapse the enterocele will be found attached to the underside of the posterior vaginal wall. Such a sac is opened, the contents reduced, and

Figure 9 Initial stages of reconstructive surgery in a patient with vault prolapse, cystocele, and enterocele.

300

Figure 10

Veronikis

Vagina is dissected off the enterocele sac. Note thickness of vaginal wall.

the sac separated from the surrounding fibromuscular tissue. The neck of the sac is closed by ligation with a nonabsorbable monofilament suture, such as polybutester (Novafil), and the sac is excised. The dissection is then carried laterally into the pararectal space, usually the right (Figs. 14 and 15). To facilitate operative exposure, proper retractors are inserted into the pararectal space. One retractor is placed to elevate the posterior vaginal wall and cardinal ligament out of harm’s way; another is placed to displace the rectum to the contralateral side. The surface of the rectal pillar or descending

Figure 11 The enterocele sac is opened. Note thickness and location of enterocele sac.

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Figure 12 Enterocele sac further dissected, with loop of small bowel protruding past introitus.

rectal septum is further exposed, and a window is created in the rectal pillar as palpation identifies the ischial spine at either the 3 o’clock or 9 o’clock position, depending on the side of the pelvis being used. Under direct visualization of the pararectal space, the window in the pararectal space is enlarged, and the retractors are repositioned within this window, exposing the coccygeus-sacrospinous ligament complex and the ischial spine. Palpation confirms the location of the coc-

Figure 13 lated.

Small bowel mesentery past introitus when contents of enterocele are manipu-

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Figure 14 The dissected right pararectal space. The medial retractor is mobilizing the rectum away from the ischial spine. The tissue forceps is pointing at the coccygeussacrospinous ligament complex. cygeus muscle containing the sacrospinous ligament in the posterolateral wall of the pararectal space that runs in a posteromedial direction from the ischial spine to the sacrum. At a point 1.5 fingerwidths medial to the ischial spine, the coccygeus muscle-sacrospinous ligament complex is penetrated perpendicular to the direc-

Figure 15 The two sutures exiting from the superior aspect of the coccygeus-sacrospinous ligament complex.

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tion of its fibers by the tip of a ligature carrier. This penetration should be medial to the ischial spine by a distance of 1 to 1.5 fingerwidths, which makes these stitches well removed from the pudendal artery and nerve that underly the ischial spine. Some resistance should be encountered during passage of the ligature carrier through the ligament, indicating that the ligament itself has been penetrated. Traction is made to the ligature carrier (an again to the suture after the ligature carrier has been removed), confirming that the stitches have been placed in the appropriate tissues. At present and for several years, I have used synthetic sutures of size 1 monofilament nonabsorbable suture (Novafil) and another of a monofilament absorbable suture such as polydioxanone (PDS). After the ligature carrier has been removed, one end of the nonabsorbable stitch is sewn to the underside of the posterior vaginal wall using a pulley-type stitch. Both of the absorbable monofilament suture arms are threaded on a free needle passed through the full thickness of the vaginal apex about 1 cm cephalad from the site of the colpopexy. Sacrospinous colpopexy may be performed bilaterally if the vaginal vault is sufficiently wide and/or if there is a paravaginal defect. The full thickness of the anterior wall is opened in the midline directly into the vesicovaginal space, and the dissection is carried the full length of the anterior vaginal wall. The dissection is performed with scissors, and the incision is carried to the anterior margin of the vesicovaginal space. The scissor dissection is continued to the distal urethral segment, creating a plane between the urethra and the vagina, which are normally fused to each other. This incision is continued to within 1 cm of the external urethral meatus. The connective tissue capsule of the bladder is separated from the underside of the full thickness of the vagina with the scissors. Funneling of the urethra with its consequent vesicalization should be reduced by one or more Kelly-type sutures of long-lasting synthetic absorbable or nonabsorbable material. If the patient has urethral funneling as the sole departure from normal, reduction of this funneling by Kelly-type sutures may be all that is required. This may be seen in certain patients with urinary stress incontinence, but without urethral hypermobility. The connective tissue capsule of the bladder is given one or more layers of interrupted mattress sutures, sufficient to restore it to a normal dimension. If a sling urethropexy is indicated, it would be placed prior to closing the anterior vaginal wall and brought to the skin surface above the pubic symphysis for securing later in the operation. Similarly, if a coincident distention cystocele and paravaginal defect lateral detachment of the vagina is present, the time to repair this defect is prior to placing the sling. The dissection is carried laterally between the bladder and vagina to the pelvic sidewall on one or both sides as indicated. The intent is to fix with permanent interrupted sutures the lateral vaginal sulcus to the arcus tendineus. Once the dissection is carried sufficiently laterally, the paravaginal space is identified by retracting the bladder medially. This permits palpation of the ischial spine, which serves as the most cephalad point of dissection, and the arcus tendineus is visualized and or palpated laterally as it traverses the pelvic sidewall from ischial spine to pubic symphysis. The paravaginal space is developed and enlarged. A series of 00 nonabsorbable, braided, double-arm sutures are placed directly into the obturator fascia at the site of the arcus tendineus. The first suture

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is placed lateral at the level of the ischial spine, and subsequent sutures are place toward the vesicourethral junction. When all the sutures (one or both sides) are in place, they are individually sewn to the underside of the full thickness vaginal wall at the site of the sulcus and then tied. The vaginal sulcus is brought to the site of the arcus tendineus on the obturator fascia. Then, all the stitches and the free ends are cut, and the knots are buried beneath the vaginal wall. After these sutures have been tied, any redundant anterior vaginal wall is trimmed, and the remaining vagina is approximated in a running subcuticular suture of polyglycolic acid type. The anatomical reconstruction and repair are surveyed to ensure that the desired result has been obtained and that all defects have been corrected. Excess full-thickness posterior vaginal wall is excised, and posterior colporrhaphy repair begins by bringing the sides of the posterior vaginal wall together by a running subcuticular suture of size 0 PDS. After the sides of the upper inch of the posterior vaginal wall incision have been approximated, any ballooning of the anterior rectal wall is corrected by a separate running locked suture placed in the fibromuscular wall of the rectum and continuing downward to the lowermost point of the rectocele, which may well be behind the site at which a perineal body will be reconstructed. Reapproximation of the posterior vaginal wall continues until the midportion of the repair has been reached, at which time the colpopexy stitches are tied on each side of the pelvis, bringing the undersurface of the vagina to the respective surface of the coccygeus muscle–sacrospinous ligament complex, making sure that no suture bridge is present. The remainder of the posterior wall is closed until the site of the perineal body has been reached. At this point, the fascia of Denonvilliers (attached to the underside of the vagina) is reattached by a figure-of-eight suture to the tissue that will become the central point of the perineal body. Additional mattress stitches are placed as necessary to restore the perineum, and the subcuticular suture is continued down the remainder of the posterior vaginal wall and closes the skin over the perineal body. Rectal examination confirms the integrity of the rectum. The paravaginal defect clinically presents as a cystocele due to a lateral separation of the vaginal wall attachments from the lateral pelvic sidewall(s). According to Bayden and Walker, such a detachment should be suspected when the anterior vaginal wall is relaxed. If there is no elevation of the anterior vaginal wall when the patient squeezes the pelvic musculature, the connective tissue and vascular supports of the anterior vaginal wall may have been detached from the arcus tendineus fascia pelvis. The lateral vaginal wall is not attached directly to the arcus tendineus fascia pelvis; instead the anterior vaginal sulcus is attached to the arcus tendineus fascia pelvis by a meshwork of intervening connective tissue, a connective tissue “bridge.” This intervening connective tissue may be subject to various strains and stretching and partial or complete avulsion. This type of strain is more common in parous patients as a consequence of trauma during labor and delivery and perhaps also can be attenuated, stretched, or avulsed with the pull of massive genital prolapse, even in the nullipara. III. VAGINAL PARAVAGINAL DEFECT REPAIR The transvaginal paravaginal defect repair is an approach to repair the lateral defects (Fig. 16) that are causing anterior segment prolapse. The intent of the re-

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Figure 16 A bilateral paravaginal defect with a midline distention cystocele. Note position of vaginal apex. pair and the tissues to be repaired are the same as for the abdominal retropubic approach. A thorough understanding of the anatomy, the use of appropriate retractors designed for deep retraction, and the ability to mentally “visualize” the retropubic space and maintain a constant mental image of the final surgical repair are essential. Patient positioning is given great detail to prevent injury and provide maximum exposure. The adjustable Allen stirrups, PAL stirrups with featherlift (Allen Medical Systems, Cleveland, OH), are also very useful for transvaginal surgery because leg elevation and hip rotation are not restricted to stirrup preselected positions. Intraoperative examination reconfirms the preoperative defects; if new defects are diagnosed, they must be repaired and the operative procedure adjusted accordingly. If vaginal hysterectomy is indicated, it is performed first. A 14F transurethral Foley is used to drain the bladder; 10 cc are placed in the bulb, and the end is clamped with a Kelly. Marking sutures may be used to mark the most cephalad and distal ends of the lateral sulcus so that as distortion during and from dissection occurs, a reference point for suture placement may be maintained. One approach to selecting the marking suture reference point is to replace the vagina to the level of the ischial spine on both sides. Sutures are then placed approximately 1 cm from the ischial spine, at the level of the bladder neck and the midpoint between the two marking sutures. Dissection of the anterior vaginal segment is initiated by placing two Allis clamps on the anterior vaginal wall at the most dependent point. The vaginal incision is made with Noble-Mayo scissors directly into the vesicovaginal space. The incision is extended for the full length of the anterior vaginal segment, from the vaginal apex to 1 cm from the urethral meatus. Care is taken to maintain the dissection within the vesicovaginal space and to avoid splitting the anterior vagi-

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nal wall. Only sharp dissection is utilized with the Noble-Mayo scissors for the entire dissection. Dissection is maintained within the vesicovaginal space and is carried cephalad, caudad, and lateral to the full lateral limits of the vesicovaginal space. If the patient has undergone previous retropubic surgery, instilling 60 ml of infant milk formula into the bladder will identify any inadvertent bladder trauma. Dissection is then carried through the lateral limits of the vesicovaginal space, and a fenestration between the vesicovaginal space and the paravaginal space is enlarged to the space of Retzius and the pelvic sidewall (Fig. 17). A long Briesky-Navratil retractor is inserted into the paravaginal space, and the bladder is mobilized medially. Dissection is further facilitated by gently pushing open sponges against the Briesky-Navratil retractor and the pelvic sidewall. The Briesky-Navratil retractor is then placed over the sponge to decrease retractor slippage and further retract the bladder and urethra medially. A total of three sponges is packed in this manner. In developing the paravaginal space, a fulllength paravaginal repair will be required. The ureters at this point are retracted medially and out of harm’s way. Illumination is critical in visualizing the pelvic sidewall, the obturator fascia, and the arcus tendineus fascia pelvis, which are fully exposed. A headlight provides hands-free directed lighting, but does require the surgeon be comfortable in wearing a headlight. Alternatively, even a lighted retractor of the free laparascopic fiber-optic cord directed into the paravaginal space will be of great help. Bleeding from small vessels may and should be controlled with electrocautery or with the use of a laparoscopic clip applicator as bleeding will decrease exposure. In contrast to the abdominal approach, after dissection of each paravaginal space, the sutures are placed through the arcus tendineus fascia pelvis and/or the obturator internus fascia. A Deschamp ligature carrier may be used and in certain clinical situations is preferred to a suture with a swedged-on needle. The disadvantage of the Deschamp ligature carrier is the need for passing all suture

Figure 17

The dissected left paravaginal space.

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ends through a Mayo needle. The advantage of the Deschamp ligature carrier is the ability to pass a suture deep in the pelvis. We have found that, with the correct retractors and focused assistants, a double-arm swedged-on needle placed with a long Haney needle driver is very efficient. The double-arm 2-0 Ethibond braided suture on an SH needle (Ethicon, Somerville, NJ) allows for both ends of the suture to be passed through the respective tissues without the use of a Mayo needle (Fig. 18). Suture twisting and entanglement may become a problem since all suture ends will exit transvaginally and are affected by gravity. This time-consuming and frustrating portion of the operation can be effectively reduced by two simple maneuvers. The first is the use of two different color sutures, a green braided and a white braided Ethibond, which are alternatively placed. One approach is to place the green braided suture closest to the ischial spine and follow with the white braided suture, and so on; generally, four sutures will be required. The second is to hold the sutures in numbered clamps, but this may still entangle the sutures as gravity is unrelenting. The use of a McIntosh suture-holding forceps (V. Mueller, Baxter Healthcare Corp., Deerfield, IL) further eliminates this problem. The McIntosh is a suture loom transversely placed on a nonpenetrating towel clamp, which is clamped onto the drapes cephalad or laterally. As each suture pass is completed, the suture ends are secured within a groove in the McIntosh suture loom. The four sutures are placed through the arcus tendineus fascia pelvis and/ or the obturator internus fascia from the ischial spine toward the symphysis pubis. Palpation of the ischial spine, the obturator foramen, and the back of the pubic symphysis are easily achieved transvaginally. Even if the arcus tendineus fascia pelvis has and can be seen as well as palpated, it is helpful for the surgeon to conceptualize a trajectory of the arcus tendineus fascia pelvis as suturing is initi-

Figure 18

The sutures are placed in the left arcus tendineus fascia pelvis. The medial retractor is mobilizing the bladder away from the arcus tendineus. Note orientation of sutures with traction.

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ated and focus is continually turned from the paravaginal space to the vaginal wall and vaginal lumen. Placing the first suture 1–2 cm from the ischial spine allows the surgeon to suture in his or her direction and avoids entanglement of the distal sutures with the proximal needles and sutures during suturing while traversing the paravaginal space. Each additional suture is placed at approximately a 1-cm interval. If a vesicourethral sling will also be placed, the most distal suture should not be placed at the bladder neck because once this suture is tied, it may negate the preferential action of the sling on the bladder neck by decreasing lift. Once all the lateral pelvic sidewall sutures are placed in the position required for each individual patient, the vaginal vault is placed in the proper desired postoperative position. If marking sutures were not used or were lost during dissection, the use of a ring forceps intraoperatively is very helpful and does not obscure the lateral vaginal sulci as would the paddles from the Baden defect analyzer. With the ring forceps, the fold where the dissected anterior vaginal wall crosses the edge of the forceps is opened. The descending needle is then passed through the full thickness of the fibromuscular layer of the anterior vaginal wall. The remaining sutures are passed at the same distance on the anterior vaginal wall as they were on the lateral pelvic sidewall. All the sutures have a two-point penetration, the lateral pelvic sidewall (the arcus tendineus fascia pelvis and/or the obturator internus fascia) and the full-thickness anterior vaginal wall, excluding the squamous epithelium. Trauma to the bladder, urethra, or ureter is unlikely since all these structures are retracted medially and not involved directly in the suturing. However, a technical word of caution is required. The surgeon must attempt to estimate the amount of lateral paravaginal defect (displacement cystocele) and the extent of distention cystocele that will require midline plication. Care must be taken not to overcorrect the paravaginal defect as this may preclude midline reapproximation. Overcorrection may be achieved by placing the sutures too far medial on the anterior vaginal wall, above the arcus tendineus fascia pelvis, a chosen trajectory on the obturator internus fascia, or a combination of the aforementioned. The most significant of the above is the extent of medial suture placement on the vaginal wall. It can almost be said that the sutures cannot be placed too far laterally on the vaginal wall, and strategic placement on the vaginal wall can compensate for less-than-ideal lateral wall placement. The sutures are not tied at this time, and the same sequence of steps is performed on the contralateral side. If a vesicourethral sling is to be placed, it is done at this time, in addition to placement of any Kelly stitches to repair funneling. If a midline distention cystocele also needs repair, it is performed prior to sling placement with one or more layers of 2-0 polyglycolic acid sutures. Alternatively, suburethral plication of the pubourethrovaginal ligament portion of the urogenital diaphragm is performed with PDS suture (Ethicon, Somerville, NJ). If sacrospinous colpopexy or another apical support procedure has also been performed, those sutures are tied first. Then, the lateral paravaginal sutures are tied in the order in which they were placed, first on one side and then on the other. The midline cut edges of the vagina are brought together, trimming the excess as necessary to effect the desired midline result. The anterior full-thickness vaginal wall is closed with a running subcuticular suture, or if a vesicourethral sling has been placed, the anterior vaginal wall is closed in two layers. Any addi-

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tional posterior segment defects are repaired, and the vagina is lightly packed overnight if desired. REFERENCES 1. Kelly HA. Incontinence of urine in women. Urol Cutan Rev 1913; 17:291. 2. Henry M, Swash M. Coloproctology and the Pelvic Floor. 2nd ed. London: Butterworth-Heinemann, 1992. 3. Hirsch HA, Ka¨ser O, Ikle´ HA, eds. Atlas of Gynecological Surgery. 3rd ed. Stuttgart, Germany: Thieme, 1997. 4. Nichols DH, Randal CL. Vaginal Surgery. 4th ed. Baltimore, MD: Williams and Wilkins, 1996. 5. Nichols DH, Clarke-Pearson DL, eds. Gynecologic, Obstetric and Related Surgery. 2nd ed. St. Louis, MO: C. V. Mosby, 1999. 6. Rock J, Thompson J. TeLinde’s Operative Gynecology. 8th ed. Philadelphia, PA: Lippincott, 1996. 7. Symmonds R, Jordon L. Iatrogenic stress incontinence of urine. Am J Obstet Gynecol 1961; 82:1231. 8. Von Peham H, Amreich J. Operative Gynecology. Ferguson LK, trans. Philadelphia, PA: J. B. Lippincott, 1934. 9. Richter K. Die operative Behandling des prolabierten Scheidengrundes mach Utersextoripation Beitrag zur Vaginaefixation Sacrotuberales mach Amreich. Geburtshilfe Frauenheilkd 1967; 27: 941–954. 10. Baden WF, Walker TA. Evaluation of uterovaginal support. In: Surgical Repair of Vaginal Defects. Philadelphia, PA: J. B. Lippincott, 1992. 11. Burch JC. Urethrovaginal fixation to Cooper’s ligament for correction of stress incontinence, cystocele, and prolapse. Am J Obstet Gynecol 1961; 81:281. 12. DeLancey JOL. Corrective study of paraurethral anatomy. Obstet Gynecol 1986; 68: 91. 13. DeLancey JOL. Anatomic aspects of vaginal eversion after hysterectomy. Am J Obstet Gynecol 1992; 166:1717–1728. 14. DeLancey JOL. Structural support of the urethra as it relates to stress urinary incontinence: the hammock hypothesis. Am J Obstet Gynecol 1994; 170:1713. 15. Reiffenstuhl G. The clinical significance of the connective tissue planes and spaces. Clin Obstet Gynecol 1982; 25:811–820. 16. Shull BL. How I do abdominal paravaginal repair. J Pelvic Surg 1995; 1:43. 17. Shull BL, Baden WF. A six-year experience with paravaginal defect repair for stress urinary incontinence. Am J Obstet Gynecol 1989; 160:1432. 18. Shull BL, Benn SJ, Kuehl TJ. Surgical managament of prolapse of the anterior vaginal segment: an analysis of support defects, operative morbidity, and anatomic outcome. Am J Obstet Gynecol 1994; 171:1429. 19. Shull BL, Capen CV, Riggs MW, et al. Preoperative and postoperative analysis of site-specific pelvic support defects in 81 women treated with sacrospinous ligament suspension and pelvic reconstruction. Am J Obstet Gynecol 1992; 166:1764. 20. White GR. An anatomic operation for the cure of cystocele. Am J Obstet Dis Wom Child 1912; 65:286. 21. White GR. Cystocele: a radical cure by suturing lateral sulci of vagina to white line of the pelvic fascia. JAMA 1909; 53:1707.

19 Colpocleisis for the Treatment of Vaginal Vault Prolapse* KENNETH H. FERGUSON and R. DUANE CESPEDES Wilford Hall Medical Center San Antonio, Texas, U.S.A.

I.

INTRODUCTION

Pelvic prolapse conditions have plagued women for thousands of years; however, it is only since the late 19th century that procedures have been developed to safely and effectively treat these conditions. Even today, pelvic prolapse conditions remain a challenging problem, with vault prolapse remaining the most difficult problem to treat because multiple support defects usually coexist. A thorough understanding of pelvic anatomy, pathophysiology, and urodynamics and experience in selecting the appropriate surgical techniques are required to treat vault prolapse with minimal morbidity or treatment failures. Although the goals of a vault prolapse procedure are usually to restore normal anatomy and function, this is not always possible or necessary. For the elderly, the medically unstable, and sexually inactive individual, it may be preferable to simply “close off ” the vagina to maximize long-term results and minimize operative complications. These procedures, including colpocleisis and partial colpocleisis, are considered “destructive” procedures and are currently unpopular; however, these procedures can be extremely helpful in certain situations and should be in every reconstructive surgeon’s armamentarium. The traditional approach to colpocleisis have been simply to invert the vagina using purse-string sutures after removing the vaginal mucosa. While simple

* The opinions contained herein are those of the authors and are not to be construed as reflecting the views of the Air Force or the Department of Defense.

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to perform, after repairing two referred treatment failures with previous repairs in this manner, we began to use a different approach that emphasizes the strength of an anterior repair and extensive posterior repair, which is then sutured together. This vaginal closure is then reinforced with a strong perineorrhaphy. While this procedure does take a little more time to perform, no increased morbidity has been noted, and no treatment failures have occurred in 38 patients treated during the last 4 years. In this chapter, we review the indications, procedural aspects, and results of performing colpocleisis and partial colpocleisis for total vault prolapse. II. PATHOPHYSIOLOGY AND INDICATIONS FOR SURGERY All pelvic prolapse conditions result from weakness or damage to the normal pelvic support systems [1]. Many etiologies have been proposed for pelvic floor relaxation, including multiparity, advanced age, prior pelvic surgery, hormonal insufficiency, obesity, neurological disorders, connective tissue disorders, and strenuous physical activity [2,3]. Vaginal vault prolapse, the most severe form of pelvic prolapse, is most commonly secondary to prior hysterectomy in which the vault was not sufficiently resuspended and the cul-de-sac was not obliterated at the time of the hysterectomy [4]. The incidence of vault prolapse after hysterectomy is reported to be as high as 18.2% and is accompanied by significant prolapse in other areas in at least 72% of patients [5,6]. The most important structures providing support to the pelvic viscera are the levator ani muscle groups. The levator ani keep the pelvic floor closed, allowing the pelvic and abdominal viscera to “rest” on a levator hammock. This levator hammock reduces the tension on the supporting pelvic fascia and ligaments. Pelvic support in the normal individual can be analogized to a ship held stationary at a dock. The water on which the ship floats represents the levator ani muscle group, and the pelvic ligaments are the mooring lines that keep the ship from straying away from the dock [4,7]. Damage to the levator ani muscle group is analogous to removing the water from under the ship, leaving the ship suspended by the mooring lines. Like the mooring lines, the pelvic ligaments are not strong enough to support the pelvic viscera, with subsequent stretching and tearing of the ligaments, resulting in pelvic prolapse. It is important to understand that the pelvic ligaments are not true ligaments and are not meant to carry the increased load that occurs with the loss of levator function. The resulting prolapse condition, however, depends on which supporting structures fail. An anatomical method of evaluating the patient is to divide the vagina into upper, middle, and lower sections as different fascias and ligaments stabilize each section. The cardinal and uterosacral ligaments stabilize the upper vagina. Damage to these structures can cause either uterine or vaginal vault prolapse. In most cases, and enterocele is also present when significant vaginal prolapse occurs [8]. The middle section of the vagina is supported by several important structures. The pubocervical fascia supports the anterior vaginal wall. This fascial layer stretches between the arcus tendineus fascia pelvis (ATFP), formed from the muscular fascia on the lateral pelvic sidewalls. The attachment of the vagina to the ATFP creates the superior lateral vaginal sulcus seen on physical examination. Detachment of the pubocervical fascia from the arcus tendineus creates a lateral

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defect cystocele. Conversely, separation of the pubocervical fascia in the midline leads to a central defect cystocele. Central and lateral defects frequently coexist in the same patient. This distal vagina is attached firmly to the urethra and pubic symphysis anteriorly. Laterally, the distal vagina attaches to the levator ani muscle group. Posteriorly, the distal vagina attaches to the perineal musculature. The perineal musculature is commonly damaged with childbirth. Combinations of proximal, middle, and distal vaginal support defects frequently coexist. Diagnosis of the individual defects requires careful physical examination. Tailoring the surgical procedure to address every defect is required for long-term success. Total colpocleisis is an appropriate option for the treatment of severe, symptomatic vaginal vault prolapse in women who have been sexually inactive for many years and do not desire continued sexual function. This procedure is especially useful in elderly women with multiple medical problems for whom a definitive procedure with little risk of recurrence and minimal associated morbidity is desired [9]. Partial colpocleisis is indicated when retention of a prolapsing uterus is desired. As partial colpocleisis usually precludes future coital function and examination of the cervix is impossible, most women with a prolapsing uterus are probably better served by vaginal hysterectomy followed by a colpocleisis or one of the standard vault suspensions. As noted by Ridley, “Any operation less than a complete colpocleisis has an increased incidence of failure” [9: 1118]; therefore, we rarely utilize a partial colpocleisis. The ideal candidate for partial colpocleisis is a frail, elderly female with a documented normal cervix and uterus who has failed a trial with a pessary and is a poor surgical risk for a vaginal hysterectomy. In many of these patients, the risk of hysterectomy outweighs the risk of symptomatic prolapse recurrence because these patients are usually not physically active, which reduces the risk of subsequent recurrence.

III. EVALUATION A. History Patients with high-grade vaginal vault prolapse commonly complain of a mass prolapsing through the introitus and a feeling of vaginal fullness. When severe, the prolapse can cause difficulty walking and low back pain that worsens with activity and is relieved by lying flat. Patients frequently complain of associated voiding dysfunction. Stress incontinence can be caused by either urethral hypermobility (a sequela of pelvic relaxation) or from intrinsic sphincter deficiency (ISD) [10]. Most candidates for colpocleisis are elderly, and ISD is much more common in this age group. It is important to distinguish between these two causes of stress incontinence as suspension procedures are associated with a higher failure rate in patients with ISD. Some patients complain of frequency and urgency due to incomplete emptying from urethral obstruction, which may occur as a result of rotation of the cystocele around a partially fixated urethra. Many patients do not complain of stress incontinence due to this urethral obstruction and leak only when the prolapse is reduced on urodynamic testing. Recurrent urinary tract infections may also occur from the incomplete emptying. Bowel complaints, especially “constipation,” are common in this group of elderly patients; however, constipation alone is not specific for a rectocele or pelvic

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prolapse. Splinting or the application of digital pressure to the posterior vaginal wall to empty the bowels effectively is relatively specific for a rectocele [11]. B.

Physical Examination and Studies

In the severe cases of prolapse for which colpocleisis is indicated, the diagnosis is generally straightforward, with a pelvic exam demonstrating total prolapse of the vaginal vault (Fig. 1). Any associated conditions (e.g., cystocele, enterocele, or rectocele) will be repaired by the colpocleisis. In cases of severe prolapse, radiographic studies should be considered to rule out possible ureteral obstruction from the severe ureteral angulation that can occur. If ureteral obstruction is demonstrated, a ureteral stent should be placed if the procedure cannot be performed expeditiously [12]. We have found that it is easier to perform the vaginal exam at the same time as the urodynamics evaluation. Urodynamics should be performed on all patients to unmask “occult” stress urinary incontinence. Significant pelvic prolapse can cause urethral obstruction; therefore, the prolapse must be reduced during the stress maneuvers to create the situation that will exist after the procedure. The easiest way to reduce the prolapse and not alter the leak point pressure measurement is to pack the vagina with lubricated gauze and hold it in place with the lower blade of a vaginal speculum, taking care not to obstruct the urethra [13].

Figure 1 Total vault prolapse in an elderly patient.

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A Papanicolaou smear and endometrial biopsy should be performed if a partial colpocleisis is considered as access to the uterus will be impossible after the procedure [14]. C. Stress Incontinence: Techniques of Repair Almost all women who require a colpocleisis will also have significant urethral hypermobility, and some will complain of stress incontinence. The choice of an antiincontinence procedure is difficult in this elderly population, who are more likely to suffer the adverse consequences of anti-incontinence procedures than younger patients. The prevention of postoperative stress incontinence must be balanced with the avoidance of disabling detrusor instability or urinary retention as medical therapy may not improve symptoms, and a urethrolysis after colpocleisis can be quite difficult. Incontinence associated with urethral hypermobility can be treated with a sling or one of the suspension procedures; however, we do not perform transabdominal incontinence procedures in these patients because of the additional morbidity and similar rates of voiding dysfunction as sling procedures. A Kelly plication of the bladder neck may be considered in two patient groups [15]. If stress urinary incontinence (SUI) cannot be demonstrated with the prolapse reduced, a Kelly plication can be used to provide additional support at the bladder neck. If an elderly, debilitated patient has minimal SUI and cannot perform clean intermittent catheterization (CIC), then a Kelly bladder neck plication or minimally invasive sling may be performed. Minimally invasive sling techniques include a vaginal wall sling [16] with or without perforation of the endopelvic fascia or a paravaginal sling secured bilaterally to the arcus tendineus using a Capio needle driver (Boston Scientific, Natick, MA). These slings are minimally obstructive, and CIC is rarely necessary. Other minimally invasive alternatives to treat incontinence in these patients include attaching the sling to Cooper’s ligament using a Capio CL needle driver, a cadaveric fascial sling with bone fixation using one of the commercially available bone-anchoring devices, or possibly a tension-free vaginal tape procedure [17–19]. Transurethral collagen injections can be used if the patient develops significant stress incontinence postoperatively [20]. If ISD is detected on urodynamic testing, one of the sling procedures or collagen injections are preferentially used [21,22]. Pubovaginal slings are ordinarily used in patients with ISD if the patient is able to perform CIC postoperatively [23,24]. Cadaveric fascia or dermal grafts are utilized in all sling procedures to minimize the morbidity of autologous fascia harvest. Transient retention is common in this elderly group of patients, and all undergoing sling procedures should be instructed on CIC techniques preoperatively. Debilitated patients who cannot perform CIC may undergo a minimally invasive sling or Kelly plication with collagen injections if the SUI is not adequately treated. IV. SURGICAL TECHNIQUES A. Total Colpocleisis Colpocleisis is performed with the patient in standard lithotomy position. A 16F Foley catheter is placed into the bladder for continuous drainage, and labial retraction sutures and a weighted vaginal speculum provide the necessary exposure.

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An anti-incontinence procedure and anterior colporrhaphy are performed first. A midline vaginal mucosal incision is made on the anterior wall 2 cm proximal to the urethral meatus and extending just beyond the site of the proposed new vaginal cuff. In most cases, the vagina will only be 2–3 cm long when the colpocleisis is complete. The vaginal mucosa is dissected off the pubocervical fascia in the usual manner, and multiple interrupted permanent sutures are ordinarily used to perform the anterior repair [25,26]. The extent of the anterior repair depends on which anti-incontinence procedure is performed. The anti-incontinence procedure is then performed, and the mucosa is closed. The posterior vaginal wall and perineum are then repaired. A triangular perineoplasty incision is made, and the mucosa defined by this incision is excised. Injectable saline is infiltrated into the posterior vaginal mucosa to aid dissection. Caudal retraction with an Allis clamp placed on the edge of the perineoplasty incision greatly facilitates the dissection of the mucosa from the posterior vaginal wall. The previously closed incision on the anterior vaginal wall defines the proximal extent of the posterior vaginal wall dissection (Fig. 2). Lateral mucosal dissection is continued to the posterior lateral sulcus. Dissection of the mucosa from the enterocele sac is usually slow and tedious, espe-

Figure 2 The incontinence procedure and anterior repair have been completed. The gaping introitus and severe apical and posterior wall defects can be clearly seen.

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cially at the cuff; however, unlike a vault suspension, the enterocele sac is not opened or ligated [27]. A colpocleisis obliterates the vaginal canal; therefore, an enterocele has no place to recur [28]. In addition, we have seen redundant bladder, small bowel, and rectum misidentified as “the sac” and mistakenly opened. If the enterocele can be manually reduced into the abdomen, the enterocele can be left alone. If the enterocele will not remain reduced, purse-string absorbable sutures that incorporate the sac and uterosacral remnants can be used to reduce the sac. If these sutures are placed, cystoscopy should be performed after intravenous administration of indigo carmine to ensure ureteral patency. The foundation of the repair is the creation of multiple strong tissue layers that will resist the enterocele and pelvic prolapse. Basically, an extensive posterior repair and perineoplasty are used to create this barrier. In most cases, three sequential layers of pararectal and levator fascia are brought together in the midline using a combination of permanent and absorbable interrupted sutures (Figs. 3– 5). Two sequential purse-string sutures incorporating the completed anterior repair and the extensive posterior repair ensure permanent closure of the vagina. As seen in Fig. 6, after redundant posterior vaginal mucosa is excised, the lateral wall vaginal mucosa is dissected free and “rolled” anteriorly to form the new posterior vaginal wall. Generally, the vagina is 2–3 cm deep after the col-

Figure 3. The first layer has been closed on the posterior wall, and the lateral vaginal wall incisions later used to form the new posterior vaginal wall have been made.

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Figure 4 An intraoperative photograph showing the closure of the second layer on the posterior wall. The strong tissue layers used to close the vagina can be clearly seen with a suture placed through them. The diminishing size of the vagina is also evident. pocleisis is completed. The remaining posterior vaginal mucosal edges are brought together in the midline using a running chromic catgut suture. An extensive perineoplasty is the final step in the procedure. This is performed by placing multiple O-Vicryl sutures deeply into the central tendon and bulbocavernosus muscles using horizontal mattress sutures. The perineal skin is then closed with an absorbable suture. It is important that the perineorrhaphy not be extended too far anteriorly or the urethral meatus will be obstructed. The result can be seen in Fig. 7. Our experience using this colpocleisis procedure in 38 patients (mean age 77 years, range 68–88 years) has been favorable. No recurrent vault prolapse, rectoceles, enteroceles, or cystoceles have been observed with a mean follow-up of 24 months (range 3–52 months). Three patients who underwent a Kelly plication have mild stress incontinence, with 2 successfully treated with collagen injections. One patient who underwent a pubovaginal sling had large postvoid residuals and urge incontinence that required a urethrolysis. The mean estimated blood loss for the entire procedure was approximately 175 mL, and operating time was 145 min. Most patients were discharged within 36 h. There were no significant complications. All patients were satisfied with the results of the colpocleisis; how-

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Figure 5 The last layer has been closed on the posterior wall. The anterior repair and posterior repair will be subsequently sutured together (not shown) to create a strong barrier that will prevent future enterocele formation.

ever, 1 patient remains unsatisfied with her continence status. No patient has regretted the loss of sexual function. B. Partial Colpocleisis Many surgeons have published variations of LeFort’s original description of partial colpocleisis [29]. The Goodall and Power modification of the LeFort operation limits the LeFort closure of the medial vagina to the proximal third of the vagina [30]. This modification was designed to permit continued coital function. If preservation of sexual function is a goal, then a procedure with a vaginal hysterectomy and vault suspension is probably a better option. Miklos et al. recently published an article demonstrating that the LeFort partial colpocleisis can be safely performed using a combination of pudendal nerve block, local anesthetic infiltration, and intravenous sedation if necessary [31]. A patient with severe uterine prolapse can be seen in Fig. 8. The partial colpocleisis is initiated by excising a rectangular strip of mucosa from both the anterior and the posterior vaginal walls (Fig. 9). The proximal extent of the anterior incision is located 3–4 cm from the urethral meatus, and the distal

Figure 6 The lateral vaginal wall mucosal flaps are dissected free and “rolled” anteriorly to form the new, but much shorter, posterior vaginal wall.

Figure 7 The completed repair after the extensive perineal body closure has been performed.

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Figure 8 An elderly patient with long-standing uterine prolapse. Bilateral hydronephrosis was present, and the patient was treated expeditiously in lieu of bilateral stent placement.

extent of the incision is 2–3 cm from the cervix. The cervix is pushed into the depths of the vagina as the exposed anterior and posterior vaginal walls are sutured together using multiple interrupted absorbable sutures. We place a 14F RedRobinson catheter along the vaginal sidewalls to assist in the formation of mucosal drainage canals (Figs. 10 and 11). The vaginal mucosa overlying the supported cervix is then closed, and a tight perineal body closure is performed to lend overall strength to the repair (Fig. 12). The Robinson catheter is removed on postoperative day 4 in most cases. As for the total colpocleisis, prevention of postoperative incontinence is dependent on a careful preoperative urodynamic assessment. Almost all patients will require an anterior repair in addition to an incontinence procedure. For ISD, a pubovaginal or paravaginal sling is used in most cases. Transurethral collagen is used to treat any patient with postoperative incontinence. V.

DISCUSSION

The long-term risk of prolapse recurrence following total colpocleisis is not well documented in the recent literature [32]. DeLancey and Morley, using a purse-

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Figure 9 The first step in a LeFort partial colpocleisis. Rectangular segments of mucosa from the anterior and posterior vaginal walls are incised and subsequently removed.

string inversion technique, reported 1 recurrence in 33 patients after a mean follow-up of 3 years [28]. Over the past 3 years, we have seen 2 individuals with these inverted “purse-string”-type colpocleisis procedures performed elsewhere present to us with recurrent prolapse and subcutaneous enteroceles. This led us to develop a different approach that emphasizes the strength of an anterior and extensive posterior repair that is then sutured together. This vaginal closure is then reinforced with a strong perineorrhaphy to provide additional support to prevent recurrence. We noted that, in almost the same time it takes to perform an inverted purse-string-type colpocleisis repair, a multicompartment colpocleisis can be performed. The results of this modified colpocleisis have been very good, with no recurrences in 38 patients at a mean follow-up of 24 months. The only other contemporary report is from Ridley, who performed a modified LeFort colpocleisis in 41 patients. No postoperative failures were noted in this 1971 series at a maximum follow-up of 6 years [9]. The morbidity associated with colpocleisis procedures appears to be quite low, especially in light of the advanced age and medical instability in these patients. This can probably be attributed to the shorter operating times and decreased blood loss associated with a colpocleisis as compared to a definitive vault

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Figure 10 The anterior and posterior incised mucosal edges are sewn together using a catheter to help form the drainage channels.

suspension. The loss of sexual function has not been a problem for any of our patients or for those in DeLancey and Morley’s report; however, these patients must be carefully selected to avoid this potential problem [28]. Partial colpocleisis, while historically yielding good results, can be problematic in some patients because the uterus and cervix are concealed from examination. With admittedly small numbers, we have not yet seen a patient return with vaginal bleeding following partial colpocleisis, and only four cases have been reported of cancer developing in these patients [8]. Therefore, we recommend this procedure be reserved for high-risk patients, and a careful preoperative assessment (incuding Pap smear and endometrial biopsy) should be performed to prevent any problems. Ureteral obstruction with resulting hydronephrosis occurs in 8% of patients undergoing surgery for pelvic prolapse [33]. Patients with severe prolapse have a higher incidence, with up to 34% of patients demonstrating hydronephrosis on preoperative upper urinary tract imaging. In almost all cases, mild-to-moderate hydronephrosis related to pelvic prolapse resolves following surgical repair. In most cases in which surgical repair is imminent, preoperative imaging rarely changes the surgical management; however, patients with severe pelvic prolapse

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Figure 11 The first layer of the anterior-to-posterior wall closure has been completed. Subsequent layers are then closed until the cervix is deeper within the vagina.

in which nonoperative therapy is pursued or surgical therapy will be delayed should undergo upper tract imaging. Stress incontinence that develops after a prolapse repair is performed has been called iatrogenic, latent, or most commonly, occult incontinence. Reports have demonstrated that up to 50% of women with vault prolapse who do not complain of stress incontinence will have leakage with the prolapse reduced, and up to 75% will have a component of ISD [34,35]. Currently, the potential for postoperative incontinence can be accurately predicted before the procedure by reducing the prolapse when performing the pelvic exam and during urodynamics. This preoperative evaluation also allows the incontinence procedure to be tailored to the patient’s specific problem, decreasing the risk of postoperative incontinence in nearly all patients. Occult incontinence was first noted in patients with high-grade prolapse by LeFort, who in 1877 published his series [29]. Ridley noted an 11% incidence of occult incontinence in his 47 patients, whereas DeLancey and Morley did not report any cases of occult incontinence [9,28]. In our series, 3 patients who had occult incontinence declined a formal incontinence procedure, and each required collagen injections postoperatively for stress incontinence.

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Figure 12 The final appearance of the LeFort partial colpocleisis after and extensive perineal body and distal rectocele closure used to strengthen the repair.

VI. CONCLUSION The goal of reconstructive pelvic surgery is to restore normal anatomy and function; however, this is not always possible or necessary. For the elderly, medically unstable, and sexually inactive individual with severe symptomatic vault prolapse, partial or total colpocleisis may be the preferred procedure because of the low incidence of morbidity and reliably durable results. Accordingly, these colpocleisis procedures should be in every reconstructive surgeon’s armamentarium. REFERENCES 1. DeLancy JOL. Anatomic aspects of vaginal eversion after hysterectomy. Am J Obstet Gynecol 1992; 166:1717–1722. 2. Norton PA. Pelvic floor disorders: the role of fascia and ligaments. Clin Obstet Gynecol 1993; 36:926–938. 3. Wall LL. The muscles of the pelvic floor. Clin Obstet Gynecol 1993; 166:910–914. 4. Berglas B, Rubin IC. Study of the supportive structures of the uterus by levator myography. Surg Gynecol Obstet 1953; 96:677–692. 5. Herbst AL, Mishell DR, Stenchever MA, Droegemueller W. Disorders of the abdomi-

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6. 7. 8. 9. 10. 11. 12. 13. 14.

15.

16.

17. 18. 19. 20. 21. 22. 23. 24. 25. 26.

27. 28.

Ferguson and Cespedes nal wall and pelvic support. In: Stenchever MA, ed. Comprehensive Gynecology. 2nd ed. Philadelphia: Mosby Yearbook, 1992:594. Richter K. Massive eversion of the vagina: pathogenesis, diagnosis and therapy of the true prolapse of the vaginal stump. Clin Obstet Gynecol 1982; 25:89–92. DeLancy JOL. Anatomic aspects of vaginal eversion after hysterectomy. Am J Obstet Gynecol 1992; 166:1717–1728. Morley GW. Vaginal approach to treatment of vaginal vault prolapse. Clin Obstet Gynecol 1993; 36:984–994. Ridley JH. Evaluation of the colpocleisis operation: a report of 58 cases. Am J Obstet Gynecol 1972; 113:1114–1119. McGuire EJ, Cespedes RD, O’Connell HE. Leak-point pressures. Urol Clin North Am 1996; 23:253–262. Siproudhis L, Lucas RJ, Raoul JL, et al. Defecatory disorders, anorectal disorders and pelvic floor dysfunction: a polygamy? Int J Colorectal Dis 1992; 7:102–106. Zimmern PE. The role of voiding cystourethrography in the evaluation of the female lower urinary tract. Probl Urol 1991; 5:23–33. Ghoniem GM, Walters F, Lewis V. The value of the vaginal pack test in large cystoceles. J Urol 1994; 152:931–934. Karram MM, Sze EHM, Walters MD. Surgical treatment of vaginal vault prolapse. In: Walters MD, Karram MM, eds. Urogynecology and Reconstructive Pelvic Surgery. 2nd ed. St. Louis, MO: C.V. Mosby, 235–256. Pelusi G. Bacchi P, Demaria F, Rinaldi A. The use of the Kelly plication for the prevention and treatment of genuine stress urinary incontinence in patients undergoing surgery for genital prolapse. Int Urogynecol J 1990; 1:196–200. Couillard D, Deckard-Janatpour K, Stone A. The vaginal wall sling: a compressive suspension procedure for recurrent incontinence in elderly patients. Urology 1994; 43:203–207. Koduri S, Goldberg RP, Sand PK. Transvaginal therapy of genuine stress incontinence. Urology 2000; 56(suppl 6A):23–27. Kobashi KC, Mee SL, Leach GE. A new technique for cystocele repair and transvaginal sling: the cadaveric prolapse repair sling. Urology 2000; 56(suppl 6A):9–14. Carlin BI, Klutke JJ, Klutke CG. The tension free vaginal tape for the treatment of stress incontinence in the female patient. Urology 2000; 56(suppl 6A):28–31. O’Connell HE, McGuire EJ, Aboseif S. Transurethral collagen injection therapy in women. J Urol 1995; 154:1463–1466. Haab F, Zimmern PE, Leach GE. Diagnosis and treatment of intrinsic sphincter dysfunction in females. AUA Update 1996; lesson 35, 15:1–10. O’Connell HM, McGuire EJ, Usui A, et al. Pubovaginal slings in 1994 [abstract 1186]. J Urol 1995; 153:525A. Cespedes RD, Cross CA, McGuire EJ. Pubovaginal fascial slings. Tech Urol 1997; 3: 195–201. Blaivas JG, Jacobs BZ. Pubovaginal sling in the treatment of complicated stress incontinence. J Urol 1991; 145:1214–1218. Beck RP, McCormick S, Nordstrum L. A 25 year experience with 519 anterior colporrhaphy procedures. Obstet Gynecol 1991; 78:1011–1015. Kohli N, Sze EHM, Roat TW, Karram MM. Incidence of recurrent cystocele after anterior colporrhaphy with and without concomitant transvaginal needle suspension. Am J Obstet Gynecol 1996; 175:1476–1481. Nichols DH, Randall CL. Enterocele. In Nichols DH, Randal CL, eds. Vaginal Surgery. 4th ed. Baltimore, MD: Williams and Wilkins, 1996:345. DeLancey JOL, and Morley GW. Total colpocleisis for vaginal eversion. Am J Obstet Gynecol 1997; 176:1228–1335.

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29. LeFort L. Nouveau procede pour la guerrion du prolapsus uterin. Bull Gen Ther 1877; 92:337–346. 30. Goodall JR, Power RM. A modification of the LeFort operation for increasing its scope. Am J Obstet Gynecol 1937; 34:968–971. 31. Miklos JR, Sze EHM, Karram MM. Vaginal correction of pelvic organ relaxation using local anesthesia. Obstet Gynecol 1995; 86:922–926. 32. Smale LE, Smale CL, Mundo NG, Rivera R. Vaginectomy: profile of success in treating vaginal prolapse. Medscape Women’s Health 1997; 2(3):5. 33. Beverly CM, Walters MD, Weber AM, Piedmonte MR, Ballard LA. Prevalence of hydronephrosis in patients undergoing surgery for pelvic organ prolapse. Obstet Gynecol 1997; 90:37–41. 34. Gallentine ML, Cespedes RD. Occult stress urinary incontinence and the effect of vaginal vault prolapse on abdominal leak point presses. J Urol 2000; 163A:264. 35. Romanzi LJ, Chaikin DC, Blaivas JG. The effect of genital prolapse on voiding. J Urol 1999; 161:581–587.

20 Technique of Vaginal Hysterectomy MARY T. McLENNAN St. Louis University St. Louis, Missouri, U.S.A.

I.

INTRODUCTION

Of approximately 650,000 hysterectomies performed annually in the United States, 80% are performed abdominally rather than vaginally. Most gynecological surgeons consider nulliparity and uterine size greater than that at 12 weeks of gestation to be contraindications for vaginal hysterectomy [1]. Dorsey et al. noted that an abdominal hysterectomy was more likely to be performed when there was a suspicion of malignancy and laparoscopic hysterectomy to be performed when there was a suspicion of endometriosis [1]. Summit et al. noted that vaginal hysterectomy was associated with shorter operative and anesthesia time and lower total hospital cost compared to the laparoscopic route [2]. A number of authors have concluded that surgeon preference largely dictates the type of hysterectomy [1,3]. Kovac stated that limiting the choice of the surgical procedure on the basis of physician’s preference and experience is no longer acceptable in clinical medicine [4]. He proposed a guideline based on pathological criteria. The three factors that should affect choice of surgical route are uterine size; attachment of the uterus, which may interfere with mobilization and access; and anatomic accessibility. He has stated that abdominal hysterectomy is indicated for a uterus size greater than that at 12 weeks of gestation. Patients with a history of endometriosis, adnexal disease, chronic pelvic pain, adhesions, and previous pelvic surgery are at high risk for adhesions, which may limit uterine mobility. Laparoscopic examination may be beneficial in these cases, and depending on the findings, a decision can be made whether to proceed with vaginal hysterectomy. Poor vaginal accessibility, as noted by a narrow pubic arch or a small bituberous diameter, has been 329

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found by another author to limit vaginal access; however, he noted that these factors apply to only 1% of hysterectomies [5]. Using the Kovac model would promote a more scientific approach to the decision-making process. This chapter does not deal with laparoscopic-assisted vaginal hysterectomy. Generally speaking, the addition of laparoscopy results in longer operating time and greater expense, which is offset by shorter hospital stays compared to the abdominal route [6–8]. There is only one randomized trial comparing laparoscopic-assisted vaginal hysterectomy to vaginal hysterectomy. Recovery time, anesthesia time, use of pain medication, reduction of hematocrit, and cost were all greater for laparoscopic-assisted compared to vaginal hysterectomy. Laparoscopic-assisted vaginal hysterectomy should be looked at as an alternative to abdominal hysterectomy, not vaginal hysterectomy [2]. The use of this technique should result in fewer abdominal hysterectomies. II. PREOPERATIVE PREPARATION/PROPHYLACTIC ANTIBIOTICS Multiple prospective studies have shown that antibiotic prophylaxis is protective against febrile and infectious morbidity associated with hysterectomy [9,10]. Reported infection rates after vaginal and abdominal hysterectomy have ranged from 10% to 78% and from 9% to 50%, respectively. Studies have shown a reduction in infection rates of approximately 56–65% for abdominal and 20–40% for vaginal hysterectomies. Because of their proven safety and broad spectrum of antimicrobial activity, cephalosporins have been the most extensively used family of drugs for prophylaxis. Meta-analysis has confirmed their effectiveness [11,12]. The more expensive second and third generations of these drugs have not been found to be superior to the first generation of drugs like cephazolin [11]. For those allergic to these drugs, metronidazole, tinidazole, and moxalactam have also been shown to be effective. Single-dose prophylaxis is as efficacious as multidose regimens [13]. Multiple regression analysis has found intravenous administration to be significantly superior to the intramuscular route for the prevention of infection, but it has similar efficacy for the prevention of febrile morbidity [10]. The antibiotic should be administered by the intravenous route prior to skin incision so that an adequate circulating concentration is present prior to incision. III. ANESTHESIA Both general and regional anesthesia techniques are applicable for vaginal surgery. Regional anesthesia has the advantage of causing less postoperative nausea and vomiting [14]. In the elderly, changes in postoperative cognitive function do not differ between regional and general anesthesia [15]. However, it has been reported that 5% of the elderly may demonstrate long-term deterioration in cognitive function after anesthesia. IV. POSITIONING After either induction of anesthesia or placement of a local anesthetic block, the patient is placed in a dorsal lithotomy position. For a simple vaginal hysterectomy

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unaccompanied by abdominal reconstructive techniques, the candy cane stirrups are the most user-friendly for the surgical assistants. These stirrups allow the patient’s legs to be elevated to a greater degree so that the feet are out of the assistant’s field. It is important that the patient’s legs not be hyperflexed on the abdomen so as to cause a lateral femoral cutaneous nerve injury. Excess elevation should also be avoided to prevent overstretching of the sciatic nerve. The newer adjustable Allen stirrups can also be used. These have the advantage that the patient’s foot and leg are supported in a lower limb and boot structure. However, the back extension can place the calf at risk, and the lateral extension can cause compression of the peroneal nerve at the fibula head [16]. Gel inserts are useful in the prevention of these compression injuries. Unfortunately, these stirrups do not allow as much flexion and elevation of the patient’s legs, so there is poorer surgical access. Thus, unless additional abdominal surgery is to be performed, the candy cane stirrups are superior for surgical access.

V.

PREOPERATIVE EVALUATION

It is important to perform a careful bimanual examination under anesthesia. Assessment of the size, position, and mobility of the uterus and thickening or nodularity in the cul-de-sac is necessary to confirm that the hysterectomy can be attempted to be performed vaginally. Palpation of the adnexa should rule out any adnexal pathology that may indicate an abdominal approach is necessary. The length of the cervix should also be assessed as an elongated cervix may make it technically more challenging to perform the hysterectomy and also indicate that the uterosacral ligaments may need to be shortened at the time of the cul-deplasty.

VI. PREPARATION The preoperative use of douching, pessaries, or gel has not been found to be effective in reducing colonization or preventing febrile or infectious morbidity with vaginal hysterectomy [17]. A 10% povidone-iodine solution, if applied repeatedly in a small amount with an exposure time of 2 min, has been found to be safe and effective for skin antisepsis during abdominal surgery [18]. This was supported by initial bacteriological studies by Monif et al. in 1980, which demonstrated an immediate dramatic effect on the vaginal flora with the use of povidone-iodine, but a rapid recovery to preexisting bacterial levels [19]. By 4 h, there was some residual effect against anaerobes, but only a borderline effect on aerobes. Reduction in febrile morbidity between those treated with povidone-iodine gel and controls was demonstrated more recently for abdominal hysterectomy [20]. These authors also noted that the protective effect of the gel diminished with increasing length of surgery. There was no increased risk of allergic reactions or skin irritation with this technique [21]. Based on current evidence, the recommendation would therefore be for the immediate application of povidone-iodine gel for at least 2 min immediately prior to surgical incision.

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VII. OPERATIVE TECHNIQUE The bladder is not routinely drained prior to surgery. The patient should void immediately prior to being transferred from the holding area to the operative suite. The presence of urine in the bladder allows for easier identification of an incidental cystotomy. A weighted speculum is placed in the posterior vaginal fornix. For the patient with marked prolapse, it may be easier to perform the surgery without a posterior retractor. For the patient with a deep cul-de-sac, a weighted speculum may not be long enough, and a Heaney-Simon retractor may be more useful. The cervix is grasped with a single-tooth tenaculum. If the cervix is too bulky to allow a single application, two single-tooth tenacula can be placed, one on the anterior and the other on the posterior lip of the cervix. It is important to assess the site visually for the circumferential incision. For the patient with an elongated cervix, the incision may be very different from that for the patient with minimal prolapse and no elongation. The tenaculum is pulled anteriorly, and the posterior cul-de-sac is assessed. The junction of the cervix and the mucosa over the posterior vaginal wall indicates the level of the cul-de-dac and the site for the incision. In a similar manner, the tenaculum is then pulled posteriorly. The junction of the vesicovaginal and cervicovaginal mucosa is assessed. In a younger patient or a well-estrogenized postmenopausal patient, the level of the rugae of the bladder will help in the identification of the vesicovaginal attachment. The incision is typically placed at the level at which the rugae disappear (Fig. 1). It may be impossible to assess visually the junction in the patient with massive prolapse. In this case, a uterine sound can be placed through the urethra (similar to placing it in a retroverted uterus) and into the bladder. It can be readily palpated through the mucosa, and an incision can be made just distal to the tip of the sound. There is very little evidence-based medicine available regarding the use of vasconstrictive agents. There is only one randomized prospective trial comparing the use of circumferential ephedrine to a control group. The authors reported that the vasoconstrictive agent did not significantly reduce blood loss, but predisposed the patient to infection of the vaginal cuff [22]. However, this study was performed in 1983, when the prophylactic use of antibiotics was not standard. There have been no studies since that time specifically addressing this issue in patients who received prophylactic antibiotics. In one of the premier vaginal surgery texts, Nichols and Randall state that, in their experience, the use of a vasoconstrictive agent has led to decreased operative blood loss, less anesthesia and postoperative analgesia, and easier development and identification of tissue planes [23]. Prior to injection, the anesthetist is informed about its intended use as there may be changes in the vital signs from injection. Lidocaine with epinephrine 1/ 200,000 or a dilute pitressin solution (10 or 20 units in 30 to 50 cc of normal saline) can be used. In patients with significant cardiac disease or hypertension, the anesthesia team may prefer the avoidance of these agents. Normal saline is an alternative as it will help delineate the tissue planes, but has no vasoconstrictive properties.

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Figure 1 Sites for circumferential incision. (From Mann WA, Stovall TG. Gynecologic Surgery. New York: Churchill Livingstone, 1996.)

Injection should be performed circumferentially, commencing at the posterior incision site. This avoids unnecessary bleeding into the operative field that occurs if anterior injection is performed first. It is important that the needle be placed superficially in the subcutaneous tissue so that good tissue distention and dissection occurs. A 22-gauge spinal needle or 1.5-inch regular 22-gauge needle is used. The former is often very flexible and bends, particularly in those patients who have keratinization of the vaginal mucosa from long-standing prolapse, so a standard needle is often more useful. It is important for the operator to aspirate prior to any injection to avoid inadvertent intravenous administration. A circumferential incision is made around the cervix at the level previously determined from inspection (Fig. 1). The use of mini-Dever retractors at the 3 and 9 o’clock positions and an appendix retractor anteriorly will help improve exposure. The incision is performed with a 10-blade knife full thickness through the mucosa. The most common mistake is to perform the incision too distally on the cervix. This makes it difficult to develop the tissue planes as the mucosa is densely attached to the cervix at that point. Should this be the case and the planes

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are unable to be developed, the operator should reevaluate the incision line and potentially go superior to the initial incision site. The posterior cul-de-sac is dissected and entered initially as posterior entry avoids bleeding into the operative field that can occur with the anterior incision. A forceps with teeth is used to grasp the posterior vaginal mucosa, and with the Mayo scissors at a 90° angle to the cervix, the overlying vaginal mucosa is incised in an attempt to free it from its cervical attachment. It is important for the assistant to apply firm countertraction in an upward direction with the posterior tenaculum. With traction on the vaginal mucosa, the cul-de-sac can usually be readily visualized. Once visualized, the peritoneum is directly grasped and incised with the use of the Mayo scissors (Fig. 2). It is very important not to push the vaginal epithelium posterior prior to identification of the cul-de-sac. This results in dissection between the vaginal epithelium and the peritoneum and increases the risk that the incision will be placed too proximal, resulting in inadvertent injury to the rectum. It may also cause bleeding, therefore making identification of the culde-sac more difficult. Should this occur, the surgeon would need to reevaluate the site of the incision. Typically speaking, if the incision is at the correct level

Figure 2 Direct entry into the posterior cul-de-sac. (From Mann WA, Stovall TG. Gynecologic Surgery. New York: Churchill Livingstone, 1996.)

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on the cervix, the cul-de-sac is very evident, and direct incision can be performed safely. Placing the tips of the Mayo scissors in the incision and opening them to their full extent widens the incision. The posterior surface of the uterus is directly palpated for evidence of any masses, adhesions, or thickening. On confirmation of entry into the posterior cul-de-sac, a Heaney-Simon retractor is placed in the incision. Some surgeons prefer not to place a retractor directly into the posterior cul-de-sac for fear of increasing the amount of intraperitoneal contamination by the vaginal flora. Clinically, this has not been a problem. Placing a retractor at this level aids in the identification of the uterosacral/cardinal ligament complex and in the placement of the clamps on the initial pedicles. If there is significant bleeding posteriorly, typically from the area of dissection between the peritoneum and vaginal cuff, several sutures of an absorbable material can be placed. This can be avoided by resisting the temptation to push the posterior vaginal cuff cephalad prior to the peritoneal incision. The technique to this point is very similar to that originally described by Heaney [24]. The following description of entry into the anterior peritoneum differs. Anterior dissection is often the area where the surgeon encounters the most difficulty during a vaginal hysterectomy. In a similar manner to the posterior entry, the full thickness of the anterior vaginal wall is grasped with a forceps with teeth and with the scissors at a 90° angle to the cervix, the fascial attachments are directly incised (Fig. 3). It is important to keep the scissors at a 90° angle as this prevents inadvertent dissection more superior than the desired level. This decreases the risk of the operator incising the bladder and ensures that the dissection is directly over the initial incision site. It is important to perform sharp dissection rather than blunt dissection as the vaginal mucosa is typically very adherent at this level, and blunt dissection may result in inadvertent perforation of the bladder. At this point, most operators would bluntly push the vaginal mucosa cephalad in an attempt to identify the vesicouterine peritoneum fold and directly incise the peritoneum (Fig. 4). This is also the technique by which most bladder injuries occur. The risk of incidental cystotomy during vaginal hysterectomy is approximately 1% [25]. Multiple studies have shown that most injuries occur during direct incision of the anterior peritoneal fold [25–27]. Two techniques have been described that provide greater safety for anterior entry. The first technique is applicable to all uterine sizes; however, the second technique is only applicable with a very small uterus. The first technique is universally applicable and is an important technique to teach all physicians. It is especially useful in cases of previous cesarean section, for which attempted direct entry is extremely difficult as the tissue plains are not readily evident [28]. It is important to be confident with this technique as it is very useful in the situation when the surgeon cannot safely enter the anterior peritoneum by direct incision and therefore would normally abandon the vaginal approach and continue abdominally. This technique allows the sharp dissection and the clamping of the lower pedicles to develop the vesicouterine space. As stated, the anterior vaginal mucosa is grasped full thickness, and the fascial attachments and bladder pillars are directly incised with the scissors at a 90° angle to the cervix. This dissection occurs from the 10 to the 2 o’clock position. It is imperative that the full thickness of the anterior vaginal mucosa, including

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Figure 3 Full thickness of the anterior vaginal wall and peritoneum is grasped to dissect the fascia from the cervix. (From Mann WA, Stovall TG. Gynecologic Surgery. New York: Churchill Livingstone, 1996.)

the bladder, is elevated vertically until all the attachments from the cervix are incised. At this stage, blunt dissection with a gauze-covered finger can be used to push the bladder superiorly. The cervix can be readily visualized and palpated, and it is evident that there is no tissue left attached to the cervix. Attention is then directed to the uterosacral ligaments. With firm traction, the assistant elevates the uterus as high as possible to expose the posterior aspect of the uterosacral ligament (Fig. 5). The posterior blade of the Heaney clamp is placed behind the posterior aspect of the ligament and then brought anteriorly and clamped at a 90° angle to the cervix. As the bladder peritoneum has not been entered, it is very important that all clamps be placed at a 90° angle to avoid the tendency of the clamps to migrate superiorly and therefore potentially place the bladder at risk. The uterosacral ligaments are cut, sutured, and ligatured with a fixation suture of a delayed absorbable type. With the advent of newer sutures, polyglactin or poliglecaprone are preferable to chromic catgut, which provides an intensive inflammatory reaction compared to the former two sutures. Fixation sutures

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Figure 4 Once the fascial attachments have been incised, the bladder and peritoneum can be bluntly dissected. (From Mann WA, Stovall TG. Gynecologic Surgery. New York: Churchill Livingstone, 1996.)

should be used as this pedicle will be tagged and used later in the subsequent support of the vaginal vault (Fig. 6). At this level, certain surgeons would include the vaginal mucosa into the pedicle to provide support to the vaginal vault. In this case, the needle is placed from the outside of the vaginal mucosa at the 4 o’clock position, through the distal end of the Heaney clamp, around the clamp in a Heaney fixation, and then back out the mucosa at the 5 o’clock position. This technique is applicable for patients who have no significant prolapse; however, it does not provide any anterior support to the vagina. It is important for the operator to palpate behind the clamp prior to placing the suture to ensure that the peritoneum is included in the pedicle. One of the common mistakes for inexperienced surgeons is not to encompass the peritoneum and to push it upward. This results in dissection between the vessels and the peritoneum and can result in significant bleeding. The cardinal ligament complex is ligated. Again, the clamp hugs the uterus, is placed initially posteriorly, is rotated at a 90° angle, and then is applied anteriorly. This pedicle is suture ligated with a single tie, as opposed to a fixation suture, as there should be no traction

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Figure 5 Clamping of the left uterosacral ligament. (From Mann WA, Stovall TG. Gynecologic Surgery. New York: Churchill Livingstone, 1996.) on this pedicle. Some authors advocate routine palpation of the ureters through the vaginal approach; however, this is often difficult even for the experienced operator. If the anterior attachments of the bladder to the cervix are dissected and the bladder retracted superiorly, the ureters will be elevated away from the operative site. This, combined with placement of clamps immediately adjacent to the cervix, reduces the risk of inadvertent ureteral injury. The uterine vessels are clamped and suture ligated with a simple suture (Fig. 7). Note that the anterior peritoneum has still not been entered. It is important prior to placement of any of the clamps that the operator ensure that the bladder has been pushed cephalad and retracted by the assistant so that it is not inadvertently clamped during control of these pedicles. A fixation suture is not used because of the risk of lacerating a vascular pedicle. At this stage, it is usually evident that the anterior peritoneum has been entered by one of the clamps, and a small defect is apparent. This defect can then be enlarged with the use of the scissors; a Heaney-Simon retractor is placed in the anterior cul-de-sac, and the bladder elevated. If this is not the case and the uterus is small, two fingers can then be placed in the posterior peritoneal opening

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Figure 6 Fixation suture of the left uterosacral ligament. (From Mann WA, Stovall TG. Gynecologic Surgery. New York: Churchill Livingstone, 1996.)

over the fundus, making the vesicouterine fold visible so it can be directly incised [29] (Fig. 8). This is the second method of entry mentioned above. If the uterus is small and mobile, successive pedicles can be developed along the broad ligament/round ligament complex up the fundus (Fig. 9). It is important for the operator to place a finger behind the clamps to ensure that no omentum or bowel inadvertently is placed in the clamp. All of these pedicles are simply sutured. The fundal attachment of the tubes, broad ligament, and utero-ovarian ligament can be clamped from above and/or below as visibility permits. This is a vascular pedicle and requires initial ligation with a free tie with the pedicle “flashed,” followed by a fixation suture. This suture is then tagged.

VIII. THE ENLARGED UTERUS Many have considered uterine enlargement greater than the size at 12 weeks gestation a relative contraindication to vaginal hysterectomy. However, recent studies have shown that a variety of morcellation techniques are useful in this setting [30–32]. Prior to any attempt at morcellation or bivalving of the uterus, the uterine

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Figure 8 For the small uterus, a hand can be placed over the fundus of the uterus to tent the peritoneum, which can be directly incised. (From Thompson JD, Rock JA. TeLinde’s Operative Gynecology. Philadelphia, PA: Lippincott, 1992.)

vessels must be ligated. Wedge resection or bivalving can be performed in patients undergoing hysterectomy for noncancerous reasons. Thorough preoperative assessment is imperative as the subsequent specimen is significantly more difficult for the pathologist to interpret. Morcellation has the advantage of typically producing an intact specimen. Strong traction is applied to the cervix by the tenaculum. A cylindrical core is developed, commencing at the serosa of the uterus. An incision is made circumferentially with the blade parallel to the body of uterus, commencing anteriorly in

Figure 7 The uterine vessels are ligated. (From Mann WA, Stovall TG. Gynecologic Surgery. New York: Churchill Livingstone, 1996.)

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Figure 9 The broad/round/utero-ovarian complex can be clamped from above or below. (From Mann WA, Stovall TG. Gynecologic Surgery. New York: Churchill Livingstone, 1996.)

a 360° circle. This allows the center of the specimen to be pulled down more, and a further incision can be made. This is performed in a manner similar to onion skinning. This results in a specimen in which the interior of the uterus can be pulled down externally, thus decompressing the bulk of the uterus and allowing easier access to the upper broad/round ligament complex (Fig. 10). It is imperative that the tip of the knife is visualized or palpated so as not to extend beyond the fundus, which would potentially place the bowel in danger. In a similar manner, a wedge resection would decompress the center of the uterus and allow the body to collapse, thus allowing greater access to the lateral pedicles. The hysterectomy would then be performed in a similar manner. Myomectomy may also be applicable in certain settings. The individual myomas may be incised and enucleated to decompress the uterus. The above techniques have enabled hysterectomies to be performed on much larger uteruses. A recent report showed the techniques were successful for removal of uterus between 200 and 700 g with no difference in major surgical

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Figure 10 Morcellation is performed on the enlarged uterus. (A) The initial incision is made parallel to the body of the uterus. (B) The tenaculum retracts the uterus and the parallel incision is extended toward the fundus. (C) The inside core is delivered, and the uterus is decompressed, allowing greater access and mobility. (From Nichols DH, Randall CL. Vaginal Surgery. Baltimore, MD: Williams and Wilkens, 1989.)

complications compared to a standard hysterectomy on a smaller-size uterus [31]. In this study by Unger, morcellation was required in 80% of the enlarged uterus specimen. The only significant difference from hysterectomy for a normal-size uterus was increased operative time. There was a linear relationship between uterine weight and operative time. Studies indicate that 84–100% of the planned vaginal hysterectomies can be completed vaginally with well-selected patients [31–32]. From the patient’s perspective, an 84% chance of completing the procedure vaginally is more appeal-

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ing than a 100% chance that it will be performed abdominally, and the patient should be given these statistical odds. The key to success is a mobile uterus, typically less than the size at 12–14 weeks of gestation, no suspected adnexal masses, good vaginal access, and an experienced surgeon. IX. ADNEXAL REMOVAL The tubes and ovaries should always be inspected after removal of the uterus. This can usually be achieved by gentle traction on the tagged upper pedicle. It is useful to place the patient in steep Trendelenburg position and place one or two moistened minilaparotomy packs in the posterior cul-de-sac. With a HeaneySimon retractor anteriorly elevating the bladder and another retracting posteriorly, a moistened sponge stick can be used to gently move the tubes and ovaries into the operative field. In the patient with uterine prolapse, typically salpingoophorectomy is relatively easy. The ovaries are grasped with a long Babcock clamp. The tube is traced to the fimbriated end and gently grasped with a separate long Babcock. Preferably, both the tube and ovary are combined into a single clamp. With gentle traction on these, a Heaney clamp is placed over the infundibulo-pelvic ligament and mesosalpinx. The tube and ovary are then removed (Fig. 11). Because of the large vessels in this pedicle, the pedicle is initially free tied with an absorbable suture,

Figure 11 The infundibulopelvic ligament is clamped if salpingo-oophorectomy is desired. (From Mann WA, Stovall TG. Gynecologic Surgery. New York: Churchill Livingstone, 1996.)

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and the clamp is “flashed.” Subsequently, a single penetration suture through the middle of the pedicle is passed front and back, then tied just distal to the free suture. The second suture is gently tagged. The area is inspected for hemostasis. The reported success rate for ovarian removal via the vaginal approach has ranged from 53% to 94% [33–35]. Sheth, in a series of 740 vaginal hysterectomies with attempted oophorectomy, noted that factors influencing success included obesity, nulliparity, decreased vaginal access, lack of uterine descent, increased uterine size, and tubo-ovarian disease [34]. Most reports noted no increased intraoperative or postoperative morbidity and mortality. Smale et al., however, in their report of 355 vaginal hysterectomies with oophorectomy, noted a single incidence of hemorrhage from an ovarian pedicle that required laparotomy [36]. X.

SUPPORT TECHNIQUES

The incidence of vaginal vault prolapse after abdominal or vaginal hysterectomy for any reason is increased. The reported incidence varies from less than 1% to 40% [37]. Incorporation of the uterosacral ligaments into the posterior vaginal mucosa is a common method of support; however, it leaves the anterior segment vulnerable. In the case of uterine prolapse, suturing the vagina to the uterosacral ligaments at the level of the circumferential cervical incision does nothing to support an already prolapsed vagina [38]. Closing the peritoneum alone, followed by closure of the vaginal mucosa does nothing to support the apical, anterior, or posterior segments. In a randomized comparison of three different surgical techniques at the time of vaginal hysterectomy to prevent prolapse, Cruikshank and Kovac noted that the McCall-type cul-de-plasty was superior to a Moschowitz-type procedure or a peritoneal closure at 3 years postsurgery [39]. Incorporating the anterior and posterior endopelvic fascia is critical for repair [40–43]. It is important to place the patient in steep Trendelenburg and to pack the bowel with minilaparotomy sponges so the cul-de-sac can be easily identified. Heaney retractors placed at the 7 o’clock position and anteriorly will help in identification of the uterosacral ligaments. If the patient has prolapse, the uterosacral ligament needs to be shortened. Traction on the previously tagged uterosacral ligament pedicle should be in a vertical direction toward the ceiling. This will allow palpation of the ligament to its sacral insertion. Once identified, a Heaney clamp is applied to the more proximal end toward the sacrum. It is important to note the relationship of the ureter to the uterosacral ligament. The ureter typically courses above the level of the ischial spine. Palpation of the spine and placement of the clamp inferiorly is important in protecting the ureter. After the uterosacral ligaments have been shortened, the lateral attachment sutures are placed. Commencing at the 2 o’clock position approximately 1 cm from the vaginal mucosa, an absorbable suture is placed through the vaginal mucosa and exiting into the intraperitoneal field. Full-thickness placement ensures that not only the vaginal mucosa, but also the underlying fascia of the anterior segment is included for support. It is worthwhile then to attempt to place this suture through the anterior peritoneum, which helps close the peritoneal cavity and ensures that the hysterectomy pedicles are extraperitoneal. This may allow for early detection of postoperative bleeding. It is not critical that the peritoneum

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is included as it does not aide in support. The suture is then placed through the shortened uterosacral ligament. Finally, it exits through the vaginal mucosa approximately 1 cm from the edge at the 4 o’clock position. In a similar manner, a suture is placed through the 10 o’clock position to the anterior peritoneum, the right uterosacral ligament, and out at the 8 o’clock position and tagged. These sutures provide support for the anterior and lateral segments. A McCall cul-de-plasty is then performed [44,45]. Internal McCall sutures are initially placed. For the right-handed surgeon, a permanent suture (e.g., 0 polyester such as Ethibond by Ethicon, Inc., Summerville, NJ) is placed through the left uterosacral ligament across the posterior cul-de-sac at the level of the rectal reflection to the right uterosacral ligament. These sutures need to be very superficial to avoid inadvertent rectal injury. The suture is tagged. A second suture just distal to the first is placed in a similar manner. Permanent sutures are used, and as long as they are not through the mucosa, rejection/erosion/sinus formations are not a problem.

Figure 12 Support of the vaginal cuff involves placement of 5 sutures. Two separate angle sutures (1 and 2) incorporate the vaginal epithelium 1 cm from the edge at the 2 and 10 o’clock positions, to the anterior peritoneum, uterosacral ligament, and exiting the vaginal epithelium at the 4 and 8 o’clock positions, respectively. Two internal McCall sutures (3, 4) run from one uterosacral ligament across the posterior peritoneum to the other uterosacral ligament. An external McCall suture (5) is placed from outside the vaginal mucosa at the 5 o’clock position, exiting between the two internal McCall sutures, to the left uterosacral ligament, right uterosacral ligament, middle of internal McCall sutures, and exiting at 7 o’clock though the cuff.

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In the case of prolapse, the apex of the vagina needs to be re-created, and an external McCall suture is placed. Commencing 1 cm from the edge of the vagina at the 5 o’clock position, an absorbable suture is placed through the vaginal mucosa into the middle of the two previous McCall cul-de-plasty sutures. The suture is then placed through the left uterosacral ligament (right-handed surgeon) to the right uterosacral ligament and then back through the middle of the permanent sutures and out the vaginal epithelium at the 7 o’clock position. The positioning of the sutures through the outside of the vaginal mucosa provides the basis for the new apex of the vagina (Figs. 12 and 13). It ensures that the highest point of the vagina is well supported by the McCall suspension sutures. The minilaparotomy sponges are then removed, and the area is checked for hemostasis. The lateral vaginal angle sutures are tied. The highest internal McCall suture, followed by the more distal one, are tied with a finger in the vagina to ensure that no bowel comes into the suture as it is secured. The external McCall suture is finally tied. This results in the apex of the vagina being well elevated and sloping toward the sacrum. The anterior, lateral, and posterior segments are well supported in the midline. The vaginal mucosa is then closed with either interrupted figure-eight absorbable sutures or a running suture. Interrupted sutures are preferable as they do not rely on a single knot for security. Should a hematoma develop, a suture can be cut for drainage without compromising the rest of the cuff. It is important to close the vaginal cuff in this case as the peritoneum is not separately closed.

Figure 13 Schematic representation of the cuff support sutures of Fig. 12.

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There is no evidence that closure of the cuff increases infectious morbidity when preoperative antibiotics are administered. This technique of support is usually adequate. In a patient with severe prolapse, there will be instances when the uterosacral ligaments are extremely attenuated or torn and the ligament cannot be adequately shortened to provide a successful reattachment site. In this case, consideration can be given to performing a sacrospinous ligament fixation at the time of hysterectomy. The McCall cul-deplasty, however, provides a more anatomical repair and superior vaginal length compared to the sacrospinous ligament fixation. For this reason, attempts should be made to preferentially perform a cul-de-plasty. The details of sacrospinous ligament fixation are beyond the scope of this particular chapter. XI. CONCLUSION Vaginal hysterectomy has the lowest morbidity and cost of the various types of hysterectomy [46]. It can be successfully completed in most well-selected patients. It is recommended that the reader review the decision-making guidelines by Kovac. In most cases, oophorectomy is feasible. Correct placement of the initial incision and correct techniques for anterior peritoneal entry are key. Some type of support technique should be included at the end of the procedure. With the increasing life expectancy for females, pelvic organ prolapse may become a significant health issue unless this is routinely considered and implemented. REFERENCES 1. Dorsey JH, Steinberg EP, Holtz PM. Clinical indications for hysterectomy route: patient characteristics or physician preference? Am J Obstet Gynecol 1995; 173:1452– 1460. 2. Summit RL Jr, Stovall TG, Lipscomb GH, Ling FW. Randomized comparison of laparoscopic-assisted vaginal hysterectomy with standard vaginal hysterectomy in an outpatient setting. Obstet Gynecol 1992; 80:895–901. 3. Kovac SR, Christie SJ, Bindbeutel GA. Abdominal versus vaginal hysterectomy: a statistical model for determining physician decision making and patient outcome. Med Decis Making 1991; 11:19–28. 4. Kovac SR. Which route for hysterectomy? Post Grad Med 1997; 102:153–158. 5. Kovac SR. Guidelines to determine the route of hysterectomy. Obstet Gynecol 1995; 85:18–23. 6. Olsson JH, Ellstrom M, Hahlin M. A randomized prospective trial comparing laparoscopic and abdominal hysterectomy. Br J Obstet Gynaecol 1996; 103:345–350. 7. Raju KS, Auld BJ. A randomized prospective study of laparoscopic vaginal hysterectomy versus abdominal hysterectomy each with bilateral salpingo-oophorectomy. Br J Obstet Gyaecol 1994; 101:1068–1071. 8. Weber AM, Lee J-C. Use of alternative techniques of hysterectomy in Ohio, 1988– 1994. N Engl J Med 1996; 335:483–489. 9. Polk BF, Tager IB, Shapiro M, et al. Randomized clinical trial of perioperative cefazolin to prevent infection following hysterectomy. Lancet 1980; 1:437–441. 10. Swartz WH. Prophylaxis of minor febrile and infectious morbidity following hysterectomy. Obstet Gynecol 1979; 54:284–288. 11. Tanos V, Rojansky N. Prophylactic antibiotics in abdominal hysterectomy. J Am Coll Surg 1994; 179:593–600.

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12. Mittendorf R, Aronson MP, Berry RE, et al. Avoiding serious infections associated with abdominal hysterectomy: a meta-analysis of antibiotic prophylaxis. Am J Obset Gynecol 1993; 169:119–124. 13. Roy S, Wilkins J, Hemsell DL, March CM, Spirtos NM. Efficacy and safety of singledose ceftizoxime versus multidose cefoxitin in preventing infection after vaginal hysterectomy. J Reprod Med 1988; 33:149–153. 14. Callesen T, Schouenborg L, Nielsen D, Guldager H, Kehlet H. Combined epiduralspinal upload-free anaesthesia and analgesia for hysterectomy. Br J Anaesth 1999; 82: 881–885. 15. Williams-Russo P, Sharrock NE, Mattis S, Szatrowski TP, Charlson ME. Cognitive effects after epidural vs general anesthesia in older adults. A randomized trial. JAMA 1995; 274:44–50. 16. Hoffman MS, Roberts WS, Cavanagh D. Neuropathies associated with radical pelvic surgery for gynecologic cancer. Gynecol Oncol 1988; 31:462–466. 17. Blackmore MA, Turner GM, Adams MR, Speller DCE. The effect of preoperative povidine iodine vaginal pessaries on vault infections after hysterectomy. Br J Obstet Gynaecol 1981; 88:308–313. 18. Shindo K. Antiseptic effect of povidine-iodine solution on abdominal skin during surgery and on thyroid-gland-related substances. Dermatology 1997; 195:78–84. 19. Monif GRG, Thompson GL, Stephens HG, Baer H. Quantitative and qualitative effects of povidine-iodine liquid and gel on the aerobic and anaerobic flora of the female genital tract. Am J Obstet Gynecol 1980; 137:432–438. 20. Eason EL, Sampalis JS, Hemmings R, Joseph L. Povidine-iodine gel vaginal antisepsis for abdominal hysterectomy. Am J Obstet Gynecol 1997; 176:1011–1016. 21. Fleischer W, Reimer K. Povidine-iodine in antisepsis—state of the art. Dermatology 1997; 195:3–9. 22. England GT, Randall HW, Graves WL. Impairment of tissue defenses by vasoconstrictors in vaginal hysterectomies. Obstet Gynecol 1983; 61:271–274. 23. Nichols DH, Randall CL. Vaginal hysterectomy. In: Nichols DH, Randall CL, eds. Vaginal Surgery. Baltimore, MD: Williams and Wilkens, 1989:188. 24. Heaney NS. Vaginal hysterectomy—its indications and technique. Am J Surg 1940; 56:284. 25. McLennan MT, Bent AE. Incidental cystotomy during benign gynecologic and obstetric surgery. J Pelvic Surg 1997; 3:260–264. 26. Copenhaver EH. Vaginal hysterectomy—an analysis of indications and complications among 1000 operations. Am J Obstet Gynecol 1962; 84:123–128. 27. Rosenzweig BA, Seifer DB, Grant WD, Rodriguez F, Birenbaum DL, Adelson MD. Urologic injury during vaginal hysterectomy. A case-control study. J Gynecol Surg 1990; 6:27–32. 28. Unger JB, Meeks GR. Vaginal hysterectomy in women with history of previous cesarean delivery. Am J Obstet Gynecol 1998; 179:1473–1448. 29. Kalogirou D, Antoniou G, Zioris C, Fotopoulos S, Karakitsos P. Vaginal hysterectomy: technique and results in the last twenty years. J Gynecol Surg 1995; 11:210–217. 30. Lash AF. A method for reducing the size of the uterus in vaginal hysterectomy. Am J Obstet Gynecol 1941; 42:452–459. 31. Unger JB. Vaginal hysterectomy for the women with a moderately enlarged uterus weighing 200 to 700 grams. Am J Obstet Gynecol 1999; 180:1337–1344. 32. Mazdisnian F, Kurzel RB, Coe S, Bosuk M, Montz F. Vaginal hysterectomy by uterine morcellation: an efficient, non-morbid procedure. Obstet Gynecol 1995; 86:60–64. 33. Ballard LA, Walters MD. Transvaginal mobilization and removal of ovaries and fallopian tubes after vaginal hysterectomy. Obstet Gynecol 1996; 87:35–39. 34. Sheth SS. The place of oophorectomy at vaginal hysterectomy. Br J Obstet Gynaecol 1991; 98:662–666.

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35. Davies A, O’Connor H, Magos AL. A prospective study to evaluate oophorectomy at the time of vaginal hysterectomy. Br J Obstet Gynaecol 1996; 103:915–920. 36. Smale LE, Smale ML, Wilkening RL, Mundy CF, Ewing TL. Salpingo-oophorectomy at the time of vaginal hysterectomy. Am J Obstet Gynecol 1978; 131:122–126. 37. Symmonds RE, Williams TJ, Lee RA, Webb MJ. Posthysterectomy enterocele and vaginal vault prolapse. Am J Obstet Gynecol 1981; 140:852–859. 38. Cruikshank SH. Preventing vault prolapse and enterocele after vaginal hysterectomy. South Med J 1988; 81:594–596. 39. Cruikshank SH, Kovac SR. Randomized comparison of three surgical methods at the time of vaginal hysterectomy to prevent posterior enterocele. Am J Obstet Gynecol 1999; 180:859–865. 40. Ross JW. Apical vault repair, the cornerstone of pelvic vault reconstruction. Int Urogynecol J Pelvic Floor Dysfunct 1997; 8:146–152. 41. Cruikshank SH, Kovac SR. Anterior vaginal wall culdeplasty at vaginal hysterectomy to prevent posthysterectomy anterior vaginal wall prolapse. Am J Obstet Gynecol 1996; 174:1863–1872. 42. Franke JJ. Vaginal apical support: cornerstone of pelvic reconstructive surgery. Tech Urol 1996; 2:86–92. 43. Borenstein R, Elchala U, Goldchmit R, Rosenman D, Ben-Hur H, Katz Z. The importance of the endopelvic fascia repair during vaginal hysterectomy. Surg Gynecol Obstet 1992; 175:551–554. 44. McCall ML. Posterior culdoplasty: surgical correction of enterocele during vaginal hysterectomy; a preliminary report. Obstet Gynecol 1957; 10:595. 45. Given FT. Posterior culdeplasty. Am J Obstet 1985; 153:135–139. 46. Dorsey JH, Holtz PM, Griffiths RI, McGrath MM, Steinberg EP. Costs and charges associated with three alternative techniques of hysterectomy. N Engl J Med 1996; 335: 476–482.

21 Urethral Diverticulum SAM BHYANI and BRUCE I. CARLIN Washington University School of Medicine St. Louis, Missouri, U.S.A.

I.

HISTORY

In 1805, Hey reported the first case of a urethral diverticulum [1]. The condition was originally thought to be very uncommon, and an extensive review of 1950 medical records of Johns Hopkins, the Mayo Clinic, and the Cleveland Clinic revealed only 100 cases [2]. In 1953, Novak wrote: “This is a relatively rare condition and no gynecologist will see more than a few in a life time” [3: 302]. However, in the next few years, technological advances allowed the diagnosis to be made more often. With the development of positive-pressure urethrography using a double-balloon catheter, in 1956 Davis and Cian reported 50 cases [4]. In the last half century, significant advances in imaging and treatment of urethral diverticula have been made. Now, a variety of diagnostic modalities exist, and effective surgical repair has been developed. II. INCIDENCE Various studies have shown the incidence of urethral diverticulum to be 1.4% to 4.7%. Aldridge et al. diagnosed diverticula urethroscopically in 1.4% of 279 patients referred for a variety of symptoms [5]. Hoffman and Adams imaged 129 asymptomatic patients using positive-pressure urethrography and found a 4.7% incidence of urethral diverticula [6]. Andersen discovered a 3% incidence in 300 patients presenting with cervical carcinoma [7]. Some studies have shown an increased incidence of urethral diverticula in African American females [8,9]. Other studies have not supported this increase [10,11]. 351

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III. ETIOLOGY Urethral diverticula classically originate from the periurethral glands. Although some authors have described a congenital origin for this condition, this is mostly of historical significance. The theories for a congenital cause were based on the observation that suburethral cysts could be found in neonates [12–14]. Most authors favor an acquired cause rather than a congenital cause of this condition. The argument against a congenital origin is based on the age of diagnosis. Urethral diverticula are rarely diagnosed in children in most series, and mean age of diagnosis has been made 36–45 years [11,15]. Trauma from childbirth has also been postulated as an etiology for the development of urethral diverticula [16]. It was theorized that high birth pressures led to urethral mucosal herniation. Now, it is well recognized that diverticula occur in nulliparous women. In a review by Ganabathi et al., 9.5% of women with urethral diverticula were nulliparous [15]. Other series have reported higher percentages of nulliparity [8,17,18]. In 1890, Routh first dispensed the theory that infection and obstruction of the periurethral glands resulted in cyst and abscess formation. The abscess eventually would rupture into the urethral lumen, creating a diverticulum [19]. The pathophysiology was further elucidated in 1948 when Huffman published his experiments with wax castings of the female urethra [20]. He discovered a complex network of periurethral glands, located primarily posterolaterally, that opened into the distal urethra. This position is coincident with the location of the majority of urethral diverticula. These studies, along with the demographics of patients with urethral diverticula, have led most investigators to believe that the disease is caused by infection and abscess of the periurethral glands with subsequent communication with the urethral lumen.

IV. SYMPTOMATOLOGY A complete history and physical exam should be performed for all patients. The classic triad of dysuria, dyspareunia, and dribbling can aid in the diagnosis of urethral diverticula, but this triad is not often present. Table 1 outlines the presenting symptoms in many large series [6,8,10,11,15,18,21–27]. Typically, patients have a history of lower urinary tract symptoms, but a small percentage of patients are asymptomatic. A history of urinary tract infections is also common. Incontinence is often present. Calculi and carcinoma have also been described in diverticula. Overall, the pathognomonic signs of diverticula present in an inconsistent fashion. Therefore, clinical suspicion must be high when treating women with unexplained voiding complaints. A recent study showed a mean interval to diagnosis of 3.2 years for palpable diverticula and 7.1 years for nonpalpable diverticula [11]. Patients often have seen multiple physicians and have been treated with courses of both anticholinergic medicines and antibiotics. On physical examination, particular attention should be focused on the anterior vaginal wall and suburethral area. A suburethral mass or purulent discharge on milking of the urethra should alert the clinician of the diagnosis. If the mass is firm, concurrent calculi or carcinoma should be considered. Stress incontinence

11 (all palpable) 11 (all nonpalpable) 15 10 21 8 22 23 24 18 25 6 26 27

2000

1994 1987 1984 1983 1980 1976 1970 1970 1966 1965 1959 1958

2000

Ref.

63 37 50 70 13 32 120 45 27 60 204 121

22

24

Patients

4.8 — — — — 20 1.6 — 11 — — 7.4

—

—

Asymptomatic

20.6 10.8 80 90 31 69 32 47 52 58 73 63

9

8

Dysuria

6.3 19 70 — — 9 32 13 15 20 14 24

32

17

Dyspareunia

Presenting Symptoms (%) of 888 Patients with Urethral Diverticula

Year

Table 1

4.8 13.5 — 5.7 — — 32 22 15 90 — 13

—

8

Postvoid dribbling/ pain

38.1 40.5 80 — 23 — 33 — — — 46 —

—

17

Recurrent urinary tract infection

— 16 — — 15 6 — 18 — 45 12 —

—

29

Mass

3.2 — — — 15 — — 31 — — — 1.6

—

—

Urethral discharge

— — 45 — — 3 30 26 — — 29 —

—

—

Urethral pain

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and organ prolapse should also be identified at pelvic examination as they may be repaired at the time of diverticulectomy. The differential diagnosis of a palpable lesion in the anterior vaginal wall includes urethral diverticulum, but also encompasses vaginal wall cyst, Gartner’s duct cyst, leiomyoma, Skene’s gland abscess, prolapsed ureterocele, mucosal prolapse, and vaginal neoplasm [28]. A careful pelvic examination can help rule out these pathologies. V.

URETHROSCOPY

Cystourethroscopy can aid in the diagnosis of urethral diverticulum. Typically, a short-beaked female cystoscope should be used with the examiner’s finger in the upper vagina. The cystoscope is withdrawn into the urethra as the examiner places pressure on the urethra. Blood, pus, or stones may be seen from the ostium of the diverticulum. The diagnostic accuracy of this technique varies from 40% to 78% [8,10,27,29,30]. Cystourethroscopy can also aid in discovering other causes of lower urinary tract symptoms, such as ectopic ureter or ureterocele, carcinoma in situ, and foreign body. VI. RADIOLOGY A variety of radiographic studies have been used to diagnose urethral diverticula. Intravenous pyelography (IVP), voiding cystourethrography (VCUG), doubleballoon urethrography (DBU), ultrasound (US), and magnetic resonance imaging (MRI) have been used successfully to diagnose urethral diverticula. Although not characteristically used as a first-line diagnostic modality for lower urinary tract symptoms, an IVP can aid in the diagnosis of urethral diverticula [31]. The postvoid film may show residual contrast in the periurethral area, hence making the diagnosis. However, postvoid views will be inadequate if they do not incorporate the entire urethra. A postvoid film with urethral views should be included in all IVPs of patients with lower urinary tract symptoms. Another use for the IVP is to rule out ureteral duplication with an ectopic ureterocele presenting as a urethral mass. If such a ureterocele is not identified, excision can result in total urinary incontinence [15]. Some authors have recommended obtaining an IVP prior to diverticulectomy to avoid this misdiagnosis [32,33]. Although IVP is not the imaging procedure of choice, it can help in the diagnosis and treatment of urethral diverticulum. Voiding cystourethrography is commonly used to diagnose urethral diverticula. The voiding films will not only indicate the presence of a diverticulum, but also indicate its size and anatomy. Filling defects in the diverticulum, possibly representing carcinoma or calculi, can be identified, and stress incontinence can be documented on straining views [15]. Many investigators have demonstrated greater than 90% sensitivity of VCUG to diagnose urethral diverticula [10,15,23]. Other investigators have found VCUG to be less reliable. Lee and Keller [34] showed a sensitivity of 65%, as did Romazi et al. [11,34]. In a review of 32 patients with urethral diverticula, Jacoby and Rowbotham found VCUG to have a sensitivity of 44% [35]. The advantages of VCUG are its relatively low cost and its simplicity. Although not the gold standard, it is an effective test for diagnosis of diverticula.

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Positive-pressure DBU should be considered if the VCUG is unrevealing. The technique was originally described in 1956 by Davis and Cian [4]. A special double-balloon catheter is placed transurethrally; the proximal balloon is inflated at the bladder neck, and the distal balloon is inflated at the urethral meatus. Contrast is then injected into the catheter to create a positive pressure urethrogram. The diagnostic accuracy of this technique has ranged from 80% to 100%, but there are some practical problems with DBU [15,34–37]. The procedure requires steady traction to prevent contrast spillage, and it is painful [15]. Anesthesia may be necessary to perform an adequate test. Positive-pressure urethrography is an efficacious diagnostic tool, but it can be cumbersome. Transvaginal and transperineal ultrasound can be very effective in aiding in the diagnosis of urethral diverticula [38,39]. In 1998, Siegel et al. reported a prospective study in which 33 women with 15 diverticula were imaged with VCUG and US [40]. Ultrasound detected 13 of 15 diverticula, as did VCUG. Ultrasound showed the necks of the diverticula in all 13 cases, while VCUG revealed it in only 2 patients. Other studies have also shown a high sensitivity of ultrasound, but most series are small [34,37,38,40]. The precise role of sonography in evaluating urethral pathology is unclear, but it is a promising technique. Since it is highly operator dependent, its usefulness may directly relate to the experience of the sonographer. MRI is the newest and most expensive modality to image urethral diverticula and aid in their diagnosis. Kim et al. reported a series of 13 patients who underwent surgery for urethral diverticula [30]. MRI correctly made the recognition of diverticula in all the patients, while urethroscopy was correct in 10 patients (77%), and urethrography was correct in 9 patients (69%). Nietlich et al. reported on 4 patients who underwent surgery for urethral diverticula [41]. MRI assisted in the diagnosis for all 4 patients, while DBU was negative for 3. MRI has many advantages over traditional contrast studies; it can detect diverticula with small ostia, allows better visualization of periurethral structures, and gives a planar image [11]. The expense of MRI may preclude it as a screening study, but if a diverticulum is highly suspected, one should consider it to be a highly accurate diagnostic modality and a useful tool. VII. URODYNAMICS Strictly, urodynamics does not have a premier role in the diagnosis of urethral diverticula. Urodynamics, however, may alert the clinician of an unsuspected urethral diverticulum. The urethral pressure profile of a patient with a diverticulum will be biphasic; there will be a depression in the pressure at the ostium of the diverticulum [42]. A review by Leach and Bavendam revealed this biphasic pattern in 21 of 29 (72%) of the profiles reviewed [10]. Urodynamics can add important information that may aid in choosing the proper surgical therapy. A urethral pressure profile can be correlated with the location of the diverticular orifice. If the orifice is distal to the maximum urethral pressure (i.e., the sphincter), then a vaginal marsupialization can be performed with minimal risk of stress incontinence [43]. If the diverticular orifice is proximal to the maximum urethral pressure point, then vaginal marsupialization should be avoided.

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Urodynamics can also identify concomitant stress incontinence in patients with urethral diverticula. If stress incontinence exists, a continence procedure can be considered at the time of diverticulectomy. VIII. CLASSIFICATION In 1993, Leach et al. proposed a uniform classification system of urethral diverticula [44]. The scheme, referred to as L/N/S/C3, is based on describing the characteristics of the diverticulum: L is location; N is number; S is size; and C3 is configuration, communication, and continence. IX. ASSOCIATED CANCER Urethral carcinoma has been found in urethral diverticula. It is a rare finding, and a review of the literature by Patanaphan et al. in 1983 revealed only 32 cases [45]. A more recent series revealed urethral carcinoma in 2 of 46 patients [11]. Urethral carcinoma should be considered if there is a firm periurethral mass, pathological adenopathy, or generalized constitutional symptoms. Biopsy of the diverticulum can be performed transurethrally or transvaginally through endoscopic or open technique, respectively. Adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma have been described as arising from urethral diverticula. Treatment usually consists of multimodality therapy with anterior exenteration and radiotherapy [45,46].

Figure 1 An inverted U-shaped incision is made in the anterior vaginal epithelium.

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TREATMENT OF URETHRAL DIVERTICULA

Many surgical procedures have been described for the treatment of urethral diverticula. Most authors believe that transvaginal excision of the diverticulum is the procedure of choice. Multiple techniques have been described for transvaginal diverticulectomy. Successful procedures incorporate good surgical technique, meticulous dissection, and nonoverlapping suture lines in closure. Preoperatively, the patient should have routine blood chemistries, counts, and coagulation parameters. A chest x-ray and electrocardiogram may also be indicated. A urine culture should be obtained and treated if a urinary tract infection is detected. After induction of anesthesia, the patient is placed in the dorsal lithotomy position. The vagina and perineum are prepped and draped. The anus is draped and isolated to avoid contamination of the operative field. A Foley catheter and a weighted vaginal speculum are placed. Lidocaine with epinephrine is injected into the anterior vaginal wall. An inverted U-shaped vaginal incision is made on the anterior vaginal wall, with the apex encircling the diverticulum (Fig. 1). Using Metzenbaum scissors, the epithelium is developed proximally to create a flap. Care is taken not to dissect the deeper periurethral fascia in creating this flap. The periurethral fascia is then incised transversely (Fig. 2). A distal and proximal flap of this periurethral tissue is created sharply, thus exposing the diverticulum and urethra (Fig. 3). This dissection may be difficult secondary to infection and inflammation with resultant fibrosis. Care should be taken to avoid premature

Figure 2 The periurethral fascia is incised transversely.

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Figure 3 A distal and proximal flap of periurethral tissue is created. entry into the sac. The diverticulum is dissected in its entirety to expose its neck and the urethra (Fig. 4). The diverticulum and its neck are completely excised, thus exposing the urethral catheter. The urethra is then repaired over the urethral catheter. A 3-0 or 4-0 absorbable suture is placed in a longitudinal fashion to close the urethra. It is important that this closure be watertight to reduce the chance of fistulization. The transverse periurethral incision is closed with a 3-0 absorbable suture. The inverted U-shaped vaginal flap is closed with 2-0 absorbable suture. Care is taken when using this multilayer technique to avoid overlapping suture lines to prevent fistula formation. If the tissues are friable, a Martius flap may be interposed between the vaginal mucosal flap and the periurethral tissue. Postoperatively, antibiotics are used for 72 h, and the urethral catheter is left to gravity drainage. A vaginal pack may be placed intraoperatively and removed on postoperative day 1. After approximately 14 days, the urethral catheter is removed, and a VCUG is performed. If there is no extravasation on the voiding phase, the catheter is left out. If there is extravasation, the urethral catheter is replaced, and the VCUG is repeated in 2 to 3 weeks. XI. RESULTS AND COMPLICATIONS OF TRANSVAGINAL DIVERTICULECTOMY Overall, transvaginal diverticulectomy is a very efficacious and safe procedure. Similar to any surgical procedure, diverticulectomy can be complicated by bleed-

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Figure 4 The urethral diverticulum and its neck are dissected in entirety. ing and infection. Some minor blood loss is expected as the vaginal mucosa is very well vascularized. Meticulous hemostasis should be observed throughout the operation. A vaginal pack can help to tamponade the operative bed in the postoperative period. Infection may be minimized with the use of perioperative antibiotics and the presence of sterile urine preoperatively. Bladder spasms may develop as a reaction to the urinary catheter. These can be controlled with anticholinergic medicines as needed. Anticholinergics should be stopped 1 day prior to the VCUG to help ensure that the patient will void. Other complications include urethrovaginal fistula, stress incontinence, recurrent diverticulum, urethral stricture, and recurrent urinary tract infection. Table 2 outlines these complications [6,8,15,17,21,24,26,27,47]. Recurrence of diverticulum can be avoided by complete excision of the entire diverticulum and its neck. MRI or US may help the surgeon in assessing the size of the sac and the location of the neck and may help to avoid this complication. Urethrovaginal fistula is an infrequent, but important, complication. The avoidance of overlapping suture lines and the use of a Martius flap may help to minimize this complication. If it does occur, delayed repair should be undertaken. XII. OTHER SURGICAL PROCEDURES Although the preferred approach to diverticulectomy is transvaginal, other procedures have been used as well. Distal diverticula can be treated by a vaginal marsu-

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Table 2 Complications of Diverticulectomy of Larger Published Series (ⱖ50 patients)

Year

Ref.

Patients

Urethrovaginal fistula (%)

1956 1958 1959 1965 1970 1981 1984 1984 1994

47 27 26 6 24 21 8 17 15

58 84 130 60 98 50 50 108 56

7 — 5.4 1.7 4.1 2 1.9 0.9 1.8

Recurrent diverticulum (%)

Stress incontinence

Urethral stricture (%)

— 12 1.5 — 1 — 25 9.3 3.6

1.7 — “Several” 6.7 — — — 15 16.1

5. — — 1. — 2 1. 1. 0

pialization, as described by Spence and Duckett [43]. In this procedure the distal urethra is opened to the diverticulum, and the edges of the urethral mucosa are sutured to the vagina. This procedure should only be used for distal diverticula as proximal diverticula may be close to the sphincter muscles. Disruption of these muscles may result in total incontinence. Transurethral endoscopic incision of urethral diverticula has been described [48,49]. In this procedure, a urethrotomy is made from the meatus to the diverticular neck. There are no large series of studies of this technique, but it may be considered for distal diverticula. XIII. CONCLUSION Urethral diverticulum should be considered in the setting of any woman with lower urinary tract symptoms. The clinical suspicion must be high, and effective imaging techniques do exist to diagnose this condition. Transvaginal diverticulectomy is the procedure of choice and is highly successful. REFERENCES 1. Hey W. Practical Observations in Surgery. Philadelphia: James Humphries, 1805:304– 305. 2. Moore TD. Diverticulum of the female urethra: an improved technique of surgical excision. J Urol 1952; 68:611. 3. Novak R. Editorial comment. Obstet Gynecol 1953; 47:302. 4. Davis HJ, Cian LG. Positive pressure urethroscopy: a new diagnostic method. J Urol 1956; 75:753. 5. Aldridge CW, Beaton JH, Nanzig RP. A review of office urethroscopy and cystometry. Am J Obstet Gynecol 1978; 131:432. 6. Hoffman M, Adams W. Recognition and repair of urethral diverticula. Am J Obstet Gynecol 1965; 92:106. 7. Anderson M. The incidence of diverticula in the female urethra. J Urol 1967; 98:96. 8. Ginsburg DS, Genadry R. Suburethral diverticulum: classification and therapeutic considerations. Obstet Gynecol 1983; 61:685.

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9. Benjamin J, Elliott L, Cooper JF, et al. Urethral diverticulum in adult female: clinical aspects, operative procedure, and pathology. Urology 1974; 30:407–415. 10. Leach GE, Bavendam TG. Female urethral diverticula. 1987; Urology 30:110. 11. Romanzi LJ, Groutz A, Blaivas JG. Urethral diverticulum in women: diverse presentation resulting in diagnostic delay and mismanagement. J Urol 2000; 164:428–433. 12. Nel J. Diverticulum of the female urethra. Br J Obstet Gynecol 1955; 62:90. 13. Ratner M, Ritz I, Siminovitch M. Diverticulum of the female urethra with multiple calculi. Can Med Assoc J 1949; 60:510. 14. Pinkerton J. Diverticulum of the female urethra. Br J Obstet Gynecol 1956; 63:76. 15. Ganabathi K, Leach GE, Zimmern PE, et al. Experience with the management of urethral diverticulum in 63 women. J Urol 1994; 152:1445. 16. Mcnally A. Diverticula of the female urethra. Am J Surg 1935; 28:177. 17. Lee RA. Diverticulum of the female urethra. 1983; 61:52. 18. Pathak U, House M. Diverticulum of the female urethra. Obstet Gynecol 1970; 36:786. 19. Routh A. Urethral diverticulum. Br Med J 1890; 1:361. 20. Huffman JW. The detailed anatomy of the paraurethral ducts in the adult human female. Am J Obstet Gynecol 1948; 55:86. 21. Rozsahegyi J, Magasi P, Szule E. Diverticulum of the female urethra: a report of 50 cases. Acta Chir Hung 1984; 15:33. 22. Woodhouse CRJ, Flynn JT, Molland EA, et al. Urethral diverticulum in females. Br J Urol 1980; 52:305. 23. Peters WH, Vaughan ED. Urethral diverticulum in the female. Obstet Gynecol 1976; 47:549. 24. Davis BL, Robinson DG. Diverticula of the female urethra. J Urol 1970; 104:850. 25. Kittredge R, Bienstock M, Finby N. Urethral diverticula in women. Am J Roentgenol 1966; 98:200. 26. Mackinnon M, Pratt PH, Pool TL. Diverticulum of the female urethra. Surg Clin N Am 1959; 39:953. 27. Davis HJ, TeLinde RW. Urethral diverticula. J Urol 1958; 80:34. 28. Dmochowski RR, Ganabathi K, Zimmern PE, et al. Benign female periurethral masses. J Urol 1994; 152:1943. 29. Butler WJ. The diagnosis of urethral diverticula in women. J Urol 1966; 95:63. 30. Kim B, Hricak H, Tanagho EA. Diagnosis of urethral diverticula in women. Am J Roentgenol 1993; 161:809. 31. Goldfarb S, Mieza M, Leiter E. Postvoid film of intravenous pyelogram in diagnosis of urethral diverticulum. Urology 1981; 17:390. 32. Blacklock ARE, Shaw RE, Geddes JR. Late presentation of ectopic ureter. Br J Urol 1982; 54:106. 33. Leach GE, Trockman BA. Surgery for fistulas and diverticulum. In: Walsh P, Retik A, Vaughan E, Wein A, eds. Campbell’s Urology. Philadelphia, PA: W. B. Saunders, 1998. 34. Lee TG, Keller FS. Urethral diverticulum: diagnosis by ultrasound. Am J Roentgenol 1977; 128:690. 35. Jacoby K, Rowbotham RK. Double balloon positive pressure urethrography is a more sensitive test than voiding cystourethrography for diagnosing urethral diverticulum in women. J Urol 1999; 162:2066. 36. Kolhorn EI, Glickman MG. Technical aids in investigation and management of urethral diverticula in the female. Urology 1992; 40:322. 37. Greenberg M, Stone D, Cochran ST, et al. Female urethral diverticula: double balloon catheter study. Am J Roentgenol 1981; 136:259. 38. Keefe B, Warshauer DM, Tucker MS, et al. Diverticula of the female urethra: diagnosis by endovaginal and transperineal sonography. Am J Roentgenol 1991; 156:1195.

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39. Fontana D, Porpiglia F, Morra I, et al. Transvaginal ultrasonography in the assessment of organic diseases of female urethra. J Ultrasound Med 1999; 18:237. 40. Siegel CL, Middleton WD, Teefey SA, et al. Sonography of the female urethra. Am J Roentgenol 1998; 170:1269. 41. Nietlich JD, Foster HE, Glickman MG, et al. Detection of urethral diverticula in women: comparison of a high resolution fast spin echo technique with double balloon urethrography. J Urol 1998; 159:408. 42. Bhatia NN, McCarthy TA, Ostergard D. Urethral pressure profiles of women with urethral diverticula. Obstet Gynecol 1981; 58:375. 43. Spence HM, Duckett JW. Diverticulum of the female urethra: clinical aspects and presentation of a single operative technique for care. J Urol 1970; 104:432. 44. Leach GE, Sirls LT, Ganabathi K, et al. LNSC3: a proposed classification system for female urethral diverticula. Neurourol Urodyn 1993; 12:523. 45. Patanaphan V, Prempree T, Sewchand W, et al. Adenocarcinoma arising in female urethral diverticulum. Urology 1977; 10:58. 46. Evans KJ, McCarthy MP, Sands JP. Adenocarcinoma of a female urethral diverticulum. J Urol 1981; 126:124. 47. Wharton LR, TeLinde RW. Urethral diverticulum. Obstet Gynecol 1956; 7:503. 48. Spencer WF, Streem SB. Diverticulum of the female urethral roof managed endoscopically. J Urol 1987; 138:147. 49. Miskowiak J, Honnens de Lichtenburg M. Transurethral incision of urethral diverticulum in the female. Scand J Urol Nephrol 1989; 23:235.

22 Evaluation and Management of Urinary Fistulas ELIZABETH A. MILLER University of Washington Seattle, Washington, U.S.A. GEORGE D. WEBSTER Duke University Medical Center Durham, North Carolina, U.S.A.

I.

INTRODUCTION

Urinary fistulas have been recognized in the literature for centuries as a distressing problem that results most commonly from birth trauma or urogynecological surgery. This chapter focuses on the etiology, diagnosis, and surgical management of the most common urinary fistulas: vesicovaginal, urethrovaginal, and ureterovaginal.

II. VESICOVAGINAL FISTULA A. Etiology Historically, birth trauma resulting from prolonged, obstructed labor has been the most common cause of vesicovaginal fistula. Compression of the anterior vaginal wall and bladder neck or trigone of the bladder between the engaged fetal head and pubis symphysis was thought to result in pressure necrosis of the tissue, tissue slough, and ultimate fistula formation. Advances in modern obstetrics have markedly reduced the occurrence of this morbid complication. However, birth trauma continues to be the leading cause of vesicovaginal fistula formation in 363

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underdeveloped countries [1]. Elkins estimated the incidence of postobstetric vesicovaginal fistula to be 1 to 3 per 1000 deliveries in West Africa during the past decade [1]. Contemporary figures in developed countries show that gynecological surgery is the most common cause of vesicovaginal fistula. Leading these causative surgeries is abdominal hysterectomy, which accounts for 80% to 84% of all surgeries that result in vesicovaginal fistula [2,3]. Other, less common causes of vesicovaginal fistula include anterior colporrhaphy, pelvic radiation therapy, foreign body erosion, and pelvic fracture [4]. Two theories have been offered to explain fistula formation. The first is that a stitch placed at the reflection of the vaginal cuff and posterior bladder wall causes pressure necrosis and subsequent sloughing of the necrotic tissue. These women often present with continuous urine leakage per vagina 10–14 days postoperatively [5]. The second theory is that a direct injury to the bladder results in a pelvic urinoma, with the only route of evacuation being the vaginal cuff suture line [6]. Regardless of the mechanism, it has been shown that fistula formation may occur in as many as 21% of hysterectomies during which an inadvertent injury to the bladder was recognized and repaired [3,7]. Therefore, careful dissection between cervix/uterus and bladder to identify anatomy and avoid injury is imperative for the prevention of fistula formation. B.

Clinical Presentation

Continuous loss of urine from the vagina occurring 5–14 days following surgery is the single most common presenting symptom. Fistulas resulting from radiation therapy can occur as long as 30 years following treatment [8]. The volume of leakage depends on the size of the fistula; however, most women complain of large-volume leakage with the loss of normal filling/emptying bladder cycles [9,10]. Postoperative pelvic pain, hematuria, and prolonged ileus are other signs and symptoms that have been associated with vesicovaginal fistula [6,11]. C.

Evaluation

Vesicovaginal fistula must be differentiated from other sources of continuous vaginal discharge, such as bacterial vaginosis, peritoneal fluid, pelvic infection, or fallopian tube communication with the cuff [12]. If the diagnosis is in question, determination of urine leakage from the vagina can be made by testing the fluid for creatinine and pH or administering oral pyridium after placing a tampon. The orange discoloration of the tampon ensures the diagnosis of a urine leak [11]. Similarly, methylene blue can be instilled in the bladder during inspection of the vaginal cuff. Efflux of blue through the fistula confirms the presence of a vesicovaginal fistula [13]. Once determination of a urinary fistula is confirmed, a vaginal exam or vaginoscopy will usually identify the vaginal location of the fistula. Most posthysterectomy fistulas are located at the vaginal cuff, and sometimes more than one fistula is present [14]. Cystoscopy is strongly recommended prior to planned surgical repair to identify the location of the fistula in the bladder and its relation to the ureteral orifices. Most posthysterectomy fistulas are found slightly cephalad to the interureteric ridge (supratrigonal) [7,15]. Intravenous urography (IVU) is recommended for identification of ureterovaginal fistula or ureteral obstruction,

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which may be seen in 10–15% of vesicovaginal fistulas [16]. IVUs may not be diagnostic when, in fact, ureteral involvement is present. If the IVU is suspicious but nondiagnostic, or a ureteral orifice is close to the fistula, retrograde urography is recommended [11,13]. Complete evaluation will enable the surgeon to make appropriate decisions regarding surgical approach and timing of the repair. D. Treatment Conservative, or nonsurgical, treatment, which consists of a period of bladder drainage usually with a transurethral catheter, is the initial treatment of choice. Most patients are managed this way for weeks to months prior to urologic referral. Small vesicovaginal fistulas will heal with catheter drainage alone [3]. However, if after 4 weeks of uninterrupted bladder drainage the fistula has not healed, there is little role for further conservative management [17]. Trancer et al. reported 3 of 151 vesicovaginal fistulas were treated successfully with nonsurgical management [3]. Endoscopic treatment using electrocautery fulguration may be effective in treating small (1–3 mm) fistulas. Stovsky et al. reported successful treatment of 11 of 17 small fistulas in this manner, emphasizing the importance of using the pediatric size bugbee on low-energy settings [18]. Surgical therapy is the mainstay of vesicovaginal fistula treatment when conservative management fails. General surgical principles apply to all techniques of repair: tension-free, watertight closure; infection-free tissue; and the use of multiple nonoverlapping suture lines. A consensus regarding the timing of the repair (early versus delayed) and surgical approach (vaginal versus abdominal) has not been reached. O’Connor, the father of vesicovaginal fistula repair, described repair at 3–6 months following initial injury to allow tissue edema and swelling to resolve [19,20]. Since this landmark report, others have enjoyed similar success using the delayed repair [2,21,22]. However, during the past decade, similar success with more expedient repair (within 3 months of injury) has been reported [23–28]. Carr and Webster suggest that patients be examined every 2 weeks and that timing of repair be based on resolution of tissue edema (usually 4–8 weeks) [7]. Early repair avoids the emotional stress often associated with continuous urine leakage in otherwise young, healthy women. In addition, by reducing the duration of catheter drainage, infection risk is lessened. The tradition of delayed repair evolved during a time when large obstetric fistulas, with extensive tissue damage, were the most commonly seen type of vesicovaginal fistula. However, contemporary fistulas, which result from sterile, localized injury to the urinary tract, may be managed more expediently since local tissue damage is limited. For this reason, delayed repair should be reserved for fistulas resulting from radiation therapy, cancer recurrence, or large obstetric fistulas. Vaginal and abdominal approaches appear to be equally effective and are chosen based on the surgeon’s preference. However, the vaginal approach has many advantages over the abdominal, including earlier patient recovery, less blood loss, and avoidance of extensive bladder dissection, which can contribute to postoperative bladder irritability and failure of the repair. We reserve the abdominal approach for patients for whom there is coexistent pathology in the pelvis that requires associated procedures, such as ureteroneocystotomy, bladder augmentation, or cancer extirpation. Some believe that a narrow introitus, deep vagi-

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nal vault, or high-lying fistula (supratrigonal) may prevent adequate vaginal exposure, thereby making the abdominal approach more suitable [29]. However, excellent exposure can be gained regardless of vaginal anatomy by using a tablefixed retractor such as the perineal Bookwalter. In addition, posterolateral relaxing incisions in the introitus may provide exposure in the narrow vagina [30]. Therefore, we have found that fistulas are rarely inaccessible via the vaginal approach, and we perform transvaginal repairs in the majority of our patients. 1. Transvaginal Repair Three types of vaginal approaches have been described. Historically, the first vaginal repair was described by Latzko in 1942, regarding the performance of a partial colpocleisis [31]. The success of the procedure was reproducible by others [3,15]; however, the obvious disadvantage of vaginal shortening soon made this procedure acceptable only for those sexually inactive women. The second vaginal procedure is our preferred approach and involves excision of the vaginal cuff [9,32]. The perineal Bookwalter retractor provides excellent exposure even for deeply fixed vaginal cuffs. A small Foley catheter is placed in the fistula tract and used for additional retraction. A mark is placed circumferentially around the cuff scar at a distance of 2–3 mm. The vaginal cuff scar and fistula tract are excised, leaving fresh, viable vaginal wall and bladder margins (Figs. 1a, 1b). A three-layer closure consisting of bladder, pubocervical to prerectal fascia, and vaginal wall is completed using 4.0 vicryl interrupted sutures. Each layer may be closed in a 90° orientation from the previous to avoid overlapping suture lines. The advantages of this technique over other techniques described below, are that multiple, unrecognized fistulas may be present in the cuff scar, which if not addressed, would be the source of recurrence. Therefore, excising the entire cuff removes all possible fistulas. In addition, we believe in excision of the fistula tract, thereby removing all scar tissue, creating healthy tissue margins for closure, and lessening the chances of recurrence. Amundsen et al. have recently reported a first-attempt cure rate of 100% in 34 women using this technique [9]. The third technique is the most widely used vaginal technique for repair of vesicovaginal fistulas. The fistula is catheterized, and a vaginal wall flap is created. Leach and Trockman describe creating an anteriorly based U-shaped flap with the fistula located at the base of the U [11]. Raz et al. [33] and Sussman [29] create an inverted J-flap with the curved portion of the flap circumscribing the fistula. The fistula can also be circumferentially incised without the creation of a flap [34]. Regardless of the type of flap created, the general principles remain the same. The vaginal mucosa is elevated anteriorly and posteriorly beyond the fistula, and the tract is dissected down to the level of the bladder. The fistula may either be left in situ and its margins used as the first layer of closure or excised completely as previously described. Raz et al. [33] and Leach and Trockman [11], proponents of this vaginal flap repair, close the fistula with interrupted sutures placed such that the fistula edges are inverted. The second layer, perpendicular to the first, is of perivesical (pubocervical) fascia, and the vaginal wall closure comprises the final layer. Leach and Trockman [11], McVary and Marshall [34], and Dupont and Raz [35] maintain that excision of the fistula tract widens the bladder hiatus and enlarges the fistula in the event of failure. Others argue that excision of all scarred

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(a)

(b)

Figure 1 (a) The vaginal cuff and fistula are excised to the level of the bladder. (b) Cuff and fistula are completely excised, leaving clean margins for closure. (From Ref. 9.)

and inflamed tissue is required for successful repair [29,32,26]. Successful outcomes are seen with both approaches; therefore, this topic continues to be unresolved in the urogynecological literature. The transvaginal repairs have proven to be highly successful at first attempt, in the range of 82–100% long-term success [2,3,16,32,33]. Because of low patient morbidity and successful outcome, we recommend this approach for all for whom it is appropriate.

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2. Abdominal Repair O’Conor and Sokol [19] first described repair of vesicovaginal fistulas using a bladder-splitting transabdominal technique. An infraumbilical incision is used to enter the peritoneal cavity. Once the space of Retzius is developed and exposure is established, an anterior cystotomy is made and extended posteriorly until the fistula is encountered. This fistula is incised at the level of the bladder in a racquet fashion. The fistula is completely excised. The plane between the posterior bladder wall and anterior vaginal wall may be circumferentially developed to improve exposure during closure of the vaginal hiatus. The vaginal hiatus is closed with continuous 2-0 absorbable suture. The bladder is closed in two layers: mucosal and seromuscular (Fig. 2a–2c). Drainage of the bladder is accomplished with either a suprapubic or transurethral catheter. O’Conor [20] reported a success rate of 85% in 20 patients. Others have had similar success: Kristensen and Lose [37], Wein et al. [21], and Nesrallah et al. [38] reported success rates of 94%, 88%, and 100%, respectively. Because of its reproducible success, the O’Conor procedure remained the standard of treatment for vesicovaginal fistulas for years. Since O’Conor’s first description, others have used a modified approach that requires less bladder dissection. In 1988, Cetin et al. published a description of a simple suprapubic transvesical repair that avoids entry into the peritoneal cavity [39]. Through a limited vertical anterior cystotomy, the fistula is incised circumferentially. The fistula tract is mobilized and excised completely. The vagina and bladder are closed separately. Cetin at al. reported on 23 patients, 14 of whom had obstetric-related fistulas; 93% were successfully repaired using this approach [39]. Motiwala et al. [40] and Leng et al. [41] reported similar success rates of 94% in 55 women and 100% in 7 women, respectively. These authors argue that, by remaining extraperitoneal and using a limited cystotomy, perioperative morbidity is reduced, thereby improving inpatient and outpatient recovery time to a level that is comparable to that of vaginal repairs. E.

Postoperative Management

Uninterrupted bladder drainage and avoidance of bladder spasms in the postoperative time period are imperative for repair success. We recommend suprapubic tube drainage for 3 weeks postoperatively; however, others have reported 10–14 days is sufficient [11,41]. We prefer suprapubic catheter drainage since it is less irritating to the bladder and therefore allows less bladder spasm. Belladonna and opium suppositories and anticholinergic medications are also helpful in reducing the number and duration of bladder spasm. A voiding cystourethrogram may be performed prior to catheter removal to ensure fistula closure. Patients are advised to avoid the use of tampons and refrain from sexual activity for 2 months postoperatively. F.

Complications

The most common postoperative complications are fistula recurrence and ureteral injury. Recurrent fistulas should be managed initially with bladder drainage, which is successful in some cases. If conservative management has failed, a sec-

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(a)

(b)

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Figure 2 (a) Anterior cystotomy is extended posteriorly to the fistula and the fistula tract is excised completely. (b) The vaginal wall and bladder are closed separately. (c) Omentum is used as interpositional graft. (From Chapple CR. Lower urinary tract fistulae. In: Webster GD, Kirby R, King Lowell, Goldwasser B, eds. Reconstructive Urology. 1st ed. Boston: Blackwell Scientific, 1993:561–572.)

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ondary repair may be attempted once tissue inflammation has resolved. Secondary vaginal repairs may be as successful as primary, as long as there has been close adherence to general surgical principles [24]. The type of approach chosen for the secondary repair again is dependent on the surgeon’s experience. There is no contraindication to performing the same type of repair at the second attempt as was performed primarily. Ureteral injury is managed with percutaneous renal drainage temporarily, followed by either endoscopic or open repair. Ureteral repairs are discussed in the section on ureterovaginal fistula. G.

Flap Coverage

Tenuous repairs, such as those in irradiated patients or secondary repairs, may be reinforced with interposition flaps. For vaginal closures, a Martius flap is most commonly employed [5,24,27,42]. The Martius flap is a labial fat pad flap that is based on the pudendal artery. The flap is created by making a vertical incision in the labia majora and mobilizing the labial fat pad from the bulbocavernosus muscle (Fig. 3a). Preservation of the blood supply inferiorly is important to ensure flap viability. The fat pad is tunneled beneath the labia minora and vaginal tissue to the operative site and sutured in place between bladder closure and vaginal wall (Figs. 3b, 3c). Alternatively, in deeply located fistulas for which a Martius flap may not be technically possible, a peritoneal flap can be utilized. The posterior dissection is continued beyond the bladder to the peritoneal reflection. The peritoneal edge is mobilized from the posterior bladder surface, advanced over the bladder closure, and 2-0 absorbable suture is used to secure the flap in place over the fistula closure [33]. Rarely, for large defects that require more coverage than a Martius graft or peritoneal flap can provide, a gracilis flap may be employed. A medial thigh skin incision is made that extends from the medial femoral chondyle to 2 cm below the pubis symphysis. The muscle insertion site is identified, and the attachments from the medial chondyle are released. The gracilis muscle is mobilized from its insertion site to a distance that will be sufficient for tension-free coverage. The flap is based on femoral artery branches that enter the muscle medially [34]. Care must be taken to preserve these vessels during the medial dissection. Omental flaps may be used for interposition during abdominal repairs [43,44]. The omentum will reach the pelvis without mobilization in 30% of cases. In an additional 30%, division of the left lienorenal ligament is adequate for mobilization; in the remaining 40%, extensive mobilization is required [43]. The omentum has a dual blood supply from the left gastroepiploic and splenic arteries and from the right gastroepiploic and gastroduodenal arteries. Omental flaps can be based on either arterial supply; however, the right gastroepiploic is usually more robust than its contralateral supply and is therefore most often selected as the pedicle. If a right omental flap is chosen, the left gastroepiploic artery is divided close to the greater curvature of the stomach. Multiple gastric branches extending from the greater curvature to the omentum must be ligated to gain mobility of the omentum. Separation of the omentum from the mesocolon is accomplished by entering the avascular plain between the two. The omentum should be passed into the pelvis retroperitoneally, which requires mobilization of the right colon

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Figure 3 (a) Martius flap: fat pad is mobilized from surrounding fascia and bulbocavernosus muscle. (b) Flap is tunneled from labial incision to fistula repair. (c) Flap sutured into position over bladder closure; pubocervical fascia retracted laterally. (From Chapple CR. Lower urinary tract fistulae. In: Webster GD, Kirby R, King Lowell, Goldwasser B, eds. Reconstructive Urology. 1st ed. Boston: Blackwell Scientific, 1993:561–572.)

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Figure 4 (a) Omentum is released from transverse colon. (b) Omentum is mobilized from the greater curvature of the stomach after ligating short gastrics and left gastroepiploic arteries. (c) Omental flap is passed behind the right colon into the pelvis. (Modified from Ref. 42.)

(Figs. 4a–4c). Sufficient omental length may be gained by these steps to allow an omental flap to reach well into the pelvis for interposition between bladder and vagina. III. URETHROVAGINAL FISTULA Urethrovaginal fistula is an uncommon problem, usually resulting from urogynecological procedures, anterior colporraphy and urethral diverticulectomy being the most common. Other causes of urethrovaginal fistulas include obstructed labor, pelvic fractures, and vaginal or urethral cancer [45]. Obstructed labor remains the most common etiology in underdeveloped countries [1]. Management is usually surgical and depends on the size, location, and etiology of the fistula. A.

Clinical Presentation and Preoperative Evaluation

Symptoms are variable and are based on the location of the fistula. Distal fistulas may cause vaginal voiding (urine sequestration in the vagina after voiding with resulting postvoid incontinence) or a split stream. Fistulas involving the mid- to proximal urethra may present with stress-type or continuous incontinence. Urethroscopy, cystoscopy, and careful vaginal examination must be a part of the preoperative assessment. Urethroscopy with concurrent speculum vaginal examination will usually identify the fistula. Cystoscopy is necessary to evaluate for associated vesicovaginal fistulas. Intravenous urography should be performed when the fistula involves the trigone or a coexisting vesicovaginal fistula is pres-

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ent. Voiding cystourethrogram is not necessary if thorough cystourethroscopy has been performed. Urodynamics is indicated in women for whom intrinsic sphincter dysfunction is suspected in addition to the diagnosed fistula. B. Treatment Surgical treatment is dependent on fistula location and includes urethral marsupialization [46] for distal fistulas, fistula closure with Martius flap, and urethral reconstruction using vaginal or bladder flaps. Urethrovaginal fistulas that are small and isolated may be repaired by closing the fistula in two or three layers, using a Martius flap if necessary. Webster et al. describe making a circumferential incision in the vaginal mucosa, around the fistula tract [45]. The fistula tract is dissected to the level of the urethral hiatus and excised completely. The urethral wall and periurethral tissue comprise the first two layers of closure. A Martius flap can be used to cover the closure prior to vaginal wall closure. Alternatively, an eccentric vaginal flap can be used to complete the closure. Webster et al. reported a success rate of 100% in seven women following urethrovaginal fistula repair using a Martius flap in four and an eccentric vaginal flap coverage in the remaining three [45]. A variant of this procedure has been described by Leach in which an inverted U-shaped incision in the anterior vaginal wall is made, with the apex just proximal to the fistula and the base located at the bladder neck [47]. The vaginal U-flap is developed, and the fistula tract is circumferentially incised, but not excised. The tract is closed with a running, locking 4-0 absorbable suture. The second layer of closure is of periurethral fascia using Lembert-type sutures to invert the edges. The vaginal flap is advanced over the repair, providing the third layer of closure. Again, if necessary based on integrity of the repair, a Martius flap may be used to cover the closure prior to advancing the vaginal flap. Construction of a neourethra is necessary when partial or complete urethral loss is present. The goals of the procedure as described by Blaivas are to create a continent, nonobstructed urethra of sufficient length to prevent vaginal voiding [48]. These goals may be accomplished with either a bladder or a vaginal wall flap to create a neourethra. The posterior bladder flap procedure, first described by Young [49] and later modified by Dees [50] and Leadbetter [51], and the anterior bladder flap described by Tanagho [52], proved to be successful, but required retropubic or abdominal surgery. Urethral reconstruction using vaginal flaps was first described by Harris [53], and further refined by others [16,54,55]. Transvaginal surgery has since proven to be successful and less morbid and has therefore largely replaced the earlier described bladder flap procedures, except in cases when there is total urethral loss. Blaivas described a vaginal flap procedure in which a urethra is constructed using vaginal flaps [48]. An inverted U-shaped anterior vaginal wall flap is mobilized with its apex at the distal-most portion of the remaining urethra. The neourethra is constructed by making two parallel vaginal wall incisions on either side of the urethral catheter placed in the proximal fistula tract. The vaginal flaps are elevated and tubularized over the catheter using 4-0 chromic cat gut. A Martius flap is used to cover the neourethra, and the previously fashioned vaginal flap is advanced over the Martius flap as the final layer of closure. Alternatively, full-

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thickness perineal flaps, myocutaneous gracilis flaps, or labial-cutaneous flaps may be used for reconstruction in more complex cases in which local vaginal tissue loss is too extensive to use vaginal mucosa. Blaivas recommends that an antiincontinence procedure consisting of an abdominal or vaginal cystourethropexy or pubovaginal sling be used in combination with urethral reconstruction in all patients. In his series in which an anti-incontinence procedure was performed with a urethral reconstruction, a 79% continent success rate was achieved [56]. Others have reported similarly good fistula cure rates using urethral reconstruction alone; however, incontinence rates ranged from 16% to 40% [57,58]. Continence rates depend on the degree of urethral loss, primarily of the proximal urethra. Therefore, choice of concurrent anti-incontinence surgery should depend on the surgeon’s estimate, based on physical exam and clinical history/exam, of proximal urethral damage. An antiincontinence procedure may be performed following fistula repair without compromise to the repair; therefore, timing of this procedure should be the decision of the surgeon and informed patient. C.

Postoperative Management and Complications

Postoperative management should include suprapubic and transurethral catheter bladder drainage. Antibiotics and anticholinergic medication is used to reduce incidence of failure from infection and bladder irritability. The transurethral catheter may be removed in the early postoperative period (postoperative days 3–5), and the bladder is decompressed via the suprapubic tube for an additional 10–14 days. A voiding cystourethrogram is recommended prior to suprapubic catheter removal to ensure adequate healing. The suprapubic catheter may be used to measure postvoid residual volumes for several days to ensure efficient bladder emptying prior to its removal. The most common complications following urethrovaginal fistula repair are fistula recurrence, high postvoid residuals, and stress incontinence. Recurrence is initially managed with bladder drainage, followed by secondary reconstruction if the former fails. Expectant management and routine postvoid residual measurement in women with inefficient voiding are most appropriate. Catheterization per urethra is not recommended until the surgical site is healed, 6–8 weeks postoperatively. Stress incontinence, as discussed in the previous section, is managed with the most appropriate anti-incontinence surgery. The type of surgery chosen is based on the etiology of the incontinence as determined by urodynamic studies. IV. URETEROVAGINAL FISTULA Ureterovaginal fistula is an uncommon problem resulting from unrecognized ureteral injuries during pelvic surgery. Total abdominal hysterectomy for benign or malignant disease is the most commonly reported causative procedure [16,59– 61]. Obstetric causes are rare and are usually the result of cesarean section [59,61]. Other etiologies include anterior colporrhaphy, repair of ruptured uterus, and colorectal surgery. Unrecognized ureteral injuries account for most ureterovaginal fistulas. Recurrent cancer and radiation therapy are responsible for a small minority. The

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mechanism of ureteral injury is due either to direct injury by ligation or crushing clamps or ischemic injury. Ischemic injury is thought to result from stripping the ureter from its fascial encasement in the broad ligament during Wertheim’s hysterectomy (radical). These injuries often result in damage of the distal one-third of the ureter. However, most iatrogenic ureteral injuries are the result of direct injury to the ureter with a suture ligature. Of ureteral injuries, 80–90% occur in the terminal distal ureter, where it passes beneath the uterine vessels. In this location, the ureter can be inadvertently included in the uterine artery pedicle ligature and severed. Similarly, at this distal location the left ureter is more closely associated with the cervix than the right and is therefore more often injured [16,62,63]. More proximal ureteral injuries may occur during salpingo-oophorectomy because of the proximity of the ureter to the infundibulopelvic ligament. However, these injuries are less common than those previously described. A. Clinical Presentation Presentation will be determined by the nature of the ureteral injury. The development of urinary ascites may lead to fevers, abdominal pain, and elevation of serum creatinine and blood urea nitrogen. A contained pelvic urinoma may lead to fewer clinical symptoms, but can be associated with urine leakage from either the abdominal or vaginal cuff suture line. There are 10% of women who report flank pain postoperatively. However, this incidence is likely underrepresented since flank pain may be masked by surgical pain and narcotic use in the immediate postoperative period. Intense postoperative pain and wound infection should heighten the suspicion for ureterovaginal fistula [61]. B. Evaluation Evaluation should always include an intravenous urogram; however, in about 10% of cases, this study may be normal [16,64]. Others have described a combination dye test in which one color dye is instilled in the bladder, while another color dye is given either orally or intravenously, and a tampon is inserted. However, despite the outcome of these tests, if the clinical suspicion remains high, cystoscopy with retrograde pyelography should be performed. C. Treatment 1. Endoscopic Management Initial management of ureterovaginal fistula with percutaneous nephrostomy drainage is advocated for most patients, especially for those who have impaired renal function, flank pain, and/or infection of the affected kidney. Placement of a percutaneous nephrostomy tube not only achieves drainage of the renal unit and diversion of urine away from the site of extravasation, but also provides access for antegrade stent placement to manage the ureteral injury. However, rarely will ureterovaginal fistulas heal with percutaneous urinary diversion alone [61]. Traditionally, open surgical techniques have been advocated for repair. However, in recent years, proponents of endoscopic techniques have reported good results with antegrade or retrograde stent placement [61,65]. Use of an internal stent is often not possible in patients with complete ureteral occlusion or tran-

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section (13/20 in Selzman’s study). In these situations, an endoscopic “cut-to-thelight” procedure has been described with variable success [66]. 2. Surgical Management When endoscopic procedures are technically not possible or fail, open repair is recommended. Timing of the repair has been debated. Traditionally, repairs were performed 3–6 months after injury to allow for resolution of edema [67]. Yeates was the first to advocate repair 4–6 weeks following injury, arguing that early repair may lessen the ischemic damage to the ureter and improve outcome [68]. Subsequently, others have found early repair to be just as effective as delayed and therefore recommend the more expedient repair in most women [59,69]. All surgical repairs include ureteroneocystostomy. However, the steps to achieve this end point are variable and depend on the anatomy, bladder characteristics, and location of ureteral injury. Since most injuries involve the distal segment of the ureter, the majority of ureteroneocystostomies can be performed with either a psoas hitch or a Boari flap. Either a low midline or Pfhannenstiel incision is used when performing a psoas hitch. The ureter is identified at the level of injury and mobilized cephalad, taking care to preserve its blood supply by avoiding aggressive stripping of the periureteral adventia. The distal stump is ligated with 2-0 absorbable suture, and the proximal ureteral end is excised to the level of healthy ureter. A stay suture is placed in the proximal ureteral end for future reimplant. The lateral peritoneal and pelvic sidewall attachments on the contralateral side of the bladder may be released to allow adequate bladder mobility. A semioblique incision is made at the bladder’s equator (approximately at the convergence of the anterior wall and dome (Fig. 5a). The surgeon’s index finger is placed in the bladder, elevating the bladder to the ureteral end. The transverse incision becomes vertically oriented, gaining more length at the bladder end (Fig. 5b). If additional mobility is required, the contralateral superior vesical artery may be transected. The ureteral end

(a)

(b)

Figure 5 (a) Psoas hitch: semioblique incision at the equator of the bladder. (b) Two nonabsorbable stitches are used to tack bladder to psoas minor tendon. (From Stone AR, Moran ME. Management of the ureteral defect. In: Webster GD, Kirby R. King Lowell, Goldwasser B, eds. Reconstructive Urology. 1st ed. Boston: Blackwell Scientific, 1993:361–388.)

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should overlap the planned reimplant site by approximately 3 cm to ensure a tension-free ureteroneocystostomy. Once sufficient mobility is gained, the bladder is tacked extravesically to the psoas minor tendon with two interrupted nonabsorbable sutures, taking care to avoid entering the bladder lumen. Care should be taken to avoid placement of the sutures too deeply or too laterally, which could injure the femoral or genitofemoral nerves, respectively. The ureteroneocystotomy is then performed, preferably with interrupted 5-0 absorbable suture, and the semioblique incision is closed vertically with a running 3-0 absorbable suture in two layers [70]. If bladder mobility is not sufficient to allow for a tension-free ureteral reimplant, a Boari flap can be utilized. The bladder and ureter are prepared as described above. An obliquely oriented random bladder flap is created along the posterior wall and dome of the bladder. The base of the flap should be at least 4 cm wide, while the distal end should be at least 2 cm in width. If a semioblique incision had been made for a planned psoas hitch, this incision can be incorporated into the bladder flap incision at its distal end. Once the flap is created, the ureteroneocystotomy is performed (refluxing or nonrefluxing). The flap is tubularized by closing its edges anteriorly with running absorbable suture [71]. Success of ureteroneocystostomy in the treatment of ureterovesical fistula has been reported to be 100% [16,61,72]. The most common complication is ureteral stricture, which may be successfully managed with balloon dilatation or endoscopic incision, obviating open surgical revision [61]. Distal ureteral slough is a rare complication and requires revision of the ureteroneocystostomy [60]. Proximal ureteral injuries that are not amenable to either psoas hitch or Boari flap can be managed with a transureteroneocystostomy, ileal ureter replacement, or nephrectomy. Nephrectomy is only appropriate in complicated cases with high ureteral injuries, persistent pyelonephritis, or nonfunctioning renal unit. In addition, multiple failed repairs may necessitate ultimate nephrectomy.

REFERENCES 1. Elkins TE. Surgery for the obstetric vesicovaginal fistula: a review of 100 operations in 82 patients. Am J Obstet Gynecol 1994; 170:1108–1120. 2. Lee AL, Symmonds RE, Williams TJ. Current status of genitourinary fistula. Obstet Gynecol 1988; 72:313–319. 3. Tancer ML. Observations on prevention and management of vesicovaginal fistula after total hysterectomy. Surg Gynecol Obstet 1992; 175:501–506. 4. Moir JC. Personal experience in the treatment of vesicovaginal fistulas. Am J Obstet Gynecol 1956; 71:476. 5. Zimmern PE, Ganabathi K, Leach GE. Vesicovaginal fistula repair. Atlas Urol Clin North Am 1994; 2:87–99. 6. Kursh ED, Morse RM, Resnik MI, Persky L. Prevention and development of vesicovaginal fistula. Surg Gynecol Obstet 1988; 166:409–412. 7. Carr LK, Webster G. Abdominal repair of vesicovaginal fistula. Urology 1996; 48:10– 11. 8. Zoubek J, McGuire E, Noll F, Delancey JO. The late occurrence of urinary tract damage in patients successfully treated by radiotherapy for cervical carcinoma. J Urol 1989; 141:1347–1349. 9. Amundsen CL, Guralnick ML, Webster GD. Functional success of vaginal cuff exci-

378

10. 11.

12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26.

27. 28. 29. 30. 31. 32. 33. 34.

Miller and Webster sion as a technique for transvaginal repair of vesicovaginal fistulae after hysterectomy. J Pelvic Surg 2001; 7(1):15–18. Woo HH, Rosario DJ, Chapple CR. The treatment of vesicovaginal fistulae. Eur Urol 1996; 29:1–9. Leach GE, Trockman BA. Surgery for fistulas and diverticulum. In: Walsh PC, Retik AB, Vaughan ED, Wein AJ, eds. Campbell’s Urology. 7th ed. Philadelphia, PA: W. B. Saunders, 1998:1135–1153. Leach GE, Yip CM, Donovan BJ, Raz S. Tubovaginal leakage: an unusual cause of incontinence. J Urol 1987; 137:287–288. Smith GL, Williams G. Vesicovaginal fistula. Br J Urol 1999; 83(5):564–569. Tancer ML. The post-total hysterectomy (vault) vesicovaginal fistula. J Urol 1980; 123: 839–841. Margolis T, Mercer LJ. Vesicovaginal fistula. Obstet Gynecol Surg 1994; 49(12):840–847. Goodwin WE, Scardino PT. Vesicovaginal and ureterovaginal fistulas: a summary of 25 years of experience. J Urol 1980; 123:370–374. Gerber GS, Schoenberg HW. Female urinary tract fistulas. J Urol 1993; 149:229–236. Stovsky MD, Ignatoff JM, Blum MD, et al. Use of electrocoagulation in the treatment of vesicovaginal fistulas. J Urol 1994; 152:1443–1444. O’Conor V, Sokol J. Vesicovaginal fistula from the standpoint of the urologist. J Urol 1951; 66:367–369. O’Conor VJ Jr. Review of experience with the vesicovaginal fistula repair. J Urol 1980; 123:367–369. Wein AJ, Mallory TR, Carpiniello VL, et al. Repair of vesicovaginal fistula by a suprapubic transvesical approach. Surg Gynecol Obstet 1980; 150:57–60. McVay KT, Marshall FF. Urinary fistulas. In: Gillenwater J, Howards SS, Duckett JW, eds. Adult and Pediatric Urology. Philadelphia, PA: C. V. Mosby, 1996:1355–1377. Persky L, Herman G, Guerrier K. Nondelay in vesicovaginal fistula repair. Urology 1979; 13:273–275. Raz S, Little NA, Juma S. Female urology. In: Walsh PC, Retik AB, Stamey TA, eds. Campbell’s Urology. 6th ed. Philadelphia, PA: W. B. Saunders, 1992:2782–2828. Zimmern PE, Schmidbauer CP, Leach GE, et al. Vesicovaginal and urethrovaginal fistulae. Semin Urol 1986; 4:24–29. Blandy JP, Badenoch DF, Fowler CG, Jenkins BJ, Thomas NWM. Early repair of iatrogenic injury to the ureter or bladder after gynaecological surgery. J Urol 1991; 146: 761–765. Blaivas JG, Heritz DM, Romanzi LI. Early versus late repair of vesicovaginal fistulas: vaginal and abdominal approaches. J Urol 1995; 153:1110–1113. Wang Yu, Hadley R. Nondelayed transvaginal repair of high-lying vesicovaginal fistula. J Urol 1990; 144:34–36. Frohmu¨ller HGW. Vesicovaginal fistula. In: Graham SO, Glenn JF, eds. Glenn’s Urologic Surgery, 5th ed. Philadelphia: Lippincott Williams & Wilkins, 1998. Zimmern PE, Ganabathi K, Leach GE. Vesicovaginal fistula repair. Atlas Urol Clin North Am 1994; 2:87–99. Latzko W. Postoperative vesicovaginal fistulas; genesis and therapy. Am J Surg 1942; 58:211–213. Iselin C, Aslan P, Webster GD. Transvaginal repair of vesicovaginal fistulas after hysterectomy by vaginal cuff excision. J Urol 1998; 160:728–730. Raz S, Bregg KJ, Nitti VW, Sussman E. Transvaginal repair of vesicovaginal fistula using peritoneal flap. J Urol 1993; 150:56–59. McVary KT, Marshall FF. Urinary fistulas. In: Gillenwater JY, Grayhack JT, Howards SS, Duckett JW, eds. Adult and Pediatric Urology. St. Louis, MO: Mosby-Yearbook, 1996:1355–1377.

Urinary Fistula Evaluation and Management

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35. Dupont MC, Raz S. Vaginal approach to vesicovaginal fistula repair. Urology 1996; 48:7–9. 36. Sims JM. On the treatment of vesico-vaginal fistula. Am J Med Sci 1852; 23:59–82. 37. Kristensen JK, Lose G. Vesicovaginal fistulas: the transperitoneal repair revisited. Scand J Urol Nephrol 1994; 157(suppl):101–105. 38. Nesrallah LJ, Srougi M, Gittes RF. The O’Conor technique: the gold standard for supratrigonal vesicovaginal fistula repair. J Urol 1999:566–568. 39. Cetin S, Yazicioglu A, Ozgur S, Ilker Y, Dalva I. Vesicovaginal fistula repair: a simple suprapubic transvesical approach. Intl Urol Nephrol 1988; 20(3): 265–268. 40. Motiwala HG, Amlani JC, Desai KD, Shah KN, Patel PC. Transvesical vesicovaginal fistula repair: a revival. Eur Urol 1991; 19:24–28. 41. Leng WW, Amundsen CL, McGuire EJ. Management of female genitourinary fistulas: transvesical or transvaginal approach? J Urol 1998; 160(1):1995–1999. 42. Martius H. Die operative Wiedeherstellung der volkommen fehlenden Harnrohre und des Schiessmuskels derselben. Zentralbl Gynak 1928; 52:480. 43. Turner-Warwick R, Wynne EJC, Handley-Ashken M. The use of the omental pedicle graft in the repair and reconstruction of the urinary tract. Br J Surg 1967; 54:849–853. 44. Wein AJ, Mallory TR, Greenberg SH, et al. Omental transposition as an aid in genitourinary reconstructive procedures. J Urol 1980; 20:473–477. 45. Webster GD, Sihelnik SA, Stone AR. Urethrovaginal fistula: a review of the surgical management. J Urol 1984; 132:460–462. 46. Lamensdorf H, Compere DE, Begley GF. Simple surgical correction of urethrovaginal fistula. Urology 1977; 10:152–153. 47. Leach GE. Urethrovaginal fistula repair with Martius labial fat pad graft. Urol Clin North Am 1991; 18(2):409–413. 48. Blaivas JG. Vaginal flap urethral reconstruction: an alternative to the bladder flap neourethra. J Urol 1989; 141:542–545. 49. Young HH. An operation for the cure of incontinence associated with epispadias. J Urol 1922; 7:1–3. 50. Dees JE. Congenital epispadias with incontinence. J Urol 1964; 91:261–267. 51. Leadbetter GW. Surgical correction of total urinary incontinence. J Urol 1964; 91:261– 267. 52. Tanagho EA. Bladder neck reconstruction for total urinary incontinence: 10 years of experience. J Urol 1981; 125:321–324. 53. Harris SH. Reconstruction of the female urethra. Surg Gynecol Obstet 1935; 61:366– 369. 54. Ellis LR, Hodges CV. Experience with female urethral reconstruction. J Urol 1969; 102:214–216. 55. O’Conor VJ. Repair of vesicovaginal fistula with associated urethral loss. Surg Gynecol Obstet 1978; 146:250–253. 56. Blaivas JG. Treatment of female incontinence secondary to urethral damage or loss. Urol Clin North Am 1991; 18:356–363. 57. Patil U, Waterhouse K, Laungani G. Management of 18 difficult vesicovaginal and urethrovaginal fistulas with a modified Ingleman-Sundgberg and Martius operations. J Urol 1980; 123:653–655. 58. Hamlin RHJ, Nicholson EC. Reconstruction of urethra totally destroyed by labor. Br Med J 1969; 1:147–150. 59. Badenoch DF, Tiptaft RC, Thakar DR, Fowler CG, Blandy JP. Early repair of accidental injury to the ureter or bladder following gynaecological surgery. Br J Urol 1987; 59: 516–518. 60. Mandal AK, Sharma SK, Vaidyanathan S, Goswami AK. Ureterovaginal fistula: summary of 18 years experience. Br J Urol 1990; 65:453–456.

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61. Selzman AA, Spirnak JP, Kursh ED. The changing management of ureterovaginal fistulas. J Urol 1995; 153:626–628. 62. Mattingly RF, Borkowf HI. Acute operative injury to the lower urinary tract. Clin Obstet Gynecol 1978; 5:123–149. 63. Dowling RA, Corriere JN, Sandler CM. Iatrogenic ureteral injury. J Urol 1986; 136: 912–915. 64. Murphy DM, Grace PA, O’Flynn JD. Ureterovaginal fistula: a report of 12 cases and review of the literature. J Urol 1982; 128:924–929. 65. Elabd S, Ghoniem G, Elsharaby M, et al. Use of endoscopy in the management of postoperative ureterovaginal fistula. Int Urogynecol J Pelvic Floor Dysfunct 1997; 8(4): 185–190. 66. Lingeman JE, Wong MY, Newmark JR. Endoscopic management of total ureteral occlusion and ureterovaginal fistula. J Endourol 1995; 9(5):391–396. 67. Mattingley RF, Thompson JD. Vesico-vaginal fistulas. In: Mattingley RF, Thompson JD, eds. Te Linde’s Operative Gynecology. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 1985:645–660. 68. Yeates WK. Ureterovaginal fistulae. In: Stanton SL, Tanagho EA, eds. Surgery for Female Incontinence. Berlin: Springer-Verlag, 1986:212–227. 69. Blandy JP, Badenoch DF, Fowler CG, Jenkins BJ, Thomas NWM. Early repair of iatrogenic injury to the urether or bladder after gynecological surgery. J Urol 1991; 146: 761–765. 70. Droller MJ. Psoas hitch procedure. In: Hinman F Jr, ed. Atlas of Urologic Surgery. 2nd ed. Philadelphia, PA: W. B. Saunders, 1998:818–821. 71. Browsher WG, Shah PJR, Costello AJ, Tiptaft R, Paris AMI, Blandy JP. A critical appraisal of the Boari flap. Br J Urol 1982; 54:682–685. 72. Akman RY, Sargin S, Ozdemir G, Yazicioglu A, Cetin S. Vesicovaginal and ureteralvaginal fistulas: a review of 39 cases. Int Urol Nephrol 1999; 31(3):321–326.

23 Iatrogenic Urological Trauma STEVEN B. BRANDES Washington University School of Medicine St. Louis, Missouri, U.S.A.

I.

INTRODUCTION

Lower urinary tract injury during gynecological surgery is relatively uncommon. Bladder injuries are the predominant iatrogenic urological injury. Bladder injuries are usually recognized and repaired immediately, and potential complications are typically minor. Ureteral injuries, however, are typically recognized in a delayed fashion and have the potential to be life threatening or to result in permanent kidney damage or nephrectomy [1].

II. URETERAL INJURIES Iatrogenic ureteral injuries are a potential complication of any open or endoscopic pelvic operation. Gynecological surgery accounts for more than 50% of all iatrogenic ureteral injuries, with the remaining occurring during colorectal, general, vascular, and urologic surgery [2–4]. The ureter is injured in roughly 0.5–2% of all hysterectomies and routine gynecological pelvic operations and in 10% (range 5–30%) of radical hysterectomies [4–6]. Ureteral complications from radical hysterectomy have declined over the years due to improved patient selection, surgery limitation to mostly low-stage disease, decreased use of preoperative radiation, and modifications in surgical technique that limit extreme skeletonization of the ureter [6]. Of iatrogenic ureteral injuries from gynecological surgery, roughly 50% are from radical hysterectomy, 40% from abdominal hysterectomy, and less than 5% from vaginal hysterectomy [1]. All gynecological ureteral injuries occur to the distal third of the ureter. 381

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The ureter can be injured in any anterior vaginal wall surgery that extends to the bladder neck (e.g., vaginal hysterectomy, bladder neck suspension surgery, anterior colporrhaphy, enterocele repair, and neovagina construction). Repairs of high-grade pelvic prolapse (i.e., grade 4 cystocele or total uterine prolapse) are at particular risk for ureteral injury. The majority of ureteral injuries here are during vaginal vault reconstruction or vaginal cuff closure, for which sutures can ligate the ureter or kink the ureter by displacing it medially. Patients with prolapse can have grossly dilated and thin ureters that can be enclosed in the prolapse and thus be predisposed to potential ureteral injury [7]. Similarly, in pregnancy, the ureters are dilated, exposure is difficult, and the risks are increased. Other gynecological procedures that can result in ureteral injury are abdominal oophorectomy, pelvic mass resection, salpingectomy, cesarian section, adnexectomy, extended pelvic lymphadenectomy, and laparoscopy [8–10].

III. URETERAL ANATOMY The adult ureter is roughly 30 cm in length, from the level of the uretero-pelvic junction (at roughly L1, L2) to the ureterovesical junction (at the level of the ischial spine). From cephalad to caudad, the ureter travels posterior to the gonadal vessels, anterior to the iliac vessels at the level of the iliac bifurcation, and then into the pelvis adherent to the posterior surface of the peritoneum. At the pelvic brim, the ureter lies in the posterior peritoneal layer of the broad ligament and runs parallel and medial to the infundibulopelvic ligament (in which lie the ovarian vessels). It then courses posterior to the ovary, travels along the lateral aspect of the uterus, and then posterior and in close proximity to the uterine vessels (roughly 1 to 2 cm lateral to the upper cervix and above the lateral fornix of the vagina). The ureter then turns anterior and medial and into the trigone of the bladder [11,12].

IV. URETERAL BLOOD SUPPLY Ureteral blood supply is extensive and from multiple and variable sources. Unlike bowel, the blood supply to the ureter does not branch into arcades, but rather runs between the ureter’s muscular wall and adventitia. In the majority (80%) of ureters, a single artery runs down its length. The upper one third of the ureter is supplied medially by branches of the renal and gonadal artery. The mid-ureter is supplied medially by branches from the aorta, gonadal artery, and common iliac artery. The lower one third of the ureter is supplied laterally by vessels from the superior and inferior vesical, middle hemorrhoidal (rectal), vaginal, and uterine arteries. Thus, above the iliac vessels, the blood supply to the ureter is located medially, while within the pelvis it is located laterally. In order not to devascularize the ureter, dissection should be lateral to the ureter, above the pelvic brim, and medial and anterior, below the pelvic brim. Since the ureter’s blood supply courses through its adventitial layer, skeletonization should be avoided to prevent ischemic injury [11,12].

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PREVENTION OF AND RISK FACTORS FOR URETERAL INJURY

A. Prevention The most reliable method to avoid ureteral injury is to clearly identify the ureter throughout the operative field. The ureter can usually be predictably identified on the medial aspect of the psoas fascia at the level of the kidney’s inferior pole, anterior to the bifurcation of the common iliac artery at the pelvic brim, and posterior, between the leaves of the broad ligament, in the paracervical region. For anticipated difficult pelvic operations or for patients with large pelvic masses, pelvic inflammatory disease (PID), prior pelvic surgery, or prior irradiation, the use of preoperative ureteral radiographic imaging by intravenous urography (IVU) or computed tomography (CT) has been widely advocated. However, ureteral stent placement or pelvic imaging are not recommended on a routine basis. In fact, most ureteral injuries are during technically straightforward hysterectomies for minimal disease [2,10]. In the majority of cases, ureteral identification is not difficult, thus preoperative stents are unnecessary. Stent placement, however, clearly helps identify a ureteral injury when it does occur. Furthermore, if surgical dissection is difficult, stents can be placed intraoperatively, cystoscopically, or through a small cystotomy. When pelvic tumor is large or ureteral anatomy is distorted on preoperative imaging, preoperative stents may increase the ability to palpate the ureters, minimize the need for ureteral dissection, and minimize ureteral kinking by adjacent suturing [13]. The initial point in preventing ureteral injury is acknowledging and recognizing the risk for injury. Regardless of the ureteral position on imaging, it is important to recognize the potential hazards and to identify the ureters above the level of distortion/disease and through its pelvic course. In general, generous surgical exposure, meticulous surgical technique, and visual ureteral identification are all more useful than preoperative body imaging or ureteral stenting. B. Risk Factors The majority (80–90%) of ureteral injuries occur to the distal one third of the ureter, specifically from the uterine artery to the UVJ [1–5,14]. The four areas where ureteral injuries typically occur with pelvic surgery are (1) at or above the infundibulopelvic ligament near the pelvic brim; (2) in the broad ligament base, lateral to the cervix and vaginal fornix (where the uterine artery crosses the ureter); (3) along the pelvic sidewall (just above the uterosacral ligaments); and (4) where the ureter passes through the cardinal ligament and turns medial and anterior to the intramural bladder tunnel [14] (Fig. 1). In vaginal hysterectomy, the primary risk point is on the clamping and ligation of the cardinal ligaments. As the cervix is pulled down through the introitus, the bladder and ureters follow. Therefore, if the incision is high on the cervix, the bladder/ureters can be incorporated in the incision. Ureteral obstruction on ligation of the cardinal ligaments is typically due to ureteral kinking from a proximity suture rather than from a ligation injury [15]. Abnormalities of the ureter and/or surrounding tissues can alter normal

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Figure 1 Lateral view of the uterus and vagina demonstrating the four areas typically at risk for ureteral injury during abdominal hysterectomy: 1. cardinal ligament; 2. ureterosacral ligament; 3. uterine artery; 4. infundibulopelvic ligament.

retroperitoneal and pelvic anatomy and substantially increase the risk for ureteral injury. Such anatomic abnormalities are usually found with endometriosis or pelvic tumors. Congenital abnormalities, such as ureteral duplication, megaureter, ectopic ureter, or ectopic kidney, predispose to injury. The ureter is also predisposed to injury by extreme lateral displacement of the cervix, mass adherence to the pelvic peritoneum, myomas or other tumors of the broad ligament, abscess or mass in the broad ligament base, retroperitoneal tumor, and cervical cancer. However, the majority of reported ureteral injuries have occurred in patients with no identifiable risk factors. In fact, over 75% of ureteral injuries due to gynecological surgeries occur during procedures that surgeons describe as uncomplicated and routine and for which pelvic anatomy was normal [10]. Intraoperative hemorrhage is a clear and main risk factor for ureteral injury. Sudden hemorrhage should never be treated with blind cautery or suturing, but rather by direct pressure, sharp dissection, and exposure of the bleeding vessels, followed by accurate and precise suturing [2,3,10]. As stated above, abdominal hysterectomy (total, subtotal, stump excision, and radical) is the most common cause for iatrogenic surgical ureteral injury. Here, the potential for ureteral injury is greatest during the ligation and division of the uterine arteries, followed by division of the ovarian vessels and infundibulopelvic ligament. In radical hysterectomy, the ureter can be skeletonized when dissecting out adjacent tumor, so risking ischemia and delayed necrosis. Radical hysterectomy may also require en bloc resection of a segment of ureter (to achieve a tumor-free margin). Prior irradiation can compromise ureteral blood supply (by obliterative end arteritis) and increase the injury risk (after hysterectomy by three-

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to fourfold). Fistulas from the radiated ureter are very difficult to repair and typically require two or more operations [16]. Prior episodes of endometriosis or pelvic inflammatory disease can lead to dense ureteral adherence and so increase the chances for iatrogenic injury. Neoplasms can directly invade and can fix the ureter or distort its course. Adnexal masses can also distort the infundibulopelvic ligament and displace the ureter into the pedicle. Severe pelvic prolapse can also increase the risk of ureteral injury. Postoperative infection (i.e., peritonitis, pelvic cellulitis, abscess, or hematoma) and inflammation are other important contributing factors for ureteral injury [17].

VI. DIAGNOSIS A. Intraoperative If injury to the ureter is suspected intraoperatively, the ureter must be meticulously examined in the area of interest. As others, we have found that direct exploration and visual inspection are the most common and most accurate methods for diagnosis. If no obvious urine leak is noted at the suspected injury site, to help delineate the ureteral injury, indigo carmine can be injected retrograde into the ureteral orifice by a 6F pediatric feeding tube (after the bladder has been opened) or injected directly into the ureter or renal pelvis with a 25-gauge needle. Also helpful is the intravenous injection of indigo carmine coupled with Lasix diuresis, which colors the urine blue, typically within 5 min. Extravasation of blue-tinged urine helps confirm injury [12,18]. Even without extravasation, a ureter that visually appears contused or bruised can have significant trauma from either a crush or ischemic injury (from excessive dissection). Ways to determine if a ureter has been devascularized is to note wall discoloration, absence of capillary refill, or most reliably, inspection of the ureteral edge for bleeding after incising the ureter. The visual presence of ureteral peristalsis is not a clear indication of ureteral viability or of adequate vascularity. Some have advocated the use of intravenous fluorescein and a Wood’s lamp to assess ureteral viability [12]. B. Postoperative The IVU findings that are suggestive of ureteral injury are delayed or nonvisualization of the involved kidney, hydronephrosis, urinary (contrast) extravasation, or incomplete visualization of the entire ureter. Retrograde urography is typically the most sensitive radiographic modality to evaluate for ureteral extravasation, ligation, and injury. Ultrasound or CT can identify a hematoma, urinoma, or hydronephrosis, all suggestive of ureteral injury. C. Signs and Symptoms The findings of a missed ureteral injury are generally nonspecific. Suggestive of urinary leak are a prolonged adynamic ileus, persistent flank or abdominal pain, a palpable abdominal mass, an elevation in blood urea nitrogen, fever/sepsis, leukocytosis, or prolonged and persistent drainage from the vagina or from the

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operative drains/drain sites. Frequently, ureteral injury is not discovered until an obvious fistula occurs. VII. MANAGEMENT AND TYPES OF INJURY The common types of iatrogenic pelvic ureteral injuries, in descending order of frequency, are ligation, kinking by suture, division, partial laceration, crush, and devascularization (leading to delayed necrosis/stricture) [19]. A.

Management

The method of ureteral repair is determined by multiple factors, including the location and length of ureteral injury, the time of diagnosis (intraoperative, early postoperative, or delayed), the type of injury, and the presence of associated medical or surgical illnesses. Clearly, the optimal time for repair of a ureteral injury is intraoperatively, when it initially occurs. At the time of injury, the tissues are typically in their best condition, with the options and likelihood for success the greatest. Immediate recognition and repair allow for better results and fewer complications than in a delayed fashion. Unfortunately, the majority (⬎80%) of iatrogenic ureteral injuries from gynecological surgery are discovered in a delayed fashion [1]. Injuries that are detected postoperatively tend to be more complex, require more complex repairs, require multiple procedures, and have more complications than those detected and repaired intraoperatively [20,21]. B.

Suture Ligation Injury

When the ureter has been inadvertently ligated intraoperatively (such as during ligation of the uterine artery during hysterectomy), often all that is necessary is removal of the suture. Typically, ureteral damage is minimal, if recognized immediately, as these injuries most frequently include other tissue in the ligature. Visual inspection is imperative to exclude significant ureteral injury. If there is any question of ureteral viability, a ureteral stent (for 1–2 weeks) at minimum should be placed. When an absorbable suture is determined in the postoperative period to have entrapped the ureter, conservative management with percutaneous nephrostomy tube drainage until the suture absorbs has been reported to be successful [11]. Ureteral injuries during vaginal surgery are typically ligations and are not detected until after the operation [1–5]. To assess ureteral integrity, it is prudent after all vaginal hysterectomies, grade 4 cystocele repairs, enterocele repairs, and bladder neck suspensions to assess ureteral integrity with intravenous indigo carmine. When no indigo is cystoscopically observed from the ureteral orifice, a ureteral stent should be placed. If ureteral obstruction is partial and a stent will not pass, placement under direct ureteroscopic visualization can often be successful. If complete ureteral obstruction is noted during cystocele, enterocele, and bladder neck suspension surgery, the offending sutures are removed. After vaginal hysterectomy, sutures to the pedicle of the uterus or the vaginal cuff should not be

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removed due to the potential for excessive bleeding. In such situations, the vaginal operation should be completed and the ureter reimplanted [15]. C. Crush Injury If the ureter has been crushed by a clamp, the likelihood for a significant injury is high. Generally, this occurs during an attempt to control bleeding and/or clamping/division of the uterine artery during abdominal hysterectomy. The adventitia must be carefully inspected since it often takes several days for the ischemic injury to manifest itself. Ureteral injury severity is dependent on the size of the clamp, the time the clamp was applied, and the amount of tissue crushed. For minor injuries by a small crushing instrument, the ureter should be stented and drained, at minimum [11,12]. For severe contusions, or if ureteral viability is in doubt, the ureter should be segmentally resected, debrided, and reanastomosed over a double-J stent. The type of ureteral repair is dependent on the level and extent of the injury (see below for details).

VIII. TRANSECTIONS/LACERATION INJURY A. Lacerations Most partial transections (less than one half ureteral wall) can be managed by primary sutured closure. Most of these injuries should also be stented and drained. If more than half the diameter of the ureter is lacerated, we favor an aggressive approach of ureteral division and ureteroureterostomy or reimplant be performed. B. Transections Once the injured ureter is exposed, general principles for ureteral repair include (1) careful ureteral mobilization (with care to preserve the adventitia); (2) debridement of nonviable tissue until a bleeding edge; (3) mucosa to mucosa, spatulated, tension-free, and watertight anastomosis; (4) urinary diversion (usually with an internal double-J stent); and (5) a retroperitoneal drain. Ureteral stents are available in a variety of diameters and lengths. In general, double-J stents 6- or 7-F in diameter and 24 to 28 cm long are employed [11,12]. 1. Ureteroureterostomy Ureteroureterostomy repairs are typically employed for the abdominal ureter (above the iliac artery bifurcation) or for the pelvic ureter when dissection is not extensive and the vascular supply to the distal ureter is not compromised. Deep in the pelvis, however, ureteroureterostomy can be technically challenging. Typically, ureteroureterostomy is performed by careful proximal and distal mobilization of the ureter to allow 1–2 cm overlap, and thus a spatulated and tension-free anastomosis, over a double-J ureteral stent. To ensure surgical success, it is essential that the distal end of the stent lies in the bladder. Distal stent placement in the bladder can be confirmed by filling the bladder retrograde with blue-colored

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saline. Blue saline refluxing out the proximal end of the stent confirms bladder placement [11,12]. 2. Ureteral Reimplant Injuries to the distal one third of the ureter, including the intramural ureter, usually require a ureteroneocystostomy (reimplantation into the bladder) for repair. In general, pelvic ureter viability distal to the ureteral injury is unreliable due to extensive prior dissection. Here a ureteral reimplant is often the more conservative option, with success rates higher than 90%. Deliberate segmental excision of the distal ureter, such as during resection of large adnexal masses from neoplasm, abscess, or inflammation, can result in a long defect (usually ⬎2 cm). Long distal ureteral defects typically require a psoas hitch or Boari flap. After the proximal end of the ureter is debrided until viable tissue and spatulated, it is brought through a cystotomy in the posterior bladder wall. To prevent ureteral kinking and obstruction when the bladder fills, the ureter is usually not reimplanted in a highly mobile area of the bladder. A tunneled, nonrefluxing anastomosis is generally unnecessary, especially since reflux is usually clinically insignificant in the adult. However, if time allows and reflux is a concern, a modified Politano-Leadbetter nonrefluxing reimplant is most often employed. Here, the ureter is brought through the posterior bladder wall in a position medial to the original hiatus. Placement in the more mobile lateral wall may result in ureteral kinking. To prevent reflux, a submucosal tunnel is sharply dissected out to a length roughly four times the ureteral diameter. Interrupted absorbable sutures are then used to anastomose the spatulated ureter to the bladder mucosa (over a ureteral stent) and to close the mucosal defect. The cystotomy is then closed in two layers. A prevesical closed suction drain is typically put in place (alternatively, a Penrose drain can be used). To keep the bladder decompressed, a suprapubic tube has been typically described, yet generally is unnecessary. Large-caliber Foley catheter drainage is usually adequate. A cystogram is usually performed before Foley catheter removal, at 7 to 14 days. The ureteral stent is removed after 2 to 6 weeks (pending on physician preference). Intravenous urography is generally performed after several weeks (i.e., 4–6 weeks) to exclude silent ureteral obstruction [11,12]. 3. Psoas Hitch When the extent of ureteral loss is great or tension on the anastomosis is of concern, a psoas hitch or Boari flap to the ipsilateral psoas muscle is needed. To perform a psoas hitch, the peritoneum is stripped from the dome of the bladder, and the bladder is separated from the cervix and the proximal vagina. To facilitate additional bladder mobilization, the ipsilateral obliterated umbilical vessels and the contralateral superior vesical pedicle are ligated. The bladder is then opened longitudinally, pulled cephalad and lateral, and sutured to the psoas minor tendon (Fig. 2). If the psoas minor is not present (10% of patients), the belly of the psoas major muscle is adequate. Care should be taken to avoid the genitofemoral nerve. By fixing the bladder to a point, the ureter will not kink on bladder filling. The ureter is spatulated and reimplanted over a ureteral stent.

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Figure 2 Psoas hitch. (A) Cystotomy made in the bladder dome. (B) Bladder manually displaced on to the psoas tendon/muscle and sutured (“hitched”) in place. (C) Distal ureter brought through posterior bladder wall, into submucosal tunnel, and sutured to bladder mucosa. (D) Cystotomy closed and suprapubic tube placed. Another advantage to the Psoas hitch is that it facilitates performing a long ureteral tunnel. In the adult patient, however, ureteral reflux usually has little clinical significance or sequelae. Furthermore, a tunneled ureteral reimplant has an increased risk for ureteral orifice obstruction. A suprapubic tube, urethral Foley catheter, and a retroperitoneal drain are typically placed, and the bladder is closed in two or three layers. The suprapubic tube is maintained until after a normal cystogram at 10 to 14 days (Figs. 2A, 2B). The ureteral stent is commonly removed after 4 to 6 weeks [22]. 4. Boari Flap When the psoas hitch does not achieve sufficient length (usually for ureteral defects over 6 cm), typical options are a Boari flap or transureteroureterostomy (TUU). A Boari flap (Fig. 3) is constructed by first mobilizing the bladder and taking down the contralateral superior vesical pedicle. Stay sutures are placed at the base (at least 4 cm apart) and at the apex of the bladder (3 cm apart). The bladder is then opened with electrocautery to create a flap that is roughly 10 to 15 cm long. If ureteral length is still insufficient for a tension-free repair, caudal kidney mobilization and nephropexy can add additional ureteral length (up to 6 cm). As with the psoas hitch, the base of the flap should be tacked to the psoas muscle

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Figure 3 Boari flap. (A) Bladder incised to create flap. (B) Bladder fixed to psoas tendon/ muscle. (C) Bladder flap tubularized and ureter reimplanted. (D) Cystotomy closed and suprapubic tube placed.

to fix it in place. The ureter is spatulated and anastomosed over a ureteral doubleJ stent to the apex of the flap. Again, submucosal tunneling of the ureter is usually unnecessary. A suprapubic tube and urethral Foley catheter are typically put in place, and the bladder is closed in two layers. After 10 to 14 days, a cystogram is performed prior to suprapubic tube removal. After 4 to 6 weeks, the ureteral stent is typically removed [23]. 5. Transureteroureterostomy When the defect to the lower ureter is extensive and the bladder is small, fibrotic, or not easy to mobilize, then a transureteroureterostomy (TUU) is particularly useful. Relative contraindications to a TUU are upper tract urothelial cancer, genitourinary tuberculosis, recurrent nephrolithiasis, pelvic irradiation, retroperitoneal fibrosis, chronic pyelonephritis, or anomalies of the recipient ureter. A TUU is performed by bringing the injured (donor) ureter across the midline through a window in the colonic/sigmoid mesentery. To prevent the ureter from kinking on the inferior mesenteric artery (IMA), it is often necessary to place the ureter through a window above the IMA. The contralateral (recipient) ureter is minimally mobilized, incised about 1.5 cm, and end-to-side anastomosed to the spatulated donor ureter over a double-J stent. The main disadvantages of the TUU

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are the potential for damage to the recipient ureter and endangerment of both kidneys [24]. C. Devascularization Devascularization injuries are typically not recognized until late and present at several days to weeks postoperatively with a urine leak or ureteral stricture [10,11]. When noted intraoperatively, extensive skeletonization or thermal injury of the ureter that results in obvious nonviable ureter should be managed by ureteral segment excision until reaching healthy tissue and then repaired as detailed above. In the majority of cases, viability is difficult to assess, and it is prudent to place a ureteral stent in any equivocal case. Delayed injury to the ureter can also be minimized by covering the ureter with omentum or peritoneum. D. Laparoscopic Injury Ureteral injuries during laparoscopic gynecological surgeries typically occur during laser ablative endometriosis surgery or laparoscopic-assisted vaginal hysterectomy (LAVH) [25]. There are also reports of ureteral injury during laparoscopic tubal ligation, adnexectomy, and laparoscopic uterosacral ligament ablation (LUNA). Most LAVH ureteral injuries occur near the cardinal and uterosacral ligaments due to either thermal-electrocautery or sharp dissection [25]. There are also reports of ureteral injury by CO 2 laser, endoscopic linear stapler, and loop ligature [26,27]. Ureteral injuries, ranging from a small partial tear to complete ureteral avulsion, typically occur in patients with a history of pelvic irradiation or prior extensive pelvic surgery. Overall, complications are often related to surgical experience [28]. As with open surgery, preoperative IVU or ureteral stent placement are of limited routine value in preventing ureteral injury [29]. For technically difficult cases, ureteral catheters in laparoscopy may enhance identification and facilitate dissection. Lighted ureteral catheters are also available and may help in ureteral identification [26,27]. Partial ureteral lacerations or thermal injuries that are diagnosed intraoperatively can be managed by endoscopic placement of a ureteral stent (for 4 to 6 weeks). Laparoscopic suturing of the lacerated ureter has also been performed successfully. When the ureteral transection is complete, an immediate, open surgical approach is typically required [9]. If the surgeon is particularly skilled and the injury site is favorable, a laparoscopic ureteroureterostomy may be possible. The majority of ureteral injuries, however, are diagnosed in a delayed fashion, typically several days postoperatively [25,26]. Diagnosis and management of such injuries are detailed below. IX. DELAYED URETERAL COMPLICATIONS When a ureteral injury is diagnosed and repaired at the initial presentation/exploration, rarely is there high morbidity. When the diagnosis is delayed, however, morbidity (including sepsis, loss of renal function, and possible death) can occur in up to 50% of patients. Nephrectomy rates for delayed diagnosis, overall, are

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seven times as common. Leakage of urine can also cause abscess and scarring about the ureter, leading to obstruction and fistula formation [30]. A.

Urinary Extravasation

Initially, a missed transected ureter produces no symptoms until a urinoma collection causes abdominal swelling; ileus; infection; fever; low back, flank, or abdominal pain; or ileus and/or peritoneal signs. Persistent hematuria, leukocytosis, and/or urinary (fluid) leakage from the vagina are other reliable signs of injury. Absorption of the urine by the peritoneum will often cause a rise in the serum urea nitrogen. Such injuries have been successfully managed by a variety of methods, from ureteral stent place for minor injuries to open surgical repairs. When the patient is medically unstable, septic, or the injury is not detected for more than 2–3 weeks, the patient typically requires proximal urinary diversion (i.e., percutaneous nephrostomy tube and, if technically possible, ureteral stent placement), as well as percutaneous drain placement into the urinoma. The extravasated urine may also cause retroperitoneal fibrosis severe enough to cause ureteral obstruction, particularly if the area is not drained properly. At 2 to 3 weeks after surgery, reexploration is typically difficult and fraught with danger due to inflammation, fibrosis, adhesions, hematoma, and distorted anatomy. Definitive repair is performed in a delayed/staged fashion [1,11]. B.

Fistula

Fistulas (mainly ureterovaginal) are rare after ureteral repair. They usually develop when the ureteral injury is undiagnosed intraoperatively, and the ureter undergoes a delayed necrosis and/or stricture (obstruction). Other factors that contribute to fistula formation are infection (abscess, peritonitis), inflammation, foreign body, and neoplasia [31]. A history of prior pelvic irradiation (i.e., for cervical cancer) is another independent risk factor, increasing the risk for fistula formation after hysterectomy by three- to fourfold and complicating the difficulty of the fistula repair [10,16,25]. Ureteral fistulas usually do not require an open operation and typically close spontaneously with proper drainage and ureteral stenting [31,32]. Further details into the types, diagnosis, and treatment of ureteral fistulas are detailed in another chapter. C.

Stricture

Strictures develop when an ischemic ureter, often from extensive adventitial dissection, heals by scar tissue. Flank or abdominal pain and urinary tract infection/ pyelonephritis are common presentations. Ureteral strictures that are diagnosed early (within 6–12 weeks), distal, and relatively short in length (⬍2 cm) can be managed successfully (in about 50–80% of cases) by balloon dilation or endoscopic incision and stenting for 6 weeks. For endoscopic failures, an open surgical repair is indicated. When the stricture is discovered late, is particularly dense or long, or is radiation induced, open segmental excision and repair are usually necessary [31,33].

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BLADDER INJURIES

When a bladder injury is discovered during pelvic surgery, it is wise also to investigate for a concomitant ureteral injury. Direct inspection of the surgically exposed ureter or after indigo carmine administration is often sufficient. If the patient had received prior pelvic irradiation, the bladder repair should be covered with omentum or peritoneum (if available) to prevent possible fistulization. Bladder rest by use of a Foley catheter is typically for 7 to 14 days. A suprapubic tube is generally unnecessary for female bladder trauma unless there is considerable gross hematuria that could obstruct the catheter. A suction drain is placed in the prevesical space until drainage is minimal. If drainage output remains high, the drainage fluid should be sent for creatinine concentration. Creatinine levels greater than in the serum indicate a urine leak, while levels equal to that of the serum indicate peritoneal or lymphatic fluid. Persistent urinary leakage typically resolves with an additional 2 to 4 weeks of bladder drainage [32]. A. Abdominal Hysterectomy In gynecological surgery, bladder injury most commonly occurs during abdominal hysterectomy. The bladder can be injured at four specific sites (Fig. 4): on incising the parietal peritoneum; entering the vesicouterine fold; separating the bladder from the uterine fundus, cervix, or upper vagina; entering the anterior vagina; or mobilizing or suturing the vaginal vault. If a bladder injury is noted at this time, it can usually be easily managed by a two- or three-layer closure with absorbable suture and Foley catheter bladder drainage. Retrograde bladder filling with blue-colored saline again facilitates bladder injury diagnosis.

Figure 4 Midsagittal view of the female pelvis demonstrating the four areas typically at risk for bladder injury during abdominal hysterectomy: 1. parietal peritoneum; 2. vesicouterine fold; 3. bladder-uterus plane; 4. vaginal vault.

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Vaginal Surgery

Most bladder injuries during vaginal hysterectomy are in the supratrigonal area of the bladder base (and only rarely involve the trigone). Anterior colporrhaphy and stress incontinence surgery bladder injuries typically involve the floor and/ or the trigone; thus, ureteral orifice integrity and proximity must be assessed [14]. For such bladder injuries, cystoscopy is helpful to identify the location of the injury. If there is any suspicion for a concomitant ureteral injury, intravenous indigo carmine should be given and the ureteral orifices observed for blue dye. Once ureteral injury is excluded, the bladder injury can be repaired in two or three layers transvaginally. Transvaginal closures require certainty of a watertight closure and separation of the vaginal and bladder closures (to prevent fistulas). Tenuous closure or a radiated pelvis should have tissue interposed (i.e., Martius flap), if possible. The adequacy (watertightness) of the bladder closure can be tested by retrograde filling of the bladder with saline. A Foley catheter is typically left indwelling for 7 to 14 days. After the bladder laceration has been repaired, the vaginal surgery can be completed. C.

Laparoscopy

When injured, the bladder is usually penetrated during initial placement of the Veress needle or trocar. Trocar injuries are typically to the bladder dome and have an entry and exit wound. To avoid bladder injuries, it is essential that the bladder is decompressed by a Foley catheter at the beginning of the case. The position of the bladder should be assessed on initial examination with the laparoscope. All secondary trocars should be placed under direct visualization. Bladder injuries occur most often with midline and lower abdominal trocar placement. A full bladder or one with distorted anatomy from previous pelvic surgery, endometriosis, or adhesions is more likely to be injured laparoscopically [26]. Intraoperatively, the diagnosis of bladder injury is suggested by the presence of gas insufflation of the Foley bag or gross hematuria. Other signs of injury are urinary/fluid drainage from an accessory trocar site incision or fluid (urinary ascites) pooling in the abdomen/pelvis. If a bladder injury is suspected, the bladder should be filled retrograde with methylene blue–colored saline. Extravasation of fluid/dye indicates an intraperitoneal bladder injury. If there is no extravasation and an extraperitoneal bladder injury is suspected, a cystogram should be performed. Extraperitoneal injuries are managed conservatively by prolonged Foley drainage. Delayed diagnosis of bladder injury is also by cystography. Peritoneal irritation that persists over 12 h postlaparoscopy should also raise suspicion for an undiagnosed bladder injury [9,26,29]. Veress needle injuries and other small injuries to the bladder can be successfully managed conservatively by catheter drainage for 7 to 14 days, followed by cystography. Large bladder injuries, such as from 5- to 10-mm trocar or surgical dissection, often require suturing the injuries closed (either laparoscopically or by open repair) and prolonged catheter drainage. To reestablish a pneumoperitoneum for laparoscopic repair, the Foley needs to be clamped. Recognized bladder injury by laser or electrocautery should be closely evaluated and typically managed with catheter drainage for 5 to 10 days. Sharp dissection, electrocautery,

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and laser bladder injuries also have been reported during LAVH, adnexectomy, diagnostic laparoscopy, and endometriosis surgery [9,26].

XI. DELAYED BLADDER INJURY/DIAGNOSIS Cystography with a postdrainage film will assess for an intraperitoneal and/or extraperitoneal injury. Intraperitoneal injuries warrant surgical closure and drainage, while extraperitoneal injuries can be successfully managed by prolonged Foley catheter drainage. Decreased urine output, anuria, azotemia, elevated blood urea nitrogen, hematuria, suprapubic bruising, and abdominal swelling suggest a missed bladder injury. Undiagnosed intraoperative injuries to the bladder typically present days to weeks after surgery. In patients with prior pelvic irradiation, fistulas can present months to even years after hysterectomy. Typical delayed bladder complications are vesicovaginal, vesicouterine, enterovesical, vesicocutaneous, and vesico-peritoneal fistula. In the evaluation of a vesicovaginal fistula, an IVU should be performed since a ureterovaginal fistula occurs concomitantly in 10–12% of cases. If the IVU is abnormal or shows obstruction, a retrograde urogram should be performed. For further details on bladder fistulas, see subsequent chapters [26,31].

REFERENCES 1. Selzman AA, Spirnak JP. Iatrogenic ureteral injuries: a 20-year experience in treating 165 injuries. J Urol 1996; 155:878. 2. Higgins CC. Ureteral injuries during surgery. A review of 87 cases. JAMA 1967; 199: 82. 3. Neuman M, Eidelman A, Langer R, Golan A, Bukovsky I, Caspi E. Iatrogenic injuries to the ureter during gynecologic and obstetric operations. Surg Gynecol Obstet 1991; 173:268. 4. Dowling RA, Corriere JN Jr, Sandler CM. Iatrogenic ureteral injury. J Urol 1986; 135: 912. 5. Fry DE, Milholen L, Harbrecht PJ. Iatrogenic ureteral injury. Arch Surg 1983; 118:454. 6. Underwood PB Jr, Wilson WC, Kreutner A, Miller MC III, Murphy E. Radical hysterectomy: a critical review of 22 years experience. Am J Obstet Gynecol 1979; 134:889. 7. Kontogeorgos L, Vassiloppoulos P, Tentes A. Bilateral severe hydroureteronephrosis due to uterine prolapse. Br J Urol 1985; 57:360. 8. Eisenkop SM, Richman R, Platt LD, Paul RH. Urinary tract injury during cesarean section. Obstet Gynecol 1982; 60:591. 9. Grainger DA, Soderstrom RM, Schiff SF, Glickman MG, DeCherney AH, Diamond MP. Ureteral injuries at laparoscopy: insights into diagnosis, management, and prevention. Obstet Gynecol 1990; 75:839. 10. Symmonds RE. Ureteral injuries associated with gynecologic surgery: prevention and management. Clin Obstet Gynecol 1967; 19:623. 11. Guerriero WG. Injuries to the ureter: part 1, mechanisms, prevention and diagnosis. AUA Update 1983; 2(22):1. 12. Presti JC, Carroll PR, McAninch JW. Ureteral and renal pelvic injuries from external trauma: diagnosis and management. J Trauma 1989; 29:370. 13. Rodriguez L, Payne CK. Management of urinary fistulas. In: Taneja SS, Smith RB,

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14. 15. 16.

17. 18. 19. 20. 21. 22. 23. 24. 25. 26.

27. 28. 29. 30. 31. 32.

33.

Brandes Erlich RM, eds. Complications in Urologic Surgery. 3rd ed. Philadelphia: W. B. Saunders, 2001:186–205. Mattingly RF, Borkowf HI. Acute operative injury to the lower urinary tract. Clin Obstet Gynecol 1978; 5:123. Williams TJ. Urologic injuries. In: Wynn RM, ed. Obstetrics and Gynecology Annual. New York: Appleton-Century-Crofts, 1975:327–368. Green TH, Meigs JV, Ulfelder H, Curtin RR. Urologic complications of radical Wertheim hysterectomy: incidence, etiology, management, and prevention. Obstet Gynecol 1962; 20:293. Talbert LM, Palumbo L, Shingleton H, et al. Urologic complications of radical hysterectomy for carcinoma of the cervix. South Med J 1965; 58:11. Campbell EW, Filderman PS, Jacobs SC. Ureteral injury due to blunt and penetrating trauma. Urology 1992; 40:216. Higgins CC. Ureteral injuries during surgery: a review of 87 cases. JAMA 1967; 199: 118. Zinman LM, Libertino JA, Roth RA. Management of operative ureteral injury. Urology 1978; 12:290. Fry DE, Milholen L, Harbrecht PJ. Iatrogenic ureteral injury: options in management. Arch Surg 1983; 118:454. Turner-Warwick R, Worth PHL. The psoas bladder-hitch procedure for the replacement of the lower third of the ureter. Br J Urol 1969; 41:701. Konigsberg H, Blunt KJ, Muecke EC. Use of Boari flap in lower ureteral injuries. Urology 1975; 5:751. Pearse HD, Barry JM, Fuchs EF. Intraoperative consultation for the ureter. Urol Clin North Am 1985; 12:423. Tamussino KF, Lang PFJ, Breinl E. Ureteral complications with operative gynecologic laparoscopy. Am J Obstet Gynecol 1998; 178:967. Saidi MH, Sadler RK, Vancaillie TG, Akright BD, Farhart SA, White AJ. Diagnosis and management of serious urinary complications after major operative laparoscopy. Obstet Gynecol 1996; 87:272. Woodland MB. Ureter injury during laparoscopic-assisted vaginal hysterectomy with the endoscopic linear stapler. Am J Obstet Gynecol 1992; 167:756. See WA, Cooper CS, Fisher RJ. Predictors of laparoscopic complications after formal training in laparoscopic surgery. JAMA 1993; 270:2689. Daly JW, Higgins KA. Injury to the ureter during gynecologic surgical procedures. Surg Gynecol Obstet 1988; 167:19–22. McGinty DM, Mendez R. Traumatic ureteral injuries with delayed recognition. Urology 1977; 19:115. Mandal AK, Sharma SK, Vaidyanathan S, Doswani AK. Ureterovaginal fistula: summary of 18 years experience. Br J Urol 1993; 65:453. Williams RD. Urologic complications of pelvic surgery. In: Jewett MAS, ed. Urologic Complications of Pelvic Surgery and Radiotherapy. Oxford, UK: Isis Medical Media, 1995:1–39. Meirow D, Moriel EZ, Zilberman M, Farkas A. Evaluation and treatment of iatrogenic ureteral injuries during obstetric and gynecologic operations for nonmalignant conditions. J Am Coll Surg 1994; 178:144.

24 Surgical Treatment of Rectovaginal Fistulas and Complex Perineal Defects DIONYSIOS K. VERONIKIS St. John’s Mercy Medical Center St. Louis, Missouri, U.S.A.

I.

INTRODUCTION

The vaginal fistulas remain one of the most demanding problems to the pelvic reconstructive surgeon, as well as one of the most stringent tests of diagnostic acumen, patience, and above all, surgical skill. The uncontrolled presence of flatus and stool in the vagina and on the perineum is the dreadful manifestation of rectovaginal fistula. A rectovaginal fistula (RVF) may occur at any level within the vagina, but is most common in the lower third. Most of these have resulted from obstetric trauma, most often at the apex of an improperly healed fourth degree laceration. The patient may give a history of postdelivery constipation with difficulty expelling the fecal bolus of the first bowel movement, perhaps after much straining, which probably compromises the obstetric repair. Disruption and breakdown occurs cranial to the perineum, often between the fifth and tenth day after repair. Other causes of RVF are related to surgical trauma. These can include posterior colporrhaphy; enterocele repair; postabdominal hysterectomy; erosion of a foreign body into the rectum, such as a pessary or a stent after construction of a neovagina; Crohn’s disease; ulcerative colitus; diverticular disease; postpelvic radiation, particularly after trauma to the vagina in the presence of endarteritis obliterans; and the growth of residual or recurrent cancer. The most common form of RVF is that related to obstetric injury. The true incidence of perineal morbidity (RVF, “cloacalike” defects, external anal sphincter disruption, and fecal incontinence) following vaginal delivery remains unknown. 397

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The inability to control and retain rectal gas and liquid or solid stool becomes a source of considerable social embarrassment and emotional anguish for the women involved. Therefore, some form of effective therapy is indicated and required to restore anatomy and function. II. DIAGNOSIS OF RECTOVAGINAL FISTULA AND PERINEAL DEFECTS The diagnosis of RVF is usually easy. The patient can usually diagnose the condition and will complain of the passage of malodorous vaginal flatus, stool per vagina, and at times fetid vaginal discharge in varying amounts. Inspection of the vaginal side of the fistula, the low-pressure side, will usually reveal an area of granulation tissue. As this is wiped, especially with a digital finger in the rectum, the ostium may be visualized. Other visual clues are dimpling of the vaginal mucosa, at times in such a manner as to conceal the fistula from visualization. The fistula tract may burrow and branch out in the rectovaginal septum, giving rise to an induration maze of tracts and sinuses. There may be more than one fistulous opening, especially in cases when previous surgery or abscess formation has occurred. The vaginal and rectal mucosa must be very carefully inspected by probing, digital rectal examination, and if required, by rectosigmoidoscopy if the fistula is at the vaginal apex and is remote from adequate visualization during an office examination. The use during an office examination of lacrimal probes, passed transvaginally toward the rectum with concomitant rectal palpation, is a very useful method to identify low and midvaginal RVFs, as well as fistulas at the vaginal apex. At times, a small but symptomatic RVF may not be easily identified; radiologic tests have not been helpful as the thick barium paste is not easily passed into the vagina. In such clinical cases, the use of indigo carmine mixed with rectal lubricant may be injected transrectally with a tuberculin syringe. Gentle massage of the blue lubricant into the anterior rectal wall transrectally with comcomitant vaginal inspection will reveal a blue spot at the site of the vaginal fistula. The fistula may be single or multiple, or a single fistula may have several connecting tracts that communicate with the subepithelial tissues with one another, occasionally originating from several openings in the rectal lumen. Less commonly, a single opening of the rectal mucosa may communicate with several fistulous openings in the vagina and perineal skin. The relationship of the fistulous track or tracks to the external anal sphincter is of paramount importance when planning surgical repair. The possibility that a gastrointestinal vaginal fistula exists in the upper vagina or vaginal apex is suggestive if recent gynecological surgery was performed for hysterectomy or there was construction of a neovagina. The distinction that the RVF arises from the large bowel or arises from the small bowel should be considered if the patient passes liquid stool through the vagina while passing solid stool through the rectum or if the vagina and vulva are excoriated as might result from the digestion of the skin and small intestinal digestive enzymes. In addition to evaluating the rectovaginal septum, a careful and complete evaluation of any other concomitant defects existing in the perineal body and/ or external anal sphincter complex is critical to a complete reconstruction. Defects

Figure 1 A rectovaginal septal defect. The metal vaginal probe is traversing the rectovaginal septum from the vaginal canal through the rectum. The perineal body and external anal sphincter are intact.

Figure 2 A rectovaginal septal defect (fistula). The rectal finger is distending the anterior rectal wall and posterior vaginal wall; the perineal body is attenuated, and the anal sphincter is intact.

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(a)

(a)

Figure 3 (a) An attenuated perineal body and incompetent anal sphincter. The rectovaginal septal defect is not visible due to camera angle. The rectal mucosa is easily visualized transanally. (b) The rectovaginal septal defect not visible in Fig. 3a due to camera angle is seen here. Large rectovaginal septal defect with an attenuated perineal body and incompetent anal sphincter.

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Figure 4 An absent rectovaginal septum (“cloacalike”), absent perineal body, and absent anal sphincter. The rectal mucosa is at the perineal surface.

to the rectovaginal septum include all RVFs and cloacalike defects. The perineal body may be considered attenuated if on physical examination it measures less than 2 cm from the posterior vaginal wall to the anterior anoderm. The integrity of the external anal sphincter should be assessed by history and digital rectal examination, as well as with endoanal ultrasound. Four combinations of rectovaginal septal defects (fistulas) and complex perineal defects by site-specific anatomic structure exist considering injury in sequence to the rectovaginal septum, perineal body, and external anal sphincter: 1. Rectovaginal septal defect (fistula), intact perineal body, and intact anal sphincter (Fig. 1). 2. Rectovaginal septal defect (fistula), attenuated perineal body, and intact anal sphincter (Fig. 2). 3. Rectovaginal septal defect (fistula), attenuated perineal body, and incompetent anal sphincter (Figs. 3a and 3b). 4. Absent rectovaginal septum (cloacalike), absent perineal body, and absent anal sphincter (Fig. 4)

III. PREOPERATIVE PREPARATION AND REPAIR All patients should undergo a mechanical bowel preparation in a standardized manner 1 day prior to surgical repair. I have found that polyethylene glycol (GoLYTTELY, Braintree Laboratories, Braintree, MA) without erythromycin and neomycin is adequate since systemic antibiotics administered preoperatively and for a short perioperative interval have little effect on intestinal colonization. Clear liquids are taken the day before surgery.

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The surgical principles that underlie the successful management of RVF are 1. 2. 3. 4.

5.

Fistula repair should be undertaken when inflammation has decreased to a minimum. The epithelialized fistulous track must be excised and the edges inverted into the lumen. The repair must interrupt the continuity of the fistula by addressing the formal repair to the high-pressure side of the fistula. The fistula should be closed securely in two layers, usually in the transverse axis, and without tension. The second imbricating layer reinforces the first layer and takes tension off the first suture line. An independent blood supply within the rectovaginal space may be interposed, if necessary, with recurrent/persistent fistulas, as well as with postirradiation fistulas.

The basic operative procedures most useful to the reconstructive surgeon include (1) vaginal layered closure of the fistula without disrupting the perineum; (2) re-creating an episioproctotomy with closure of the anterior rectal wall, vagina, anal sphincter complex, and perineum in layers; (3) transperineal layered closure ventral to an intact external sphincter; and the (4) Noble-Mengert-Fish anterior rectal flap operation. The choice of procedure for repair of rectovaginal septal defects is determined for the most part by the location of an RVF (low, midway, or high within the vagina), the presence of absence of a perineal body, and the integrity of the exterior anal sphincter. The effective combination must be thoughtfully planned, carefully executed, and individualized for each patient depending on the defects. It must be remembered that for fistulas there is a high-pressure side and a low-pressure side, with the flow of material from the high-pressure side to the low-pressure side. With RVFs, the rectum is the high-pressure side, and the vagina is the low-pressure side. Material flows from the rectum into the vagina, not from the vagina into the rectum. Primary attention must be give to the closure of the high-pressure side, which must be closed securely and effectively. The vaginal low-pressure side will close spontaneously once the continuity of the fistula has been interrupted and the high-pressure side closed. When the fistula is in the low-to-middle vagina and the external anal sphincter and the perineal body are intact, a layered closure may be considered. The full thickness of the vaginal wall is incised and separated. The rectovaginal space is developed, and the rectum and vagina are carefully separated from each other. The fistulous track is transected, and the epithelial track is excised in its entirety. The rectal wall is closed by two layers of submucosal, interrupted, size 3-0 polyglycolic acid–type sutures. It is best to place the sutures transversely in the muscular wall of the rectum. Depending on available exposure, longitudinal placement may be acceptable if the rectal lumen is not compromised. A second layer not only reinforces the first, but also takes some of the tension off the first-layer closure. When the surgeon has chosen to repair the fistula after an episioproctotomy and episioproctorrhaphy, all the layers are repaired essentially in the manner of repairing a fourth-degree obstetric laceration. The fistulous track and the scar tissue are excised, and the wound is repaired as if it were a fresh fourth-degree laceration. Care is always taken to avoid tension of all of the suture lines. One

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consideration of episioproctorrhaphy in the treatment of RVFs is that in the event of a postoperative infection with abscess formation, a previously intact perineal body and external anal sphincter may be destroyed with breakdown of the repair. An alternative approach in patients with a fistula to the midvagina with an intact perineum and external anal sphincter is the operation of Thompson using a transverse perineal incision for exposure to the rectovaginal space and fistula. In this approach, a transverse perineal incision is made between the introitus and the external anal sphincter. The rectovaginal space is identified and entered. The fistula is identified, the rectum and vagina are separated, and the fistula is transected. The epithelialized track is excised, and the rectal defect is closed transversely with two layers. The perineal skin may be closed transversely in the direction of the incision. For the RVFs associated with complex perineal defects and recurrent/persistent RVFs with or without anal sphincter rupture, the method I most prefer is the Noble-Mengert-Fish anterior rectal flap operation. This approach begins with a curvilinear incision placed at the mucocutaneous junction encompassing the full 180° of the anal opening, between the 9 and 3 o’clock positions. In patients with cloacalike defects, the incision is placed along the scarred edge of the anteiror rectal wall. The dissection is performed sharply through the scar tissue until the rectovaginal space has been entered and developed, which will then permit effortless dissection up to the vault of the vagina. The margin of lateral dissection is the full width of the rectovaginal space. The overall extent of the dissection is individualized and tailored to each patient’s defect. Specifically, the anterior rectal wall is mobilized sufficiently so that, after excision of the defect, the rectal wall flap will reach the site where it is to be anchored on the external anal sphincter, as well as the perineal skin, creating a “new” mucocutaneous junction without tension. Site-specific reconstructive surgery must also be performed to reconstruct the perineal body and/or the external anal sphincter through the surgical exposure created by the semicircular incision at the mucocutaneous junction or through the incision placed at the scarred edge of the posterior vaginal and anterior rectal walls. The exposure afforded by the strategic placement of the incision, the dissection through the scar tissue, and the development of the rectovaginal space permits surgical exploration, identification of associated site-specific defects, and surgical reconstruction of each site-specific defect. The retracted ends of the external anal sphincter complex are identified by directing the dissection laterally for at least 2 cm until adequate mobilization of the external anal sphincter can be achieved. The mobilized sphincter ends may be grasped by Allis clamps and, ensuring overlapping, are sutured with 2-0 delayed absorbable synthetic suture polydioxanone (PDS; Ethicon Inc., Somerville, NJ). As described by Aronson, the intent of the sphincter plication was to reconstruct the external anal sphincter over at least a 3-cm area in an attempt to better restore the high-pressure zone of the anal canal. Reconstruction of the perineal body is performed by mobilizing the laterally displaced soft tissues and uniting them in the midline by a series of interrupted 2-0 polyglycolic acid sutures in the fashion of an extensive perineorrhaphy over the intact portion of the mobilized anterior rectal wall. The cranial tissues mobilized to the midline for reconstruction were fibers of the pubococcygeal muscles

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and caudally the superficial and deep transverse perinei muscles [9,10]. Vaginal ridges, shelving, and introital stenosis can and should be avoided by careful suture placement. Once the perineal body is reconstructed, the ends of the external anal sphincter are overlapped around the anal aperture by tying the previously placed sutures. The excess anterior rectall wall is incised above the defect, excising the distal full-thickness rectal wall with encompassing fistula and damaged tissue. The anterior rectal wall is anchored with interrupted 2-0 polyglycolic acid sutures at the level of the external anal sphincter. The mobilized cut edge of the anterior rectal wall is sutured to the skin, creating a new mucocutaneous junction with interrupted sutures of 2-0 polyglycolic acid sutures. A single interrupted suture approximates the vaginal defect to reduce postoperative granulation tissues. No vaginal packs or other drains are used except for a transurethral Foley catheter that is removed after 48 h. The Noble-Mengert-Fish operation provides the surgeon with surgical versatility that allows repair of multiple defects through a single surgical exposure, permitting optimal tailoring of the procedure to the individual patient’s sitespecific anatomical defects. IV. POSTOPERATIVE CARE AFTER FISTULA REPAIR It is of paramount importance to avoid any trauma and distention of the newly approximated tissue whether the layered or flap techniques have been used. The following postoperative management has been used to avoid the complications of distention. A clear liquid diet is ordered postoperatively for 3 days and then a low residue diet is given for 6 to 8 weeks, with a tapered return to a normal diet. Stool softeners should be given for 8 weeks, and a bowel movement should be expected between the 5th and 7th day postoperatively. No coitus is permitted for 2 to 3 months postoperatively. REFERENCES 1. Aronson MP, Lee RA, Berquist TH. Anatomy of anal sphincters and related structures in continent women studied with magnetic resonance imaging. Obstet Gynecol 1990; 76:846–851. 2. Hibbard LT. Surgical management of rectovaginal fistulas and complete perineal tears. J Obstet Gynecol 1986; 67:806–809. 3. Laird DR. Procedures used in treatment of complicated fistulas. Am J Surg 1948; 76: 701–708. 4. Menaker GH. The use of antibiotics in surgical treatment of the colon. Surg Gynecol Obstet 1987; 164:581–586. 5. Mengert WF, Fish SA. Anterior rectal wall advancement technic for repair of complete perineal laceration and rectovaginal fistula. Obstet Gynecol 1955; 3:262–267. 6. Nichols DH, Randall CL. Vaginal Surgery. 4th ed. Baltimore: Williams and Wilkins, 1996. 7. Noble GH. A new operation for the complete laceration of the perineum designed for the purpose of eliminating danger of infection from the rectum. Trans Am Gynec Soc 1902; 27:357–363.

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8. Noble GH. A flap sliding operation for the recto-vaginal fistula, leaving perineum and sphincter intact. 1909; Am J Obstet Gynecol 2:607–612. 9. Veronikis DK, Nichols DH, Spino C. The Noble-Mengert-Fish operation. Revisited: a composite approach for recurrent/persistent rectovaginal fistula and complex perineal injuries. Am J Obstet Gynecol 1998; 179:1411–1417. 10. Wiskind AK, Thompson JD. Transverse transperineal repair of rectovaginal fistulas in the lower vagina. Am J Obstet Gynecol 1992; 167:694–699.

25 Pessaries KIM KENTON Loyola University Medical Center Maywood, Illinois, U.S.A.

I.

INTRODUCTION

Pessaries have been used for the treatment of pelvic organ prolapse since the days of Hippocrates, when a pomegranate was inserted into the vagina to reduce a prolapsed uterus [1]. Since those early days, many different devices have been used for uterine support, including linen soaked in astringent, hammered brass, and cork. The success rates with these devices were variable and usually quite poor. Despite this, mechanical devices to support a prolapsed uterus remained the most widely accepted treatment for prolapse until the mid-19th century, when the advent of anesthesia and antisepsis made surgical repair a more viable option. During the 20th century, pessaries assumed their current role as the cornerstone of nonsurgical treatment for pelvic organ prolapse and stress incontinence. Today, most pessaries are made of a steel alloy spring covered in rubber, then coated in plastic or silicon; they are available in various shapes and sizes. Despite their long history, little scientific data exist regarding indications and selection of specific pessaries or appropriate follow-up care for women with pessaries. Two recent surveys indicate that up to 90% of general obstetriciangynecologists and 98% of urogynecologists prescribe pessaries for women with pelvic organ prolapse [2,3]. In fact, 77% of urogynecologists use pessaries as a firstline treatment for prolapse. Fewer general obstetrican-gynecologists report using pessaries as an initial treatment, with 20% reserving pessaries only for poor surgical candidates.

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Table 1 Patient Indicators for Pessary Offering Prolapse or stress incontinence Wish to avoid or postpone surgery Available for regular follow-up Taking estrogen replacement

II. PATIENT CHOICE Most women who present for evaluation and treatment of pelvic organ prolapse or stress incontinence are potential candidates for pessary placement as few contraindications exist. Many women wish to avoid surgery for medical or personal reasons or prefer to postpone it to a later time. Women with pessaries must be available for regular follow-up visits. Superficial vaginal erosions can develop, and although uncommon, pessaries that have been neglected for many years can erode into the bladder, bowel, or peritoneal cavity [4–7]. Most gynecologists recommend that patients using pessaries take estrogen replacement therapy; up to two thirds of gynecologists consider hypoestrogenism a contraindication to pessary use. Unestrogenized vaginal tissues are prone to erosions; therefore, vaginal, oral, or transdermal estrogen replacement should be prescribed whenever possible. For women unable to take estrogen replacement, more frequent follow-up is advisable. Women with perineal sensory defects may not sense significant erosions or changes in bowel and bladder function and should also be followed at more frequent intervals. Table 1 contains a list of patients who should be offered a pessary.

III. PESSARY CHOICE Once a patient has elected to attempt pessary placement, the physician should have a variety of pessary types and sizes available and should tailor pessary selection to the individual patient’s anatomy and prolapse (Table 2). A pelvic exam assessing the stage of prolapse, the primary support defect (apical, anterior, or posterior), and the size of the genital hiatus and perineal body help the physician choose the appropriate size and type of pessary. Of women fitted with pessaries in a referral setting, 74% were able to retain them. Weak Kegel contraction, higher stage of prolapse, and a large genital hiatus decrease patients’ ability to retain pessaries [8]. The pessary is gently inserted into the vagina, and the patient is asked to bear down. If the pessary is not retained, a different size or type of pessary should be tried. Once a patient can comfortably retain a pessary, she is asked to stand and attempt to forceably expel the pessary using various maneuvers, such as bearing down, coughing, or running in place. The physician should step out of the room so the patient can have privacy during this part of the exam. If she does not expel the pessary with these maneuvers, she should void with the pessary in place to ensure that it does not obstruct urination. When the physician returns, the pessary should be rechecked to ensure proper positioning and patient comfort.

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Table 2 How to Choose a Pessary 1. Pelvic exam a. Apical, anterior, and posterior vaginal support b. Genital hiatus and perineal body size 2. Incontinence, prolapse, or both 3. Prolapse a. Apical—ring, doughnut, Gellhorn, cube b. Anterior—ring, Gehrung c. Posterior—ring, Gehrung 4. Incontinence a. Adequate support—ring b. Coexistent prolapse—dish 5. Supine patient can retain pessary comfortably 6. Attempt to expel pessary—Valsalva, cough 7. Urinate 8. Recheck placement

The physician should be aware of the different types of pessaries available for optimal success. Of the physicians, 78% tailor the pessary to the specific support defect—apical, anterior, or posterior [2]. Genital hiatus and perineal body size are also important as some pessaries are dependent on adequate pelvic floor support to be retained. The most commonly prescribed pessary is the ring (51%), followed in decreasing order by the doughnut (44%), Gellhorn (24%), and cube (24%) [3]. In our practice, we frequently use the incontinence dish due to the high prevalence of coexistent urinary incontinence and prolapse in our patients. IV. PROLAPSE PESSARIES A. Ring Pessary Ring pessaries (Fig. 1) are the most frequently prescribed due to the ease with which physicians and patients can insert and remove them. They are most commonly used for anterior and apical support defects in patients with an adequate perineal body and pelvic floor. B. Doughnut Pessary and Inflatoball Doughnut pessaries (Fig. 2) are the next most frequently prescribed pessaries and are typically used for advanced stage III or IV apical prolapse with a weak pelvic floor and large genital hiatus. They successfully support large prolapse by having a diameter larger than the patient’s genital hiatus. However, by being bulkier and not bendable, patients often have a more difficult time inserting and removing doughnut than ring pessaries. Some patients can remove the pessary more easily if a monofilament suture is tied around it, which they can easily grab. Like the doughnut, the inflatoball pessary (Fig. 3) is effective for treating advanced-stage prolapse in women with a weak pelvic floor and large genital hiatus. It has a doughnut-shaped inflatable chamber attached to a filling port so it can be fitted to the individual woman by increasing or decreasing the amount

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Figure 1 Ring pessary. (Courtesy Milex, Chicago, IL.) of air. This allows patients to insert and remove it more easily and decreases the risk of erosion. C.

Gellhorn Pessary

Gellhorn pessaries (Fig. 4) are the most frequently prescribed pessaries for procidentia. They have the advantage of being relatively small compared to doughnut pessaries, while still being able to support large apical defects. However, unlike the doughnut, the Gellhorn relies on an adequate perineal body for retention. D.

Cube Pessary

The cube pessary (Fig. 5) is effective at treating advanced-stage prolapse in the absence of an adequate perineal body and pelvic floor. It functions by the suction

Figure 2 Doughnut pessary. (Courtesy Milex, Chicago, IL.)

Pessaries

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Figure 3 Inflatoball pessary. (Courtesy Milex, Chicago, IL.)

action of six concave surfaces, which tightly adhere to the vaginal walls and hold the prolapse in place. Due to the cube’s tight adherence to the vaginal walls, the vagina is prone to erosions. Patients with a cube pessary should be on estrogen replacement therapy and be checked at more frequent intervals. E.

Gehrung Pessary

The Gehrung pessary (Fig. 6) has an arch-like design for treating anterior vaginal wall defects. Gehrung pessaries were the third most commonly prescribed pessaries for anterior vaginal wall prolapse [2].

Figure 4 Gellhorn pessary. (Courtesy Milex, Chicago, IL.)

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Figure 5 Cube pessary. (Courtesy Milex, Chicago, IL.)

V.

INCONTINENCE PESSARIES

The incontinence ring (Fig. 7) is a modification of the ring pessary with a knob on one side that rests under the urethra to compress it externally and prevent transurethral urine loss due to stress incontinence. The incontinence dish (Fig. 8) is thicker than the incontinence ring and provides more support to the anterior vaginal wall and apex in women with coexistent prolapse. In a small study that looked at the subjective success of the incontinence ring for treating stress incontinence, 69% of women experienced adequate symptom control and continued to use the device. It was effective in women with pure genuine stress incontinence and those with intrinsic sphincter deficiency [9]. Only 16% of gynecologists sur-

Figure 6 Gehrung pessary. (Courtesy Milex, Chicago, IL.)

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Figure 7 Incontinence ring. (Courtesy Milex, Chicago, IL.) veyed were familiar with incontinence pessaries, and only 12% thought they were effective for the treatment of stress incontinence [3]. VI. FOLLOW-UP OF PATIENTS WITH PESSARIES Many protocols exist on how and when patients with pessaries should follow up with their physician. In our practice, once we find a pessary that the patient can comfortably retain, we have her wear the pessary continually for 1 week. During this time, she should not remove and reinsert the pessary herself. At the 1-week follow-up visit, the patient is directly asked about her pelvic floor symptoms to discover if the pessary is alleviating her symptoms of prolapse or incontinence and ensure that it has not created new symptoms of incontinence or defecatory

Figure 8 Incontinence dish. (Courtesy Milex, Chicago, IL.)

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Figure 9 Pessary algorithm.

difficulty. In addition, patients are given a thorough pelvic exam to make sure the pessary is positioned properly in the vagina and has not created any erosions. If the patient’s symptoms are adequately controlled and her vagina looks healthy, the patient is taught in the office to remove and insert the pessary herself. Most women are able to do this without difficulty (Fig. 9). Recommendations regarding follow-up intervals vary among practitioners and should be individualized to the patient. We recommend that women remove

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the pessary at night and replace it in the morning. This allows the vaginal mucosa to rest and decreases the erosion rate. Women who find nightly removal difficult are often able to manage weekly removal. Occasionally, patients are unable to remove or reinsert their own pessaries. These patients are obviously at higher risk of erosion and should be monitored more frequently. We generally recommend that patients return to our office for a pelvic exam every 3 months; however, we may increase or decrease the interval based on the patient’s estrogen status and ability to care for the pessary.

VII. PESSARY CLEANING Pessaries are made of a spring covered in rubber and coated in silicon or plastic, so they can be cleaned with soap and warm water. They may become discolored after prolonged use, but this is not harmful. If the pessary cracks or losses its supportive characteristics, it should be replaced.

VIII. VAGINAL EROSION DEVELOPMENT If a patient is being followed with regular visits, any erosions should be minor and should be successfully managed by simply removing the pessary and rechecking the patient in 1 month. Most likely, the erosion will have healed during this time, the pessary can be replaced, and the patient can be monitored at more frequent intervals. If the patient has recurrent erosions, an alternative form of treatment should be agreed on by the patient and physician. Erosions that do not respond to vaginal rest when the pessary is removed should be biopsied.

IX. DISCONTINUING USE Women who choose pessaries as treatment for prolapse or incontinence may opt to discontinue pessary use for a number of reasons. Sulak et al. found that 20% of women who chose pessary treatment over surgery stopped using their pessaries within a few days to weeks due to inadequate symptom control or inconvenience [10]. Some patients who have successfully used pessaries may find their symptoms returning and can often be fitted with a larger size or different type of pessary. Recurrent or nonhealing erosions are also indications for pessary discontinuation.

X.

OTHER INDICATIONS FOR PESSARIES

A. Uterine Retroversion A strongly retroverted uterus can become incarcerated at the pelvic brim in the late first trimester of pregnancy. These women may present with acute pelvic pain or urinary retention. The patient should be given an anesthetic and the uterus gently lifted out of the pelvis. A pessary can then be placed to prevent a recurrence until the uterus is large enough to stay above the pubic symphysis.

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Diagnosing Stress Incontinence

The pessary has been used to help diagnose genuine stress incontinence in women with anterior vaginal wall prolapse that obstructs the urethra. Bergman et al. reported that 25% of women with stage II or greater anterior prolapse demonstrated genuine stress incontinence on urodynamic testing with the prolapse reduce with a pessary [11]. These women had a successful incontinence procedure done at the time of prolapse surgery. In a similar study, 15% of women undergoing preoperative evaluation for cystocele repair demonstrated stress incontinence with a pessary in place [12]. XI. SUMMARY Pessaries are a safe, effective alternative to surgery for some women with pelvic organ prolapse and stress incontinence. Practitioners who participate in the evaluation and treatment of women with pelvic floor disorders should be comfortable fitting and caring for pessaries. REFERENCES 1. Emge LA, Durfee RB. Pelvic organ prolapse, four thousand years of treatment. Clin Obstet Gynecol 1966; 9:997–1031. 2. Cundiff GW, Weidner AC, Visco AG, Bump RC, Addison WA. A survey of pessary use by members of the American urogynecologic society. Obstet Gynecol 2000; 95: 931–935. 3. Pott-Grinstein E, Newcomer JR. Gynecologists’ patterns of prescribing pessaries. J Reprod Med 2001; 46:205–208. 4. Ott R, Richter H, Behr J, Scheele J. Small bowel prolapse and incarceration caused by a vaginal ring pessary. Br J Surg 1993; 80:1157. 5. Goldstein I, Wise GJ, Tancer ML. A vesicovaginal fistula and intravesical foreign body. A rare case of neglected pessary. Am J Obstet Gynecol 1990; 163:589–591. 6. Sivasuriya M. Cervical entrapment of a polythene vaginal ring pessary—a clinical curiosity. Aust N Z J Obstet Gynecol 1987; 27:168. 7. Russel JK. The dangerous vaginal pessary. Br Med J 1961; 2:1595–1597. 8. Morgan-Jahanshir L, Shott S, Fenner D. Factors affecting patients’ ability to retain a pessary. Int Urogynecol J 1999; 10(1):81. 9. Leong F, Brubaker L. Use of the incontinence ring is stress incontinence. Presented at the American Urogynecologic Society Annual Meeting, New Orleans, LA, November 12–14, 1996. 10. Sulak PJ, Kuehl TJ, Shull BL. Vaginal pessaries and their use in pelvic relaxation. J Reprod Med 1993; 38(12):919–923. 11. Bergman A, Koonings PP, Ballard CA. Predicting postoperative urinary incontinence development in women undergoing operation for genitourinary prolapse. Obstet Gynecol 1988; 158:1171–1175. 12. Fianu S, Kjaeldgaard A, Larsson B. Preoperative screening for latent stress incontinence in women with a cystocele. Neurourol Urodynam 1985; 4:5–7.

26 Menopause and Hormone Replacement Therapy SANGEETA T. MAHAJAN, ANIL B. PINTO, and DANIEL B. WILLIAMS Washington University School of Medicine St. Louis, Missouri, U.S.A.

I.

MENOPAUSE

The menopause is defined by the World Health Organization as the point in time of permanent cessation of menstruation due to loss of ovarian function [1]. Clinically, the menopause is characterized by persistent amenorrhea for a period of 12 months. The perimenopause is defined as the time period of changing ovarian function preceding the menopause to 1 year following the final menses, generally lasting between 2 and 8 years. Today, the average age of menopause is approximately 51 years [2–5]. Laboratory findings in the menopause generally reveal serum estradiol levels of less than 40 pg/mL, with follicle-stimulating hormone (FSH) levels more than 40 mIU/mL. These values may vary depending on the assay used. Currently, the average life expectancy for a woman in the United States is approximately 80 years [3]. Consistent with this, almost one half of the average woman’s life is spent in the postmenopausal period [3]. The aging of our society is an important epidemiological phenomenon; Hammond [6] points out that, consistent with the steady growth of the older segments of the population, more than 30 million women in the United States are peri- or postmenopausal. By the year 2020, one in five people will be over 65 years old. There are several important factors that influence the age of menopause onset. Though steady results may conflict, the most convincing factors thought to influence age of menopause include (11) genetics, (2) cancer chemotherapy, (3) current cigarette smoking, (4) menstrual and reproductive history, (5) use of oral contraceptive pills (OCPs), and (6) surgical trauma to the ovarian blood supply 417

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(distinct from oophorectomy) [3]. Twin studies by Snieder et al. [7] found that 86% of monozygotic twins versus 55% of dizygotic twins underwent menopause within 5 years of one another. Permanent amenorrhea after undergoing chemotherapy has been documented to occur in 50% of women younger than 40 years old and 90% of women older than 40 years [8,9], most often secondary to direct toxicity to ovarian follicles. McKinlay et al. [2] demonstrated current smoking to result in an earlier onset of menopause by an average of 1.74 years. However, it is unclear whether the quantity a woman smokes influences how early menopause will occur. Theories regarding the mechanism by which smoking causes the premature onset of menopause include (1) toxicity of aromatic hydrocarbons to primary oocytes, thereby hastening the onset of menopause by decreasing the number of available oocytes, and (2) acceleration of ovarian involution secondary to increased oxidation of the cell membrane [10,11]. Conflicting evidence exists regarding the significance of parity and oral contraceptive use on the age of onset of menopause. Several studies have suggested that the use of OCPs delays the onset of menopause [12–15]. However, conflicting evidence also exists [10]. Unrecognized surgical trauma to the ovary or ovarian blood supply intraoperatively represents another potential cause of early menopause. II. THE TRANSITION Greendale and Sowers [3] separated the reproductive life span into three phases: the premenopause, the perimenopause, and the postmenopause (Fig. 1). The perimenopause can be further subdivided into early, middle, and late stages [3]. The premenopause consists of life from menarche to the menopause, with a bell-

Figure 1 The phases of female reproductive life, utilizing idealized ages and menopause and menarche. (From Ref. 3.)

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shaped curve describing ovarian function and fertility [16]. Collett et al. [17] studied the changes in the menstrual cycle with age and found the greatest stability and efficiency of ovarian function between the ages of 25 and 34 years. Ovulatory variability is greatest before the age of 20 and after the age of 40 years old, resulting in the increasing frequency of anovulatory cycles, erratic cycle length, and associated atypical uterine bleeding. The early perimenopause is characterized by slowly declining ovarian function, increasing frequency of anovulatory cycles, irregular cycle lengths, fluctuating gonadotropin levels, and an overall increase in FSH and luteinizing hormone (LH) levels with increasing age [18]. FSH levels, in particular, may fluctuate widely, changing with each cycle [10]. This variability in FSH level is secondary to a decreased number of ovarian follicles [18], suggesting the utility of an index for follicle numbers [20]. Furthermore, the remaining follicles respond poorly or not at all to the stimuli of pituitary gonadotropins, resulting in decreased ovarian estrogen and androgen production [6] and elevated FSH levels secondary to attempts by the pituitary gland to stimulate ovarian estrogen production and potential ovulation [21]. With loss of ovarian follicles as well as granulosa cells, inhibin levels, which normally provide negative feedback on the pituitary FSH secretion, decrease [22]. This results in the loss of the negative-feedback loop between FSH and inhibin, resulting in elevation of FSH levels [23]. MacNaughton et al. [22] demonstrated that, from birth, for every 10 years that a woman ages, her inhibin level decreases by 49.3 u/I. In contrast, FSH levels are stable through premenopause until 42.97 years of age, after which there is a significant rise once inhibin levels fall low enough to allow a rise in FSH levels. Thus, the routine use of serum FSH to determine if a woman is peri- or postmenopausal can often be misleading, reinforcing the importance of clinical evaluation in making the diagnosis of menopause [24]. The middle perimenopause is characterized by an overtly altered menstrual cycle pattern, with long intermenstrual intervals and shortened and lighter bleeding episodes [16]. Some authors auggest that abnormal uterine bleeding may become more frequent secondary to increased frequency of anovulatory cycles with long follicular phases, resulting in prolonged estrogen stimulation of the endometrium and a large amount of endometrial sloughing once estrogen levels fall [3]. In contrast, other authors have found a generalized shortening of follicle cycle length due to a shorter follicular phase secondary to dysregulation of the hypothalamic-pituitary-gonadal axis. This results in a change in the gonadotropinreleasing hormone (GnRH) pulse frequency, causing a failure of the LH surge to occur and inadequate estrogen priming of the endometrium [25]. Estrogen levels may vary with each cycle, some with high levels and others with low levels [21,26,27]. Some authors postulate that, rather than assuming anovulation to be the cause of abnormal uterine bleeding, the potential hyperestrogenic state of the perimenopause may be the cause, explaining the increased risk of endometrial hyperplasia, growth of fibroids, and dysfunctional uterine bleeding that often characterize this time of life [25,26]. Given the variable levels of gonadotropins, signs and symptoms associated with the menopause may often begin or become severe enough to cause discomfort at this point in time. Common symptoms include hot flashes, breast engorgement, endometrial hyperplasia, and menorrhagia [28].

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As the transition proceeds to the late perimenopause phase, continued alterations in the production and subsequent levels of the different steroid hormones occur. Ovulation eventually ceases, and ovarian follicles are no longer under the influence of gonadotropins, resulting in permanent loss of fertility. However, despite only minimal ovarian estrogen production, the ovarian stroma continues to form androstenedione and testosterone in significant amounts [29,30]. This persistent androgen production by the ovaries despite markedly reduced estrogen production results in a shift in the estrogen/androgen ratio [29,31], often with accompanying clinical symptoms of elevated androgen levels. As estrogen levels decline into the postmenopause range, estradiol is no longer made by the follicle, but peripherally via the conversion of estrone, testosterone, and, most importantly, androstenedione [29]. The major estrogen sources throughout this period are the adrenals via the peripheral conversion of androstenedione to estrone in adipose tissue [30,32,33]. In addition, the adrenals continue to secrete testosterone and small amounts of estrogen, as well as dihydroepiandrostenedione (DHEA) and dihydroepiandrostenedione-sulfate (DHEA-S). However, with increasing age, the adrenals produce less androgen, resulting in diminished peripheral estrogen production over time [30,34]. Consistent with this, the persistently elevated estrogen levels of obese perimenopausal women and their higher rate of endometrial cancer can be further understood [33]. Yen [35] summarized these changes in steriod hormones with the menopause in a graphic fashion (Fig. 2). With the menopause, significant reductions in estrogen levels are noted with a less significant decrease in androgen levels. No change in adrenal androgen or cortisol levels is noted. FSH and LH levels increase markedly without change in pituitary hormones. Finally, at the completion of the late perimenopause, now 12 months after the last menses and beginning of the menopause, gonadotropin levels have reached their final menopausal

Figure 2 Circulating levels of pituitary and steroid hormone levels in postmenopausal women compared to premenopausal women on days 2 to 4 of the menstrual cycle. (From Ref. 35.)

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levels. Average estrone production is 40 µg per day and estradiol 6 µg per day. The average FSH level in menopausal women is higher than 40 mIU/mL. III. SYMPTOMS OF MENOPAUSE There are a number of physiologial changes that occur during the menopause that can have a significant impact on a woman’s health. These changes can be separated by organ systems, including central nervous system (CNS), skin, genitourinary tract, cardiovascular system, and skeletal system. Goals for preventive treatment of menopause-related changes can be separated chronologically into those aimed at early symptoms, later physical changes, and finally significant diseases that often result in morbidity and mortality (Table 1). Common early symptoms of menopause include central nervous system dysregulation, in particular hot flashes, with insomnia, irritability, and mood disorders, often secondary to CNS instability. Physical changes may follow or appear concurrently with early symptoms. The most common signs of menopause include vaginal atrophy, new stress incontinence, and skin atrophy. Common long-term changes commonly associated with menopause include an alteration of lipid profile, osteoporosis, cardiovascular disease, dementia associated with Alzheimer’s disease (AD), macular degeneration, and stroke. A. Central Nervous System Vasomotor instability or the “hot flash” is a common complaint of the perimenopausal and menopausal woman, affecting 60% to 85% of all women [36]. In fact, one-half of women who suffer from hot flashes experience associated acute physical discomfort, and 75% of these women seek medical attention for these complaints [37]. Hot flashes usually occur suddenly, although some women may experience an aura or premonition of the impending hot flash; they generally begin with an intense feeling of heat in the face and thorax. Visible flushing or reddening of the face and neck often follows, with a rise in heart rate and skin blood flow. Table 1 Signs and Symptoms of Menopause Central nervous system

Skin Skeletal Cardiovascular

Genitourinary tract Eyes

Hot flashes Mood disturbances Insomnia Dementia Alzheimer’s disease Stroke Vaginal atrophy Skin atrophy Osteoporosis Hypercholesterolemia Cardiovascular disease Myocardial infarction Stress incontinence Macular degeneration

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Skin resistance drops rapidly, resulting in increased skin conductance of heat and a sensation of skin warmth. Peripheral blood flow, heart rate, and finger temperature increase, clinically resulting in palpitations and profuse sweating. Casper and Yen [38] demonstrated an average increase in skin temperature of 4.1°C with hot flash episodes. The loss of heat, from peripheral vasodilation and evaporative cooling, results in a drop in skin temperature, reaching a nadir 5 to 9 min after the start of the hot flash and clinically consistent with chills or shivering. Freedman [39] demonstrated a decrease in core body temperature of approximately ⫺0.10°C during a hot flash. Subsequent vasoconstriction and elevated metabolic rate secondary to shivering result in the return of body temperature to normal [38,40]. The average hot flash lasts approximately 4 min [41]. Hot flashes may occur for 0.5 to 5.0 years after last menses. Erlik et al. [42] found that, without treatment, 57% of women experience hot flashes for greater than 5 years and up to 10% for greater than 15 years. In studies of perimenopausal women with hot flashes, 70% to 87% experienced daily hot flashes, and the frequency ranged from 5 to 50 per day [40,43]. Women who have undergone surgical menopause are more likely to experience hot flashes than naturally menopausal women, often reaching 100% incidence in the first year postoperatively and most commonly described as severe [44–46]. This increase in severity may be due to the sudden onset of menopause in postsurgical cases. Although hot flashes often occur spontaneously, they may also be provoked by stress, emotional situations, external heat or warm weather, confining spaces, alcohol use, and caffeine use [40]. The cause of hot flashes remains unclear, but they are thought to occur secondary to sudden changes in hypothalamic control of temperature regulation [41], explaining why they are often termed “vasomotor instability.” Estrogen is believed to moderate the firing rate of thermosensitive neurons in the preoptic area of the hypothalamus [47]. Further research by Walsh and Schiff [48] revealed that estrogen enhances α-2-adrenergic activity, explaining why the withdrawal of estrogen and subsequent diminished α-2-adrenergic activity results in vasomotor instability and the deregulation of hypothalamic thermal control in perimenopausal and menopausal women. Hot flashes are often worse at night for many women, resulting in the phenomenon of night sweats, multiple episodes of awakening, and overall nonrestful sleep. Woodward and Freedman demonstrated postmenopausal hot flash sufferers to have associated increased stage 4 sleep, a shortened first eye movement (REM) period and disrupted sleep [50,51]. The resulting decreased sleep efficiency caused by hot flashes may explain the associated chronic fatigue and irritability from which many menopausal women suffer. The best treatment for hot flushes is estrogen. Usually, 0.625 mg of conjugated estrogen or estrone sulfate, 1 mg of estradiol, or 50 µg of transdermal estrogen or equivalent doses of other estrogens will alleviate these symptoms, but in some patients, higher doses are required [52]. B.

Skin

Skin changes associated with the menopause are well-recognized symptoms of this life transition. There are 14 major types of collagen identified in human skin, with the two major forms being type I and type III. As individuals age, the ratio

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of type III to type I collagen decreases, in contrast to the maximum value seen in neonatal skin [53]. As postmenopausal women age, there is a linear decrease in skin collagen content of 2.1% and skin thickness of 1.13% per year from premenopausal levels during the initial 15 to 18 postmenopausal years [54]. Many studies have focused on the therapeutic effects of estrogen for these menopausal changes. Callens et al. [55] noted an increased skin thickness with estrogen treatment of 7% to 15% dependent on site. Savvas et al. [53] noted increased type III collage levels in women treated with estrogen. The maximal effect of estrogen therapy was noted after 6 months of treatment, with type III collagen levels equivalent to those after 8 years of therapy. This increase in type III collagen resulted in a favorable shift of the ratios of type III to type I collagen that were equivalent to premenopausal levels. Skin ultrasound after estrogen therapy demonstrated increased dermis thickness by 30% and skin thickness by 11.5% in postmenopausal women [56]. C. Genitourinary Tract The association between menopause and genitourinary complaints is well known, but is still a subject of some debate. Levin et al. [57] demonstrated the presence of estrogen-sensitive tissue within the genitourinary system. Dionne et al. [58] and Ekstrom et al. [59] also clearly demonstrated the presence of estrogen receptors in the estrogen-responsive tissues of the perineum and genitourinary system. With declining estrogen levels, vaginal pH rises from acidic to basic levels, resulting in the decline of the previously predominant lactobacilli and a newly hospitable environment to previously atypical bacteria colonizing the vagina, most significantly enterobacteria [60]. As estrogen-sensitive vaginal mucosa dries, thins, and loses elasticity, similar changes occur in the urinary tract, consistent with their shared embryologic origin. These changes include (1) marked atrophic changes of the urethra, resulting in dysuria and frequency; (2) thinning of the urethral epithelium; (3) atrophy of the bladder trigone muscles; (4) decreased α-adrenergic receptors in the bladder neck and urethral sphincter; (5) sclerosis of periurethral tissues; and (6) elevated vaginal pH [61,62]. The significant decrease in urethral mucosa thickness and atrophic changes significantly compromise the ability to create a urethral seal to maintain continence, thought to be a key component in the increased prevalence of incontinence with menopause [63]. Consistent with the altered physiology of the genitourinary tract, genuine stress incontinence may appear for the first time or seem to worsen with menopause [64]. Urinary incontinence affects approximately 29% to 37% of communitydwelling older women, and in 20–25% of these individuals, it is severe [65,66]. In nursing homes, over 50% of women are incontinent [67]. The primary causes of involuntary urine loss in elderly women are detrusor instability and urethral sphincter incompentence [68]. The above-noted changes in the genitourinary tract mediated by estrogen deficiency are thought to play a key role in the development of these disorders. Furthermore, the change in vaginal pH secondary to loss of estrogen stimulation and resultant altered vaginal flora allow the proliferation of gram-negative organisms and a subsequent marked increase in urinary tract infections in elderly women [61]. Illustration of the effects of estrogen therapy was demonstrated by Bump

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and Friedman [69], who found significant increases in functional urethral length, paralyzed total urethral pressure profilometry (UPP) area, and paralyzed UPP area to maximal urethral closure pressure (MUCP) in castrated baboons treated with estrogen. Bhatia et al. [70] demonstrated subjective improvement of symptoms in 55% of patients treated with estrogen. Among these patients, they found significantly increased urethral closure pressures and increased abdominal pressure transmission to the proximal one-third of the urethra to correlate with successfully treated patients. Other studies claim a 45% decrease in urge incontinence and a 50% decrease in stress urinary incontinence with estrogen therapy [71,72]. The utility of estrogen further includes a decrease of the incidence of urinary tract infection (UTI) in postmenopausal women, as clearly demonstrated by Raz and Stamm [73], with only 0.5 UTI episodes per patient-year in a group treated with estrogen versus 5.9 episodes in those in the placebo group. Although these studies suggest a beneficial effect of estrogen on incontinence, they are limited by small numbers, lack of standardization, reporter bias, and variable results [62]. Other studies have demonstrated no improvement in incontinence symptoms or urodynamic measurements in postmenopausal women treated with estrogen [74,75]. Given the wide spectrum in findings on the effects of estrogen on postmenopausal incontinence, Fantl et al. [62] performed a metaanalysis examining all studies from 1969 to 1992 on this subject. Of 166 studies in the literature, only 6 controlled clinical trials and 17 uncontrolled trials exist. Examination of these studies via metaanalysis revealed that estrogen subjectively improved incontinence, but there was no improvement in urodynamic parameters. Outcomes of the studies examined vary greatly, with 5 showing increased maximal urethral closure pressure, 2 revealing a decrease, and 1 with no change. The placebo effect in controlled trials was noted to be as high as 56%. Furthermore, methods to objectively quantify the amount of urine lost, as well improvements of this parameter, were deficient. Considerable lack of standardization in patient selection, diagnostic criteria, study design, therapeutic intervention, follow-up, and outcome variables was noted, as well as a strong bias toward reporting positive results. Thus, given these findings, the conclusion of this meta-analysis was that estrogen has only a small effect on urinary incontinence. D.

Osteoporosis

Osteoporosis is defined pathologically as an absolute decrease in the amount of bone secondary to greater bone resorption than bone formation and resulting in an increased risk of fracture with minimal trauma [76]. The World Health Organization further recommends that the interpretation of diminished bone mass be based on bone density assessment by dual-energy x-ray absorptiometry (DEXA) [77]. Established osteoporosis is defined as a bone mineral density (BMD) greater than 2.5 standard deviations (SDs) below the mean value of peak bone mass in young normal women (T score of ⫺2.5 or lower; see discussion in Sec. III.D.1) plus the presence of fractures. Osteoporosis itself is defined as a BMD greater than 2.5 SD below the mean value of peak bone mass in young normal women (T score of ⫺2.5 or less), but without associated fractures. Osteopenia, or low bone mass, is defined as a BMD between 1 and 2.5 SD of the mean value peak bone mass in young women (T score between ⫺1 and ⫺2.5). Finally, normal bone mass is defined

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as a BMD not more than 1 SD below the mean value of peak bone mass in young normal women (T score ⫺1 or higher) [77]. Osteoporosis is one of the major long-term health risks associated with the menopause. In 1990, there were 1.66 million hip fractures worldwide, with 1,197,000 cases in women and 463,000 cases in men [78]. Hip fracture incidence appears to be race dependent, with a lifetime risk of hip fracture of 17.5% in white women, but only 5.6% in African American women. However, although hip fractures are much less common in non-whites, they remain a significant problem for all elderly women and men, regardless of race. By extreme old age, one of every three women and one of very six men will have a hip fracture. Of all hip fractures, 12% to 20% will be fatal, and 50% of survivors will be long-term nursing home bound, resulting in total annual costs of $6.1 billion in the United States [76,79]. 1. Pathophysiology The skeleton is made up of 20% trabecular bone and 80% cortical bone. Cortical bone predominates in the shafts of long bones, while trabecular bone occurs in the vertebrae, pelvic and other flat bones, and the ends of long bones. Trabecular bone not only has greater surface area, but also is more metabolically active than cortical bone and is quicker to respond to mineral and hormonal changes within the body [76]. After closure of the endochondral growth plate, bone mass increases by radial growth until age 30. After a transient period of stability, age-related bone loss begins. Over the course of a woman’s lifetime, she will lose 35% of her cortical bone and 50% of her trabecular bone, while men will lose only two thirds of this amount [76]. Cortical bone loss starts at age 40 in both men and women at a rate of 0.3 to 0.5% each year. In postmenopausal women, a phase of accelerated cortical bone loss occurs in the first year of menopause, with a rate of bone loss of 2% to 3%. This accelerated rate of loss then decreases exponentially over the next 8 to 10 years, to rejoin the slow rate of loss or stop altogether [76]. The pathophysiology of osteoporosis is based on a disruption of the boneremodeling unit coupling process. Bone density is dependent on the amount of bone resorption relative to the amount of bone formation. During normal bone remodeling (Fig. 3), small areas of bone, called bone remodeling units, are adhered to by osteoclasts, which then proceed to break down and remove bone using acidification and proteolytic digestion. Soon after the osteoclasts are done and have left the resorption site, osteoblasts invade the area and begin to form new bone by secreting osteoid (a matrix of collagen and other proteins), which is then mineralized to form new bone. Once bone formation is complete, lining cells consisting of terminally differentiated osteoblasts cover the surface of the bone [76,80]. In normal bone remodeling, bone resorption equals bone formation. In adults, 25% of trabecular bone and 3% of cortical bone is absorbed and replaced each year. [81]. Osteoporosis occurs when bone resorption by osteoclasts is greater than bone formation by osteoblasts. With menopause, an increase in osteoclast numbers results in increased rates of bone resorption and the formation of deeper resorption cavities. Despite normal bone formation, the deeper resorption cavities are inadequately filled by normally functioning osteoblasts. This is referred to as the early phase of bone loss in osteoporosis [81]. Later, with aging, a progressive decline in osteoblast numbers occurs in the face of normal osteoclast function and

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Figure 3 The stages of bone remodeling: (1) stable bone covered by terminally differentiated osteoblasts, called lining cells (LC); (2) pre-osteoclasts (POC) adhere to bone remodeling units; (3) osteoclasts (OC) breakdown bone contained in bone remodeling units via acidification and proteolytic digestion; (4) osteoclasts depart, leaving an empty resorption site; (5) osteoblasts (OB) aggregate and begin to lay down new bone by secreting osteoid. Osteoid is then remineralized to form new bone; (6) lining cells once again cover the surface of bone. (From Ref. 80.) increased total numbers. As a result, osteoblasts are unable to refill even normal depth resorption cavities, resulting in inadequate bone formation and subsequent loss of bone structure, connectivity, and strength with decreased BMD, referred to as the phase of late bone loss in osteoporosis development [81]. Bone loss associated with menopause or the discontinuation of estrogen replacement therapy (ERT) results from increased levels of the cytokines interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF), granulocyte-macrophage colony stimulating factor (GM-CSF), and prostaglandin E2. IL-1 and TNF are known stimulants of bone resorption and inhibitors of bone formation that act indirectly on osteoclasts and directly on osteoblasts. IL-6, M-CSF, and GM-CSF are induced by IL-1 and TNF and regulate the differentiation osteoclast precursor cells into mature osteoclasts [82]. The result is increased osteoclast activity with declining osteoblast activity. Consistent with this difference, bone loss associated with menopause occurs primarily in trabecular bone, while the slow progressive bone loss consistent with aging occurs primarily in cortical bone [81]. As a result, two distinct fracture patterns occur. In postmenopausal women, fractures occur mostly

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in trabecular bone, such as the distal forearm (Colles’ fracture) and vertebrae. The incidence of trabecular bone fractures increases markedly after menopause. In contrast, the incidence of fracture in areas containing equal amounts of cortical and trabecular bone, such as the humerus, proximal tibia, and pelvis, increases slowly with age until late in life, when it increases exponentially [83]. Causes of bone loss are thought to be multifactorial. The most important causes have been identified as low bone density, trauma, inadequate peak bone mass, increased bone loss, and other secondary or miscellaneous causes [83]. Decreased bone mass is by far the most important causative factor of osteoporosis. However, trauma is another important risk factor for fracture. The most common cause of fracture in the elderly is a simple fall from standing height or lower [83]. Inadequate peak bone mass explains the racial and sexual stratification of fracture incidence, with women having lighter skeletons than men, and white and Asian women having lighter skeletons than African American women. Other factors associated with aging include decrease in intestinal calcium absorption, often paired with poor dietary intake of calcium, and decreased function of the renal enzyme 25-hydroxyvitamin D [25(OH)D] 1-α-hydroxylase, which converts 25(OD)H to 1,25(OH)2D3. Decreased serum levels of 25(OH)D are also noted with aging, secondary to decreased absorption and dermal synthesis from solar exposure of vitamin D. Consistent with increased bone loss, the accelerated osteoclast function noted with menopause also may play a role. Finally, other related risk factors for osteoporosis include family history, low body weight, inactivity, excessive glucocorticoid use or Cushing’s syndrome, osteomalacia, long-term heparin therapy, multiple myeloma, long-term anticonvulsant use, hyperthyroidism, hepatobiliary disease, excessive caffeine intake, smoking, heavy alcohol use, and type I diabetes mellitus [83,84]. For determination of BMD and bone mass at the HIP and spine, DEXA is the gold standard. DEXA utilizes transmission of two energy beams passed through bone and then comparison is made to a standardized control. This method is highly accurate, precise, and widely available. Several other techniques also exist to determine BMD, but they are limited by cost, radiation exposure, and accuracy of different sites of BMD evaluation in reflecting total body BMD. All test methods calculate a T score, which is a comparison of the patient’s BMD relative to a young healthy woman (mean ⫽ 0). A T score of ⫺2.0 is 2 SDs below this mean and is designated as the threshold for increased fracture risk [85]. Although measurement of BMD can be a useful clinical tool for treating patients with or at risk for osteoporosis, it is not a general screening tool [86]. The Society for Clinical Densitometry has described BMD measurements as an important tool to predict risk of future fractures, and that it should be used widely in at-risk patients [85]. Presently, indications for bone mass measurement include (1) presence of risk factors for osteoporosis; (2) evidence of vertebral deformity; (3) history of fragility fracture of hip, spine, or wrist; (4) monitoring of therapy; and (5) determination of need for preventive treatment [85]. Biochemical markers of bone metabolism that reflect bone formation or breakdown may be useful in the clinical treatment of patients with osteoporosis. These markers can be differentiated as indicators of bone formation and those of bone resorption. The three principal markers of bone formation are alkaline phosphatase, osteocalcin, and procollagen I carboxy peptide (PCIP).

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Alkaline phosphatase is an enzyme localized in the membranes of osteoblasts and released into the serum; therefore, it is directly measurable. Four different isozymes of this enzyme exist, but the most common are the liver or bone isoforms. Serum alkaline phosphatase is a commonly used enzyme for monitoring both liver function and bone mineralization. The largest increases in the bone isoform are secondary to conditions associated with increased bone mineralization, although bone demineralization may also cause an increase in the serum level. Osteocalcin (bone gla protein, BGP) is a small protein found in the extracellular matrix of bone bound to hydroxyapatite and released into the serum with bone formation. The precise function of osteocalcin is unknown, but serum levels have been noted to decrease with menopause and return to normal once hormone replacement therapy is instituted. PCIP is a precursor of type I collagen with bone matrix. The rate of synthesis of type I collagen can be determined by measuring the concentration of PCIP. However, the usefulness of determinations of PCIP levels has not been determined [87]. Markers of bone resorption include hypoxyproline, hydroxylysine glycosides, collagen cross-link molecules, and N-telopeptide. Hydroxyproline is found mainly in collagen, making up 13% of the amino acid content of collagen. Of the body’s collagen, 50% is located in bone. On breakdown of collagen into the free amino acids it contains, the amino acids are excreted by the kidneys in urine and later reabsorbed by the liver. Despite the ease of measuring urine hydroxyproline levels, the lack of specificity of tissue origin makes this measurement a poor indicator of bone turnover. Hydroxylysine glycosides are also found in collagenlike molecules, are excreted in urine, and offer potential use as an indicator of bone resorption. Collagen crossline molecules consist mainly of pyridinoline and deoxypyridinoline, which form covalent crosslinks between adjacent collagen chains, thereby stabilizing the extracellular matrix. Pyridinoline is mainly present in cartilage, while deoypyridinoline is found in bone collagen. On disruption of these crosslinks during osteoclast degradation, these compounds are released and excreted in urine. No assay is available at this time to measure urinary levels of these substances. The NTx (N-telopeptide assay) is a newer technique to assess bone resorption by measurement of the N-terminal end of the cross-linked collagen peptides in urine utilizing enzyme-linked radioimmunoassay. Levels of NTx appear to correlate well with bone resorption, and commercially available assays make this a useful new tool to monitor responses to osteoporosis treatment [87,88]. BMD measurements have proven to be useful predictors for risk of fracture. Melton et al. [85] utilized BMD measurements of five different areas, including the lumbar spine, cervical and intertrochanteric regions of the right proximal femur, and distal and middle radius, to demonstrate a moderate predictive value for osteoporosis-associated fracture risk for 8 to 10 years. This study emphasized the value of BMD measurement at multiple site to predict fracture risk and determine baseline BMD [85]. Steiger et al. [89] demonstrated the strong correlation between age and bone mass with measurements of bone density at Ward’s triangle and the calcaneous on DEXA scan to be superior to those at the spine in reflecting

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overall bone mass to determine risk of fracture. Cummings et al. [90] demonstrated BMD at the femoral neck to be a better predictor than at the spine, radius, and calcaneus for risk of hip fracture. Rizzoli et al. [91] compared DEXA scans of femoral neck and spinal BMD and found femoral neck BMD to be a significantly better predictor of fracture risk of the proximal femur/hip. Hans et al. [92] found the combination of ultrasound of the calcaneous and DEXA scan of the hip to be a significantly better predictor of proximal femur fracture risk than conventional anterosposterior spinal measurements of BMD [93,94]. Thus, despite the wide array of possible sites of BMD determination, measurements of BMD at the femoral neck and spine are still considered the gold standard. 2. Prevention/Treatment Estrogen. Once osteoporosis is recognized, interventions must focus on the prevention of further bone loss, increasing bone mass, and reducing future fracture risk. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial [95] was one of the first long-term, multicenter, prospective, double-blind, placebo-controlled studies to examine the effects of hormone therapy on coronary heart disease risk factors and BMD at the spine and hip in postmenopausal women. The PEPI Trial utilized a group of 875 healthy postmenopausal women between the ages of 45 and 64 years. They were assigned to several different hormonal treatment regimens, including (1) placebo; (2) 0.625 mg/day conjugated equine estrogens (CEE) only; (3) 0.625 mg/day CEE plus 10 mg/day cyclic medroxyprogesterone acetate (MPA) on days 1 through 12; (4) 0.625 mg/day CEE plus continuous MPA 2.5 mg/day; and (5) 0.625 mg/day CEE plus 200 mg/day cyclic micronized progesterone (MP) on days 1 through 12. All medications were taken orally, and BMDs at the hip and lumbar spine of all patients were determined using DEXA scanning at baseline, 12 months, and 36 months. Calcium intake was divided into low-, moderate-, and high-intake groups. Results of the PEPI Trial demonstrate the importance of estrogen therapy in the prevention of further BMD loss (Fig. 4). At 36 months, all patients taking any active hormonal regimen were noted to have a 3.5% to 5.0% higher spinal BMD than at baseline, while members of the placebo group had an average 1.8% loss (0.6% per year) in spinal BMD over the 3-year period. Changes in hip BMD also demonstrated increases (1.7%) in women taking any hormonal regimen over patients receiving placebo (⫺1.7%), although no individual regimen demonstrated significantly better outcomes. On separation of the participants into those 45 to 55 years old and those 55 to 64 years old, the younger group taking the placebo was noted to have significantly greater BMD losses from the spine (⫺4.0%) and hip (⫺3.0%) than older women taking the placebo (⫺2.0% and ⫺1.6%, respectively). Older women taking the hormonal regimen gained significantly more BMD in the spine (5.9%) and hip (2.6%) than younger women (3.9% and 2.0%, respectively). Among women taking the placebo, smokers lost more hip BMD (⫺3.5%) than nonsmokers (⫺1.9%), and women with the highest calcium intake had significantly less spinal BMD loss (⫺1.8%) than women with moderate calcium intake (⫺3.6%). In addition, thin women taking the placebo lost significantly more spinal bone (⫺4.7%) than heavier women (⫺1.4%). Participants with the lowest baseline BMD taking any hormone therapy had the greatest gain in spine and hip BMD (6.2% and 2.8%, respec-

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Figure 4 Unadjusted mean percent change in bone mineral density at the spine (left) and hip (right) by treatment assignment and visit in compliant PEPI Trial participants, consisting of those receiving: (1) placebo; (2) conjugated equine estrogen (CEE) 0.625 mg/day; (3) CEE 0.625 mg/day and medroxyprogesterone acetate (MPA) 10 mg/day on days 1 through 12 of each month; (4) CEE 0.625 mg/day and MPA 2.5 mg/day daily; and (5) CEE 0.625 mg/ day and micronized progesterone (MP) 200 mg/day on days 1 through 12. (From Ref. 95.)

tively) than women with the highest BMD at entry (3.9% and 1.9%, respectively). In examination of those who ever used hormones, recent hormone users taking a placebo lost significantly more BMD from the spine and hip (⫺5.3% and ⫺3.9%, respectively). No difference in fracture risk or fracture occurrence was seen between the placebo and treatment groups. The results of the PEPI Trial illustrate several key points in the treatment of osteoporosis and prevention of fractures and BMD loss. A regimen of continuous MPA with CEE was superior to CEE alone or CEE with cyclic MPA or MP. Consistent with the faster bone turnover rates in trabecular bone, spine BMD showed more significant changes with hormonal therapy. One of the most significant findings was the slower rate of bone loss in older women taking a placebo, but greater increase in BMD in older women taking hormonal therapy. The PEPI Trial confirmed the increased rates of bone loss in smokers, thin women, and women with baseline low BMD. Overall, the PEPI Trial confirmed the benefit of hormone replacement therapy (HRT) for the prevention of bone loss [95]. Further studies have examined not only the minimum dose of estrogen needed to prevent bone loss, but also have compared the efficacy with different routes of administration. Ettinger et al. [97] confirmed the beneficial effects of 0.625 mg/day CEE on BMD and demonstrated an equivalent effect of 1.0 mg/ day micronized estradiol for the prevention of further loss of BMD. However, Ettinger et al. [98] also demonstrated some beneficial effects of 0.3 mg/day CEE in conjunction with 1500 mg calcium daily to prevent further BMD loss, but this treatment did not have any statistically significant positive effects on BMD. Other studies have examined the efficacy of transdermal 17B-estradiol for HRT and treatment of osteoporosis. Field et al. [99], in a 2-year randomized, dou-

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ble-blind, placebo-controlled study, demonstrated comparable maintenance and gain of bone mass in the lumbar spine with 0.625 mg/day oral CEE versus 0.05 mg/day transdermal 17B-estradiol. These findings suggest the comparable efficacy of different routes of estrogen delivery in the treatment of osteoporosis. Selective Estrogen Receptor Modulators. Selective estrogen receptor modulators (SERMs) are an attractive alternative to estrogen for the treatment of postmenopausal osteoporosis. Raloxifene and tamoxifen are two of the best-known and most studied SERMs. As a group, SERMs are characterized by their high affinity for estrogen receptors, comparable to that of estrogen itself [100]. However, unlike estrogen, SERMs exert mixed effects in different tissues. Some SERMs have potent estrogen agonist effects in some tissues, while exerting estrogen antagonist effects in others [101]. This differential effect can be explained by the high affinity of SERMs to estrogen receptors, resulting in competition with endogenous estrogens for binding to estrogen receptors [102]. Once bound to the estrogen receptor, SERMs may either activate or block estrogen action, mediated by SERM-specific effects on the ligand (SERM versus estrogen), receptor, and the effector site [102]. However, the exact mechanism by which SERMs effect their mixed agonist and antagonist effects has yet to be elucidated. Tamoxifen is a well-known SERM that has been used for many years as an effective adjuvant therapy for breast cancer, this use is based on its antiestrogenic effects in the breast [102]. However, tamoxifen has been shown to have estrogen agonistic effects on bone, lipid profiles, and endometrial tissues [103,104]. Secondary to this, tamoxifen use is associated with improved bone mass and cholesterol profiles, as well as stimulation of the endometrium and increased risk of endometrial hyperplasia and cancer in postmenopausal women [105]. In contrast to other SERMS, raloxifene has a unique mixed agonist-antagonist profile that makes it particularly useful for the treatment of osteoporosis. Raloxifene has been shown to have solely estrogen antagonist effects in the breast and endometrium, but has estrogen agonist effects in bone and on lipid profiles [106]. Thus, raloxifene has all of the beneficial effects of estrogen on bone and lipids without increasing the risk for endometrial hyperplasia and stimulation of breast cells. In the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, Ettinger et al. [107] examined the effects of raloxifene on bone density and fracture risk in postmenopausal women with osteoporsis. Utilizing baseline DEXA scans and follow-up scans at 24 and 36 months and a 60 mg/day or 120 mg/day raloxifene dose, Ettinger et al., via a prospective randomized, blinded trial, demonstrated beneficial effects on vertebral bone density and fracture rates with raloxifene treatment (Fig. 5). Women treated with raloxifene 60 mg/day and 120 mg/day demonstrated 2.1% and 2.4% increases in bone density in the femoral neck and 2.6% and 2.7% increases in bone density in the spine, respectively, after 2 years of treatment with raloxifene compared to placebo-treated controls. Furthermore, women treated with raloxifene 60 mg/day and 120 mg/day demonstrated relative risks of 0.7 and 0.5, respectively, for new vertebral fracture compared to controls. Interestingly, women treated with raloxifene had a lower incidence of breast cancer during this study, but an increased risk of venous thromboembolism was noted. Delmas et al. [108] examined the effects of raloxifene on serum lipid profiles.

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Figure 5 Reduction in new vertebral fracture rates among participants in the Multiple Outcomes of Raloxifene Evaluation (MORE), separated by those with and without preexisting vertebral fractures at the beginning of the study. RR indicates relative risk; CI indicates confidence interval. (From Ref. 107.) In women treated with 60 mg/day of raloxifene, a marked decrease in total cholesterol levels and low-density lipoprotein (LDL) was noted, with a minimal reduction in high-density lipoprotein (HDL) levels. Specific effects of raloxifene on the endometrium were examined by Cohen et al. [109], who found no difference in endometrial thickness between postmenopausal women less than 60 years old and women treated with raloxifene 60 mg/day or placebo for 3 years. Similar findings were noted by Delmas et al. [108] in women treated with raloxifene for two years versus placebo treatment. These studies illustrate the antiestrogenic effects of raloxifene on endometrial tissue and its safety for use in postmenopausal women. Thus, the findings of the MORE trial and other recent studies illustrate the utility of raloxifene in the treatment of osteoporosis without the increased risk of breast cancer or endometrial hyperplasia and cancer associated with estrogen replacement use. Bisphosphonates. Bisphosphonates are potent inhibitors of bone resorption that are currently being utilized in the treatment of osteoporosis [110]. Bisphosphonates are carbon-substituted synthetic analogues of pyrophosphates that exert a direct inhibitory effect on mature osteoclasts, thereby preventing bone resorption and osteoclast recruitment [110,111]. One mechanism by which bisphosphonates act is via their high affinity for hydroxyapatite crystals in bone, unlike pyrophosphates, thereby making them resistant to enzymatic hydrolysis by osteoclasts. As a result, bisphosphonates remain strongly bound to hydroxyapatite crystals, the

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primary sites of bone remodeling, thereby allowing them to influence bone formation and resorption through an unclear process, but one that is believed to act primarily on osteoclasts or their precursors [112,113]. The result is an alteration of the process of bone resorption and bone formation secondary to bisphosphonates and their effects. Among the bisphosphonates, alendronate is the best studied. However, alendronate has low bioavailability, ranging from 1.5% to 3.5%, explaining the importance of taking this medication on an empty stomach with no liquid other than water and of separating it from calcium supplements by at least 2 h due to very poor absorption following oral ingestion [112–116]. Multiple clinical trials have demonstrated the utility of bisphosphonates in the treatment of osteoporosis utilizing a variety of treatment regimens. McClung et al. [117] examined the effects of 3 years of treatment with alendronate doses of 5, 10, and 20 mg/day on BMD at the lumbar spine, femoral neck, and trochanter in a double-blind, randomized controlled trial in women without osteoporosis. In this study, alendronate was found to decrease bone resorption markedly within 3 months and to decrease markers of bone formation within 6 to 12 months, with persistently normal bone quality. BMD increased by 1% to 4% at all sites examined in patients treated with alendronate, while a BMD loss of 2% to 4% was noted in placebo-treated controls. These findings were supported by a later study by Ravn et al. [118], who looked at the effects of 4 years of treatment with alendronate 5 mg/day or 2.5 mg/day versus placebo or estrogen plus progesterone. They found that 4 years of treatment with both alendronate 5 mg/day or estrogen-medroxyprogesterone resulted in equivalent increase in bone mass. Further studies have explored the significance of dosing frequency by examining the benefits of once-weekly alendronate dosing for potential improvement of tolerance without compromising efficacy. Bone et al. [110] suggested that, based on the knowledge that osteoclasts reabsorb exposed mineralized tissue over approximately 2 weeks at each resorption site, while remineralization of an osteoblast-refilled resorption site takes 1 to 2 weeks. Once bound to bone surface, alendronate has an elimination half-life of several weeks [120]. Bisphosphonates dosed at 2-week intervals had previously been shown to increase BMD in animal models of osteoporosis [121]. This knowledge, combined with the fact that turnover of the esophageal mucosa occurs approximately every 5 days, suggested the efficacy of once-a-week alendronate dosing, thereby minimizing injury to esophageal mucosa induced by gastric acid. Rossini et al. [122] compared the effects on BMD of dosing regimens of 20 mg/week (weekly alendronate group) and 10 mg/day for 1 month of 3 months (cyclic alendronate group) in otherwise healthy postmenopausal women. After 1 year, a significantly increased BMD was noted in both groups at the spine (2.2 and 2.5, respectively) and at the femoral neck (1.6 and 1.5, respectively). Schnitzer et al. [123] compared the efficacy of oral alendronate dosing (70 mg once a week, 35 mg twice a week, and 10 mg daily) in a double-blind study of postmenopausal women aged 42 to 95 years old. Increased in BMD at the total hip, femoral neck, trochanter, and total body were similar for all three dosing regimens after 12 months of therapy. Increased lumbar spine BMD in the group who received the 70 mg weekly dose was 5.1% (95% confidence interval [CI] 4.8 to 5.6) compared to 5.4% (95% CI 5.0 to 5.8) in the grouped dosed at 10 mg daily. Overall, both the daily and weekly treatment regimens demonstrated significant

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increases in BMD, but with fewer serious upper gastrointestinal adverse experiences among those patients receiving the weekly dosing regimen. Thus, alendronate at a dose of 70 mg a week is an effective new alternative treatment for osteoporosis for patients for whom estrogen therapy is not an option. HRT can be safely given in conjunction with bisphosphonate therapy, with some cumulative effect seen in the spine BMD, but not the hip BMD [124,125]. Other Treatments. Calcitonin is another agent that can be used to prevent osteoporosis; it acts by inhibition of the resorptive activity of osteoclasts. Calcitonin appears to maintain or increase bone density at the spine, with an increase of about 1–2%. However, there is less evidence to determine the effectivenesss of bone density in the hip. With regard to fractures, there appears to be about a 75% reduction in vertebral fractures over a 2-year treatment period, but no confirming controlled trials are available to show fracture prevention in the hip at this time. Calcintonin can be given as an intranasal spray at a dose of 200 IU/day [126,127]. Sodium fluoride has also been shown to increase bone density. Studies that examined the efficacy of fluoride therapy demonstrated increased cancellous bone, but decreased cortical bone mineral density and increased skeletal fragility with 75 mg fluoride and 1500 mg calcium daily [128]. In addition to the gastric mucosa irritation and ulcers noted with high-dose fluoride, a potentially increased fracture rate associated with increased skeletal fragility suggested that high-dose fluoride would be a poor choice for the treatment of osteoporosis. In contrast, Pak et al. [129] examined the benefits and safety of 25 mg slow-release fluoride with 400 mg calcium twice daily for 4 years and found inhibition of new, but not recurrent, fractures and increased spinal and femoral bone mass. The use of slow-release and lower dose fluoride was better tolerated and avoided the gastric complications of fluoride therapy, suggesting the utility of fluoride given in this manner for the treatment of osteoporosis. The use of fluoride might be expected to reduce the vertebral fracture rate by about 50%, but the effectiveness in preventing other types of fractures is unknown. It is recommended that patients receiving sodium fluoride receive adequate intake of vitamin D and calcium to ensure normal bone mineralization. Calcium alone has also been investigated as a possible agent in the prevention of bone loss. Riis et al. [130], using both SPA and DPA, demonstrated that when compared to 17-β-estradiol, patients taking either placebo or oral calcium at a dosage of 2000 mg/day showed a significant loss of bone. Ettinger et al. [98] found that a lower dose of estrogen (0.3 mg of conjugated estrogens) was effective in preventing bone loss when combined with increased calcium intake (1500 mg/ day). In older women, there may be up to a 10% decrease in fracture rates compared to placebo. It is generally recommended that postmenopausal women receiving estrogen have a dietary calcium intake of 1200 mg/day in addition to more specific therapy. E.

Cardiovascular Disease

Cardiovascular disease is the leading cause of death in women over the age of 50 years in the United States [131]. Before the age of menopause, cardiovascular disease occurs predominantly in males in a 3:1 ratio [132]. However, after menopause and the subsequent decline in estrogen levels with the loss of ovarian func-

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tion, the rate of cardiovascular disease in women increases until it eventually equalizes with that of men by age 70. The risk associated with loss of ovarian function is further illustrated in the increased incidence of cardiovascular disease in women undergoing menopause prematurely (including ovarian failure and surgical menopause) with no continued estrogen supplementation [132]. Estrogen replacement therapy has been shown by numerous studies to be significantly cardioprotective and to protect postmenopausal women from the cardiac disease that plagues estrogen-deficient men and women. To understand the full effect of estrogen therapy, we can divide its cardioprotective effects into three types: (1) alteration of lipid profile, (2) endothelial effects, and (3) systemic effects [133]. 1. Lipids Of the many benefits of estrogen replacement therapy, alteration of lipid profile is a key element of estrogen’s preventive effects on cardiovascular disease. As demonstrated by the PEPI Trial, the cardioprotective effects of estrogen are significantly mediated through its positive effects on lipid profile [134] (Table 2). Estrogen replacement therapy has been shown to decrease total cholesterol, decrease LDL, decrease lipoprotein A [Lp(a)], decrease LDL oxidation, and increase HDL levels. Favorable lipid effects have been noted with both oral estrogen and estrogen patches. Thus, regardless of the form of hormone replacement therapy used, beneficial alteration of the lipid profile remains an important benefit. Bush and Miller [135] performed an extensive review of the literature and found an average increase of 10% in HDL and a 4% decrease in LDL levels among postmenopausal women taking 0.625 mg of estrogen daily. Walsh et al. [136] found even more impressive changes with oral estrogen treatment, with an average HDL increase of 16% and LDL decrease of 15%. The significance of these changes can be understood on noting that a 1 mg/dL increase in HDL is associated Table 2 Distribution of Baseline Primary and Selected Secondary Outcome Measures in PEPI Trial Participants Randomized to the Different Treatment Arms

Source: Ref. 134.

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with an approximately 3% decrease in risk of coronary artery disease. A 1 mg/ dL decrease in LDL is associated with a 2% decrease in cardiovascular risk [137]. Gruchow et al. [138] examined cholesterol profiles of women presenting for angiography and found a strong statistical correlation between estrogen use and lower degrees of coronary stenosis. The addition of HDL levels to the statistical analysis resulted in more significant findings, suggesting that increased levels of HDL are an important mechanism of estrogen-related cardiac benefits. However, studies by Bush et al. [139], although finding similar results short term, found that after long-term follow-up, the HDL effect was only a moderate portion of the reduced risk of cardiovascular disease among estrogen users. Their findings suggest that only about a quarter of estrogen’s cardioprotective effects are based on increased HDL levels. Other studies have specifically examined the significance of decreased levels of LDL on cardiovascular disease resulting from estrogen therapy. Wagner et al. [140] performed prospective randomized studies of ovariectomized monkeys fed an atherogenic diet. They noted that the monkeys treated with estrogen had a 70% reduction in LDL uptake and products of LDL degradation in coronary arteries compared to those receiving placebo, despite no significant differences in plasma lipid profiles between the two groups. Thus, estrogen reduces atherosclerosis by preventing the oxidation of LDL, thus diminishing the formation of atherosclerotic lesions. Another study by Wagner et al. [141] further demonstrated that the decreased accumulation and metabolism of LDL with estrogen treatment was specific to the arterial system and did not occur in the liver or other peripheral tissues. In this study, arterial LDL metabolism was more active (per gram of tissue) in the coronary arteries and carotid bifurcation, suggesting that increased LDL metabolism accounts for less atherosclerotic disease in these vessels. This theory was demonstrated by Sack et al. [142], who demonstrated that estrogen therapy reduced the susceptibility of LDL to oxidation, resulting in a 16% prolongation of lag time of LDL oxidation after 3 weeks of therapy in women. This resistance to oxidation was lost on stopping estrogen therapy. Level of Lp(a) is another important independent risk factor for cardiovascular disease found to be affected by estrogen therapy. Elevated Lp(a) levels have been demonstrated in many studies on male cardiovascular health to be a significant risk for cardiac disease, but not to be affected by any of the lipid-lowering medication currently available. However, estrogen and progesterone have been found to lower Lp(a) levels. Shlipak et al. [143] examined participants in the Heart and Estrogen/Progestin Replacement Study (HERS), a randomized, blind, placebo-controlled secondary prevention trial and examined Lp(a) levels of participants and their cardiovascular outcomes. This study demonstrated that, in women with an elevated baseline Lp(a) level and a history of previous coronary heart disease, estrogen and progesterone replacement decreased Lp(a) levels and decreased the risk for recurrent cardiac events. Thus, decreased levels of Lp(a) may be another beneficial component in the overall favorable affects of estrogen on cardiovascular health. Positive effects on lipids can be obtained with a variety of estrogen dosing routes and formulations. Ottosson et al. [144] demonstrated the effect of estrogen on HDL to be independent of the form of estrogen used. Women receiving daily

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parenteral ethinyl estradiol were noted to have a 1.5 to 2.5 times greater increase in HDL levels than those receiving a comparable dose of parenteral estradiol valerate, although both treatments resulted in satisfactory increases in HDL levels and overall lipid profile. Barnes et al. [145] also found favorable effects of lipids with a 0.625 dose of parenteral conjugated estrogen. However, in some patients (i.e., patients with a history of cirrhosis), it would be preferable to avoid the potential hepatic side effects encountered with oral therapy. In these patients, transdermal estrogen is a good choice, thereby illustrating the need to consider side-effect profiles in the care of each individual patient. Stanczyk et al. [146] demonstrated both 50-mg subdermal pellets and 0.1-mg transdermal patches to have favorable effects on lipid profiles after 6 months of therapy, while avoiding first-pass liver effects. These findings were reinforced by Jensen et al. [147], who found favorable effects with percutaneous estrogens. Thus, the choice between oral or transdermal estrogen must be based on an individual patient’s medical history as well as patient preference, but all current forms of estrogen therapy appear to affect lipid profiles positively. 2. Lipids and Progestin Use Despite the beneficial effects of estrogen, the direct correlation between unopposed estrogen to the development of endometrial hyperplasia and endometrial carcinoma requires the use of a progestin with estrogen replacement in all nonhysterectomized women, despite progesterone’s negative effects on lipid profiles. The addition of a progestin to ERT has been shown to reduce the risk of endometrial hyperplasia and carcinoma significantly by preventing estrogen overstimulation of the endometrium. In general, the combination of a progestin and estrogen diminishes the degree of the estrogen-stimulated rise in HDL, but does not affect the concurrent decline in LDL level. Ottosson et al. [148] examined the effects of different progestin forms on lipid profiles. Comparing levonorgestrel, MPA, and natural MP, they found a significant decrease in total HDL levels, specifically in subfraction 2 of HDL levels in patients treated with progesterone. No change in the third subfraction of HDL was noted, and a beneficial decrease in apolipoprotein A1 was noted. Similar lipid effects were found when levonorgestrel and MPA were compared. In contrast, natural MP had no influence on HDL levels or any of its subfractions, suggesting that this form of progestin may be a valuable future alternative to currently available medications. Barnes et al. [145] compared the effects of depo-medroxyprogesterone acetate versus conjugated estrogen therapy in postmenopausal women. After 1 year of therapy with estrogen or progesterone, similar declines in total cholesterol and LDL levels were noted in the progesterone-treated group compared to the estrogen-treated group. The only notable difference between the two groups was an absence of elevation in HDL in the progesterone-treated group. Thus, despite its lack of effect on HDL, progesterone alone still offers the important benefits of decreased total cholesterol and LDL. However, despite its beneficial effects on total cholesterol and LDL, the decrease in HDL associated with progesterone must be accepted to avoid the risk of endometrial hyperplasia and possible carcinoma that may occur in patients with intact uteri undergoing unopposed estrogen therapy.

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3. Endothelial Effects Significant changes in the vascular endothelium are an important component of the cardioprotective effects of estrogen therapy. Coronary angiography offers an accessible and quantitative measure of the preventive effects of atherosclerosis and vasoconstriction mediated by estrogen replacement. Factors affecting the formation of coronary plaques include (1) increases in LDL oxidation and uptake; (2) increases in insulin levels, endothelin levels, thromboxane levels, adhesion molecules, and various cytokines; (3) decreases in nitric oxide and PGI2 [133]. Estrogen has been demonstrated to directly inhibit the formation of atherosclerotic plaques through its endothelial effects, including increasing nitric oxide levels, decreasing endothelin, increasing prostacyclin (PGI2), decreasing thromboxane A2, decreasing adhesion molecules, and decreasing cytokine levels [133]. As a result, significantly decreased levels of atherosclerosis, coronary artery stenosis, and arterial spasm are noted in estrogen-treated postmenopausal women. Vasodilation. Estrogen receptors are present in the muscularis of arteries, explaining the beneficial effects of estrogen treatment on blood flow in multiple different studies. Orimo et al. [149] demonstrated by Northern blot analysis the presence of estrogen receptor protein and mRNA in the vascular smooth muscle cells obtained from rat aorta. The presence of estrogen receptors in vascular smooth muscle was further supported by Williams et al. [150], who demonstrated significant arterial constriction on infusion of acetylcholine (Ach) in the coronary arteries of ovariectomized monkeys not receiving replacement. In contrast, monkeys receiving estrogen replacement therapy not only showed no sign of vasoconstriction following acetylcholine administration, but also demonstrated minimal vasodilation. Consistent with this, decreased systemic vascular resistance was noted in ewes after estrogen administration by Magness et al. [151]. Mugge et al. [152] demonstrated an approximately 18% direct relaxant effect, 40 min after estrogen administration to coronary artery rings of explanted hearts. Gilligan et al. [153] infused coronary arteries of postmenopausal women with acetylcholine and demonstrated prevention of arterial constriction, increased coronary blood flow, and decreased coronary resistance in women receiving estrogen therapy. Doppler echocardiography of the aorta of postmenopausal women by Pines et al. [154] found marked improvement of central and peripheral hemodynamic parameters (i.e., peak flow velocity, mean ejection time) after 2.5 months of estrogen use compared to controls treated with a placebo. Similar results were noted in carotid arteries after transdermal estrogen therapy for 9 weeks by Gangar et al. [155]. The beneficial effects on vasodilation were further illustrated by Rosano et al. [156], who noted improved treadmill time and decreased symptoms in women with coronary artery disease after they received estrogen. The protective effects of estrogen on the coronary vasculature are mediated primarily through endothelial effects, specifically endothelium-dependent vasodilation. Gilligan et al. [157] demonstrated the potentiation of forearm vessel vasodilation with acetylcholine administration in women treated with intravenous 17B-estradiol. Women with risk factors for vascular dysfunction were noted to have significantly decreased responses to acetylcholine when not

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also receiving estrogen. This difference in effect demonstrated the potentiation of endothelium-dependent vasodilation by estradiol administration. Gerhard et al. [158] demonstrated similar favorable effects on endothelium-derived vasodilation with estrogen administration via oral and transdermal routes. No attentuation of this effect was noted with the addition of MP. This improvement in vasodilation is mediated, in part, through increased availability of endothelium-derived nitric oxide. Nitric oxide acts to inhibit platelet aggregation, synthesize monocyte chemotactic factors, and reduce vascular smooth muscle cell proliferation [158]. Wilcox et al. [159] demonstrated decreased levels of plasma endothelin-1, a potent vasoconstrictor, independent of route of administration of estrogen. Decreased endothelin levels in women treated with estrogen is thought to be another key factor in the multifactorial effects of estrogen on decreasing coronary artery disease (CAD) in postmenopausal women. A further study by Mikkola et al. [160] demonstrated elevated PGI2 levels in vascular endothelial cells treated with estrogen. In this study, administration of 17B-estradiol was noted to cause a 26% to 66% increase in PGI2 levels in endothelial cells, resulting in vasodilation and antiplatelet aggregation effects. Other studies have demonstrated decreased levels of thromboxane A2, decreased adhesion molecules, and decreased cytokines to be additional important factors in the estrogen-mediated vasodilatory effect of coronary arteries. Thus, an important aspect of estrogen’s cardioprotective effects is its effect on the vascular endothelium, specifically its ability to restore normal coronary vasomotor responses to acetylcholine and increase coronary blood flow via vasodilation. Inhibition of Atherosclerosis. Angiographic studies further prove the significant effect of estrogen on the development of CAD. Hong et al. [161] examined lipid profiles and estrogen use in women undergoing coronary angiography. They not only found a higher mean HDL and lower total/HDL cholesterol ratio in women receiving estrogen, but also noted a 87% reduction in the angiographic prevalence of CAD among women on ERT. These findings have been supported by several other authors, all noting a significant reduction in the angiographic prevalence of CAD in women receiving estrogen therapy [162,163]. Sullivan et al. [163] examined the effects of estrogen replacement in women with established CAD (defined as 70% or greater reduction in luminal diameter of one or more epicardial vessels) compared to controls with no stenosis. Retrospectively examining the use of estrogen, Sullivan et al. [163] demonstrated an odds ratio for the risk of CAD for estrogen users compared to nonusers of 0.44 (P ⬍ .037), after adjustment for age, smoking, cholesterol, and hypertension. Gruchow et al. [162] similarly found an age-adjusted odds ratio of 0.59 (P ⬍ 0.001) for postmenopausal estrogen users among women with moderate to severe occlusion of the coronary arteries. Herrington et al. [164] directly measured angiographic changes with acetylcholine administration in those with exertional angina taking and not taking estrogen. Women taking estrogen were noted to have vasodilatory responses to acetylcholine and nitroglycerin infusion. These findings indicate a statistically significant protective effect of estrogen use on the development of CAD.

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4. Systemic Effects Inhibition of Clotting. The last important area of estrogen effect on cardiovascular health is systemic changes, including arterial clotting and insulin sensitivity. Inhibition of arterial clotting is an important systemic effect of estrogen and is primarily mediated through (1) decreased fibrinogen levels, (2) decreased plasminogenactivator inhibitor type 1 (PAI-1), and (3) decreased Lp(a) levels [133]. Fibrinogen is an important component of the clotting cascade and the characteristics of blood flow. This topic was examined by Kannel et al. [165] utilizing data from the Framingham study. The Framingham study included both men and women; it had 3595 subjects and prospectively examined the health status of these individuals over 12 years. Of the total cohort, 1499 had fibrinogen levels evaluated and compared to their incidence of cardiovascular disease. In this study, an elevated fibrinogen level was found to be significantly related to the incidence of cardiovascular disease in both men and women. The average fibrinogen level was 2.9 g/L, with a rise of 1.0 g/L noted with each decade of life and consistently higher levels seen in women than in men. Fibrinogen is directly related to atheroma formation and atherosclerotic disease via thrombotic effects. In addition, the authors suggested that fibrinogen-induced platelet aggregation causes increased blood viscosity, thereby promoting clot and atheroma formation. Examination of the effects of estrogen on fibrinogen levels was performed in the PEPI Trial [166]. This study found significantly decreased fibrinogen levels in those receiving any combination of estrogen with or without a progestin, with no significant difference between the different regimens of HRT used. In contrast, fibrinogen levels of placebo-treated patients increased. Thus, a decreased fibrinogen level is an important aspect of the favorable cardiovascular effects of estrogen. PAI-1 is an important inhibitor of fibrinolysis, thereby promoting clot and atheroma formation. PAI-1 has been shown to inhibit tissue plasminogen activator and urokinase plasminogen activator in endothelial and smooth muscle cells [167]. Increased levels of PAI-1 have been noted in atheromatous arteries [168]. A strong correlation has been noted between elevated PAI-1 levels and higher risk for atherosclerotic disease [169,170]. Koh et al. [171] examined the effects of estrogen on PAI-1, insulin, and Lp(a) levels. They demonstrated reduced mean plasma levels of PAI-1 with both estrogen alone and estrogen with MPA, with a 50% reduction seen in both hormone replacement gorups. In contrast, transdermal estrogen did not alter PAI-1 levels. Thus, PAI-1 levels are significantly decreased with estrogen therapy, thereby increasing fibrinolytic activity and significantly diminishing the proatherosclerotic state associated with elevated levels. Glucose Metabolism. Further systemic effects of estrogen therapy are related to glucose metabolism. Koh et al. [171] found decreased insulin levels in patients treated with estrogen only, but overall increased insulin in those receiving estrogen and progesterone therapy. The PEPI Trial [166] specifically examined the effects of estrogen on fibrinogen, fasting glucose, and fasting insulin levels. They noted a slight, but not statistically significant, decline in fasting insulin levels. However, women taking estrogen were noted to have significantly lower fasting glucose levels. However, elevated 2-h glucose levels were observed in all treatment arms of the PEPI Trial. These results support the controversy and lack of

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conclusions regarding the role of estrogen therapy and carbohydrate metabolism. One small clinical trial did demonstrate decreasing fasting insulin levels with estrogen treatment, but the study was limited by small numbers as well as lack of a control group [172]. Thus, the exact effect of estrogen replacement on glucose metabolism in terms of cardioprotection is not yet known.

IV. REVIEW OF THE LITERATURE Currently, the large number of observational studies that strongly support the use of estrogen in menopausal women for both primary and secondary prevention of cardiovascular disease is being challenged. The HERS trial [173], which was a prospective, randomized trial, suggested no benefit of hormone replacement therapy in terms of secondary prevention of cardiovascular disease compared to a placebo group. As reviewed here, the individual effects of estrogen on lipid profile, atherosclerosis, vascular flow, atheroma formation, and glucose and insulin levels suggest clear benefits and reduced cardiovascular mortality among women receiving estrogen with or without a progestin. A review of the major studies follows. A. Primary Prevention The issue of primary versus secondary prevention of myocardial infarction (MI) is the central issue of current discussions regarding the role of estrogen in prevention of cardiovascular disease. Several studies have examined the effects of estrogen on primary prevention of MI through observational studies (Table 3). Overall, these studies have found positive effects of estrogen therapy. Wolf et al. [174] utilized 1944 women contacted using the National Health and Nutrition Examination Survey; these women were followed for up to 16 years afterward with an observational study. Participants were split into ever users and never users of estrogen, as well as those with surgical versus natural menopause. After adjusting for age and cardiovascular risk factors, ever use of estrogen was associated with a significant reduction in deaths related to cardiovascular disease (RR ⫽ 0.66, 95% CI 0.48 to 0.90). Patients with a history of previous surgical menopause experi-

Table 3 Primary Prevention of Cardiovascular Disease Author/year

Estrogen use

Relative risk of recurrence or death from cardiovascular disease

Wolf, 1991 Stampfer, 1985

Ever users Ever users Current users Ever users Current users Current users Ever users Current users Current users

0.66 (95% CI 0.48 to 0.90) 0.5 (95% CI 0.3 to 0.8) 0.3 (95% CI 0.2 to 0.6) 0.80 (95% CI 0.7 to 0.91) 0.69 (95% CI 0.47 to 1.02) 0.69 (95% CI 0.54 to 0.86) 0.9 (95% CI 0.7 to 1.2) 0.9 (95% CI 0.2 to 3.3) 0.42 (95% CI 0.13 to 1.10)

Henderson, 1991 Psaty, 1994 Falkeborn, 1992 Rosenberg, 1993 Petitti, 1987 Bush, 1987

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enced a smaller reduction in relative risk of cardiovascular death among women treated with estrogen. The Nurses Health Study remains one of the largest and most important prospective cohort studies to examine the role of estrogen and cardiovascular disease [175–178]. Stampfer et al. [175] established the Nurses Health Study in 1976; it used a survey to follow 121,964 female nurses between the ages of 30 and 55 years. After 3.5 years, nonfatal MI was reported by 3958 participants. Deaths associated with MI were confirmed by examination of hospital records. Ever users of estrogen had a relative risk of 0.5 (95% CI 0.3 to 0.8) of death from cardiovascular disease, while current users had a relative risk of 0.3 (95% CI 0.2 to 0.6). Adjustment for cardiovascular risk factors did not alter this result, although all patients with a history of MI were excluded from the study. However, among women with multiple major risk factors for cardiovascular disease but no diagnosed disease at the time, estrogen therapy resulted in a 49% decrease in death from all causes compared to never users of estrogen [176]. Further examination of these data confirmed the benefits of estrogen in preventing coronary artery disease, but showed no associated change in stroke risk among participants [177]. The addition of a progestin to the treatment regimens of participants receiving ERT did not attenuate its positive cardiovascular effects [178]. However, the Nurses Health Study demonstrated no improvement in survival with prolonged use of estrogen therapy, primarily secondary to increased incidence of breast cancer with long-term estrogen use [176]. Results of the Leisure World Study [179] also support the beneficial effects of estrogen on cardiovascular health. Utilizing a retirement community in southern California, Henderson et al. [179] followed 8841 women aged 40 to 101 for 5.5 years. All-cause mortality rates were decreased to a relative risk of 0.80 (95% CI 0.70 to 0.981) with ever use of estrogen compared to nonusers. Adjustment for cardiovascular disease did not alter this outcome, demonstrating improved general survival of women receiving estrogen therapy. Separation of estrogen use into use in the distant past and present use demonstrated a 40% reduction in overall morality among women using estrogen for more than 15 years. Beneficial effects resulting in decreased morality included decreased acute and chronic arteriosclerotic disease and cerebrovascular disease. In specifically examining risk of death from acute MI, current use of estrogen was associated with a relative risk of 0.47, while past users had a relative risk of 0.62 compared to never users of estrogen [180]. These beneficial effects of estrogen use were found in all patients, including those with a history of cardiovascular disease, consistent with effective secondary prevention. Dose of estrogen received also appeared possibly to affect outcomes. Patients given a 0.625-mg dose of estrogen, rather than 1.25 mg dose, were noted to have further decreased mortality than those receiving the larger dose, though this finding was not statistically significant. Further evaluation of these data revealed a marked reduction in morality rates among present and past users of estrogen. Psaty et al. [181] conducted a population-based, case-control study using members of a heatlh cooperative group. They found a relative risk of 0.69 (95% CI 0.47 to 1.02) for MI among current estrogen users and a relative risk of 0.68 (95% CI 0.38 to 1.22) among users of estrogen and progesterone therapy compared to nonusers.

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Thus, a reduced risk of MI was seen with estrogen use with or without the addition of a progestin agent. Falkeborn et al. [182] performed an observational cohort study using Swedish women identified by pharmacy records as using noncontraceptive estrogen therapy. Overall, fewer first MIs than expected were noted among estrogen users, resulting in a relative risk of 0.81. MI rates were noted to be 30% lower among women under the age of 60 receiving estrogen only (RR ⫽ 0.69, 95% CI 0.54 to 0.86) or estrogen plus levonorgestrel (RR ⫽ 0.53, 95% CI 0.30 to 0.87). Rosenberg et al. [183] performed a similar observational, case-control study among women in Massachusetts aged 45 to 69 years, specifically examining the effects of length of estrogen use. Overall, they found a relative risk of 0.9 (95% CI 0.7 to 1.2) for ever use of estrogen. Risk of MI was reduced with length of estrogen use, with a maximum reduction of 40% after 5 or more years of use, but statistical significance of this trend was found only among recent users and not past users. In addition, little effect was noted with ever use of estrogen. In response to this, Petitti et al. [184] followed a cohort of 6093 women from the Kaiser Permanente medical program for an average of 10 to 13 years. Mortality rate from cardiovascular disease was not significantly lower among estrogen users (RR ⫽ 0.9, 95% CI 0.2 to 3.3). After adjustment for cardiovascular risk factors, the relative risk associated with estrogen use was 0.6 (95% CI 0.3 to 1.1). Until randomized studies are completed, observational studies still strongly suggest that estrogen has a role in primary prevention of MI. B. Secondary Prevention Before the HERS trial, secondary prevention of cardiovascular disease appeared to be a most compelling argument for the benefit of ERT. Several studies have examined the effects of estrogen in women with a history of cardiovascular disease and/or MI (Table 4). Newton et al. [185] retrospectively examined survivors of MI and examined rates of reinfarction relative to estrogen use. Relative risk for reinfarction while currently on ERT after MI, adjusted for age and time since MI, was 0.64 (95% CI 0.32 to 1.30). A past history of estrogen use resulted in a relative risk of 0.90. The relative risk for all-cause mortality with estrogen use was 0.50 (95% CI 0.56 to 1.09) and for those with a history of estrogen use, the relative risk was 0.79 (95% CI 0.56 to 1.09). Overall, estrogen use appears to improve survival of women who survive an MI and to improve overall mortality. A healthy users effect has been suggested to be an important component of this effect, but history Table 4 Secondary Prevention of Cardiovascular Disease Author/year

Estrogen use

Relative risk of recurrence of death from cardiovascular disease

Newton, 1997 Bush, 1987 Sullivan, 1990 Wilson, 1985 Hulley, 1998

Current users Current users Ever users Ever users Current users

0.64 (95% CI 0.32 to 1.30) 0.34 (95% CI 0.12 to 0.81) 0.16 (95% CI 0.04 to 0.66) 1.76 (P ⬍ .01) Unchanged to increased (see Table 5)

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of previous MI as inclusion criteria should negate this issue, suggesting that patients have true underlying disease with outcomes altered by estrogen use. Bush et al. [139] utilized longitudinal data from the Lipid Research Clinics Program Follow-Up Study to evaluate the role of improved lipid profile secondary to estrogen use and cardiovascular disease. Initial data demonstrated a significant increase in HDL levels and decrease in LDL levels with estrogen administration. Despite a higher baseline incidence of caridiovascular disease among estrogen users, this prospective cohort study revealed an age-adjusted relative risk of 0.34 for death related to cardiovascular disease (95% CI 0.12 to 0.81) among patients receiving estrogen. Furthermore, the exclusion of all women with cardiovascular disease (primary prevention) (resulted in an almost unchanged relative risk of 0.42 (95% CI 0.13 to 1.10). This beneficial effect of estrogen therapy was mediated primarily through increased HDL levels. Sullivan et al. [186] assessed the survival of women treated with estrogen who had a history of varying degrees of angiographically diagnosed coronary artery stenosis. A group consisting of 1178 postmenopausal women with severe coronary artery stenosis (⬎70%), 644 patients with mild-to-moderate coronary artery disease (5% to 69% stenosis), and 446 controls (0% stenosis) were treated with estrogen and followed. After 10 years of treatment, the survival of patients with severe coronary artery stenosis who received estrogen was 97.0% compared to only 60% of patients with severe coronary stenosis who did not receive estrogen therapy. Survival was also improved among patients with mild-to-moderate stenosis on estrogen, with 96% survival in users of estrogen and 85% survival of nonusers after 10 years. Thus, estrogen use was noted to have a significant, independent effect on survival in women, which was most apparent in those women with severe coronary artery stenosis. These results not only suggest that estrogen therapy is indicated in patients with coronary artery disease, but also that patients with severe coronary stenosis may benefit the most from this therapy. Initial results of the Framingham Heart Study challenged the apparent benefits of estrogen on cardiovascular disease demonstrated by other cohort studies. Wilson et al. [187] utilized a cohort of 2873 female residents of Framingham, Massachusetts, who were followed biannually for a period of 12 years. Participants were classified as estrogen users if that medication appeared on their medication form during the initial 8 years of the study. Of the 1234 postmenopausal women included, 302 had used estrogens at some point during the study period. Final data analyses, after adjusting for age, hypertension, smoking, obesity, total cholesterol, HDL level, and alcohol use, revealed a 1.76 RR (P ⬍ .01) of cardiovascular disease for ever users of estrogen compared to never users. However, later reanalysis of the data demonstrated that these results were affected by choice of baseline examination time. Reanalysis of the data by Eaker et al. [188] was limited to cardiovascular disease without angina noted at two exam periods. Averaging the findings of these two sets of calculations revealed a relative risk of 0.4 (P ⬎ .05) of ever users of estrogen for cardiovascular disease compared to never users, although this protective effect was not found to be statistically significant [189]. In contrast to the findings of multiple other cohort studies regarding secondary prevention, the findings of Hulley et al. [173] in the HERS challenge the previously apparent benefits of estrogen of the secondary prevention of cardiovascular disease. In this prospective, randomized clinical trial, Hulley et al. demonstrated

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no change in the rate of cardiovascular events among women with established CAD and even an increased rate of cardiovascualr events during the first year. Utilizing a cohort of 2763 postmenopausal women with CAD less than 80 years old and with an intact uterus, participants were treated with 0.625 mg CEE and 2.5 mg medroxyprogesterone or placebo (Table 5). No differences in demographic characteristics were noted at the beginning of the study. Primary outcome in this study [173] was nonfatal MI or death related to cardiovascular disease. Secondary outcomes included coronary revascularization, unstable angina, congestive heart failure, resuscitated cardiac arrest, stroke, or transient ischemic attack. Other outcomes examined included lipid profile, overall mortality, thromboembolic events, gallbladder disease, cancer, and fracture. No significant difference in primary or secondary outcomes was noted between the

Table 5 Outcomes by Treatment Group and Years Since Randomization

* RH indicates relative hazard; CI confidence interval; and CHD, coronary heart disease. † Event rates per 1000 women-years in the estrogen plus progestin of placebo group. ‡ P values for tests of continuous trend in log-relative hazard. § Primary CHD events include nonfatal myocardial infarction and CHD death. ¶ Coronary revascularization includes coronary artery bypass graft surgery and percutaneous coronary revascularization. Source: Ref. 173.

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two groups for an average follow-up of 4.1 years, suggesting that the daily use of combination HRT did not reduce the overall risk of nonfatal MI or death related to cardiovascular disease. On further follow-up, estrogen users were noted to have a lower incidence of cardiovascular events during years 4 and 5 of estrogen therapy. An increased incidence of deep venous thrombosis, pulmonary emboli, and gallbladder disease was noted among women treated with estrogen. These results led Hulley et al. to caution against starting women on estrogen therapy for secondary prevention of cardiovascular disease, but to suggest its continuation only among women already receiving estrogen therapy. Estrogen use in healthy postmenopausal women appears to be cardioprotective. As cardiovascular disease is the leading cause of death in women of this age group, the use of estrogen for primary prevention of cardiovascular disease is reasonable. With regard to secondary prevention, the use of estrogen may not provide the same benefits, and further studies are needed to answer this question. Finally, it is important to remember that there are other ways to reduce the risk of cardiovascular disease. Statins can significantly reduce the risk of major coronary events in patients with hypercholesterolemia. The use of vitamin E (400 to 800 IU/day) has been shown to significantly reduce the rate of recurrent MI [190]. Folic acid appears to reduce serum levels of homocysteine, which is an independent cardiovascular risk factor [191]. Aspirin has also been shown to reduce the risk of MI, cerebrovascular accident, and death in patients at high risk for cardiovascular disease [192]. V.

RISKS OF ESTROGEN REPLACEMENT THERAPY

Despite appearing to be a panacea for the multiple symptoms and medical risks associated with the menopause, there are some risks associated with ERT. The most important of these include (1) endometrial cancer, (2) breast cancer, (3) venous thromboembolic events (VTEs), (4) gallbladder disease, and (5) minor symptoms (i.e., breast tenderness and bleeding). A thorough discussion of the associated risk and benefits of HRT should take place between the patient and her physician prior to starting therapy. A.

Endometrial Cancer

Currently, endometrial cancer is the most common of all gynecological malignancies and the fourth most common cancer in women [193]. Classic risk factors for the development of endometrial cancer have traditionally included obesity, nulliparity, and late menopause. However, with the advent of HRT, a strong relationship between unopposed estrogen therapy and the development of endometrial hyperplasia with atypia and eventual endometrial cancer has been noted. The association between estrogen and endometrial cancer was first noted by Novak and Yui in 1936. Examination of women with estrogen-secreting tumors revealed a high incidence of concurrent endometrial cancer or hyperplasia in these women [194,195]. Multiple studies since then have demonstrated a strong correlation between the use of exogenous unopposed estrogen and an increased incidence of endometrial cancer. Smith et al. [196] retrospectively reviewed women with adenocarcinoma of the endometrium and found that 48% of these women

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Table 6 Comparative Outcomes of 170 Patients with Simple and Complex Hyperplasia and Atypical Hyperplasia

Source: Ref. 197.

had previously been treated with unopposed exogenous estrogen. On statistical analysis, a 4.5-fold increased risk of developing endometrial cancer was noted with the use of unopposed estrogen therapy. These findings were supported by Kurman et al. [197], who performed the landmark study on the effect of continuous unopposed estrogen therapy in women with intact uteri. In their long-term follow-up of women with untreated endometrial hyperplasia, Kurman et al. demonstrated a 29% progression of patients with complex atypical hyperplasia to carcinoma (Table 6). In contrast, only 8% of patients with simple atypical hyperplasia developed carcinoma, while only 1% of patients with simple hyperplasia without atypia went on to develop endometrial cancer. Thus, unopposed estrogen therapy encourages the development of endometrial hyperplasia, which when complex in nature and associated with cellular atypia strongly predisposes to the development of endometrial carcinoma. Studies of women with Stein-Leventhal syndrome (excessive estrogen production by the ovaries) with resulting endometrial hyperplasia with atypia have revealed up to 25% progression to endometrial carcinoma [198]. The addition of progesterone to estrogen replacement therapy was demonstrated by Gambrell and Teran [199] to decrease the incidence of endometrial cancer significantly. The addition of progesterone induced endometrial regression and stabilization, thereby preventing the development of hyperplasia, especially hyperplasia with atypia of the endometrium. Thus, the importance of prescribing a combination of estrogen and progestin therapy in women with an intact uterus who are receiving hormone replacement therapy is clear. B. Breast Cancer Breast cancer is the leading cause of death in American women aged 40 to 55 years [200]. Currently, one in nine women will be diagnosed with breast cancer [201]. Of all American women, 12.6% will be diagnosed with breast cancer in their lifetime, and 3.5% of all women will die of this disease [202]. Well-known risk factors for breast cancer include low parity, early age at menarche, late age at menopause, birth of first child after 30 years of age, menopausal status, anovulatory infertility, and family history [200]. Miller et al. [203] demonstrated that, de-

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spite an apparent increase in the overall incidence of breast cancer, the incidences of large tumors and of those with regional or distant metastases are unchanged or slightly decreased. Today, a woman’s risk of developing breast cancer is a direct function of her age. Feuer et al. [204] demonstrated a 1.6% risk of developing cancer by age 50 in a 40-year-old woman compared to a 10.3% chance in the same women at age 80. In contrast, a 70-year-old woman who has never had breast cancer has only a 4.1% risk of developing it by age 80. Unfortunately, the peak incidence of breast cancer occurs among postmenopausal women, the same women for whom the choice of whether to take ERT becomes an issue, along with its apparent risks and benefits. A review of the literature demonstrates that there is no clear consensus of the relationship of ERT to breast cancer incidence, although metanalysis does reveal an overall slightly increased relative risk of breast cancer among women on long-term ERT with and without a progestin added. In the past 20 years, over 30 case-control and cohort studies have been performed to examine the relationship between breast cancer and ERT [201]. All meta-analyses have demonstrated no significant increased incidence of breast cancer among ever users of estrogen compared to never users [205–209]. Range of breast cancer risk associated with ever users of estrogen was 1.0 to 1.07. However, not even findings of slightly elevated risk were found to be statistically significant, indicating no increased risk of breast cancer associated with ever having used estrogen replacement. Sillero-Arenas et al. [205] specifically examined the risk of breast cancer among current estrogen users. Utilizing only studies employing a 0.625 estrogen dose, they demonstrated a relative risk of 1.63 (P ⬍ .001) with current estrogen use for the development of breast cancer, suggesting only a small increase in risk. The addition of progesterone to estrogen therapy resulted in a relative risk of 0.99, demonstrating an essentially unchanged risk from baseline of estrogen and progesterone therapy. Further metanalysis by Colditz et al. [206] found a relative risk of 1.40 with current estrogen use, but that discontinuation of estrogen for 2 or more years resulted in no increase in risk. 1. Duration of Use Examination of the effect of duration, dose, and type of estrogen use on breast cancer risk was performed using several metanalyses. Steinberg et al. [207] found a 30% increased risk of breast cancer (RR ⫽ 1.3, 95% CI 1.2 to 1.6) after 15 years of use based on case-control studies. Similar findings were obtained by Colditz et al. [206], who demonstrated a relative risk of 1.23 (95% CI 1.08 to 1.40) among women using estrogen for 10 years or longer. These results demonstrated the fallacy of the presumption that increased length of use results in increased breast cancer risk. Dupont and Page [208] demonstrated no significant increases in breast cancer risk among those taking the different doses of estrogen for replacement therapy. Their findings of a relative risk of 1.07 with the 0.625 dose and relative risk of 1.08 with the 1.25 dose of estrogen were supported by similar findings of SilleroArenas et al. [205] and Colditz et al. [206]. Bergkivist et al. [210] compared women receiving estradiol versus those receiving conjugated estrogen preparations and found a 20% increased risk of breast

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cancer with increasing length of exposure among women taking estradiol. This increased risk with increased length of use was not found in women receiving conjugated estrogens. Further studies by Hulka et al. [211] demonstrated a fourfold increase in breast cancer risk among women receiving estrogen injections. Based on data from prospective observational studies, it would seem that long-term use of ERT/HRT (⬎5 years) would increase the risk of breast cancer by about 30%. Certainly, randomized clinical trials will be necessary to answer this question definitively. Despite this, the potential benefits of ERT/HRT would certainly seem to outweigh that possible risk. 2. Benign Breast Disease/Family History The increased breast cancer risk in women on ERT with a history of benign breast disease or a family history of breast cancer remains a controversial issue. Dupont and Page [208] demonstrated no significant increases in risk of breast cancer among women with a history of benign breast disease receiving estrogen replacement (RR ⫽ 1.16, 95% CI 0.89 to 1.5). However, Steinberg et al. [207] demonstrated a significantly increased risk of breast cancer among women with a family history of breast cancer on ERT (RR ⫽ 3.4, 95% CI 2.0 to 6.0). In contrast, Armstrong [209] and Colditz et al. [206] found no relationship between family history of breast cancer and ERT. Thus, ERT is associated with no increased risk in women with a history of benign breast disease. However, among women with a family history of breast cancer, the evidence remains controversial; in the end, the decision needs to be made by the patient with the aid of the physician. 3. Prior History of Breast Cancer The question of estrogen use in women with a prior history of breast cancer has emerged as a new area of controversy in recent literature. With improved screening and detection of early stage cancers and aggressive and effective chemotherapy and hormonal therapy, more and more women with breast cancer are surviving following ovarian failure secondary to treatment [201]. DiSaia et al. [212] performed a retrospective review of 110 patients with breast cancer survivors who elected to take HRT. Receptors status, stage, age, and node status were known, but did not affect choices of individual patients to take HRT; median interval between diagnosis and starting HRT was 24 months. Among these patients, a total of seven recurrences was noted (6%). Overall, no significant adverse effects were noted in patients with a history of breast cancer taking HRT, and their rates of breast cancer recurrence were not any higher than those women not taking HRT. Although only a preliminary study, DiSaia et al. suggest the potential use and safety of HRT in breast cancer survivors, although ethical dilemmas and patient fear of recurrent breast cancer make further in-depth prospective randomized research on this topic difficult to perform. The topic of breast cancer and HRT remains on the forefront of medical research. Recent data have indicated that tamoxifen may reduce the incidence of invasive breast cancer by 49% in women at high risk compared to placebo [213]. Most of this reduced risk was seen in tumors positive for estrogen receptor (ER). The length of use for prevention is unknown, but for cancer patients, treatment longer than 5 years does not seem to provide additional benefit and may increase the incidence of ER-negtive tumors [213,214]. Based on these findings, a great deal

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of interest has been generated regarding the use of newer SERMs such as raloxifene. Recently, Cauley et al. [215] published study findings that suggest a decrease of 62% in the incidence of all types of breast cancer and of 72% among invasive breast cancers among women taking raloxifene for treatment of osteoporosis as part of the Multiple Outcomes of Raloxifene Study (MORE). These findings may give patients with a strong family history of breast cancer a reasonable alternative for menopausal therapy. C.

Venous Thromboembolic Events

The VTEs represent a broad category (including pulmonary embolus and deep venous thrombosis) of significant life-threatening risks associated with ERT and contraindications to placing patients on ERT. Jick et al. [216], in a case-controlled study, examined the use of postmenopausal estrogen and the incidence of idiopathic venous thromboembolism. Utilizing hospital admission for VTE as an end point, women receiving estrogen therapy had a three times higher risk of idiopathic VTE than nonestrogen users. However, the absolute risk of VTE was low for both estrogen users and nonusers, resulting in only a modest increase in morbidity for both groups. Grodstein et al. [217], in the Nurses Health Study, examined the relationship between postmenopausal hormone use and thrombotic disease. Using primary pulmonary embolus as an end point among participants with no identified previous cancer, trauma, surgery, or immobilization risk factors, they found a 2.1 relative risk for primary pulmonary embolus among current hormone users (95% CI 1.2 to 3.8). Among past users of HRT, no increased risk of pulmonary embolus was noted, with a relative risk of 1.3 (95% CI 0.7 to 2.4). Thus, risk of pulmonary embolus is slightly increased only among current hormone users, although this risk is minimal, and overall VTE remains an uncommon problem among healthy women. Daly et al. [218] also examined the relationship between HRT and VTE and found not only an increased relative risk of 3.5 (P ⬍ .001, 95% CI 1.8 to 7.0), but also that the risk of VTE appeared to be highest among short-term current users (P ⫽ .011). Daly et al. found that, overall, the increased risk of VTE among HRT users amounted to only one extra case among every 5000 users, which they believed to be an acceptable increased risk given the multiple significant benefits of HRT. In contrast, several studies have found no relationship between estrogen use and VTE. Devor et al. [219] examined all women 45 years or older with a primary or secondary discharge diagnosis of thrombophlebitis, venous thrombosis, or pulmonary embolism; they examined a total of 121 cases and 236 matched controls. No relationship was found between exogenous estrogen use and incidence of thrombosis after excluding women with a history of thrombosis, thrombosis that occurred after admission, women less than 50 years old, and women with indeterminate estrogen use. ERT did not increase the risk for thrombosis. Saleh et al. [220] found similar results while examining HRT use and VTE incidence utilizing enzyme-linked immunosorbent assays for prothrombin fragments 1 and 2 and thrombin-antithrombin III complex, markers of factor Xa and thrombin generation, respectively. They found no statistically significant differences in any of the

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clotting or in vivo clotting factors examined among women receiving estrogen therapy versus nonuser controls. Thus, although there does not appear to be a small increased risk of VTE associated with estrogen replacement use, this risk is minimal and should not dissuade women from utilizing this therapy for its cardiovascular, osteoporotic, and symptomatic benefits. However, a current VTE remains a contraindication to HRT. In contrast, several studies have found no relationship between estrogen use and VTE. Devor et al. [219] examined all women 45 years or older with a primary or secondary discharge diagnosis of thrombophlebitis, venous thrombosis, or pulmonary embolism; they examined a total of 121 cases and 236 matched controls. No relationship was found between exogenous estrogen use and incidence of thrombosis after excluding women with a history of thrombosis, thrombosis that occured after admission, women less than 50 years old, and women with indeterminate estrogen use. ERT did not increase the risk for thrombosis. Saleh et al. [220] found similar results while examining HRT use and VTE incidence utilizing enzyme-linked immunosorbent assays for prothrombin fragments 1 and 2 and thrombin-antithrombin III complex, markers of factor Xa and thrombin generation, respectively. They found no statistically significant differences in any of the clotting or in vivo clotting factors examined among women receiving estrogen therapy versus nonuser controls. Thus, although there does appear to be a small increased risk of VTE associated with estrogen replacment use, this risk is minimal and should not dissuade women from utilizing this therapy for its cardiovascular, osteoporotic, and symptomatic benefits. However, a current VTE remains a contraindication to HRT. D. Alternative Benefits of Hormone Replacement Therapy Currently, several areas of research are at the forefront of both the lay and scientific press in regard to ERT and its preventive or inhibitory effects. The most significant of these include colon cancer, AD, stroke, and macular degeneration. 1. Colon Cancer Multiple recent epidemiological studies have demonstrated a preventive role of estrogen in the development of colon cancer. Currently, colon cancer is the third leading cancer and cause of cancer death in women [221]. Among the recent body of research on this topic, work by Grodstein et al. [222] and Calle et al. [223] convincingly demonstates the significance of the preventive effect of estrogen on the development of colon cancer. Grodstein et al. [222] examined data from the Nurses Health Study, a prospective cohort of 59,002 women, with regard to colon cancer incidence and estrogen use. This study included approximately 75% person-time among estrogenonly users and the remaining 25% estrogen and progesterone users. Of these women, 470 developed colorectal cancer, and 838 developed distal colorectal adenomas. Current use of ERT was associated with a significantly decreased risk of colon cancer, with a relative risk of 0.65 (95% CI 0.50 to 0.83). This protective effect was noted to be diminished in past users (RR ⫽ 0.84, 95% CI 0.67 to 1.05) and nonexistent in women who had not used HRT for more than 5 years (RR ⫽ 0.92, 95% CI 0.70 to 1.21). Duration of use greater than 5 years did not affect the relative

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risk of colon cancer. After exclusion of women who reported having had a screening colonoscopy, relative risk of developing colon cancer was still lower among current hormone users compared to nonusers (RR ⫽ 0.64, 95% CI 0.49 to 0.82). In addition, current users of HRT also had a lower risk of developing large (ⱖ1 cm) adenomas than never users. Besides suggesting more intensive screening among users of HRT, Grodstein et al. [222] convincingly demonstrated an association between current and recent HRT use and a reduction in the incidence of colorectal cancer. In a larger study, Calle et al. [223] also clearly illustrated the inverse relationship between colon cancer incidence and HRT use, utilizing fatal colon cancer as an end point. A cohort of 422,373 postmenopausal women who were free of cancer at study entry were examined as part of a nationwide prospective study on mortality. Among these postmenopausal women, 897 colon cancer deaths occurred. On examination of HRT use, ever users were noted to have a significantly lower risk of fatal colon cancer (RR ⫽ 0.71, 95% CI 0.61 to 0.83). This protective effect was strongest among current estrogen users (RR ⫽ 0.55, 95% CI 0.40 to 0.76). Unlike Grodstein et al. [222], Calle et al. [223] found a significant decrease in risk with increased years of use, with a relative risk of 0.81 among users for 1 year or less and a relative risk of 0.54 among users for more than 11 years (95% CI 0.63 to 1.03 and 0.39 to 0.76, respectively) (Table 7). Calle et al. [223] postulated that estrogen might exert a hormonal influence on bile acid synthesis and production, thereby diminishing the colon cancer–promoting effects of increasingly concentrated fecal bile acids. In addition, estrogen may directly affect colonic mucosa, thereby inhibiting the growth of colon cancer cells, an effect demonstrated in studies in vitro [224,225]. Although the exact mechanism remains unclear, significant

Table 7 Colon Cancer Mortality by Duration and Time Since Estrogen Use

Source: Ref. 223.

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evidence for the role of estrogen in the prevention of colon cancer further supports the multiple benefits of HRT among postmenopausal women. 2. Alzheimer’s Disease Alzheimer’s disease (AD) is a significant health problem for aging men and women in the United States. After age 65, the prevalence of AD exponentially increases with age, with the number of affected persons doubling every 5 years; it commonly affects women far more often than men [226]. Consistent with this, 30% to 50% of all women older than 85 years suffer from dementia [227,228]. Currently, neurologists view AD as a syndrome with multiple determinants that result in the significant loss of mental capabilities to a degree that interferes with daily life and function [229]. Factors thought to increase the risk of developing AD include female sex, prior head injury, lack of exposure to anti-inflammatory medications, and lack of use of ERT [229]. Estrogen has been shown to have distinct effects on the brain, and subpopulations of neurons have been shown to express intranuclear ERs to which estrogen binds, thereby regulating the production of specific gene products. Via this pathway, estrogen has an impact on other neuronal processes indirectly by modifying neuron excitability, affecting neurotransmitter release (particularly acetylcholine), and promoting neuronal survival [229,230]. Brinton et al. [231] demonstrated the ability of estrogen to enhance viability and survival necortical neurons grown in culture, thereby illustrating estrogen’s neurotrophic effects. Thus, ERT exerts significant neurotrophic effects, thereby promoting the survival and viability of neurons both in vitro and in vivo. ERT and its role in the prevention and treatment of AD remains an important area of current clinical research in the health maintenance of women in the menopause. The largest epidemiological study by Paganini-Hill et al. [232,233] to show a favorable effect of estrogen in the prevention of AD examined the effects of different estrogen preparations and duration of therapy on the risk of AD among 8877 women in a nested case-control study. The risk of AD was significantly reduced among estrogen users versus nonusers, with an odds ratio of 0.65 (95% CI 0.49 to 0.88). However, when specific doses were examined, only patients receiving 1.25 mg of CEE had a significant reduction in the incidence of AD (RR ⫽ 0.54, 95% CI 0.32 to 0.92). Users of estrogen for longer than 15 years also had a lower incidence of AD, with an odds ratio of 0.44 (P ⬍ .001, 95% CI 0.26 to 0.75). However, despite the fact that most of the participants in these studies received unopposed estrogen, the results as a whole demonstrate the important neurotrophic effects of estrogen in the central nervous system in vivo and the significant preventive role of estrogen therapy on the development of AD. Debate currently exists regarding the influence of estrogen on cognitive function among menopausal women with and without neurologic disease. Szklo et al. [234] demonstrated that healthy menopausal women using estrogen had superior cognitive function based on World Fluency Test scores than nonusers, with higher scores correlating to longer duration of estrogen use. In contrast, Barret-Connor et al. [235] found no improvement in cognitive function among menopausal women without AD receiving ERT in their review of participants of the Rancho Bernardo prospective study. Mulnard et al. [236] examined the effect of ERT in women with established mild-to-moderate AD. After 1 year of therapy,

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estrogen replacement failed to slow the progression of AD and did not improve global, cognitive, or functional outcomes in these patients. Thus, epidemiological data would suggest that estrogen may prevent the development of AD, although it appears to have little effect on cognitive function in individuals already suffering from AD-related dementia. 3. Stroke The relationship between stroke and ERT is a new and interesting area of research. Stroke is the most frequent cause of death in women over the age of 50 years, yet it remains an uncommon event among premenopausal women [202,237]. Multiple prospective studies have demonstrated a variety of results, ranging from no change to a decreased risk of stroke among ERT users. Among those finding beneficial effects of estrogen on stroke incidence, Paganini-Hill et al. [238] examined participants in the Leisure World Study demonstrated significant favorable effects of estrogen in the form of a prospective trial. Using mortality from stroke among users and nonusers of estrogen therapy as an end point and after correcting for age-adjusted mortality rates, they found a relative risk of 0.53 (95% CI 0.31 to 0.91) for stroke among current users of ERT compared to nonusers. This protective effect was present in women both with and without hypertension and in both smokers and nonsmokers. Consistent with these findings, Longstreth et al. [239], a case-control study, demonstrated a 50% reduction in the risk of subarachnoid hemorrhage with the use of ERT, with even greater protective effects demonstrated in smokers. Falkeborn et al. [240] demonstrated a reduction of stroke incidence with a variety of hormone replacement formulations, comparing effects of estradiol versus CEE compounds and estrogen and progestin treatments. Women receiving either 1 to 2 mg/day estradiol or 0.625 to 1.25 mg/day CEE had a 30% reduced risk of any stroke (RR ⫽ 0.72, 95% CI 0.58 to 0.88) and 40% reduced risk of acute stroke (RR ⫽ 0.61, 95% CI 0.46 to 0.79). Women receiving estrogen and progesterone therapy also had a similarly lowered risk of stroke (RR ⫽ 0.61, 95% CI 0.40 to 0.88), suggesting that the beneficial effects of estrogen on stroke incidence were not affected by progestin use. Despite the positive correlation between estrogen use and reduced stroke incidence demonstrated in several studies, several other authors have found estrogen to have no risk to a slightly increased risk of stroke with estrogen use. Grodstein et al. [178], in the Nurses Health Study failed to demonstrate a protective effect of estrogen use on stroke incidence and in fact demonstrated a slight increase in the risk of thromboembolic stroke among current estrogen users, although not statistically significant. Pedersen et al. [241], in a large Danish casecontrol study, found no impact of estrogen or combined estrogen and progesterone use on the incidence of nonfatal stroke, both thromboembolic or hemorragic. Despite the multiple conflicting results and unclear final opinion on the effect of estrogen therapy on stroke incidence, a consistent finding in all studies has been a decrease in the incidence of stroke-related death among estrogen users. Finucane et al. [242], utilizing a large cohort of women in the National Health and Nutrition Examination Survey (NHANES), demonstrated an age-adjusted relative risk of 0.41 of stroke mortality among ever users of estrogen compared to nonusers (95% CI 0.17 to 1.03). This resulted in a 31% reduction in stroke incidence and

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63% reduction in stroke-related death among estrogen users. This reduced risk of fatal stroke among estrogen users remained even after correcting for a variety of comorbid factors (i.e., hypertension, age, obesity, smoking, etc.). Given the large study size and significant effect of estrogen use, convincing evidence for the reduction by estrogen in the incidence of death from stroke exists. However, final consensus regarding the effects of estrogen on the incidence of stroke remains unresolved. 4. Macular Degeneration Macular degeneration (MD) is currently the leading cause of legal blindness in the United States, accounting for 25% to 60% of all new cases [243]. The pathogenesis of MD is unknown, and currently there is no effective medical therapy, with surgical photocoagulation being useful in only a limited number of patients [243]. Vingerling et al. [244] examined the association between menopause and MD using a cohort of spontaneously and surgically menopausal women. They found that women who underwent menopause at an early age had a 90% increased risk of signs of late MD compared with those who went through menopause at a later age. In a case-control study, the Eye-Disease Case-Control Study Group [243] demonstrated estrogen replacement to inhibit the development of MD. They found current users of estrogen therapy to have a relative risk of 0.3 (P, .0005, 95% CI 0.1 to 0.6) of developing MD and past users a relative risk of 0.6 (P ⬍ .0005, 95% CI 0.4 to 0,9). However, a larger study by Klein et al. [245] showed a smaller but statistically insignificant 2% reduction in the development of MD with estrogen therapy (P ⫽ .09). Thus, a significant role of estrogen in the prevention of the development of MD has yet to be defined, and further studies in this area are needed. VI. REGIMENS FOR HORMONE REPLACEMENT Estrogen therapy should be given at the lowest possible dose that relieves menopausal symptoms while affording cardiovascular protection and maintaining bone mass. As previously discussed, estrogen can be administered by either a parenteral or a transdermal route with similar effects, and there are several different formulation choices available. Continuous estrogen therapy is usually recommended, although doses and dosing schedules can be changed relative to patient needs and characteristics. Commonly used estrogen formulations and the standard starting doses that are thought to achieve both bone and heart protection are listed in Table 8. There are lower doses available that may prevent bone loss. It is important to remember that a woman with an intact uterus should receive a progestin in addition to her estrogen for endometrial protection. There are a number of different progestin agents that are typically used in the United States for menopausal treatment (Tables 9–11). The 21-carbon progestins, such as MPA, are commonly used, and like all progestins, they can be given in a cyclic or continuous manner. MP is another 21-carbon compound that is being used more frequently. The 19-nor testosterone agents, such as norethinodrone, have also been used for menopausal treatment, but more commonly in Europe. More recently, 19-nor testosterone derivatives such as norethindrone and norges-

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Table 8 Types of Estrogens Used for Standard Hormone Replacement Therapy Estrogen Conjugated estrogens Micronized estradiol Estropipate (piperazine estrogen sulfate) Ethinyl estradiol Estradiol valerate Esterified estrogens Transdermal estradiol

Dose 0.625 mg 1.0 mg 1.25 mg 5 µg 1.0 mg 0.625 mg 50 µg

timate have been used in a combination pill along with ethinyl estradiol or 17-Bestradiol. Estrogens are usually administered daily, with differences in regimens dependent on how the progestin is given. Cyclic therapy usually involves the administration of the progestin agent for 10–14 days each month. Since the estrogen is given daily, it is easiest to administer the progestin agent from the 1st to the 12th of each month. This usually results in a predictable monthly withdrawal bleed. Quarterly therapy consists of daily administration of estrogen with a progestin administered for 14 days every 3 months. This typically will result in a withdrawal bleed every 3 months, which may be preferable for some patients. Continuous therapy involves the daily administration of both an estrogen and a progestin. The goal of continuous therapy is to produce amenorrhea by inhibition of endometrial growth. Tables 9–11 list the various types and doses of estrogen and progestins used in cyclic, quarterly, or continuous therapy. A.

Calcium and Vitamin D

In addition to estrogen replacement, calcium and vitamin D supplementations are important components in maintaining the health of postmenopausal women. While dietary intake of calcium is essential throughout a woman’s lifetime, calTable 9 Hormonal Doses Used in Cyclic Hormone Replacement Therapy Daily estrogen 0.625 mg conjugated estrogens 1.25 mg estropipate 1.0 mg micronized estradiol 50 µg transdermal estrogen Cyclic progestin 0.7 mg norethindrone 200 mg micronized progesterone 5 mg medroxyprogesterone acetate* 10 mg medroxyprogesterone acetate† * Monthly progestin. † Quarterly progestin.

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Table 10 Hormonal Doses Used in Continuous Hormone Replacement Therapy Daily estrogen 0.625 mg conjugated estrogens 1.25 mg estropipate 1.0 mg micronized estradiol 50 µg transdermal estrogen Daily progestin 0.35 mg norethindrone 100 mg micronized progesterone 2.5 mg medroxyprogesterone acetate* * Can use 5.0 mg in patients with breakthrough bleeding.

cium needs increase in the menopausal and postmenopausal years with the increased rate of bone turnover that accompanies this life transition. Dietary recommendations for premenopausal women consist of 1000 mg of elemental calcium daily, usually obtained through diet with or without a supplement. In contrast, dietary recommendations for postmenopausal women consist of 1500 mg of elemental calcium daily. Most postmenopausal women require supplementation to achieve this level of daily intake of calcium on a regular basis [246]. Clinical studies have shown that calcium supplementation alone may be partially effective in preventing bone loss. Dawson-Hughes et al. [247] treated 86 women with 1000 mg calcium daily for 4 years. Their study demonstrated a sustained reduction in bone loss at the lumbar spine and proximal femur by BMD examination with calcium supplementation versus those receiving a placebo. Interestingly, the majority of this effect was noted during the first year of calcium supplementation [248]. Recker et al. [249] compared women over 60 years of age who consumed less than 1000 mg of calcium daily with women over 60 years old receiving 1200 mg calcium supplementation daily for 4 years. They noted a 59% reduction in the rate of vertebral fractures with calcium supplementation among women with vertebral fractures at baseline. Currently available calcium formulations contain calcium carbonate, calcium citrate, calcium lactate, and calcium phosphate, with the first two forms the most common. Each commercially available supplement differs in the amount of calcium contained in each tablet, resulting in a need for women to be vigilant in reading ingredients and recommended dosage information on supplement labels to ensure that they are receiving an adequate amount of calcium. Table 11 Continuous Hormone Replacement Therapy—Combination Formulations Product name

Hormonal content (Estrogen/Progestin)

Prempro

Conjugated equine estrogens (0.625 mg)/medroxyprogesterone acetate (2.5 or 5.0 mg) Estradiol (1.0 mg)/norethindrone acetate (0.5 mg) Ethinyl estradiol (5 µg)/norethindrone acetate (1.0 mg) Estradiol (1.0 mg)/norgestimate (0.09 mg)

Activella Femhrt Ortho-Prefest

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Vitamin D acts to increase calcium absorption and may have a direct effect on bone, making it an important component in the health maintenance of postmenopausal women. Although readily available through skin exposure to sunlight, many contemporary women do not receive adequate amounts of sun exposure to fulfill their vitamin D requirement, particularly during the winter months and with increasing age. As a result, it is currently recommeded that premenopausal women receive 400 IU of vitamin D supplementation during winter months or if they have minimal sunlight exposure. As women age and become perimenopausal, vitamin D supplementation improves their already increasingly compromised calcium absorption. As a result, current recommendations are for postmenopausal women to receive 800 IU daily of vitamin D in addition to calcium supplementation. Although the use of vitamin D has been shown in clinical trials to increase the risk of hypercalcemia, much of the elderly population is vitamin D deficient, making supplementation appropriate in addition to calcium supplementation [250]. Several studies have examined the effects of combination calcium and vitamin D supplementation on fracture rates in postmenopausal women. Chapuy et al. [251] examined 3270 institutionalized women in France who were treated with 1200 mg calcium and 800 IU vitamin D daily for 3 years. They found a 30% reduction in the rate of hip fracture in the group treated with calcium and vitamin D compared to those receiving a placebo. Dawson-Hughes et al. [252] treated 389 men and women over the age of 63 years with 500 mg calcium and 700 IU vitamin D daily for 3 years and noted a decrease in the rate of nonvertebral fractures. In contrast, vitamin D alone appears to have little to no effect on fracture rates. Lips et al. [253] treated 2578 women of similar age in the Netherlands with 400 IU vitamin D or a placebo for 3.5 years with no supplemental calcium. They found similar rates of hip fracture amomng the two groups, suggesting no beneficial effects of vitamin D supplementation independent of calcium on fracture rates. Thus, the combination of vitamin D and calcium supplementation are important components in the maintenance of bone mass among postmenopausal women. However, calcium alone is not sufficient to prevent loss of bone mass. As demonstrated in the PEPI Trial [96], the placebo group who received calcium alone had an average 1.8% loss of spinal BMD over 3 years compared to a 3.5% to 5.0% gain in spinal BMD among participants receiving active hormonal therapy. Although calcium and vitamin D supplementation do appear to help maintain BMD in postmenopausal women, their use in conjunction with HRT offers the greatest benefits for maintaining BMD in postmenopausal women. Use of either calcium or vitamin D alone is not sufficient to prevent further loss of BMD. B.

Postmenopausal Bleeding

Because of the potential appeal to abolish withdrawal bleeding, the continuous regimen has become somewhat popular. However, breakthrough bleeding is a common and annoying side effect that may be seen during the first 6 months of therapy, although this atypical bleeding is less common in women taking cyclic therapy. After 1 year of therapy, many women may become amenorrheic, with no bleeding therefore. However, if atypical bleeding should occur, an endometrial biopsy should be performed to rule out endometrial hyperplasia or cancer. This

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would include possible evaluation of endometrial thickness using transvaginal ultrasound. There is also some evidence that assessment of the uterine cavity using hysterosonography or hysteroscopy can be helpful in determining intrauterine lesions, such as polyps or fibroids [254]. If the endometrial biopsy is negative, an increased progesterone dose may be used to stabilize the endometrium and prevent abnormal bleeding in patients taking continouous therapy. If bleeding persists, assessment of the uterine cavity sould be performed if not done previously. In perimenopausal women, the incidence of breakthrough bleeding can be minimized with the use of cyclic therapy or even more effectively with low-dose (20 µg ethinyl estradiol) oral contraceptives. However, menopausal women who have not had a menstrual period in more than 1 year may prefer continuous therapy and therefore have the potential for freedom from monthly withdrawal bleeding. Recently, a number of companies have developed continuous therapy in the form of combination pills, with the estrogen and progestin agent in one pill (see Table 11). The decision of which mode of therapy to use depends on patient and physician preference. VII. ALTERNATIVE THERAPIES A. Local Therapy Estrogen creams, estrogen tablets, and the estrogen ring are alternative options for localized hormonal therapy. This allows estrogen therapy to be given locally, avoiding systemic effects. However, a small amount of estrogen does consistently enter the systemic circulation [255]. The estradiol vaginal ring offers another form of estrogen therapy to the vagina only, but is associated with no detectable changes in blood estradiol or estrone levels [256]. Thus, these alternative methods of localized estrogen therapy offer important alternatives for those women who cannot, or choose not to, receive oral or parenteral therapy. B. Hot Flashes Alternative therapies for women who are symptomatic from menopausal hot flashes but cannot take estrogen therapy include progesterone, low-dose clonidine, veralipride, bellergal, methyldopa, and venlafaxine hydrochloride [257]. Low-dose progestins are effective in the treatment of menopausal symptoms to a moderate degree, but still entail a form of hormonal therapy and are therefore a source of concern in patients with a history of breast cancer [258]. Low-dose clonidine, a common antihypertensive, is partially effective in the relief of hot flashes, but adequate therapy requires substantial doses, which are associated with significant potential associated side effects [257]. Veralipide is a dopamine antagonist that has been shown to be active in the hypothalamus, thereby inhibiting flushing at a dose of 100 mg/day. However, it is associated with the major side effects of galactorrhea and mastodynia [259,260]. Bellergal is a combination of belladonna alkaloids, ergotamine tartrate, and phenobarbital that has been proven to be slightly better than placebo in the treatment of hot flashes, but with significant sedating effects [261]. Methyldopa, at doses of 500 to 1000 mg/day, has been shown to be twice as effective for the treatment of hot flashes compared to a placebo, which suggests a role for adrenoreceptors in the physiology of hot

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flashes [262]. Venlafaxine hydrochloride is a serotonin reuptake inhibitor that effectively reduces hot flash incidence at a dose of 25 mg daily [263]. Finally, vitamin E, at a dose of 800 IU daily, is slightly more effective than a placebo in the treatment of menopausal symptoms [264]. C.

Phytoestrogens

Phytoestrogens remain a controversial alternative therapy for the treatment of menopause-associated symptoms. Phytoestrogens are plant-derived compounds that mimic the effects of estrogens and may be consumed as part of the normal daily diet [265]. These naturally occurring estrogens may be classfied into three groups: (1) isoflavones, (2) coumestans, and (3) lignans [257]. Isoflavones are found mainly in soy, beans, and chickpeas, while lignans and flavones are found in most cereals and fruits. Coumestans occur in high concentrations in clover sprouts [265]. Soybeans are particularly rich sources of phytoestrogens, with approximately 1 to 3 mg of phytoestrogen per gram of soy protein. However, the estrogenic effects of isoflavones are mixed, with some exhibiting agonist effects, others antagonistic effects, and others with no effect on or affinity for estrogen receptors [265]. However, rather than using recent information on the benefits of phytoestrogens to improve the diet composition, many individuals have opted to take dietary supplements derived from phytoestrogens. Unfortunately, these dietary supplements are not considered to be drugs by the Food and Drug Administration (FDA) and therefore are not subject to the strict regulation and safety guidelines imposed on conventional medications [265]. As a result, significant variation often occurs in the doses of estrogen contained in each batch of supplement produced. Furthermore, with the absence of FDA regulation, advertisers may recommend doses of phytoestrogen far in excess of the equilvalent safe, FDA-regulated estrogen doses. However, isoflavones in soy products have been shown to reduce the incidence and severity of hot flashes, favorably affect lipid profiles, and increase BMD [266]. Unfortunately, these studies are limited by their small numbers, lack of prospective data, and difficulty in regulating the specific dose of phytoestrogen received in food or dietary supplements. In the end, phytoestrogens are an appealing new option in therapy for menopausal women that deserves further study and regulation. VIII. SUMMARY It is important to note the absolute contraindications to HRT, which currently include (1) unexplained vaginal bleeding, (2) acute or chronic liver disease, (3) recent venous thrombosis, and (4) breast or endometrial cancer [257]. However, as discussed, even some of these guidelines are now being questioned by current research results. In the end, the decision regarding whether to take HRT is a personal one to be decided by the patient with guidance from her informed physician. The menopause is a normal life event that carries with it an increased risk of morbidity and mortality. The use of HRT can be beneficial in obtaining preventive health benefits. Whether a woman chooses HRT or an alternative, the decision should be based on factual information about the risks and benefits of a given treatment. It should certainly be remembered that lifestyle changes such as proper

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diet, exercise, and smoking cessation are also quite beneficial in terms of longterm health. REFERENCES 1. World Health Organization. Report of a WHO Scientific Group: Research on the Menopause. Geneva, Switzerland: World Health Organization, 1981. WHO Technical Report Series 670. 2. McKinlay SM, Bifano NL, McKinlay JB. Smoking and age at menopause in women. Ann Int Med 1985; 103(3):350–356. 3. Greendale GA, Sowers M. The menopause transition. Endocrin Metab Clin North Am 1997; 26(2):261–277. 4. Oldehave A, Jaszmann LJB, Haspels AA, Everaerd WT. Impact of climacteric on well-being. Am J Obstet Gynecol 1993; 168(3 pt 1):772–780. 5. Brambilla DJ, McKinlay SM. A prospective study of factors affecting age at menopause. J Clin Epidemiol 1989; 42(11):1031–1039. 6. Hammond CB. Menopause and hormone replacement therapy: an overview. Obstet Gynecol 1996; 87(2 suppl):2s–15s. 7. Snieder H, MacGregor AJ, Spector TD. Genes control the cessation of a woman’s reproductive life: a twin study of hysterectomy and age at menopause. J Clin Endocrin Metab 1998; 83(6):1875–1880. 8. Bonadonna G, Valaguss P, Rossi A, Tancini G, Brambilla C, Zambetti M, Veronesi U. Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res Treat 1985; 5:95–115. 9. Richards MA, O’Reilly SM, Howell A, George WD, Fentiman IS, Chaudary MA, Crowther D, Rubens RD. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with axillary node-positive breast cancer: an update of the Guy’s Manchester Trial. J Clin Oncol 1990; 8:2032–2039. 10. Mattison DR, Thorgeirsson SS. Smoking and industrial pollution and their effects on menopause and ovarian cancer. Lancet 1978; 1(8057):187–188. 11. Tappel AL. Vitamin E and selenium protection from in vivo lipid peroxidation. Ann N Y Acad Sci 1980; 355(8057):18–31. 12. Van Noord PAH, Dubas JS, Dorland M, Boersma H, Velde E. Age at natural menopause in a population-based screening cohort: the role of menarche, fecundity, and lifestyle factors. Fertil Steril 1997; 68(1):95–102. 13. Khaw KT. Epidemiology of the menopause. Br Med J 1992; 48(2):249–261. 14. van Keep PA, Brand PC, Lehert P. Factors affecting the age at menopause. J Biosoc Sci Suppl 1979; (6):37–55. 15. Stanford JL, Hartge P, Brinton LA, Hoover RN, Brookmeyer R. Factors influencing age at natural menopause. J Chron Dis 1987; 40(11):995–1002. 16. McKinlay SM, Brambilla PJ, Posner JG. The normal menopause transition. Maturitas 1992;14(2):103–115. 17. Collett ME, Wertenberger GE, Fiske VM. The effect of age upon the pattern of the menstrual cycle. Feril Steril 1954; 5(5):437–447. 18. Metcalf MG, Livesey JH. Gonadotropin excretion in fertile women: effect of age and the onset of the menopausal transition. J Endocrin 1985; 105(3):357–362. 19. Channing CP, Gagliano P, Hoover DJ, Tanabe K, Batta SK, Sulewski J, Lebech P. Relationship between human follicular fluid inhibin F activity and steroid content. J Clin Endocrinol Metab 1981; 52(6):1193–1198. 20. Swartzman LC, Edelberg R, Kemmann E. Impact of stress on objectively recorded menopausal hot flushes and on flush report bias. Health Psychol 1990; 9(5):529–545.

462

Mahajan et al.

21. Sherman BM, West JH, Korenman SG. The menopausal transition; analysis of LH, FSH, estradiol and progesterone concentrations during the menstrual cycles of older women. J Clin Endocrinol Metab 1976; 42(4):629–636. 22. MacNaughton J, Banah M, McCloud P, Hee J Burger H. Age related changes in follicle stimulating hormone, luteinizing hormone, estradiol and immunoreactive inhibin in women of reproductive age. Clin Endocrinol 1992; 36(4):339–345. 23. Burger HG, Dudley EC, Hopper JL, Shelley JM, Green A, Smith A, Dennerstein L, Morse C. The endocrinology of the menopausal transition: a cross-sectional study of a population based sample. J Clin Endocrinol Metab 1995; 80(12):3537–3545. 24. Ahmed Ebbiary NA, Lenton EA, Cooke ID. Hypothalamic pituitary ageing: progressive increase in FSH and LH concentrations throughout the reproductive life in regularly menstruating women. Clin Endocrinol (Oxf) 1994; 41(2):199–206. 25. Treolar AE, Boynton RE, Behn BG, Brown BW. Variation of the human menstrual cycle through reproductive life. Int J Fertil 1967; 12(1):77–127. 26. Reyes FI, Winter JS, Faiman C. Pituitary ovarian relationships preceeding the menopause. I. A cross-sectional study of serum follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, and progesterone levels. Am J Obstet Gynecol 1977; 129(5):557–564. 27. Shideler SE, DeVane GW, Kalra PS, Benirschke K, Lasley BL. Ovarian pituitary hormone interactions during the perimenopause. Maturitas 1989; 11:331–339. 28. Vagenakis AG. Endocrine aspects of menopause. Clin Rheumatol 1989; 8(suppl 2): 190–251. 29. Judd HL, Judd GE, Lucas WE, Yen SS. Endocrine function of the postmenopausal ovary. Concentrations of androgens and estrogens in ovarian and peripheral vein blood. J Clin Endocrinol Metab 1974; 39:1020–1024. 30. Meldrum DR, Davidson BJ, Tataryn IV, Judd HL. Changes in circulating steroids with aging in postmenopausal women. Obstet Gynecol 1981; 57(5):624–628. 31. Longcope C, Franz C, Morello C, Baker R, Johnston CC. Steroid and gonadotropin levels in women during the peri-menopausal years. Maturitas 1986; 8(3):189–196. 32. Grodin JM, Siiteri PK, MacDonald PC. Source of estrogen in postmenopausal women. J Clin Endocrinol Metab 1973; 36(2):207–214. 33. Judd HL, Shamonki IM, Frumar AM, Lagasse LD. Origin of serum estradiol in postmenopausal women. Obstet Gynecol 1982; 59(6):680–686. 34. Purifoy FE, Kooprano LH, Tatum RW. Steroid hormones and aging: free testosterone and androstenedione in normal females age 20–87 years. Hum Biol 1980; 52(2):181– 191. 35. Yen SS, The biology of menopause. J Reprod Med 1977; 18(6):287–296. 36. Ginsberg ES, Hot flashes—physiology, hormonal therapy, and alternative therapies. Obstet Gynecol Clin North Am 1994; 21(2):381–390. 37. Voda AM. Climacteric hot flash. Maturitas 1981; 3:73–90. 38. Casper RF, Yen SS. Neuroendocrinology of menopausal flushes: an hypothesis of flash mechanism. Clin Endocrinol 1985; 22(3):293–312. 39. Freedman RR. Biochemical, metabolic, and vascular mechanisms in menopausal hot flashes. Fertil Steril 1998; 70(2):332–337. 40. Kronenberg F. Hot flashes: epidemiology and physiology. Ann N Y Acad Sci 1990; 592:52–86. 41. Mashchak CA, Kletzky OA, Artal R, Mishell DR. The relation of physiologic changes to subjective symptoms in postmenopausal women with and without hot flushes. Maturitas 1984; 6:301–308. 42. Erlik J, Meldrum DR, Judd HL. Estrogen levels in postmenopausal women with hot flashes. Obstet Gynecol 1982; 59:403–407.

Menopause and Hormone Replacement Therapy

463

43. McKinlay SM, Jefferys M. The menopausal syndrome. Br J Prev Soc Med 1974; 28: 108–115. 44. Feldman BM, Voda MA, Gronseth E. The prevalence of hot flash and associated variables among perimenopausal women. Res Nurs Health 1985; 8:261–268. 45. Sherman BM, Wallace RB, Bean JA, Chang Y, Schlabaugh L. The relationship of menopausal hot flushes to medical and reproductive experience. 1981; 36(3):306–309. 46. Chakravarti S, Collins WP, Newton JR, Oram DH, Studd JW. Endocrine changes and symptomatology after oophorectomy in premenopausal women. Br J Obstet Gynaecol 1977; 84(10):769–775. 47. Silva NL, Boulant JA. Effects of testosterone, estradiol, and temperature on neurons in preoptic tissue slices. Am J Physiol 1986; 250(4 pt 2):R625–R632. 48. Walsh B, Schiff I. Vasomotor flushes. Ann N Y Acad Sci 1990; 592:346–356. 49. Woodward S, Freedman RR. The thermoregulatory effects of menopausal hot flashes on sleep. Sleep 1994; 17(6):497–501. 50. Roffward HP. Diagnostic classification of sleep and arousal disorders. Sleep 1979; 2:1–137. 51. Shaver J, Giblin E. Lentz M, Lee K. Sleep patterns and stability in perimenopausal women. Sleep 1988; 11(6):556–561. 52. Schiff I, Regestein Q, Tulchinsky D, Ryan KJ. Effects of estrogens on sleep and psychological status of hypogonadal women. JAMA 1979: 242(22):2405–2407. 53. Savvas M, Bishop J, Laurent G, Watson N, Studd J. Type III collagen content in the skin of postmenopausal women receiving oestradiol and testosterone implants. Br J Obstet Gynaecol 1993; 100(2):154–156. 54. Brincat M, Kabalan S, Studd JW, Moniz CF, de Trafford J, Montgomery J. A study of the decrease of skin collagen content, skin thickness, and bone mass in the postmenopausal women. Obstet Gynecol 1987; 70(6):840–845. 55. Callens A, Vaillant L, Lecomte P, Berson M, Gall Y, Lorette G. Does hormonal skin aging exist? A study of the influence of different hormone therapy regimens on the skin of postmenopausal women using non-invasive measurement techniques. Dermatology 1996; 193(4):289–294. 56. Maheux R, Naud F, Rioux M, Grenier R, Lemay A, Guy J, Langevin M. A randomized double-blind, placebo-controlled study on the effect of conjugated estrogens on skin thickness. Am J Obstet Gynecol 1994; 170(2):642–649. 57. Levin RM, Jacobowitz D, Wein AJ. Autonomic innervation of rabbit urinary bladder following estrogen administration. Urology 1981; 27(5):449–453. 58. Dionne FT, Lesage RL, Dube JY, Tremblay RR. Estrogen binding proteins in rat skeletal and perineal muscles: in vitro and in vivo studies. J Steroid Biochem 1979; 11(2): 1073–1080. 59. Ekstrom J, Iosif CS, Malmberg L. Effects of long-term treatment with estrogen and progestrone on in vitro muscle responses of the female rabbit urinary bladder and urethra to autonomic drugs and nerve stimulation. J Urol 1993; 150:1284–1288. 60. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med 1993; 329(11):753–756. 61. Greendale GA, Lee NP, Arriola ER. The menopause. Lancet 1999; 353:571–580. 62. Fantl JA, Cardozo l, McClish DK. Estrogen therapy in the management of urinary incontinence in postmenopausal women: A meta-analysis. First report of the Hormones and Urogenital Therapy Committee. Obstet Gynecol 1994; 83(1):12–18. 63. Zinner NR, Sterling AM, Ritter RC. Role of urethral softness in urinary incontinence. Urology 1980; 16:115–117. 64. Mattingly RF, Davis LE. Primary treatment of anatomic stress urinary incontinence. Clin Obstet Gynaecol 1984; 27:445–458.

464

Mahajan et al.

65. Diokno AC, Brock BM, Brown D. Prevalence of urinary incontinence and other urological symptoms in the non-institutionalized patient. J Urol 1986; 136:1022–1025. 66. Iosif CS, Bekassy Z. Prevalence of genito-urinary symptoms in the late menopause. Acta Obstet Gynecol Scand 1984; 63:257–260. 67. Ouslander JG, Kane RL, Abrass IB. Urinary incontinence in elderly nursing home patients. JAMA 1982; 248:1194–1198. 68. Fantl JA, Wyman JF, McClish DK, Bump RC. Urinary incontinence in communitydwelling women: clinical, urodynamic, and severity characteristics. Am J Obstet Gynecol 1990; 162(4):946–951. 69. Bump RC, Friedman CI. Intraluminal urethral pressure measurements in the female baboon: effects of hormonal manipulation. J Urol 1986; 136:508–511. 70. Bhatia NN, Bergman A, Karram MM. Effects of estrogen on urethral function in women with urinary incontinence. Am J Obstet Gynecol 1989; 160(1):176–181. 71. Hinton P, Tweddell AL, Mayne C. Oral and intravaginal estrogens alone and in combination with alpha adrenergic stimulation in genuine stress incontinence. Int Urogynecol J 1990; 1:80–86. 72. Walter S, Wolf H, Barlebo H. Urinary incontinence in postmenopausal women treated with estrogens. Urol Int 1978; 33:135–143. 73. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med 1993; 329:753–760. 74. Fantl JA, Bump RC, Robinson D, McClish DK, Wyman JF. The Continence Program for Women Research Group. Efficacy of estrogen supplementation in the treatment of urinary incontinence. Obstet Gynecol 1996; 88(5): 745–749. 75. Wilson PD, Faragher B, Butler B, Bu’Lock D, Robinson EL, Brown AD. Treatment with oral piperazine oestrone sulphate for genuine stress incontinence in postmenopausal women. Br J Obstet Gynaecol 1987; 94(6): 568–574. 76. Riggs BL, Melton JL. Involutional osteoporosis. N Engl J Med 1986; 314(26):1676– 1686. 77. World Health Organization. Assessment of Fracture Risk and Its Application for Postmenopausal Osteoporosis. Geneva, Switzerland: World Health Organization, 1994. Technical Report Series. 78. Melton LJ. Hip fractures: a worldwide problem today and tomorrow. Bone 1993; 14: S1–S8. 79. Melton LJ, Chrischilles EA, Cooper C, Lane AW, Riggs BL. Perspective: how many women have osteoporosis? J Bone Mineral Res 1992; 7(9):1005–1010. 80. Parfitt AM, Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem 1994; 55(3):273–286. 81. Manolagas SC, Jilka RL. Bone marrow, cytokines and bone remodeling: emerging insights into the pathophysiology of osteoporosis. N Engl J Med 1995; 332(5):305– 311. 82. Pacifici R. Estrogen, cytokines and pathogenesis of postmenopausal osteoporosis. J Bone Mineral Res 1996; 11(8):1043–1051. 83. Riggs BL. Overview of osteoporosis. West J Med 1991; 154(1):63–77. 84. Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, Cauley J, Black D, Vogt TM. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 1995; 332(12):767–773. 85. Melton LJ, Atkinson EJ, O’Fallon WM, Wahner HW, Riggs BL. Long-term fracture prediction by bone mineral assessed at different skeletal sites. J Bone Mineral Res 1993; 8(10):1227–1233. 86. Miller PD, Bonnick SL, Rosen C. Guidelines for the clinical utilization of bone mass measurement in the adult population. Society for Clinical Densitometry. Calcif Tissue Int 1995; 57:251–252.

Menopause and Hormone Replacement Therapy

465

87. Price CP, Thompson PW, The role of biochemical tests in the screening and monitoring of osteoporosis. Ann Clin Biochem 1995; 32(pt. 3):244–260. 88. Gertz BJ, Shao P, Hanson DA, Quan H, Harris ST, Genant HK, Chestnut CH, Eyre DR. Monitoring bone resorption in early postmenopausal women by an immunoassay for cross-linked collagen peptides in urine. J Bone Mineral Res 1994; 9(2):135– 142. 89. Steiger P, Cummings SR, Black DM, Spencer NE, Genant HK. Age-related decreements in bone mineral density in women over 65. J Bone Mineral Res 1992; 7(6): 625–632. 90. Cummings SR, Black DM, Nevitt MC, Bronner W, Cauley J, Ensrud K, Genant HK, Palermo L, Scott J, Vogt TM. Bone density at various sites for prediction of hip fractures. Lancet 1993; 341(8837):72–75. 91. Rizzoli R, Slosman D, Bonjour JPH. The role of dual energy x-ray absorptiometry of lumbar spine and proximal femur in the diagnosis and follow-up of osteoporosis. Am J Med 1995; 98(A):33s–36s. 92. Hans D, Dargent-Molina P, Schott AM, Sebert JL, Cormier C, Kotzki PO, Delmas PD, Pouilles JM, Breart G, Meunier PJ. Ultrasonographic heel measurements to predict hip fracture in elderly women: the EPIDOS prospective study. Lancet 1996; 348(9026):511–514. 93. Black DM, Cummings SR, Genant HK, Nevitt MC, Palermo L, Bronner W. Axial and appendicular bone density predict fractures in older women. J Bone Mineral Res 1992; 7(6):633–638. 94. Stewart A, Reid DM, Porter RW. Broadband ultrasound attenuation and dual energy x-ray absorptiometry in patients with hip fractures: which technique discriminates fracture risk? Calcif Tissue Int 1994; 54(6):466–469. 95. The Writing Group for the PEPI Trial. Effects of hormone therapy on bone mineral density: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA 1996; 276(17):1389–1396. 96. Nordin BE. Guidelines for bone densitometry. Med J Aust 1994; 160(8):517–520. 97. Ettinger B, Genant HK, Steiger P, Madvig P. Low-dosage micronized 17B-estradiol prevents bone loss in postmenopausal women. J Obstet Gynecol 1992; 166:479–488. 98. Ettinger B, Gennat HK, Cann CE. Postmenopausal bone loss is prevented by treatment with low-dosage estrogen with calcium. Ann Intern Med 1987; 106(1):40–45. 99. Field CS, Ory SJ, Wahner HW, Herrmann RR, Judd HL, Riggs BL. Preventive effects of transdermal 17B-estradiol on osteoporotic changes after surgical menopause: a two year placebo-controlled trial. AM J Obstet Gynecol 1993; 168(1 pt 1):114–121. 100. Watts BN. Postmenopausal osteoporosis. Obstet Gynecol Survey 1999; 54(8):532– 538. 101. Goldstein SR. Selective estrogen receptor modulators: a new category of therapeutic agents for extending the health of postmenopausal women. Am J Obstet Gynecol 1998; 179(6 pt 1):1479–1484. 102. Khovidhunkit W, Shoback DM. Clinical effects of raloxifene hydrochloride in women. Ann Int Med 1999; 130(5):431–439. 103. Love RR, Mazess RB, Barden HS, Epstein S, Newcomb PA, Jordan VC, Carboro PP, DeMets DL. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N E Engl J Med 1992; 326(13):852–856. 104. Grey AB, Stapleton JP, Evans MC, Reid IR. The effects of anti-estrogen tamoxifen on cardiovascular risk factors in normal postmenopausal women. J Clin Endocrinol Metal 1995; 80(11):3191–3195. 105. Van Leeuwen FE, Benraadt J, Coebergh JW, Kiemeney LA, Gimbrere CH, Otter R, Schonten LJ, Damhuis RA, Botenbal M, Diepenhorst FW, et al. Risk of endometrial cancer after tamoxifen treatment of breast cancer. Lancet 1994; 343:448–452.

466

Mahajan et al.

106. Mitlak BH, Cohen FJ. In search of optimal long-term female hormone replacement: the potential of selective estrogen receptor modulators. Horm Res 1997; 48:155– 163. 107. Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Gluer CC, Krueger K, Cohen FJ, Eckert S, Ensrud KE, Avioli LV, Lips P, Cummings SR. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene. Results from a three-year randomized clinical trial Multiple Outcomes of Raloxifene Evaluation (MORE investigators. JAMA 1999, 282(7):637–645. 108. Delmas PD, Bjarnason NH, Mitlak BH, Ravoux AC, Shah AS, Huster WJ, Draper M, Christiansen C. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997; 337(23):1641–1647. 109. Cohen FJ, Watts S, Shah A, Akers R, Plouffe L. Uterine effects of three-year raloxifene therapy in postmenopausal women younger than age 60. Obstet gynecol 2000; 95(1): 104–110. 110. Guiliana N, Pedrazzoni M, Negri G, Passeri G, Impicciatore M, Girasole G. Bisphosphonates stimulate formation of osteoblast precursors and mineralized nodules in murine and human bone marrow cultures in vitro and promote early osteoblastogenesis in young and aged mice in vitro. Bone 1998; 22(5):455–461. 111. Nishikawa M, Akatsu T, Katayama Y, Yatsutomo Y, Kado S, Kugal N, Yamamoto M, Nagata N, Bisphosphonates act on osteoblastic cells and inhibit osteoclast formation in mouse marrow cultures. Bone 1996; 18(1):9–14. 112. Beauchesne MF, Miller PF. Etidronate and alendronate in the treatment of postmenopausal osteoporosis. Ann Pharmacother 1999; 33:587–598. 113. Watts NB. Treatment of osteoporosis with bisphosphonates. Endocrinol Metab Clin North Am 1998; 27(2):419–439. 114. Lorwood DL. The pharmacology and therapeutic utility of bisphosphonates. Pharmacotherapy 1998; 18:779–789. 115. Rosen CJ, Kessenich CR. Comparative clinical pharmacology and therapeutic use of bisphosphonates in metabolic bone disease. Drugs 1996; 51:537–551. 116. Papapoulos SE. The role of bisphosphonates in the prevention and treatment of osteoporosis. Am J Med 1993; 95(suppl 5A):48–52. 117. McClung M, Clemmesen B, Daifotis A, Gilchrist NL, Eisman J, Weinstein RS, Fuleihan Gel-H, Reda C, Yates AJ, Ravn P. Alendronate prevents postmenopausal bone loss in women without osteoporosis: a double blind, randomized, controlled trial. Alendronate Osteoporosis Prevention Study Group. Ann Int Med 1998; 128(4):253–261. 118. Ravn P, Bidstrup M, Wasnich RD, Davis JW, McClung MR, Balske A, Coupland C, Sahota O, Kaur A, Daley M, Cizza G. Alendronate and estrogen-progestin in the long-term prevention of bone loss: four year results from the Early Postmenopausal Intervention Cohort Study: a randomized controlled trial. Ann Intern Med 1999; 131(12):935–942. 119. Bone HG, Adami S, Rizzoli R, Favus M, Ross PD, Santora A, Prahalada S, Daifotis A, Orloff J, Yates J. Weekly administration of alendronate: rationale and plan for clinical assessment. Clin Ther 2000; 22(1):15–28. 120. Khan SA, Kanis JA, Vasikaran S, Kline WF, Matuszewski BK, McCloskey EV, Beneton MN, Gertz BJ, Sciberras DG, Holland SD, Orgee J, Coombes GM, Rogers SR, Porras AG. Elimination and biochemical responses to intravenous alendronate in postmenopausal osteoporosis. J Bone Mineral Res 1997; 12(10):1700–1707. 121. Lin JH, Russell G, Gertz B. Pharmacokinetics of alendronate: an overview. Int J Clin Pract Suppl 1999; suppl 100:18–26. 122. Rossini M, Girardello S, Braga V, James G, Adami S. Effects of two intermittent alen-

Menopause and Hormone Replacement Therapy

123.

124.

125.

126.

127.

128.

129.

130. 131.

132. 133. 134.

135.

136.

137. 138. 139.

467

dronate regimens in the prevention or treatment of postmenopausal osteoporosis. Bone 2000; 27(1):119–122. Schnitzer T, Bone HG, Crepaldi G, Adami S, McClung M, Kiel D, Felsenberg D, Recker RR, Tonino RD, Roux C, Pinchera A, Foldes AJ, Greenspan SL, Levine MA, Emkey R, Santora AC, Kaur A, Thompson DE, Yates J, Orloff JJ. Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis. Aging Clin Exp Res 2000; 12(1):1–12. Wimalawansa SJ. Combined therapy with estrogen and etidronate has an additive effect on bone mineral density in the hip and vertebrae: four-year randomized study. Am J Med 1995; 99:36–42. Lindsay R, Cosman F, Lobo RA, Walsh BW, Harris ST, Reagan JE, Liss CL, Melton ME, Byrnes CA. Addition of alendronate to ongoing hormone replacement therapy in the treatment of osteoporosis: a randomized, controlled clinical trial. J Clin Endocrinol Metab 1999; 84(9):3076–3081. Mazzzuoli GF, Passeri M, Gennari C, et al. Effects of salmon calcitonin in postmenopausal osteoporosis: a controlled double-blind clinical study. Calcif Tissue Int 1986; 38(1):3–8. Muff R, Dambacher MA, Fisher JA. Formation of neutralizing antibodies during intranasal synthetic salmon calcitonin treatment of postmenopausal osteoporosis. Osteoporosis Int 1991; 1(2):72–75. Riggs BL, Hodgson SF, O’Fallon WM, Chao EY, Wahner HW, Muhs JM, Cedel SL, Melton J. Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. N Engl J Med 1990; 322(12):802–809. Pak CYC, Sakhaee K, Adams-Huet B, Piziak V, Peterson RD, Poindexter JR. Treatment of postmenopausal osteoporosis with slow-release sodium fluoride: final report of a randomized controlled trial. Ann Int Med 1995; 123(6):401–408. Riis B, Thomsen K, Christiansen C. Does calcium supplementation prevent postmenopausal bone loss? N Engl J Med 1987; 316(4):173–177. National Center for Health Statistics. Vital Statistics of the United States. 1992 Volume II Part A. Washington, DC: Public Health Service, 1996. DHHS Publication 961101. Stampfer MJ, Colditz GA, Willet WC. Menopause and heart disease: a review. Ann N Y Acad Sci 1990; 592:193–203. Wyeth-Ayerst Laboratories. Advances in HRT for Disease Prevention and Treatment. Slide presentation. The Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. JAMA 1995; 273:199– 208. Bush TL, Miller VT. Effects of pharmacologic agents used during menopause. Impact on lipids and lipoproteins. In: Mischell D, ed. Menopause: Physiology and Pharmacology. Chicago, IL: Year Book Medical, 1986:187–208. Walsh BW, Schiff I, Rosner B, Greenberg L, Ravinikar V, Sacks FM. Effects of postmenopausal estrogen replacement on the concentration and metabolism of plasma lipoproteins. N Engl J Med 1991; 325(17):1196–1204. Grodstein F, Stampfer M. The epidemiology of coronary heart disease and estrogen replacement in postmenopausal women. Prog Cardiovasc Dis 1995; 38(3):199–210. Gruchow HW, Anderson AJ, Barboriak JJ, Sobocinski KA. Postmenopausal use of estrogen and occlusion of coronary arteries. Am Heart J 1988; 115(5):954–963. Bush TL, Barrett-Connor E, Cowan LD, Criqui MH, Wallace RB, Suchindran CM, Tyroler HA, Rifkind BM. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study. Circulation 1987; 75(6):1102–1109.

468

Mahajan et al.

140. Wagner JD, Clarkson TB, St Clair RW, Schwenke DC, Shively CA, Adams MR. Estrogen and progesterone replacement therapy reduces low density lipoprotein accumulation in the coronary arteries of surgically postmenopausal cynomolgus monkeys. J Clin Invest 1991; 88(6):1995–2002. 141. Wagner JD, St Clair RW, Schwenke DC, Shively CA, Adams MR, Clarkson TB. Regional differences in arterial low density lipoprotein metabolism in surgically postmenopausal cynomolgus monkeys: effects of estrogen and progesterone replacement therapy. Arteriosclerosis Thrombosis 1992; 12(6):717–726. 142. Sack MN, Rader DJ, Cannon RO. Oestrogen and inhibition of oxidation of lowdensity lipoproteins in postmenopausal women. Lancet 1994; 343(8892):269–270. 143. Shlipak MG, Simon JA, Vittinghoff E, Lin F, Barrett-Connor E, Knopp RH, Levy RI, Hulley SB. Estrogen and progestin, lipoprotein(a), and the risk of recurrent coronary heart disease events after menopause. JAMA 2000; 283(14):1845–1852. 144. Ottosson UB, Carlstrom K, Johansson BG, von Schoultz B. Estrogen induction of liver proteins and high-density lipoprotein cholesterol: comparison between estradiol valerate and ethinyl estradiol. Gynecol Obstet Invest 1986; 22(4):198–205. 145. Barnes RB, Roy S, Lobo RA. Comparison of lipid and androgen levels after conjugated estrogen or depo-medroxyprogesterone acetate treatment in postmenopausal women. Obstet Gynecol 1985; 66(2):216–219. 146. Stanczyk FZ, Shoupe D, Nunez V, Macias-Gonzales P, Vijod MA, Lobo RA. A randomized comparison of nonoral estradiol delivery in postmenopausal women. Am J Obstet Gynecol 1988(6):1540–1546. 147. Jensen J, Riis BJ, Strom V, Nilas L, Christiansen C. Long-term effects of percutaneous estrogens and oral progesterone on serum lipoproteins in postmenopausal women. Am J Obstet Gynecol 1987; 156(7):66–71. 148. Ottosson UB, Johansson BG, von Schoultz B. Subfractions of high-density lipoprotein cholesterol during estrogen replacement therapy: a comparison between progestogens and natural progesterone. Am J Obstet Gynecol 1985; 151(6):746–750. 149. Orimo A, Inoue S, Ikegami A, Hosoi T, Akishita M, Ouchi Y, Muramatsu M, Orimo H. Vascular smooth muscle cells as target for estrogen. Biochem Biophys Res Commun 1993; 195(2):730–736. 150. Williams JK, Adams MR, Klopfenstein HS. Estrogen modulates responses of atherosclerotic coronary arteries. Circulation 1990; 81(5):1680–1687. 151. Magness RR, Rosenfeld CR. Local and systemic estradiol-17β: effects on uterine and systemic vasodilation. Am J Physiol 1989; 256:536–542. 152. Mugge A, Riedel M, Barton M, Kuhn M, Lichtlen PR. Endothelium independent relaxation of human coronary arteries by 17B-estradiol in vitro. Cardiovasc Res 1993; 27(11):1939–1942. 153. Gilligan DM, Quyyumi AA, Cannon RO. Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. Circulation 1994, 89(6): 2545–2551. 154. Pines A, Fisman EZ, Levo Y, Averbuch M, Lidor A, Drory Y, Finkelstein A, HetmanPeri M, Moshkowitz M, Ben-Ari E, et al. The effects of hormone replacement therapy in normal postmenopausal women: measurements of Doppler-derived parameters of aortic flow. Am J Obstet Gynecol 1991; 164(3):806–812. 155. Gangar KF, Vyas S, Whitehead M, Crook D, Meire H, Campbell S. Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause. Lancet 1991; 338(8771):839–842. 156. Rosano GMC, Sarrel PM, Poole-Wilson PA, Collins P. Beneficial effect of eostrogen on exercise-induced myocardial ischemia in women with coronary artery disease. Lancet 1993; 342(8864):133–136.

Menopause and Hormone Replacement Therapy

469

157. Gilligan DM, Badar DM, Panza JA, Quyyumi AA, Cannon RO. Acute vascular effects of estrogen in postmenopausal women. Circulation 1994; 90(2):786–791. 158. Gerhard M, Walsh BW, Tawakol A, Haley EA, Creager SJ, Seeley EW, Ganz P, Creager MA. Estradiol therapy combined with progesterone and endotheliumdependent vasodilation in postmenopausal women. Circulation 1998; 98(12):1158– 1163. 159. Wilcox JG, Hatch IE, Gentzschein E, Stanczyk FZ, Lobo RA. Endothelin levels decrease after oral and nonoral estrogen in postmenopausal women with increased cardiovascular risk factors. Menopause 1997; 67(2):273–277. 160. Mikkola T, Turunen P, Avela K, Orpana A, Viinikka L, Ylikorkala O. 17B-Estradiol stimulates prostacyclin, but not endothelin-1, production in human vascular endothelial cells. J Clin Endocrinol Metab 1995; 80(6):1832–1836. 161. Hong MK, Romm PA, Reagan K, Green CE, Rackey CE. Effects of estrogen replacement therapy on serum lipid values and angiographically defined coronary artery disease in postmenopausal women. Am J Cardiol 1992; 69:176–178. 162. Gruchow HW, Anderson AJ, Barboriak JJ, Sobocinski KA. Postmenopausal use of estrogen and occlusion of coronary arteries. Am Heart J 1988; 115(5):954–963. 163. Sullivan JM, Zwaag RV, Lemp GF, Hughes JP, Maddock V, Kroetz FW, Ramanathan KB, Mirvis DM. Postmenopausal estrogen use and coronary atherosclerosis. Ann Intern Med 1988; 108(3):358–363. 164. Herrington DM, Braden GA, Williams JK, Morgan TM. Endothelial-dependent coronary vasomotor responsiveness in postmenopausal women with and without estrogen replacement therapy. Am J Cardiol 1994; 73(13):951–952. 165. Kannel WB, Wolf PA, Castelli WP, D’Agostino RB. Fibrinogen and risk of cardiovascular disease: the Framingham study. JAMA 1987; 258(9):1183–1186. 166. The Writing Group for the PEPI Trial. Effects of estrogen and estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA 1995; 273(3):199–208. 167. Sprengers ED, Kluft C. Plasminogen activator inhibitors. Blood 1987; 69:381–387. 168. Lupu F, Bergonzelli GF, Heim DA, Cousin E, Genton CY, Bachmann F, Kruithof EK. Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries. Arterioscler Thromb 1993; 13(70):1090–1100. 169. Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet 1993; 342(8879):1076–1079. 170. Oloffsson BO, Dahlen G, Nilsson TK. Evidence for increased levels of plasminogen activator inhibitor and tissue plasminogen activator in plasma of patients with angiographically verified coronary artery disease. Eur Heart J 1989; 10(1):77–82. 171. Koh KK, Mincemoyer R, Bui MN, Csako G, Pucino F, Guetta V, Waclawin M, Cannon RO. Effects of hormone-replacement therapy on fibrinolysis in postmenopausal women. N Engl J Med 1997; 336(10):683–690. 172. Lobo RA, Pickar JH, Wild RA, Walsh B, Hirvonen E. Metabolic impact of adding medroxyprogesterone acetate to conjugated estrogen therapy in postmenopausal women. Obstet Gynecol 1994; 84(6):987–995. 173. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vitinghoff E. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280(7):605–613. 174. Wolf PH, Madans JH, Finucan FF, Higgins M, Kleinman JC. Reduction of cardiovascular disease-related mortality among postmenopausal women who use hormones: evidence from a national cohort. Am J Obstet Gynecol 1991; 164(2):489–494. 175. Stampfer MJ, Willett WC, Colditz GA, Rosner B, Speizer FE, Hennekens CH. A pro-

470

176.

177.

178.

179. 180.

181.

182.

183. 184.

185.

186.

187.

188.

189.

190.

191.

192.

Mahajan et al. spective study of postmenopausal estrogen therapy and coronary heart disease. N Engl J Med 1985; 313(17):1044–1049. Grodstein F, Stampfer MJ, Colditz GA, Willett WC, Manson JE, Joffe M, Rosner B, Fuchs C. Hankinson SE, Hunter DJ, Hennekens CH, Speizer FE. Postmenopausal hormone therapy and mortality. N Engl J Med 1997; 336(25):1769–1775. Stampfer MJ, Colditz GA, Willett WC, Manson JE, Rosner B, Speizer FE, Hennekens CH. Postmenopausal estrogen therapy and cardiovascular disease. Ten-year followup from the Nurses Health Study. N Engl J Med 1991; 325(11):756–762. Grodstein F, Stampfer MJ, Manson JE, Colditz GA, Willett WC, Rosner B, Speizer FE, Hennekens CH. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med 1996; 335(7): 453–460. Henderson BE, Paganini-Hill A, Ross RK. Decreased mortality in users of estrogen replacement therapy. Arch Intern Med 1991(1); 151:75–78. Henderson BE, Paganini-Hill A, Ross RK. Estrogen replacement therapy and protection from acute myocardial infarction. Am J Obstet Gynecol 1988, 159(2):312– 317. Psaty BM, Heckbert SR, Atkins D, Lemaitre R, Koepsell TD, Wahl PN, Siscovick DS, Wagner EH. The risk of myocardial infarction associated with the combined use of estrogens and progestins in postmenopausal women. Arch Intern Med 1994; 154(12): 1333–1339. Falkeborn M, Persson I, Adami HO, Bergstrom R, Eaker E, Lithell H, Mohsen R, Naessen T. The risk of acute myocardial infarction after oestrogen and oestrogenprogestogen replacement. Br J Obstet Gynecol 1992; 99(10):821–828. Rosenberg L, Palmer JR, Shapiro S. A case-control study of myocardial infarction in relation to use of estrogen supplements. Am J Epidemiol 1993; 137(1):54–63. Petitti DB, Perlman JA, Sidney S. Noncontraceptive estrogens and mortality: longterm follow-up of women in the Walnut Creek Study. Obstet Gynecol 1987; 70(3 pt. 1):289–293. Newton KM, LaCroix AZ, McKnight B, Knopp RH, Siscovick DS, Heckbert SR, Weiss NS. Estrogen replacement therapy and prognosis after first myocardial infarction. Am J Epidemiol 1997; 145(3):269–277. Sullivan JM, Vander Zwaag RV, Hughes JP, Maddock V, Kroetz FW. Ramanathan KB, Mirvis DM. Estrogen replacement and coronary artery disease. Effect on survival in post-menopausal women. Arch Intern Med 1990; 150:2557–2562. Wilson PW, Garrison RJ, Castelli WP. Postmenopausal estrogen use, cigarette smoking, and cardiovascular morbidity in women over 50: the Framingham Study. N Engl J Med 1985; 313(17):1038–1043. Eaker ED, Castelli WP. Coronary heart disease and its risk factors among women in the Framingham Study. In: Eaker E, Packard B, Wenger NK, Clarkson TB, Tyroler HA, Eds. Coronary Heart Disease in Women. New York: Haymarket Doyma, 1987: 122–132. Stampfer MJ, Colditz GA. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med 1991; 20(1):47– 63. Koh KK, Blum A, Hathaway L, Mincemoyer R, Casko G, Waclawiw MA, Panza JA, Cannon RO. Vascular effects of estrogen and vitamin E therapies in postmenopausal women. Circulation 1999; 100(18):1851–1857. De Leo V, La Marca A, Morgante G, Ciani F, Zammarchi E, Setacci C. Low-dose folic acid supplementation reduces plasma levels of the cardiovascular risk factor homocysteine in postmenopausal women. Am J Obstet Gynecol 2000; 183(4):945– 947. Garcia Rodriguez LA, Varas C, Patrono C. Differential effects of aspirin and nonste-

Menopause and Hormone Replacement Therapy

193. 194. 195. 196. 197.

198. 199.

200. 201. 202. 203. 204. 205.

206.

207.

208. 209. 210.

211. 212.

213.

471

roidal antiinflammatory drugs in the primary prevention of myocardial infarction in postmenopausal women. Epidemiology 2000; 11(4):382–387. DiSaia PJ, Creasman WT. Clinical Gynecologic Oncology. St. Louis, MO: Mosby, 1997:107–167. Gusberg SB, Kardon P. Proliferative endometrial response to thecal granulosa cell tumors. Am J Obstet Gynecol 1971; 111(5):633–643. Norris HJ, Taylor HB. Prognosis of granulosa-theca tumors of the ovary. Cancer 1968; 21(2):255–263. Smith DC, Prentice R, Thompson DJ. Herrmann WL. Association of exogenous estrogen and endometrial carcinoma. N Engl J Med 1975; 293:1164–1167. Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia: a long-term study of ‘‘untreated’’ hyperplasia in 170 patients. Cancer 1985; 56:403– 412. Chamlian DL, Taylor HB. Endometrial hyperplasia in young women. Obstet Gynecol 1970; 36(5):659–666. Gambrell RD, Teran AZ. Changes in lipids and lipoproteins with long-term estrogen deficiency and hormone replacement therapy. Am J Obstet Gynecol 1991; 165(2): 307–315. Harris JR, Lippman ME, Veronesi U, Willett W. Breast cancer: first of three parts. N Engl J Med 1992; 327(5):319–328. Roy JA, Sawka CA, Pritchard KI. Hormone replacement therapy in women with breast cancer: do the risks outweigh the benefits? J Clin Oncol 1996; 14(3):997–1006. Miller, et al., eds. SEER Cancer Statistics Review 1973–1993. National Cancer Institute, 1997. Miller BA, Feuer EJ, Hankey BF. [Letter]. N Engl J Med 1992; 327(24):1756–1757. Feuer EJ, Wun L-M, Boring CC, Flanders WD, Timmel MJ, Tong T. The lifetime risk of developing breast cancer. J Natl Cancer Inst 1993; 85(11):892–897. Sillero-Arenas M, Delgado-Rodriguez M, Rodigues-Canteras R, Bueno-Cavanillas A, Galvez-Vargas R. Menopausal hormone replacement therapy and breast cancer: a meta-analysis. Obstet Gynecol 1992; 79(2):286–294. Colditz GA, Egan KM, Stampfer MJ. Hormone replacement therapy and risk of breast cancer: results from epidemiologic studies. Am J Obstet Gynecol 1993; 168(5): 1473–1480. Steinberg KK, Thacker SB, Stroup DF, Zack MM, Flanders WD, Berkelman RL. A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer. JAMA 1991; 265(15):1985–1990. Dupont WD, Page DL. Menopausal estrogen replacement therapy and breast cancer. Arch Int Med 1991; 151:67–72. Armstrong BK. Oestrogen therapy after the menopause—boon or bane? Med J Aus 1988; 148:213–214. Bergkvist L, Adami HO, Persson I, Hoover R, Schairer C. The risk of breast cancer after estrogen and estrogen-progestin replacement. N Engl J Med 1989; 321(5):293– 297. Hulka BS, Chambless LE, Deubner DC, Wilkinson WE. Breast cancer and estrogen replacement therapy. Am J Obstet Gynecol 1982;143(6):638–644. DiSaia PJ, Grosen EA, Odicino F, Cowan B, Pecorelli S, Wile AG, Creasman WT. Replacement therapy for breast cancer survivors: a pilot study. Cancer 1995; 76(10 suppl):2075–2078. Fisher B, Dignam J, Bryant J, DeCillis A, Wickham DL, Wolmark N, Constantino J, Redmond C, Fisher ER, Bowman DM, Deschenes L, Dimitrov NV, Margolese RG, Robidoux A, Shibata H, Terz J, Paterson AH, Feldham MI, Farrar W, Evans J, Lickley HL. Five versus more than five years of tamoxifen therapy for breast cancer patients

472

214.

215.

216.

217.

218.

219. 220.

221. 222.

223.

224. 225. 226. 227.

228.

229. 230. 231.

Mahajan et al. with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 1996; 88:1529–1542. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieland S, Tan-Chiu E, Ford L, Wolmark N. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998; 90(18):1371–1388. Cauley JA, Norton L, Lippman ME, Eckert S, Kreuger KA, Purdie DW, Farrerons J, Karasik A, Mellstrom D, Ng KW, Stepan JJ, Dowles TJ, Morrow M, Costa A, Silfen SL, Walls EL, Schmitt H, Muchmore DB, Jordan VC. Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: four-year results from the MORE Trial. Multiple outcomes of raloxifene evaluation. Breast Cancer Res Treat 2001; 65(2):125–134. Jick H, Derby LE, Myers MW, Vasilakis C, Newton KM. Risk of hospital admission for idiopathic venous thromboembolism among users of postmenopausal oestrogens. Lancet 1996; 348(9033):981–983. Grodstein F, Stampfer MJ, Goldhaber SZ, Manson JE, Colditz GA, Speizer FE, Willett WC, Hennekens CH. Prospective study of exogenous hormones and risk of pulmonary embolus in women. Lancet 1996; 348(9033):983–987. Daly E, Vessey MP, Hawkins MM, Carson JL, Gough P, Marsh S. Risk of venous thromboembolism in users of hormone replacement therapy. Lancet 1996; 348:977– 980. Devor M, Barrett-Connor E, Renvall M, Feigal D, Ramsdell J. Estrogen replacement therapy and the risk of venous thrombosis. Am J Med 1992; 92:275–282. Saleh AA, Dorey LG, Dombrowski MP, Ginsburg KA, Hirokawa S, Kowalczyk C, Hirata J. Bottoms S, Cotton DB, Mammen EF. Thrombosis and hormone replacement therapy in postmenopausal women. Am J Obstet Gynecol 1993; 169(6):1554–1557. American Cancer Society. Cancer Facts and Figures. 1997. Grodstein F, Martinez E, Platz EA, Giovannucci E, Colditz GA, Kautzky M, Fuchs C, Stampfer MS. Postmenopausal hormone use and risk for colorectal cancer and adenoma. Ann Intern Med 1998; 128(9):705–712. Calle EE, Miracle-McMahill HL, Thun MJ, Heath CW. Estrogen replacement therapy and risk of fatal colon cancer in a prospective cohort of postmenopausal women. J Natl Cancer Inst 1995; 87(7):517–523. Murakami H, Hasui H. Hormonal control of human colon carcinoma cell growth in serum-free medium. Proc Natl Acad Sci USA 1980; 77:3464–3468. Lointier P, Wildrick DM, Boman BM. The effects of steroid hormones on human colon cancer cell line in vitro. Anticancer Res 1992; 12:1327–1330. Jorm AF, Koren AE, Henderson AS. The prevalence of dementia: a quantitative integration of the literature. Acta Psychiatr Scand 1987; 76:465–479. Evans DA, Funkenstein H, Albert MS, Scherr PA, Cook NR, Chown MJ, Hebert LE, Hennekens CH, Taylor JO. Prevalence of Alzheimer’s disease in a community population of older persons: higher than previously reported. JAMA 1989; 262:2551–2556. Bachman DL, Wolf PA, Linn R, Knoefer JE, Cobb J, Belanger A, D’Agostino RB, White LR. Prevalence of dementia and probable senile dementia of the Alzheimer’s type in the Framingham Study. Neurology 1992; 42(1):115–119. Henderson VW. Estrogen and Alzheimer’s disease: current status. Menopausal Med 1999; 7(1):1–5. Henderson VW. Estrogen, cognition, and a woman’s risk of Alzheimer’s disease. Am J Med 1997; 103(suppl 3A):11–18. Brinton RD, Tran J, Profitt P, Montoya M. 17B-Estradiol enhances the outgrowth and survival of neocortical neurons in culture. Neurochem Res 1997; 22(11):1339–1351.

Menopause and Hormone Replacement Therapy

473

232. Paganini-Hill A, Henderson VW. Estrogen replacement therapy and risk of Alzheimer’s disease. Arch Intern Med 1996; 156(19):2213–2217. 233. Paganini-Hill A, Henderson VW. Estrogen deficiency and risk of Alzheimer’s disease in women. Am J Epidemiol 1994; 140(3):256–261. 234. Szklo M, Cerhan J, Diez-Roux AV, Chambless L, Cooper L, Folsom AR, Fried LP, Knopman D, Nieto FJ. Estrogen replacement therapy and cognitive functioning in the Atherosclerosis Risk Communities (ARIC) Study. Am J Epidemiol 1996; 144(11): 1048–1057. 235. Barrett-Connor E, Kritz-Silverstein D. Estrogen replacement therapy and cognitive function in older women. JAMA 1993; 269(20):2637–2641. 236. Mulnard RA, Cotman CW, Kawas C, et al. Estrogen replacement therapy for treatment of mild to moderate Alzheimer’s disease: a randomized controlled trial. JAMA 2000; 283(8):1007–1015. 237. National Center for Health Statistics. Vital Statistics of the United States 1992. Vol. 2. Part A. Washington, DC: Public Health Service, 1996. DHHS publication 96-1101. 238. Paganini-Hill A, Ross RK, Henderson BE. Postmenopausal oestrogen treatment and stroke: a prospective study. Br Med J 1988; 297(6647):519–522. 239. Longstreth WT Jr, Nelson LM, Koepsell TD, van Belle G. Subarachnoid hemorrhage and hormonal factors in women: a population-based case-control study. Ann Intern Med 1994; 121:168–173. 240. Falkeborn M, Persson I, Terent A, Adami HO, Lithell H, Bergstrom R. Hormone replacement therapy and the risk of stroke. Follow-up of a population-based cohort in Sweden. Arch Intern Med 1993; 153(10):1201–1209. 241. Pedersen AT, Lidegaard O, Kreiner S, Ottesen B. Hormone replacement therapy and risk on non-fatal stroke. Lancet 1997; 350:1277–1283. 242. Finucane FF, Madans JH, Bush TL, Wolf PH, Kleinmen JC. Decreased risk of stroke among postmenopausal hormone users. Results from a national cohort. Arch Intern Med 1993; 153:73–79. 243. The Eye-Disease Case-Control Study Group. Risk factors for neovascular age-related macular degeneration. Arch Ophthalmol 1992; 110:1701–1708. 244. Vingerling JR, Dielemans I, Witteman JC, Hofman A, Grobbee DE, de Jong DT. Macular degeneration and early menopause: a case-control study. Br Med J 1995; 310(6994):1570–1571. 245. Klein BE, Klein R, Jensen SC, Ritter LL. Are sex hormones associated with age-related maculopathy in women? The Beaver Dam Eye Study. Trans Am Ophthalmol Soc 1994; 92:289–295. 246. Riis B, Thomsen K, Christiansen C. Does calcium supplementation prevent postmenopausal bone loss? N Engl J Med 1987; 316(4):173–177. 247. Dawson-Hughes B, Dallal GE, Krall EA, Sadowski L, Sahyoun N, Tanenbaum S. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med 1990; 323:878–883. 248. Reid IR, Ames RW, Evans MC, Gamble GD, Sharpe SJ. Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: a randomized controlled trial. Am J Med 1995; 98:331–335. 249. Recker RR, Hinders S, Davies KM, Heaney RP. Stegman MR, Lappe JM, Kimmel DB. Correcting calcium nutritional deficiency prevents spine fractures in elderly women. J Bone Miner Res 1996; 11:1961–1966. 250. Eastell R. Treatment of postmenopausal osteoporosis. N Engl J Med 1998; 338(11): 736–746. 251. Chapuy MC, Arlot ME, Delmas PD, Meunier PJ. Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. Br Med J 1994; 308: 1081–1082.

474

Mahajan et al.

252. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age and older. N Engl J Med 1997; 337:670–676. 253. Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM, Vitamin D supplementation and fracture incidence in elderly persons: a randomized, placebo-controlled clinical trial. Ann Intern Med 1996; 124:400–406. 254. Goldstein SR, Zeltser I, Horan C, Snyder JR, Schwartz LB. Ultrasonography-based triage for perimenopausal patients with abnormal uterine bleeding. Am J Obstet Gynecol 1997; 177(1):102–108. 255. Riig LA, Hermann H, Yen SS. Absorption of estrogens from vaginal creams. N Engl J Med 1978; 298(4):195–197. 256. American College of Obstetricians and Gynecologists. ACOG Educational Bulletin: Hormone Replacement Therapy. Washington, DC: American College of Obstetricians and Gynecologists, May 1998:516–525. Compendium of Selected Publications. 257. Speroff L, Glass RH, Kase NG. Postmenopausal hormone therapy. In: Clinical Gynecologic Endocrinology and Infertility. 6th ed. Baltimore: Lippincott, Williams and Wilkins, 1999:725–779. 258. Lobo RA, McCormick W, Singer F, Roy S. Depo-medroxyprogesterone acetate compared with conjugated estrogens for the treatment of postmenopausal women. Am J Obstet Gynecol 1984; 63(1):1–5. 259. David A, Don R, Trajchner G, Weissglas L. Veralipride: alternative antidopaminergic treatment for menopausal symptoms. Am J Obstet Gynecol 1988; 158(5):1107–1115. 260. Melis GB, Gambacciani M, Cagnacci A, Paoletti AM, Mais V, Fioretti P. Effects of the dopamine antagonist veralipride on hot flushes and leutinizing hormone secretion in postmenopausal women. Obstet Gynecol 1988; 72:688–692. 261. Lebherz TB, French LT. Nonhormonal treatment of the menopausal syndrome. A double-blind evaluation of an autonomic system stabilizer. Obstet Gynecol 1969; 33: 795–799. 262. Nesheim BI, Saetre T. Reduction of menopausal hot flushes by methyldopa: a double blind crossover trial. Eur J Clin Pharmacol 1981; 20:413–416. 263. Loprinzi CL, Pisansky TM, Fonesca R, Sloan JA, Zahasky KM, Quella SK, Novotny PJ, Rommans TA, Dumesic DA, Perez EA. Pilot evaluation of venlafaxine hydrochloride for the therapy of hot flashes in cancer survivors. J Clin Oncol 1998; 16(7):2377– 2381. 264. Barton DL, Loprinzi CL, Quella SK, Sloan JA, Veeder MH, Egner JR. Fidler P, Stella PJ, Swan DK, Vaught NL, Novotny P. Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. J Clin Oncol 1998; 16(2):495–500. 265. American Society for Reproductive Medicine. Status of Environmental and Dietary Estrogens—Are They Significant Estrogens? A Practice Committee Report; An Educational Bulletin, August 2000:1–5. 266. North American Menopause Society. The role of isoflavones in menopausal health: consensus opinion of the North American Menopause Society. Menopause 2000; 7: 215–229.

27 Diagnosis of Female Sexual Dysfunction CATHY K. NAUGHTON Washington University School of Medicine St. Louis, Missouri, U.S.A.

I.

INTRODUCTION

Female sexual dysfunction (FSD) is an “umbrella” term used for a range of diagnoses that affect female identity, sexuality, quality of life, and mental and physical health. It is both a frustrating and exciting time for patients and health care providers interested in this field as it is evolving in every aspect—from establishing a classification system and diagnosis definitions, to understanding the pathophysiology, to investigating the tools for evaluation, to providing the ultimate management and treatment. This chapter begins with classification, diagnosis definitions, and prevalence of FSD. The anatomy and physiology of the female sexual response are discussed. A portion of the chapter is dedicated to the etiology of FSD, including surgical effects following gynecological and urological procedures. The evaluation, management, and treatment is outlined. The chapter concludes with recommendations for furter investigation to gain better understanding of this entity. The goal of this chapter is to acknowledge FSD as a significant determinant in overall female pelvic health that should be recognized, addressed, and managed. II. CLASSIFICATION The 1999 International Consensus Classification System of Female Sexual Dysfunction (Table 1) preserves the four major categories (sexual desire disorders, 475

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Table 1 The 1999 International Consensus Classification for Female Sexual Dysfunction I. Sexual desire disorders A. Hypoactive sexual desire disorder B. Sexual aversion disorder II. Sexual arousal disorder III. Orgasmic disorder IV. Sexual pain disorders A. Dyspareunia B. Vaginismus C. Other sexual pain disorders (noncoital sexual pain disorder) Source: Adapted from Ref. 1.

sexual arousal disorder, orgasmic disorder, and sexual pain disorders) described inthe Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) of the American Psychiatric Association [2] and the World Health Organization International Statistical Classification of Diseases, 10th Revision (ICD-10) [3]. The sexual desire disorders include hypoactive sexual desire disorder and sexual aversion disorder. The sexual pain disorders include dyspareunia, vaginismus, and noncoital sexual pain disorder. Each of the major diagnosis categories is subtyped as (1) lifelong or acquired; (2) generalized or situational; and (3) organic, psychogenic, mixed, or unknown etiology. Unlike the exclusive psychiatric diagnosis of the DSM-IV or ICD-10 systems, the new consensus classification system applies to all forms of the female sexual dysfunction regardless of etiology.

III. DEFINITIONS The following definitions are related to FSD [1]: Hypoactive sexual desire disorder is the persistent or recurrent deficiency (or absence) of sexual fantasies/thoughts and/or desire for or receptivity to sexual activity, which causes personal distress. Sexual aversion disorder is the persistent or recurrent phobic aversion to and avoidance of sexual contact with a sexual partner, which causes personal distress. Sexual arousal disorder is the persistent or recurrent inability to attain or maintain sufficient sexual excitement, causing personal distress, which may be expressed as a lack of subjective excitement or genital (lubrication/ swelling) or other somatic responses. Orgasmic disorder is the persistent or recurrent difficulty, delay in, or absence of attaining orgasm following sufficient sexual stimulation and arousal, which causes personal distress. Dyspareunia is the recurrent or persistent genital pain associated with sexual intercourse.

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Vaginismus is the recurrent or persistent involuntary spasm of the musculature of the outer third of the vagina, which interferes with vaginal penetration, which causes personal distress. Noncoital sexual pain disorder is recurrent or persistent genital pain induced by noncoital sexual stimulation. The major distinction of the new diagnostic definitions from other classification systems is the “personal distress” criterion. A woman may exhibit characteristics of sexual desire, sexual arousal, or orgasmic disorders, but the diagnosis cannot be made without the condition causing the patient “personal distress.” IV. PREVALENCE In a National Health and Social Life Survey of 1749 women, 43% experienced sexual dysfunction [4]. A decline in sexual interest is noted with aging as measured by frequency of intercourse and solitary masturbation [5]. These end points as measures of a women’s sexuality or activity may be inaccurate as they are dependent on multiple factors, such as the availability of a partner, social or religious restraints, and the intrinsic level of sexual interest. Female sexuality is an experience that may not necessarily have the genital focus it may have for men [6]. The lack of consistently used end points underlies the difficulty in assessing the true prevalence and incidence of FSD. V.

ANATOMY AND PHYSIOLOGY

A. Erectile Organs The female erectile organs include the clitoris and vestibular bulbs. The clitoris, the female counterpart of the male penis, is located posterior to the anterior labial commissure. The penis and clitoris are embryologically derived from the genital tubercle. The portion of the labia minora that passes anterior to the clitoris forms the prepuce of the clitoris. The clitoris consists of three components: (1) outermost glans, (2) midline corpus, and (3) innermost crura. The glans emerges from the labia minora. The corpus, or body, consists of two paired corpora cavernosa approximately 2.5 cm long and lacks corpora spongiosum. The two crura, which form from the separation of the most proximal portions of the corpora in the perineum, attach bilateral to the undersurface of the symphysis pubis at the ischiopubic rami. The vestibular bulbs are 3 cm long and are paired structures that lie along the vaginal orifice beneath the skin of the labia. These bulbs are homologous to the corpus spongiosum of the penis, but are anatomically separated from the clitoris, urethra, and vestibule of the vagina [7]. The autonomical innervation of the clitoris is from the pelvic and hypogastric plexuses. The uterovaginal plexus, carrying sympathetic (T1–L3) and parasympathetic (S2–S4) fibers, lies bilaterally at the base of the broad ligament in the supracervical vagina. This plexus sends direct fibers to both the vagina and the clitoris. Somatic sensory innervation to the clitoris arises in the skin, travels via the dorsal nerve of the clitoris, and continues within the pudendal nerve to reach the sacral spinal cord [8].

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The iliohypogastric pudendal arterial bed provides the blood inflow into the clitoris. B.

Vagina

The vagina is a midline cylindrical organ 7–9 cm in length that extends from the vestibule of the vagina to the cervix of the uterus. The vaginal wall is composed of three layers: (1) an inner glandular layer composed of mucous-type stratified squamous cell epithelium that is hormone sensitive; (2) lamina propria; (3) the muscularis layer, which is composed of outer longitudinal and inner circular smooth muscle. The autonomic innervation of the vagina is from the hypogastric and sacral plexus. The uterovaginal nerves contain both parasympathetic and sympathetic fibers that travel within the uterosacral and cardial ligaments and supply the proximal two thirds of the vagina and corporeal bodies of the clitoris. The somatic sensory innervation is through the pudendal nerve, which reaches the perineum through the Alcock’s canal. The distribution of nerve fibers is greater in the distal compared to the proximal vagina and is greater along the anterior compared to the posterior vaginal wall [9]. The arterial supply to the proximal vagina is from the vaginal branches of the uterine artery; to the middle part of the vagina, it is from hypogastric artery. To the distal vagina, it is from branches of the middle hemorrhoidal and clitoral arteries. C.

Female Sexual Response

The female sexual response is described in four (excitement, plateau, orgasm, and resolution) [10] or three stages (desire, arousal, and orgasm) [11]. The distinction between desire and arousal is not easily made until physiological changes occur. With excitement or arousal, there is increased blood flow to the clitoris, vestibular bulbs, and vagina. The increased clitoral blood flow causes increased clitoral intracavernosus pressure, leading to tumescence and extrusion of the glans. With increased blood flow to the vestibular bulbs, the diameter of the labia minora increases, causing eversion of the labia to expose its inner surface. The increased vaginal blood flow causes engorgement and increased pressure in the vaginal capillary bed, causing plasma transudation and resultant lubrication. The outer supportive fibrous mesh (elastin and collagen) in the distal two thirds of the vagina expands in both length and diameter [12]. The sexual response results in clitoral lengthening and increased vaginal length, diameter, and lubrication [13]. Vasocongestive and neuromuscular events mediate these changes, which may be neurotransmitter-mediated vascular and nonvascular smooth muscle relaxation. There are central nervous system changes noted based on animal studies of the medial preoptic anterior hypothalamic region and related limbic hippocampal structures [14]. VI. ETIOLOGY The etiology of FSD may be categorized as organic, psychogenic, mixed, or unknown.

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A. Organic The medical causes of FSD (Table 2) include cardiovascular, endocrinological, neurological, and autoimmune disorders. Postsurgical anatomical alterations may impair sexual function. Medical conditions may directly or indirectly cause FSD. For example, atherosclerosis may directly impair sexual arousal due to decreased genital blood flow. Indeed, pelvic nerve stimulation in normal and atherosclerotic female New Zealand white rabbits showed significant decreases in nervestimulated vaginal and clitoral blood flow, vaginal wall pressure, and vaginal length changes in animals induced with atherosclerotic vascular disease of the iliohypogastric-pudendal arterial bed compared to control animals [16]. In addition, coronary artery disease may indirectly inhibit sexual activity due to dyspnea. A litany of medications is known to cause FSD (Table 3). Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, commonly used for the treatment of depression, are known to cause decreased sexual desire, arousal, genital sensation, and ability to achieve orgasm [17]. B. Psychogenic Psychosocial factors contributing to FSD may involve intrapersonal and interpersonal conflicts, historical factors, and life stressors. The individual may possess religious taboos, practice social restrictions, or struggle with sexual identity, conflicts, or guilt. The status of interpersonal relationships and conflicts is important. Table 2 Medical Causes of Female Sexual Dysfunction I. Cardiovascular disorders Hypertension Coronary artery disease Previous myocardial infarction II. Endocrinopathies Menopause Diabetes Thyroid disorders Hyperprolactinemia Adrenal disorders III. Neurological diseases Multiple sclerosis Peripheral neuropathies Stroke IV. Other causes Autoimmune disorders Renal disease (dialysis) Bowel disease (colostomy) Bladder disease (incontinence) Gynecological disease (hysterectomy, vulvectomy) Skin disorders (eczema, contact dermatitis) Neoplastic disease Source: Adapted from Ref. 15.

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Table 3 Medications and Female Sexual Dysfunction Medications that cause disorders of desire Psychoactive medications Antipsychotics Barbiturates Benzodiazepines Selective serotonin reuptake inhibitors Lithium Tricylic antidepressants Cardiovascular and antihypertensive medications Antilipid medications Beta-blockers Clonidine (Catapres) Digoxin Spironolactone (Aldactone) Hormonal preparations Danazol (Danocrine) GnRH agonists (Lupron, Synarel) Oral contraceptives Other Histamine H 2-receptor blockers and promotility agents Indomethacin (Indocin) Ketoconazole (Nizoral) Phenytoin sodium (Dilantin) Medications that cause disorders of arousal Anticholinergics Antihistamines Antihypertensives Psychoactive medications Benzodiazepines Selective serotinin reuptake inhibitors Monoamine oxidase inhibitors Tyicyclic antidepressants Medications that cause orgasmic dysfunction Methyldopa (Aldomet) Amphetamines and related anorexic drugs Antipsychotics Benzodiazepines Selective serotonin reuptake inhibitors Narcotics Trazadone (Desyrel) Tricyclic antidepressants* Source: Adapted from Ref. 15. *Also associated with painful orgasm.

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Past or current sexual, verbal, or physical abuse, as well as sexual inexperience, should be determined. Finally, financial problems, family illness, and death are only a few of the life stresses that may contribute to psychogenic FSD. C. Mixed In many cases of FSD, it is difficult to untangle the psychological factors from the physiological effects of disease and treatment because commonly both etiologies may be present. D. Unknown The etiological unknown category is recommended when the diagnosing clinician cannot ascertain a specific etiology based on patient history, physical examination, and/or laboratory tests [1].

VII. SURGICAL EFFECTS OF FEMALE SEXUAL FUNCTION A. Hysterectomy A significant percentage of women undergoing hysterectomy (with or without removal of the cervix) experience a change in sexual function; however, these effects are subject to great individual variation. For some women and/or male partners, the uterus holds special significance as it may be seen as the source of life force, energy flow, or the essence of femininity [18,19]. Even hysterectomy alone, without oophorectomy, may lead to sexual dysfunction [20]. The uterus plays a role in normal sexual function, along with the outer third of the vagina and anal sphincter, as it undergoes rhythmic muscular contraction during orgasm. For some women, cervical pressure during intercourse causes intense excitement, which is postulated to be due to transmitted pressure to the uterus, broad ligaments, and sensitive peritoneal membranes. For some women, this process constitutes and important mechanism for orgasm [21]. Supracervical hysterectomy, which spares the cervix, results in less adverse changes in sexual function. In one study of 104 women interviewed 1 month and 1 year after subtotal hysterectomy, 50% of women reported improvement, while 21% reported deterioration in their sexuality after surgery [22]. Frequency of orgasm after supracervical hysterectomy was greater than after total hysterectomy, but there was no significant difference in postoperative coital frequency, dyspareunia, or libido at 1 year between the groups [23,24]. The most important predictive factor in postoperative sexuality at 1 year after subtotal hysterectomy was preoperative sexual activity [25]. The reduction in orgasms after total compared to supracervical hysterectomy may be due to the greater disruption of proximal vaginal and cervical autonomic innervation associated with the former procedure. Presently, the normal neurovascular anatomy responsible for normal sexual arousal and function is unclear, and the role of the cervix in postoperative improvement or deterioration of sexual function remains unknown [26]. The effects of hysterectomy on FSD may be due to direct anatomical disruption of the genital organs, innervation, or both.

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The interrelated psychological factors involved in hysterectomy are difficult to study scientifically. However, the prevailing theory that FSD after hysterectomy is purely psychogenic is no longer tenable. FSD does not appear to be secondary to increased depression as the risk of depression after hysterectomy for benign disease was found to be no greater than the risk for other major operations [27]. In addition, at 1-year follow-up after subtotal hysterectomy, there was no difference in postoperative sexuality in women with and without a history of psychiatric complaints [28]. B.

Oophorectomy

The menopausal state is a natural oophorectomy. It is defined as no spontaneous menstruation for longer than 6 months or follicle-stimulating hormone (FSH) levels above 40 ng and estradiol levels less than 20 ng. The physiological changes of menopause affect the skin, breast, and bladder as well as the vagina, ovary, fallopian tubes, uterus, and cervix [15]. The vagina undergoes shortening and narrowing due to loss of elasticity. There is a rise in vaginal pH from 3.5–4.5 to greater than 5.0. Thinning of the epithelial layers and diminished physiological secretions may result in pain during or after intercourse. The ovaries and fallopian tubes diminish in size, the uterus decreases in weight, and the cervix decreases mucous production, leading to cervical atrophy. These physical changes, along with mood alterations and a diminished sense of well-being, have a negative impact on sexuality [29]. Menopause is associated with a decline in desire, arousal, and frequency of intercourse, as well as an increase in dyspareunia [30–32]. Interestingly, despite these changes, two studies demonstrate that, although baseline vaginal blood flow in menopausal and postmenopausal women is lower than in premenopausal women, there are no significant differences in vaginal blood flow between premenopausal women and untreated menopausal or postmenopausal women with sexual stimulation [33,34]. Poststimulation blood velocity in postmenopausal women not receiving hormone replacement therapy (HRT) was similar to those receiving HRT. Further research is needed to determine why postmenopausal women without HRT have persistent baseline vaginal mucosal atrophy and dryness despite the ability to demonstrate adequate blood velocity responses to sexual stimulation. There is little research specifically addressing FSD and oophorectomy. Ovarian cancer has the highest mortality of all the gynecological cancers. In addition to the real threat of death, such a diagnosis raises critical issues concerning femininity, motherhood, and sexuality following surgery, chemotherapy, and possibly radiation therapy. Castration, in addition to the hormonal changes, is a threat to a woman’s femininity, which alone may impair sexual function. C.

Vulvectomy

Traditional radical vulvectomy removes the vulva, clitoris, and femoral and inguinal lymph nodes and may remove parts of the urethra, vagina, and anal region. Although surgery for vulvar cancer is often curative, it can be disfiguring and may have direct consequences on physical aspects of sexual function, including dyspareunia, hyperesthesia, pruritus, and persistent significant numbness, making penile penetration indistinguishable [35]. Half of the patients who found sex-

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ual activity acceptable before the operation stopped sexual activity permanently because of physical and emotional changes and negative feelings about their new appearance [36,37]. Not surprisingly, postvulvectomy patients were significantly more depressed and anxious with serious body image disturbances compared to posthysterectomy patients [38]. In a more recent study of 47 postvulvectomy women asked to return an 88question survey to assess body image and the DSM-IV criteria for sexual dysfunction before and after their surgery, there was a significant decrease in sexual frequency and alteration of body image in women after vulvectomy. Of these women, 31% were diagnosed with depression following vulvectomy. There was greater dysfunction in the categories of hypoactive sexual disorder, sexual arousal disorder, and aversion disorder after vulvectomy, but no significant change in dyspareunia, vaginismus, or orgasmic disorder [39]. Reports attempting to correlate extent of surgical resection with resultant sexual dysfunction have not been consistent. There was no difference in satisfaction of patients with their level of functioning when comparing those patients who underwent simple versus radical vulvectomy [38]. Similarly, the extent of surgery or type of vulvectomy did not correlate with the degree of sexual dysfunction [39]. Perhaps preservation of the clitoris is the most important variable in predicting sexual dysfunction after vulvectomy since women with carcinoma in situ of the vulva had less sexual dysfunction if they underwent local excision instead of complete vulvectomy, which often included clitoridectomy [40]. However, since there is little evidence that minimizing the resection avoids sexual dysfunction, margins should not be compromised to preserve vulvar structures other than the clitoris if possible. The treatment of sexual dysfunction associated with vulvectomy requires management of possible concomitant depression. D. Anti-Incontinence and Corrective Prolapse Procedures Very little research is available addressing the impact of isolated anti-incontinence procedures on FSD. Most studies include corrective prolapse procedures for both stress urinary incontinence and/or gential descent. However, one study addressing sexual activity, function, and satisfaction 1 month before and 1 year after antiincontinence procedures in 44 women showed no significant difference in sexual activity before and after surgery. In this study, neither the magnitude of the leakage nor the duration of the incontinence significantly influenced sexual experiences, while continence after surgery promoted sexual desire [41]. A recent retrospective look at 56 women who underwent anterior vaginal wall suspension with or without concomitant posterior repair for stress urinary incontinence and who responded to a mailed questionnaire demonstrated no significant difference in the percentage of women who were sexually active before and after the procedure. Still, nearly 20% of women considered intercourse “to be worse” following surgery [42]. More literature is available addressing the effect of sexual function following corrective prolapse procedures; however, most studies are not based on any diagnosis classification system for FSD, and the indications for surgery are not consistent. General operative treatment of genital prolapse using a variety of surgical methods in a series of 1422 patients resulted in dyspareunia in almost 35% of the women [43]. Similarly, postoperative dyspareunia was noted in all pateints who

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complained of sexual function deterioration (20% of 30 women) after anterior colporrhaphy and colpoperineoplasty for stress incontinence and/or genital descent. Interestingly, although all women in this study were sexually active prior to the operation, 68.2% found their sexual life unsatisfactory due to various reasons (i.e., urinary incontinence, genital descent, vaginal relaxation, and urinary incontinence during intercourse) [44]. Improvement in sexual life is correlated with cessation of urinary incontinence and deterioration in sexual function is associated with dyspareunia [45,46]. Posterior colporraphy, originally described as an operation to support the uterus in case of prolapse, is used by gynecologists to treat rectocele, a herniation of the rectum through the rectovaginal septum that causes a protrusion of the posterior vaginal wall. Although the posterior vaginal defect was anatomically corrected in 76% of patients and there was postoperative relief of symptoms, preoperative sexual dysfunction in 18% of 171 women increased to 47% at a mean follow-up of 3.5 years, with de novo sexual dysfunction developing in 27% of women [47]. In assessing sexual dysfunction with posterior colporraphy, one must control for the increasing age of patients, possible postmenopausal atrophy, and higher incidence or previous vaginal surgery. In all studies involving questionnaires, the method of data gathering (by phone or in person, by physician or uninvolved party) should be considered. Efforts should be made to characterize the nonresponders as well as the responders.

VIII. EVALUATION The first challenge in evaluating a patient with FSD is to determine which major category or categories of FSD is present. This requires a detailed patient history that identifies the dysfunction then defines it as lifelong or acquired, generalized or situational. It is important to realize that more than one dysfunction may exist. The next challenge is to identify causative or confounding medical conditions contributing to the FSD. The history should include psychosocial information and establish the patient’s sexual orientation. A list of prescribed and over-the-counter medications, illicit drug use, and cigarette and alcohol abuse is critical to ascertain. Previous gynecologist and urological conditions or treatments should be elicited. The Brief Index of Sexual Functioning for Women (BISF-W) is a 21-item self-report inventory of sexual interest, activity, satisfaction, and preference. It is a validated, highly reliable instrument to discriminate between depressed and sexually dysfunctional healthy patients; howver, it is exclusively a subjective measure of sexual arousal [48,49]. The routine physical examination should search for signs of general medical conditions. The gynecological examination should be comprehensive with the goal of disease detection. In the case of sexual pain disorders, the physical examination is aimed toward reproducing and localizing the pain encountered during sexual activity. The examination begins with inspection of the external genitalia to note pubic hair amount and distribution, skin color and texture, and the presence of ulcers. The clitoris is exposed to rule out any adhesions. Skin should be assessed for turgor and thickness. If indicated, a cotton swab test is performed by

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gently touching the vestibule of the vagina with a cotton swab to elicit moderate to severe pain in case of vulvar vestibulitis [15]. A monomanual exam is performed with one or two fingers in the vagina and with the other hand away from the abdomen so as not to confuse the source of any discomfort. It allows posterior-to-anterior palpation to access the rectovaginal surface, levator ani, bladder and urethra, cervical motion tenderness, and vaginal depth. A bimanual exam is subsequently performed to palpate the uterus and adnexa. A rectovaginal examination is performed to rule out endometriosis and to obtain stool for guaiac test. The timing of the speculum exam depends on the patient’s symptoms. In patients with dypareunia, the speculum examination follows the bimanual examination because localization of pain is most critical. In contrast, in patients suspected of vaginitis, cervical cancer, or sexually transmitted disease, cultures and vaginal samples should be obtained with the speculum before the bimanual exam. The speculum exam allows evaluation of cervical discharge, vaginal mucosa, and pH. It facilitates examination for prolapse and obtaining Papanicolaou smear and cultures. Presently, no specific laboratory or radiographic testing is universally recommended. However, others have recommended documenting physiological changes during female sexual arousal. There are several instruments available to evaluate physiological changes during female sexual arousal. Vaginal photoplethysmography is a quantitative record of the extent of vasocongestion in the vaginal capillaries. A tampon-shaped probe emitting infrared light is inserted into the vagina. The probe has a photosensitive receiving sensor that detects light reflected back from the mucosa. Less infrared light is reflected back to the photosensitive sensor with increasing vaginal mucosa engorgement. It is a validated instrument to estimate vaginal blood flow, or engorgement, but measurements are subject to movement artifact, a significant limitation during stimulation [50,51]. The documentation of labial and vaginal temperature changes relies on thermal clearance techniques based on the principle that blood flow changes may be recorded by measuring heat transfer away from an intravaginal probe kept at constant temperature (slightly above body core temperature). As vaginal blood flow increases, more heat is transferred away from the heated device, thus more electrical power is needed to maintain the electrode at the fixed temperature. Therefore, higher amounts of recorded energy translate to higher levels of blood flow [52]. Duplex Doppler ultrasonography offers continuous real-time imaging of anatomical and vasogestive components of the sexual response to allow assessment of female genital hemodynamic changes during sexual arousal. It provides objective data by measuring clitoral, labial (vestibular bulb), urethral, and vaginal arterial peak systolic velocity and end diastolic velocity. Physiological parameters at baseline and following a 15-min standardized erotic video with three-dimensional surround sound glasses used for visual stimuation are measured [34]. Duplex Doppler ultrasonography allows measurements of blood velocity in the clitoral cavernosal artery and records changes in flow associated with intravaginal pressure changes with stimulation [53]. Vaginal pressure and volume changes may be measured at 0-cc and 30-cc

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increments of air installation to assess compliance or elasticity. Maximum volume is the volume at which the patient experiences vaginal pressure or fullness that is uncomfortable, but not painful. Maximum compliance is the intravaginal pressure at maximum volume. IX. MANAGEMENT AND TREATMENT A specific etiology for FSD is often not identified. If no specific etiology is discovered, basic treatment guidelines include providing education, enhancing stimulation, eliminating routine, providing distraction techniques, encouraging noncoital behaviors, and minimizing dyspareunia. In recommending even the basic treatment guidelines, the patient’s and partner’s personal tastes and comfort level must be considered. Sexual activity is not correlated with overall sexual satisfaction or intimacy in all persons [29,32]. A.

Disorders of Desire

In premenopausal women, disorders of desire may be secondary to lifestyle factors, boredom with sexual routines, medications, or another FSD, such as pain or orgasmic disorder. The patient may be able to enhance stimulation by eliminating routine with changes in position and venues and the addition of erotic materials. In peri- and postmenopausal women, estrogen therapy has been shown to correlate positively with sexual activity, enjoyment, and fantasies, the latter of which are thought to represent desire [54,55]. The women most likely to improve will demonstrate physical effects of hypoestrogenism as the mechanism of estrogen’s effects on desire occurs through improvement in urogenital atrophy, vasomotor symptoms, and depression. Progesterone therapy, on the other hand, which is necessary in estrogen-treated patients with an intact uterus, has a negative impact on desire by dampening mood and decreasing available androgens [56]. Androgens play a role in the maintenance of sexual desire in women [57]. Testosterone appears to have a direct role in sexual desire; however, these studies were conducted on mainly testosterone-deficient oophorectomized women or women who developed supraphysiological levels secondary to treatment [31]. Testosterone therapy for the treatment of inhibited desire and/or vaginismus in premenopausal women is controversial. The “normal” or “therapeutic” range of testosterone is unknown. Since there are no currently available evidence-based protocols supporting the use of testosterone therapy for the treatment of desire disorders, testosterone therapy should be considered investigational. Patients with current or previous breast cancer, uncontrolled hyperlipidemia, liver disease, acne, or hirsuitism should not receive testosterone therapy. The potential side effects of testosterone, including lower levels of high-density lipoprotein, acne, hirsuitism, clitorimegaly, and voice deepening occurs in 5–35% of patients [58]. However, lowering lipoprotein levels is rarely significant if estrogen and testosterone are coadministered; and the other side effects are reversible with medication discontinuation or lower dose adjustment [59]. Pretreatment baseline testosterone levels (free and total), lipid profile, liver

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enzymes, mammography, and Papanicolaou smear should be performed. Testosterone is administered with estrogen therapy to prevent deleterious effects on lipoprotein levels. Testosterone may be administered orally (methyltestosterone (Android) 1.25–2.5 mg daily, or micronized testosterone 5 mg twice daily), topically (testosterone proprionate (2% in petroleum) applied daily to every other day), or as testosterone injectables/pellets. None of these medications are approved by the Food and Drug Administration for treatment of desire disorders. Testosterone levels, lipid profile, and liver enzymes should be reevaluated at 3– 4 months. Symptoms and side effects should be monitored and doses adjusted to the lowest effective dose. Some authors recommend that total levels remain in the “normal” range for premenopausal women. Serum lipid levels and liver enzyme levels should be monitored every 6–12 months, and patients should have routine Papanicolaou smear and mammography studies. B. Disorders of Arousal Current treatment of disorders of arousal is limited to the use of lubricants, vitamin E, and mineral oils. If the disorder is secondary to inadequate stimulation, encourage adequate foreplay or the use of vibrators. Taking a warm bath before intercourse may increase arousal. Employing distraction techniques, such as the Kegel exercise, background music, videos, or television during intercourse, may alleviate anxiety. In postmenopausal women, urogenital atrophy is the most common cause of arousal disorders. If not contraindicated, women displaying physical effects of estrogen deficiency should be treated with estrogen replacement therapy to alleviate symptoms. Therapeutic doses of estrogen can control hot flashes for perimenopausal women. For the woman in remote menopause who suffers from symptoms of vaginal dryness or irritation, a trial of oral estrogen or topical estrogen cream is indicated. Although there is no evidence thus far that topical estrogen cream affects sexual arousal, it clearly results in decreased local vaginal pain and vaginal dryness [60]. When estrogen therapy is contraindicated, alternative therapy with clonidine [61] counteracts the excess central adrenergic activity presumably responsible for the onset of hot flashes. However, clonidine has been associated with the inability to achieve orgasm in some women as well as fatigue or sleepiness [62]. Small-vessel atheroscleroic disease of the vagina and clitoris may contribute to arousal disorders, and several studies exploring vasoactive medications have been and are presently under investigation. Besides hormonal therapy, all nonhormonal medications considered for the treatment of FSD are adopted from the treatment of male erectile dysfunction and should be considered investigational for women until further data specifically regarding FSD are available. Prostaglandin E1 (PGE1) relaxes cavernosal smooth muscle. One case report demonstrated increased clitoral blood flow and clitoral erection following PGE1 injection into the clitoral corporal erectile tissue in a case of hyperreactio luteinalis [63]. Other agents being considered for the treatment of vasculogenic FSD include phentolamine and L-arginine. Phentolamine induces vascular smooth muscle relaxation via nonspecific α-adrenergic blockage and direct smooth muscle relaxation. L-Ar-

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ginine is an amino acid precursor to nitric oxide, a mediator of vascular and nonvascular smooth muscle relaxation. Clinical studies to determine the safety and efficacy of these medications for the treatment of FSD are still pending. Sildenafil, the selective type 5 cyclic guanosine monophosphate (cGMP)– specific phosphodiesterase inhibitor that decreases the metabolism of cGMP, the second messenger in nitric oxide–mediated male erectile response, was targeted as a potential treatment for vasculogenic FSD. Although a 23% improvement in lubrication was reported with sildenafil in postmenopausal women, overall sexual dysfunction did not improve significantly [64]. In a group of estrogenized women with arousal disorder, sildenafil did not improve perceived sexual response at 12 weeks [65]. These studies indicate that successful therapy used in the treatment of male erectile dysfunction cannot simply be translated to FSD. C.

Orgasmic Disorders

Orgasmic disorders are caused by sexual inexperience or the lack of sufficient stimulation. They are common in women who have never experienced orgasm. There may also be psychological components due to “involuntary inhibition” of the orgasmic reflex secondary to medications or chronic disease. Anorgasmia is responsive to therapy. Treatment relies on maximizing stimulation and minimizing inhibition [66]. Stimulation may include masturbation and/or use of a vibrator with learned muscular control of sexual tension by alternating contraction and relaxation of the pelvic muscles during sexual arousal, similar to Kegel exercises. Methods to minimize inhibition include distraction by “spectatoring” or observing oneself from a third-party perspective, fantasizing, or listening to music. D.

Pain Disorders

Dyspareunia is subcategorized into three types: superficial, vaginal, and deep. Superficial dyspareunia occurs with attempted penetration. It is usually secondary to anatomical or irritative conditions or vaginismus. Treatment is with topical lidocaine, warm baths before intercourse, and biofeedback. Vaginal dyspareunia is pain related to friction or lubrication problems, including arousal disorders. Treatment is the same as for superficial dyspareunia with the addition of lubricants. Deep dyspareunia is pain related to thrusting, often associated with pelvic disease or inhibited relaxation [67]. The patient may find relief with position changes and nonsteroidal anti-inflammatory drugs before intercourse. Diagnosis and treatment of the underlying etiology should be aggressively searched. The physical exam must focus on the physician’s ability to re-create the pain. Pain control strategies along with treatment of the underlying disease are recommended. Treatment of vaginismus requires progressive muscle relaxation by having the patient alternate contracting and relaxing the pelvic muscles around the examiner’s finger (Kegels) and vaginal dilatation with the use of commercial dilators or tampons of increasing diameter placed into the vagina for 15 min twice daily. Success rates approach 90% [66,68].

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FUTURE

It is clear that the entity of FSD is multifaceted. Although embryological and anatomical parallels exist between men and women, the multifactorial nature of FSD is distinct. Therapies successfully used for the treatment of male erectile dysfunction are not necessarily effective in managing FSD. There are clearly differences in the underlying pathophysiology of male and female sexual dysfunction. These difference require further elucidation before any potential therapies can be studied. The first challenge is to perform epidemiological studies on prevalence, predictors, and outcomes of FSD. A recent study showed FSD to be highly prevalent, but this study was limited to women younger than 60 years [4]. Longitudinal studies to include older women, that separate a woman’s interest and activity levels from her partner’s, and with repeated measures of data to allow valid pretreatment and post-treatment assessments of women with specific disease states need to be performed. Studying the older population of women may provide better insight into the role of hormones and the effects of aging and menopause in modulating sexual desire and arousal. Several questionnaires are available in the literature that measure FSD; however, these were published before the consensus classification was developed and therefore do not address some aspects of the current definitions. New female sexual functional validated questionnaires need to be developed, first to screen a patient with FSD to identify the specific diagnosis classification. Then, another set of questionnaires aimed at delineating the specific FSD needs validation. These questionnaires must take into consideration the clinical research end points and outcomes. For example, hypoactive sexual desire disorder questionnaires should address measures of receptivity, spontaneous thoughts, or fantasies about sexual activity. For sexual arousal disorder, measures of peripheral responses (lubrication, swelling) and central responses (subjective arousal) to stimulation require investigation. Although sexual satisfaction disorder was not included as a new diagnostic category, collected clinical data should include level of sexual satisfaction to determine if this indeed should be reconsidered for a separate diagnostic category [1]. Based on the consensus definitions of “personal distress” to make the diagnosis, validated sexual distress–specific instruments need to be developed for use in clinical trials. Before any new questionnaires are used in women with FSD, a control group of sexually satisfied women should be identified and questionnaire responses correlated with physiological measures. Characterization of the normal neurovascular anatomy responsible for normal sexual arousal and function is needed. The biological mechanisms of sexual arousal and orgasm, the neurophysiology of the sexual response, the role of neurotransmitters, substances involved in vascular smooth muscle tone, vasodilation, and vaginal lubrication are still unknown. It is only after normal physiology is understood that abnormal function can be interpreted. Based on what is learned from the pathophysiology of FSD, current technologies can be utilized to validate and standardize instruments to measure female sexual responses reliably and with reproducibility. A comprehensive approach to the diagnosis, evaluation, and treatment of FSD must include the partner or spouse. As the state-of-the-art treatment for infer-

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tility is becoming more couple-directed, so too should the treatment of sexual dysfunction. It is hoped this concept will become pervasive, and the management and treatment of sexual dysfunction will become couple integrated. REFERENCES 1. Basson R, Berman J, Burnett A, Derogatis L, Ferguson D, Fourcroy J, Goldstein I, Graziottin A, Heiman J, Laan E, Leiblum S, Padma-Nathan H, Rosen R, Segraves K, Segraves RT, Shabsigh R, Sipski M, Wagner G, Whipple B. Report on the international consensus development conference on female sexual dysfunction: defintions and classification. J Urol 2000; 163:888–893. 2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Press, 1994. 3. World Health Organization. ICD-10: Classification of Mental and Behavioral Disorders. Geneva, Switzerland: World Health Organization, 1992. 4. Laumann E. Paik A, Rosen R. Sexual dysfunction in the United States: prevalence and predictors. JAMA 281:537–544. 5. Todarello O, Boscia FM. Sexuality in aging: a study of a group of 300 elderly men and women. J Endocrinol Invest 1985; 8(suppl 2):123–130. 6. Bernhard LA, Dan AJ. Redefining sexuality from women’s own experiences. Nurs Clin North Am 1985; 21:125–136. 7. O’Connell H, Hutson J, Anderson C, Plenter RJ. Anatomic relationship between urethra and clitoris. J Urol 1998; 159:1862–1897. 8. Moore KL. Clinically Oriented Anatomy. 3rd ed. Baltimore: Williams and Wilkins, 1992. 9. Hilliges M, Falconer C, Ekman-Ordeberg G, Johansson O. Innervation of the human vaginal mucosa as revealed by PGP 9.5 immunohistochemistry. Acta Anat (Basel) 1995; 153:119–126. 10. Masters WH, Johnson VE. Human Sexual Response. Boston: Little, Brown and Company, 1966. 11. Kaplan HS. The New Sex Therapy. New York: Brunner/Mazel, 1974. 12. Levin RJ. The mechanism of human female sexual arousal. Ann Rev Sex Res 1992;3:1. 13. Bancroft J. Human Sexuality and Its Problems. Edinburgh, Scotland: Churchhill Livingstone, 1989. 14. Goldstein I, Berman JR. Vasculogenic female sexual dysfunction. Int J Impot Res 1988; 10:S84–S90. 15. Phillips NA. Female sexual dsyfunction: evaluation and treatment. Am Fam Phys 2000; 62:127–136. 16. Park K, Goldstein I, Andry C, Siroky MB, Krane RJ, Azadzoi KM. Vasculogenic female sexual dysfunction: the hemodynamic basis for vaginal engorgement insufficiency and clitoral erectile insufficiency. Int J Impot Res 1987; 9:27–37. 17. Nurnberg HG, Lauriello J, Hensley P, Parker LM, Keith SJ. Sildenafil for iatrogenic serotonergic antidepressant medication-induced sexual dysfunction in four patients. J Clin Psychiatry 1999; 60:33–35. 18. Dennerstein L, Burrows GD. Hormone replacement therapy and sexuality in women. Clin Endocrinal Metab 1982; 11:661–679. 19. Holmes BC. Psychological evaluation and preparation of the patient and family. Cancer 1987; 60:2021–2024. 20. Carlson KJ. Outcomes of hysterectomy. Clin Obstet Gynecol 1997; 40:939–946. 21. Zussman L, Zussman S. Sunley R, Bjornson E. Sexual response after hysterectomyoophorectomy: recent studies and reconsideration of psychogenesis. Am J Obstet Gynecol 1981; 140:725–729.

Diagnosis of Female Sexual Dysfunction

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22. Helstrom L, Lundberg PO, Sorbom D, Backstrom T. Sexuality after hysterectomy: a factor analysis of women’s sexual lives before and after subtotal hysterectomy. Obstet Gynecol 1993; 81:357–362. 23. Kilkku P. Supravaginal uterine amputation versus hysterectomy. Effects on coital frequency and dyspareunia. Acta Obstet Gynecol Scand 1983; 62:141–145. 24. Kilkku P, Gronroos M, Hirvonen T, Rauramo L. Supravaginal uterine amputation versus hysterectomy: effects on libido and orgasm. Acta Obstet Gynecol Scand 1983; 62:147–152. 25. Helstrom L. Sexuality after hysterectomy: a model based on quantitative and qualitative analysis of 104 women before and after subtotal hysterectomy. J Psychosom Obstet Gynecol 1994; 15:219–229. 26. Johns A. Supracervical versus total hysterectomy. Clin Obstet Gynecol 1997; 40:903– 913. 27. Gitlin MJ, Pasnau RO. Psychiatric syndromes linked to reproductive function in women: a review of current knowledge. Am J Psychiatry 1989; 146:1413–1422. 28. Helstrom L, Weiner E, Sorbom D, Backstrom T. Predictive value of psychiatric history, genital pain and menstrual symptoms for sexuality after hysterectomy. Acta Obstet Gynecol Scand 1994; 73:575–580. 29. Cawood EH, Bancroft J. Steroid hormones, the menopause, sexuality and well-being of women. Psychol Med 1996; 26:925–936. 30. Bachmann GA, Leiblum SR. Sexuality in sexagenarian women. Maturitas 1991; 13: 43–50. 31. Davis SR, Burger HG. Clinical review 82: androgens and the postmenopausal woman. J Clin Endocrinol Metab 1996; 81:2759–2763. 32. Laan E, van Lunsen RH. Hormones and sexuality in postmenopausal women: a psychophysiological study. J Psychosom Obstet Gynecol 1997; 18:126–133. 33. Laan E, Everaerd W. Physiological measures of vaginal vasocongestion. Int J Impot Res 10: 1988; S107–S112. 34. Berman JR, Berman LA, Werbin TJ, Flaherty EE, Leahy NM, Goldstein I. Clinical evaluation of female sexual function: effects of age and estrogen status on subjective and physiologic sexual responses. Int J Imp Res 1999; 11(suppl 1): S31–S38. 35. Andersen BL, Hacker NF. Psychosexual adjustment after vulvar surgery. Obstet Gynecol 1983; 62:457–462. 36. Moth I, Andreasson B, Jensen SB, Bock JE. Sexual function and somatopsychic reactions after vulvectomy. Dan Med Bull 1983; 30:27–30. 37. Andreasson B, Moth I, Jensen SB, Bock JE. Sexual function and somatopsychic reactions in vulvectomy-operated women and their partners. Acta Obstet Gynecol Scand 1986; 65:7–10. 38. Stellman RE, Goodwin J, Robinson J, Dansak D, Hilgers RD. Psychological effects of vulvectomy. Psychosomatics 1984; 25:779–783. 39. Green MS, Naumann RW, Elliot M, Hall JB, Higgins RV, Grigsby JH. Sexual dysfunction following vulvectomy. Gynecol Oncol 2000; 77:73–77. 40. Andersen BL, Turnquist D, LaPolla J, Turner D. Sexual functioning after treatment of an in situ vulvar cancer: preliminary report. Obstet Gynecol 1988; 71:15–19. 41. Berglund AL, Fugl-Meyer KS. Some sexological characteristics of stress incontinent women. Scand J Urol Nephrol 1996; 30:207–212. 42. Lemack GE, Zimmern PE. Sexual function after vaginal surgery for stress incontinence: results of a mailed questionnaire. Urology 2000; 56:223–227. 43. Timonen S, Nuoranne E, Meyer B. Operative treatment of genital prolapse. Ann Chir Gynaecol Fenn Suppl 1967; 153:3–13. 44. Poad D, Arnold EP. Sexual function after pelvic surgery in women. Aust N Z J Obstet Gynaecol 1994; 34:471–474.

492

Naughton

45. Gungor T, Ekin M, Dogan M, Mungan T, Ozcan U, Gokmen O. Influence of anterior colporrhaphy with colpoperineoplasty operations for stress incontinence and/or genital descent on sexual life. J Pak Med Assoc 1997; 47:248–250. 46. Haase P, Skibsted L. Influence of operations for stress incontinence and/or genital descensus on sexual life. Acta Obstet Gynecol Scand 1988; 67:659–661. 47. Kahn MA, Stanton SL. Posterior colporrhaphy: its effects on bowel and sexual function. Br J Obstet Gynecol 1997; 104:82–86. 48. Matthew RJ, Weinmann ML. Sexual dysfunction in depression. Arch Sex Behav 1982; 11:323–328. 49. Merikangas JH, Prusoff BA, Kupfer DJ, Frank E. Marital adjustment in major depression. J Affect Dis 1985; 9:5–11. 50. Novelly A, Berone PJ, Ax AF. Photophethysmography: system calibration and light history effects. Psychophysiology 1973; 10:67–73. 51. Heiman JR Psychophysiological models for female sexual response. Int J Impot Res 1998; 10:S94–S97. 52. McCreesh Z, Evans NE, Scanlon WG. Vaginal temperature sensing using UHF ratio telemetry. Med Eng Phys 1996; 18:110–114. 53. Lavoisier P, Aloui R, Schmidt MH, Watrelot A. Clitoral blood flow increases following vaginal pressure stimulation. Arch Sex Behav 1995; 24:37–45. 54. Sherwin BB. The impact of different doses of estrogen and progestin on mood and sexual behavior in postmenopausal women. J Clin Endocrinol Metab 1991; 72:336– 343. 55. Nathorst-Boos J, Wiklund I, Mattsson LA, Sandin K, von Schoultz B. Is sexual life influenced by transdermal estrogen therapy? A double blind placebo controlled study in postmenopausal women. Acta Obstet Gynecol 1993; 72:656–660. 56. Myers LS, Dixen J, Morrissette D, Carmichael M, Davidson JM. Effects of estrogen, androgen and progestin on sexual psychophysiology and behavior in postmenopausal women. J Clin Endocrinol Metab 1991; 70:1124–1131. 57. Appelt H, Stauss B. Effects of antiandrogen treatment on the sexuality of women with hyperandrogenism. Psychother Psychosom 1984; 42:177–181. 58. Slayden SM. Risks of menopausal androgen supplementation. Semin Reprod Endocrinol 1988; 16:145–152. 59. Gelfand MM, Wiita B. Androgen and estrogen-androgen hormone replacement therapy: a review of the safety literature, 1941 to 1996. Clin Ther 1997; 19:367–368, 383– 404. 60. Ayton RA, Darling GM, Murkies AL, Farrell EA, Weisberg E, Selinus I, Fraser ID. A comparative study of safety and efficacy of continuous low dose oestradiol released from a vaginal ring compared with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal vaginal atrophy. Br J Obstet Gynaecol 1996; 103:351– 358. 61. Nagamani M, Kelver ME, Smith ER. Treatment of menopausal hot flashes with transdermal administration of clonidine. Am J Obstet Gynecol 1987; 156:561–565. 62. Smith PJ, Talbert RL. Sexual dysfunction with antihypertensive and antipsychotic agents. Clin Pharm 1986; 5:373–384. 63. Akkus E, Carrier S, Turzan C, Wang TN, Lue TF. Duplex ultrasonography after prostaglandin E1 injection of the clitoris in a case of hyperreactio luteinalis. J Urol 1995; 153:1237–1238. 64. Kaplan SA, Reis RB, Kohn IJ, Ikeguchi EF, Laor E, Te AE, Martins AC. Safety and efficacy of sildenafil in postmenopausal women with sexual dysfunction. Urology 1999; 53:481–486. 65. Basson R, McInnes R, Smith MD, Hodgson G, Spain T, Koppiker N. Efficacy and safety of sildenafil in estrogenized women with sexual dysfunction associated with female sexual arousal disorder. Obstet Gynecol 2000; 95:S54.

Diagnosis of Female Sexual Dysfunction

493

66. Kaplan HS. The Illustrated Manual of Sex Therapy. 2nd ed. New York: Brunner/ Mazel 1987:72–98. 67. Schein M, Zyzanski SJ, Levine S, Medalie JH, Dickman RL, Alemagno SA. The frequency of sexual problems among family practice patients. Fam Prac Res J 1988; 7: 122–134. 68. Rosen RC, Leiblum SR. Treatment of sexual disorders in the 1990s: an integrated approach. J Consult Clin Psychol 1995; 63:877–890.

Index

Abdominal approach to apical prolapse, 284–289 anatomy, etiology, and pathophysiology, 281–282 laparoscopic procedures, 285–287 other abdominal surgeries, 287 surgical approach to apical prolapse, 282–285 Abdominal hysterectomy, bladder injuries during, 393 Abdominal sacrocolpoperineopexy, 287 Abdominal sacrocolpopexy, technique of, 282–284 Abdominal sacrospinous ligament suspension, 287 Acute maximal functional electrical stimulation, 226–227 Adnexal removal in vaginal hysterectomy, 344–345 α-Adreneregic receptor blockers, 6 Age, incontinence and, 3–4 Alzheimer’s disease (AD), estrogen replacement therapy and, 452–453 Ambulatory monitoring, for enhanced urodynamic studies, 100–102 Amitriptyline, 272–273 Antibiotic prophylaxis in preoperative preparation for vaginal hysterectomy, 330 Anticholinergics, for treatment of IC patients, 273 Antihistamines, for treatment of IC patients, 273 Anti-incontinence surgery, effect on female sexual function of, 483–484

Apical prolapse, surgical approach to, 282–285 “Bad bladder” behavior, 197–198 Biofeedback (for incontinence), 221–222 Bladder-anal reflex, 34 Bladder augmentation, 167–175 cystomyotomy and cystomyomectomy, 167–174 enteric bladder augmentation, 174–175 Bladder injuries, 393–395 delayed, 395 Bladder maturation and pathogenesis, 196–198 Bladder outlet obstruction, 180, 184–187 diagnostic problems, 185 incidence, 184 symptoms, 184–185 urodynamic diagnosis, 185–187 Bladder physiology and neurophysiology, 27–42 brain and subcortical pathways, 27–28 neurophysiological evaluation, 30–31 reflex pathways, 28–30 urodynamic studies, 31–41 Bladder training, 220–221 see also Overactive bladder Bleeding, postmenopausal, 457–458 Blood supply to the ureter, 382 Boari flap, 389–390 Bone anchors, in incontinence surgery, 151–154 Bone injuries, pelvic pain and, 249–250 Bonney test, 22 Bovine collagen, 108 495

496 Brain and subcortical areas involved in bladder pathways, 27–28 Breast cancer, estrogen replacement therapy and, 446–449 Burch procedure, 124–129, 134 for laparoscopic surgery, 162, 163

Caffeine, 6 Calcitonin, 433–434 Calcium, 434 for postmenopausal women, 455–457 Cancers, associated with urethral diverticulum, 356 see also types of cancer Cardiovascular disease, effects of estrogen therapy and, 434–440 Catheters, for urodynnamic studies, 81– 82 Central nervous system (CNS), symptoms of menopause affecting, 421–422 Cephazolin, 330 Childbirth, incontinence and, 4 Chronic maximal functional electrical stimulation, 226–227 Clitoral-anal reflex, 34–35 Clorpactin, 274–275 Colon cancer, estrogen replacement therapy and, 450–452 Colpocleisis for treatment of vaginal vault prolapse, 311–327 evaluation, 313–315 history, 313–314 physical examination and studies, 314–315 technique of repair for stress incontinence, 315 pathophysiology and indications for surgery, 312–313 surgical techniques, 315–321 partial colpocleisis, 318–321 total colpocleisis, 315–316 Computer tomography (CT), in evaluation of urinary fistulas, 67–68 Constipation, incontinence and, 6 Continuous leakage, 12 Corrective prolpase procedures, effect on female sexual function of, 483–484 Crush injury of the ureter, 387 Cube pessary, 410–411 Cystometry, single-channel, 79

Index Cystomyomectomy, bladder augmentation by, 167–174 Cystomyotomy, bladder augmentation by, 167–174 Cystoproctography, 52–53 Cystoscopy, 22, 23 Cystourethroscopy, 49 in the diagnosis of urethral diverticulum, 354 Cytology, 22

Daytime urinary frequency and urgency, 14–15 Detrusor hyperreflexia, 13 Detrusor instability, 13, 83–86 Detrusor overactivity, oral treatment of, 219–220 Devascularization injuries, 391 Diagnostic evaluation of the female patient, 11–25 diagnostic evaluations, 16–24 family history, 18 history, 16–17 medications, 18 multisymptoms questionnaires, 20 objective tests, 22–24 pad tests, 20 past medical history, 17–18 physical examination, 20–22 provocative tests, 22 review of symptoms, 19 social history, 19 voiding diary, 19–20 female pelvic dysfunction, 12–16 frequency, urgency, nocturia, 14–15 pelvic floor prolapse, 13–14 pelvic pain, 15 sexual dysfunction, 15–16 urinary incontinence, 12–13 Diagnostic tests for IC, 267–270 Dimethyl sulfoxide (DMSO), 274 Disrupted micturition balance, 226–227 Diuretics, 6 Double-balloon urethrography (DBU), 354–355 in evaluation of urethral diverticulum, 63 Doughnut pessary, 409–410 Durasphere (FDA-approved injectable bulking agent), 116–117 Dynamic urethroscopy, 78–79

Index Dysfunctional elimination syndrome (DES), 196, 207 Dyspareunia, 16, 476 Elderly, incidence of incontinence in, 2, 3–4 Electrical stimulation, 222–223, 225–240 comparative overview of electrical stimulation therapies, 230 disrupted micturition balance, 226–229 electromagnetic stimulation, 231 mechanism of stimulation action, 227– 228 needle stimulation devices, 232 normal urine storage and evacuation, 226 sacral nerve stimulation, 232–238 transvaginal and transanal electrical stimulation devices, 229–231 as treatment modality, 228–229 Elimination diary, 198–199 Endometrial cancer, estrogen replacement therapy and, 445–446 Endothelial, cardioprotective effects of estrogen therapy and, 437–439 Enteric bladder augmentation, 174–175 Erectile organs, 477–478 Established osteoporosis, 424 Estrogen, 429–430 alternative benefits of replacement therapy, 450–454 Alzheimer’s disease, 452–453 colon cancer, 450–452 macular degeneration, 454 stroke, 453–454 phytoestrogens, 459 regimens for replacement therapy, 454–458 risks of replacement therapy, 445–454 selective estrogen receptor modulators (SERMs), 430–432 External transducer catheters, 82 Extracorporal magnetic innervation (ExMI), 231 Extraordinary daytime urinary frequency syndrome, 201 Extraurethral incontinence, 12, 13 Family history, 18 Female sexual dysfunction (FSD), 15–16, 475–493 anatomy and physiology, 477–478

497 [Female sexual dysfunction (FSD)] classification, 475–476 definitions related to, 476–477 etiology, 478–481 evaluation, 484–486 the future, 489–490 management and treatment, 486–488 prevalence, 477 surgical effects of female sexual function, 481–484 anti-incontinence and corrective prolapse procedures, 483–484 hysterectomy, 481–482 oophorectomy, 482 vulvectomy, 482–483 Female sexual response, 478 objective evaluation of, 23–24 Female voiding function, 43–49 Fiberoptic disposable catheters, 82 Fistulas, after ureteral repair, 392 see also Rectovaginal fistulas (RVFs) and complex perineal defects; Urinary fistulas; Vesicovaginal fistula Fluoroscopy, for enhanced urodynamic studies, 100–102 Four-corner bladder neck suspension procedure (for transvaginal surgery), 142–143 Functional incontinence, 13 Gabapentin, for treatment of IC patients, 273 Gaeselen’s test for sacroiliac joint instability, 254, 255 Gehrung pessary, 411 Gellhorn pessary, 410 Genital blood flow, 23 Genital stimulation, 23 Genitourinary tract, symptoms of menopause affecting, 423–424 Giggle incontinence (enuresis risoria), 196, 201–202 Gillet’s test for sacroiliac joint instability, 254 Gittes procedure (for transvaginal surgery), 141–142 Glucose metabolism, effects of estrogen therapy on, 440 Glutaraldehyde cross-linked (GAX) collagen, 108 results using, 114

498 HASTE (half-Fourier acquisition of single-shot turbo spin echo), 70 Heparin, 274 Hinman syndrome, 196, 207–209 History of the patient’s symptoms, 16–17 Hormone replacement therapy (see Menopause and hormone replacement therapy) “Hot flashes,” 421–422 alternative therapies for, 458–459 Hypoactive sexual desire disorder, 16, 476 Hysterectomy, bladder injuries during abdominal hysterectomy, 393 effect on female sexual function of, 481–482 see also Vaginal hysterectomy Iatrogenic urological trauma, 381–396 bladder injuries, 393–395 delayed bladder injury/diagnosis, 395 delayed ureteral complications, 391– 392 diagnosis, 385–386 management and types of injury, 386– 387 prevention of and risk factors for ureteral injury, 383–385 transections/laceration injury, 387–391 ureteral anatomy, 382 ureteral blood supply, 382 ureteral injuries, 381–382 Idiopathic female voiding dysfunction, 45–46 Inadequate bladder emptying, nonsurgical treatment of, 216–217 Incontinence, prevalence and incidence, 1–3 risk factors for, 3–6 symptoms, conditions, and causes of, 12–13 voiding dysfunction and, 1–9 Incontinence pessaries, 410–413 Inflatoball pessary, 409–410 Injectable treatment of stress incontinence, 107–119 complications, 115–116 future developments, 116–117 historical perspective, 107–108 patient selection, 108–110 results, 113–115 surgical technique, 111–112

Index Instrumented voiding study, 48–49 International Children’s Continence Society, 195–196 International Continence Society (ICS), 19 InterStim continence control system, 237 Interstitial cystitis (IC), 263–279 clinical presentation, 264–265 diagnostic evaluation, 267–270 etiological theories, 265–267 historical perspective, 263–264 management, 270–276 Intravenous pyelography (IVP), 22, 354 Intravesical therapies, for treatment of IC patients, 274–275 Intrinsic sphincter deficiency (ISD), 13, 109, 137–138 surgery for, 180, 182–184

Laparoscopy, bladder injuries during, 394–395 female incontinence and, 161–177 bladder augmentation, 167–175 laparoscopic urinary incontinence surgery, 161–167 vaginal wall prolapse, 175–176 laparoscopic sacrocolpopexy, 285–287 uretral injuries during laparoscopic gynecological surgery, 391 Lazy bladder syndrome, 196, 203–204 Leak point pressures (LPPs), 94–96 Lipids, cardioprotective effects of estrogen therapy and, 434–436 progestin use and, 436–437 Localized hormonal therapy, 458

Macular degeneration (MD), estrogen replacement therapy and, 454 Magnetic resonance imaging (MRI), 53– 56, 64, 68–73, 354, 355 Marshall-Marchetti-Kranz (MMK) procedure, 122–123, 134 for laparoscopic surgery, 162 Marshall test, 22 Medical causes of female sexual dysfunction, 478, 479 Medical history, 17–18 Medications, incontinence and, 6

Index Men, risk of incontinence in, 3 Menopause, hormone replacement therapy and, 417–473 alternative therapies, 458–459 menopause, 417–418 regimens for hormone replacement, 454–458 risks of estrogen replacement therapy, 445–454 symptoms of menopause, 421–440 transition from premenopause to postmenopause, 418–420 use of estrogen in menopausal women (review of the literature), 440–445 incontinence and, 4–5 Metronidazole, 330 Microtip catheters, 81 Microtip transducers, 82 Micturition reflexes, 28–29 Mild dysfunctional voiding disorders (in children), 196, 201–203 extraordinary daytime urinary frequency syndrome, 201 giggle incontinence, 201–202 postvoid dribbling, 202–203 stress incontinence, 202 Moderately dysfunctional voiding disorders (in children), 196, 203–207 dysfunctional elimination syndrome, 207 lazy bladder syndrome, 203–204 overactive bladder, 204–207 Modified Pereyra/Raz procedure (for transvaginal surgery), 141 Morcellation techniques in vaginal hysterectomy, 339–343 Moxalactam, 330 Multichannel urodynamics, 81–82 in evaluation of incontinence, 79–80 Multidisciplinary care team for IC patients, 271–272 Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 431 Multisymptom questionnaires, 20 Musculoskeletal evaluation for pelvic pain, 241–261 anatomy and function, 242–249 bone injuries, 249–250 pelvic floor dysfunction, 256–260 sacroiliac joint dysfunction, 253–256

499 [Musculoskeletal evaluation for pelvic pain] soft tissue, nerve, and muscle injury, 250–253 Myelopathy, causes of, 44 Myogenic detrusor failure (in children), 196, 209 Needle electromyography of the sphincter, 39–41 Needle stimulation, 230, 232 Needle suspension procedures for transvaginal surgery, 138–143 Nerve injury, pelvic pain and, 250–253 Nervous system lesions, with lower urinary tract sequelae, 30–31 Nocturia, 14–15 Nocturnal enuresis, 12 Noncoital sexual pain disorder, 16, 477 Nonsteroidal anti-inflammatory agents, 6 Nonsurgical treatment of incontinence, 215–224 bladder overactivity, 217–220 oral treatment of detrusor overactivity, 219–220 pelvic floor strengthening, 218–219 pharmacological treatment, 219 inadequate bladder emptying, 216–217 stress incontinence, 220–223 behavioral methods, 220 biofeedback, 221–222 bladder training, 220–221 functional electrical stimulation, 222–223 pelvic muscle strengthening, 221 strengthening with vaginal cones, 221 Normal bone mass, 424 Normal urine storage and evacuation, 226 Obesity, incontinence and, 5 Obstruction following anti-incontinence surgery, 179–194 bladder outlet obstructions, 180, 184– 187 management of voiding symptoms following anti-incontinence procedure, 187–191 prevention of, 191–192 retropubic suspension surgery, 180– 182

500 [Obstruction following anti-incontinence surgery] transabdominal approach, 180–181 transvaginal approach, 180, 181–1-82 surgery for intrinsic sphincteric deficiency, 180, 182–184 periurethral collagen injections, 183– 184 pubovaginal slings, 182–183 surgery for pelvic floor prolapse, 180 Ochoa syndrome (in children), 106, 209 Office examination of pelvic floor dysfunction, 77–79 Oophorectomy, effect on female sexual function of, 482 Oral medications for treatment of IC patients, 272–274 Oral treatment of detrusor overactivity, 219–220 Orgasmic disorder, 476 Osteoporosis, 424–434 pathophysiology of, 425–429 prevention/treatment, 429–434 bisphosphonates, 430–433 estrogen, 429–430 other treatments, 433–434 selective estrogen receptor modulators, 430–432 Overactive bladder, in children, 196, 204–207 nonsurgical treatment of, 217–220 Overflow incontinence, 13 Pad tests, 20, 78 Paravaginal repair, in treatment of stress urinary incontinence, 129–133, 134 Patrick test for sacroiliac joint instability, 254, 256 Pediatric dysfunctional voiding, 195–213 bladder maturation and pathogenesis, 196–198 classification of dysfunctional voiding, 196 epidemiology, 196 evaluation, 198–200 overview of voiding disorders, 196, 201–209 prognosis, 209–210 terminology, 195–196 Pelvic floor prolapse (POP), 13–14 floor pain and dysfunction, 256–260 floor strengthening, 218–219

Index [Pelvic floor prolapse (POP)] POP-Q system, 13–14, 18 radiological evaluation of pelvic floor relaxation, 70–73 surgery for, 180 urodynamic evaluation of pelvic floor dysfunction, 77–106 Pelvic pain, 15 see also Musculoskeletal evaluation for pelvic pain Pelvis, anatomy, etiology, and pathophysiology of, 281–282 dysfunction in the female, 12–16 examination of, 21–22 muscle strengthening of, 221 pelvic ultrasound, 23 Pentosan polysulfate sodium, for treatment of IC patients, 273 Pereyra procedure (for transvaginal surgery), 138 Perimenopause, 417, 418–420 Perineal defects (see Rectovaginal fistulas (RVFs) and complex perineal defects) Periurethral collagen injections, in surgery for ISD, 180, 183–184 Pessaries, 407–416 cleaning of pessary, 413 discontinuing use, 415 follow-up of patients, 413–415 incontinence pessaries, 412–413 other indications for pessaries, 415– 416 patient choice, 408 pessary algorithm, 414 pessary choice, 408–409 prolapse pessaries, 409–411 vaginal erosion development, 415 Pharmacological treatment for overactive bladder, 219 Physical examination, 20–22 Phytoestrogens, 459 Polytetrafluoroethylene (PTFE), 107 POP-Q system, 13–14, 18 Postmenopausal bleeding, 457–458 Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial, 429–430 Postvoid dribbling (vaginal voiding), 12, 196, 202–203 Potassium permeability testing, for IC patients, 269–270

Index Prevalence and incidence of incontinence in women, 1–3 Prolapse pessaries, 409–411 Psoas hitch, 388–389 Psychogenic factors contributing to female sexual dysfunction, 478–481 Pubovaginal slings (PVSs), 143–151 allograft fascia, 150–151 anterior vaginal wall, 146–147 in laparoscopic surgery, 166–167 in surgery for ISD, 180, 182–183 synthetic sling materials, 147–150 Q-tip test, 22 Race, incontinence and, 4 Radiological evaluation, 51–75 pelvic floor relations, 70–73 stress incontinence and voiding dysfunction, 52–56 urethral diverticulum, 56–64, 354–355 urinary fistulas, 64–70 Raloxifene, 431–432 Recreational stresses, incontinence and, 6 Rectovaginal fistulas (RVFs) and complex perineal defects, 394–405 diagnosis of, 396–401 postoperative care after fistula repair, 404 preoperative preparation and repair, 401–404 Reflex pathways, 28–30 Reimplant of the ureter, 388 Renal ultrasound, 22–23 Residual urine determination, 48–49 Retropubic suspension surgery, 180–182 Richardson procedure, for laparoscopic surgery, 162, 163 Ring pessary, 409 Risk factors for incontinence, 3–6 Sacral nerve stimulation (SNS), 230, 232– 238 causes of sacral nerve outflow dysfunction, 44 clinical efficiency, 235–238 sacral reflexes, 33–35 surgical implantation, 234–235 temporary electrode implantation, 233–234 test stimulation, 233

501 Sacroiliac joint (SJ), 242–243 dysfunction of, 253–256 Sacrospinous colpopexy and colporrhaphies, 299–304 Selective estrogen receptor modulators (SEPMs), 430–432 Sensory urge incontinence, 88 Severe dysfunctional voiding disorders (in children), 196, 207–209 Hinman syndrome, 207–209 myogenic detrusor failure, 209 Ochoa (urofacial) syndrome, 209 Sex (male and female), incontinence and, 3 Sexual arousal disorder, 16, 476 Sexual aversion disorder, 476 Sexual dysfunction (see Female sexual dysfunction) Sexual orgasmic disorder, 16 Sexual pain disorders, 16 Skin, symptoms of menopause effecting, 422–423 Smoking, incontinence and, 5 Social history, 19 Sodium fluoride, 434 Somatosensory-evoked potential studies, 35–37 Sphincter, needle electromyography of, 39–41 sphincter-nerve conduction studies, 37–39 Spontaneous uroflowmetry, 78 Stamey procedure (for transvaginal surgery), 138–140 Stress incontinence, 12, 13 in children, 196, 202 injectable treatment of, 107–119 nonsurgical treatment of, 220–223 pessaries for diagnosis of, 416 radiological evaluation of, 52–56 transvaginal surgery for, 137–160 see also Transabdominal procedures Stress testing, 22, 78 Stroke, estrogen replacement therapy and, 453–454 “Supersensitivity” testing, 41 Surgery, 6 for apical prolapse, 282–285 effects on female sexual function, 481– 484 for laparoscopic incontinence, 161–167 for stress incontinence, 132–133

502 [Surgery] for treatment of IC patients, 275–276 see also Transvaginal surgery; Vaginal hysterectomy; Vaginal surgery Suture ligation injury, 386–387 Symptoms of menopause, 421–440 cardiovascular disease, 434–440 central nervous system, 421–422 genitourinary tract, 423–424 osteoporosis, 424–434 skin, 422–423 Synthetic sling materials, 147–150 Tinidazole, 330 Total vaginal length, (TVL), 14 Transabdominal procedures, 121–136 for anti-incontinence surgery, 180– 181 Burch procedure, 124–127, 134 concurrrent surgery, 132–133 Marshall-Marchetti-Kranz procedure, 122–123, 134 paravaginal repair, 129–132, 134 postoperative care, 132–133 see also Laparoscopic approach to female incontinence Transanal electrical stimulation devices, 229–231 Transureteroureterostomy (TUU), 390– 391 Transurethral endoscopic incision of urethral diverticulum, 360 Transvaginal diverticulectomy, results and complications of, 359–360 Transvaginal electrical stimulation devices, 229–231 Transvaginal paravaginal defect repair, 304–309 Transvaginal surgery, 137–150 for anti-incontinence, 180, 181–182 complications associated with, 140 needle suspension procedures, 138– 143 four-corner bladder neck suspension, 142–143 Gittes, 141–142 modified Pereyra/Kaz, 141 Pereyra, 138 Stamey, 138–140 pubovaginal slings, 143–151 urodynamic changes following incontinence surgery, 154–156

Index [Transvaginal surgery] use of bone anchors in incontinence surgery, 151–154 Type II stress incontinence, 109 Type III stress incontinence (see Intrinsic sphincter deficiency) Ultrasonography (US), 53, 64, 65–67 in the diagnosis of urethral diverticulum, 354, 355 Unaware incontinence, 12 Uninhibited urethral relaxation, 87–88 Ureteral injuries (see Iatrogenic urological trauma) Ureteroureterostomy repairs, 387–388 Ureterovaginal fistula, 374–377 treatment of, endoscopic management, 375–376 surgical management, 376–377 Urethral-anal reflex, 34 Urethral diverticulum, 351–363 associated cancer, 356 classification, 356 etiology, 351–352 history, 351 incidence, 351 other surgical procedures, 360 radiological evaluation, 56–64, 354– 355 results and complications of transvaginal diverticulectomy, 359–360 symptomatology, 352–354 treatment of, 357–359 urethroscopy, 354 urodynamics, 355 Urethral hypermobility, 13, 137 Urethral instability, 86–87 Urethral pressure profiles (UPPs), 88–94 Urethral resistance factor, 48 Urethrocystometry, 82–88 Urethrovaginal fistula, 372–374 Urge incontinence, 12, 13 Urinary fistulas, 363–380 radiological evaluation of, 64–70 ureterovaginal fistula, 374–377 urethrovaginal fistula, 372–374 vesicovaginal fistula, 363–372 Urinary incontinence (see Incontinence) Urine storage and evacuation (normal), 226 Urodynamics, bedside, 21

Index [Urodynamics] in the diagnosis of urethral diverticulum, 355 electromyographic activity as part of urodynamic studies, 31–33 urodynamic changes following incontinence surgery, 154–156 urodynamic evaluation of pelvic floor dysfunction, 77–106 basic office evaluation, 77–79 enhanced urodynamic studies, 100– 102 leak point pressures, 94–96 multichannel urodynamics, 79–80, 81–82 urethral pressure profiles, 88–94 urethrocystometry, 82–88 voiding pressure studies, 96–100 Uroflometry, 46, 47–48 Uterine retroversion, pessary for, 415 Vagina, 478 Vaginal compliance, 23 Vaginal cones, pelvic muscle strengthening with, 221 Vaginal hysterectomy, 329–350 adnexal removal, 344–345 anesthesia, 330 enlarged uterus, 339–344 operative techniques, 332–339 positioning, 330–331 preoperative evaluation, 331 preoperative preparation/prophylactic antibiotics, 330 preparation, 331 support techniques, 345–348 Vaginal lubrication, 23 Vaginal prolapse, 175–176 surgical repair of, 291–309 sacrospinous colpopexy and colporrhaphies, 200–304 vaginal paravaginal defect repair, 304–309 vaginal reconstructive surgery, 291– 299 after vaginal hysterectomy, 345 see also Colpocleisis for treatment of vaginal vault prolapse

503 Vaginal surgery, bladder injuries during, 394 ureter injuries during, 386–387 Vaginal vault repair, laparoscopic sacrocolpopexy for, 285–287 Vaginismus, 16, 476–477 Vaginography, in evaluation of urinary fistulas, 65 Venous thromboembolic events (VTEs), estrogen replacement therapy and, 449–450 Vesicovaginal fistula, 363–372 as a delayed bladder injury, 395 treatment of, abdominal repair, 368 transvaginal repair, 366–367 Videourodynamics for enhanced urodynamic studies, 100 Vitamin D for postmenopausal women, 455–457 Voiding cystourethrography (VCUG), 52, 354 in evaluation of pelvic floor relaxation, 70 in evaluation of urethral diverticulum, 56, 57, 58, 59, 60–64 Voiding diary, 19–20 Voiding dysfunction, 43–49 evaluation of, 46–49 idiopathic female voiding dysfunction, 45–46 mechanical obstructive processes related to, 45 neuropathic processes related to, 43– 45 radiological evaluation of, 52–56 see also Incontinence and voiding dysfunction Voiding pressure studies, 96–100 Voiding symptoms following anti-incontinence surgery, management of, 187–191 Vulvectomy, effect on female sexual function of, 482–483

World Health Organization (WHO), menopause defined by, 417

About the Editors

BRUCE I. CARLIN is Assistant Professor of Urology, Washington University School of Medicine, St. Louis, Missouri. The author or coauthor of many professional publications and presentations, he received the B.S. degree (1990) in medicine and the M.D. degree (1992) from Northwestern University, Chicago, Illinois. FAH CHE LEONG is Assistant Professor in the Department of Obstetrics and Gynecology, St. Louis University School of Medicine, Missouri. He received the M.D. degree (1989) from the Stritch School of Medicine at Loyola University, Chicago, Illinois, and received his Fellowship training in Urology at Rush Medical College, Chicago, Illinois.