Hormone Replacement Therapy - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

HORMONE

REPLACEMENT THERAPY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Hormone Replacement Therapy: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83929-8 1. Hormone Replacement Therapy-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on hormone replacement therapy. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON HORMONE REPLACEMENT THERAPY ....................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Hormone Replacement Therapy.................................................... 8 E-Journals: PubMed Central ....................................................................................................... 64 The National Library of Medicine: PubMed ................................................................................ 65 CHAPTER 2. NUTRITION AND HORMONE REPLACEMENT THERAPY ........................................... 115 Overview.................................................................................................................................... 115 Finding Nutrition Studies on Hormone Replacement Therapy................................................. 115 Federal Resources on Nutrition ................................................................................................. 120 Additional Web Resources ......................................................................................................... 120 CHAPTER 3. ALTERNATIVE MEDICINE AND HORMONE REPLACEMENT THERAPY..................... 123 Overview.................................................................................................................................... 123 The Combined Health Information Database............................................................................. 123 National Center for Complementary and Alternative Medicine................................................ 124 Additional Web Resources ......................................................................................................... 133 General References ..................................................................................................................... 136 CHAPTER 4. DISSERTATIONS ON HORMONE REPLACEMENT THERAPY....................................... 139 Overview.................................................................................................................................... 139 Dissertations on Hormone Replacement Therapy...................................................................... 139 Keeping Current ........................................................................................................................ 141 CHAPTER 5. CLINICAL TRIALS AND HORMONE REPLACEMENT THERAPY ................................. 143 Overview.................................................................................................................................... 143 Recent Trials on Hormone Replacement Therapy...................................................................... 143 Keeping Current on Clinical Trials ........................................................................................... 145 CHAPTER 6. PATENTS ON HORMONE REPLACEMENT THERAPY ................................................. 147 Overview.................................................................................................................................... 147 Patents on Hormone Replacement Therapy............................................................................... 147 Patent Applications on Hormone Replacement Therapy ........................................................... 164 Keeping Current ........................................................................................................................ 182 CHAPTER 7. BOOKS ON HORMONE REPLACEMENT THERAPY ..................................................... 183 Overview.................................................................................................................................... 183 Book Summaries: Federal Agencies............................................................................................ 183 Book Summaries: Online Booksellers......................................................................................... 188 The National Library of Medicine Book Index ........................................................................... 192 Chapters on Hormone Replacement Therapy............................................................................. 193 CHAPTER 8. MULTIMEDIA ON HORMONE REPLACEMENT THERAPY .......................................... 195 Overview.................................................................................................................................... 195 Video Recordings ....................................................................................................................... 195 Bibliography: Multimedia on Hormone Replacement Therapy ................................................. 196 CHAPTER 9. PERIODICALS AND NEWS ON HORMONE REPLACEMENT THERAPY ....................... 197 Overview.................................................................................................................................... 197 News Services and Press Releases.............................................................................................. 197 Newsletter Articles .................................................................................................................... 199 Academic Periodicals covering Hormone Replacement Therapy ............................................... 200 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 201 Overview.................................................................................................................................... 201 U.S. Pharmacopeia..................................................................................................................... 201 Commercial Databases ............................................................................................................... 202 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 205

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Overview.................................................................................................................................... 205 NIH Guidelines.......................................................................................................................... 205 NIH Databases........................................................................................................................... 207 Other Commercial Databases..................................................................................................... 209 APPENDIX B. PATIENT RESOURCES ............................................................................................... 211 Overview.................................................................................................................................... 211 Patient Guideline Sources.......................................................................................................... 211 Finding Associations.................................................................................................................. 219 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 221 Overview.................................................................................................................................... 221 Preparation................................................................................................................................. 221 Finding a Local Medical Library................................................................................................ 221 Medical Libraries in the U.S. and Canada ................................................................................. 221 ONLINE GLOSSARIES................................................................................................................ 227 Online Dictionary Directories ................................................................................................... 227 HORMONE REPLACEMENT THERAPY DICTIONARY..................................................... 229 INDEX .............................................................................................................................................. 301

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with hormone replacement therapy is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about hormone replacement therapy, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to hormone replacement therapy, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on hormone replacement therapy. Abundant guidance is given on how to obtain free-ofcharge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to hormone replacement therapy, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on hormone replacement therapy. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON HORMONE REPLACEMENT THERAPY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on hormone replacement therapy.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and hormone replacement therapy, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “hormone replacement therapy” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Hormone Replacement Therapy and Its Relationship to Lipid and Glucose Metabolism in Diabetic and Nondiabetic Postmenopausal Women Source: Diabetes Care. 25(10): 1675-1680. October 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Among postmenopausal women, those with diabetes experience more cardiovascular diseases than those without diabetes. In this study, the authors examined the relationship of hormone replacement therapy (HRT) with indicators of lipid and glucose metabolism using a national sample of postmenopausal women with and

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without diabetes. The authors used data from the Third National Health and Nutrition Examination Survey, conducted from 1988 to 1994. A total of 2,786 postmenopausal women aged 40 to 74 years participated in an oral glucose tolerance test (OGTT), had blood drawn for lipid (fats) assessment, and responded to HRT questions. The results showed that postmenopausal women with diabetes had increased dyslipidemia compared with nondiabetic women. Among diabetic women, current users of HRT had significant different lipid and glucose control levels than never users of HRT for the following variables: total cholesterol, non-HDL, apoA, fibrinogen, glucose, insulin, and glycosylated hemoglobin. The authors conclude that women with diabetes and nondiabetic postmenopausal women currently taking HRT had better lipoprotein profile than never or previous users of HRT. Women with diabetes currently taking HRT had better glycemic control than never or previous users of HRT. 3 tables. 29 references. •

Menopause: The Latest on Hormone Replacement Therapy Source: Diabetes Self-Management. 19(4): 90, 92, 95-97. July-August 2002. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Website: www.diabetes-self-mgmt.com. Summary: Hormone replacement therapy (HRT) is a medical therapy option that can alleviate and treat both the short-term symptoms and some of the long-term consequences of menopause. HRT can also increase the risk for certain health problems, so a menopausal woman and her physician need to consider her individual risk factors before starting HRT. This article discusses the benefits, risks, and alternatives to HRT for women with diabetes. Other topics include common symptoms of perimenopause and menopause, the long-term consequences of menopause, the effects of menopause on diabetes, the different types of HRT, the effects of HRT on diabetes, and alternative treatments.

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Secondary Hyperparathyroidism and Vitamin D Hormone Replacement Therapy: New Treatment Perspectives Source: Dialysis and Transplantation. 30(2): 109-111, 125. February 2001. Contact: Available from Dialysis and Transplantation, Attn.: Subscriptions. P.O. Box 10535, Riverton, NJ 08076. (800) 624-4196 or (609) 786-0871. Summary: Secondary hyperparathyroidism (SHPT) affects nearly all patients with chronic renal (kidney) failure (CRF). Recent evidence indicates that complications of SHPT are systemic, and not merely limited to renal bone disease. The link between SHPT and these co morbid conditions has prompted clinicians to make SHPT management a higher patient care priority. This article reviews the development of SHPT, the historical lack of appropriate treatment, and how vitamin D hormone replacement therapies could be used to prevent or limit its effects. In recent years, two vitamin D analogs that have been shown to be less calcemic, paricalcitol (Zemplar IV) and doxercalciferol (Hectorol oral and IV), have been approved for the treatment of SHPT in renal patients. Paricalcitol is active upon administration, with similar pharmacokinetic (how the drug works in the body) characteristics. However, doxercalciferol is a prohormone that, like endogenous vitamin D, must undergo metabolic transformation in the liver in order to form the active vitamin D hormone. This results in a pharmacokinetic profile that, at normal doses, provides blood levels of active vitamin D hormones that peak in 8 hours and remain in the physiologic range for

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more than 40 hours. This mimics the body's natural metabolism of vitamin D hormone, the ideal treatment for vitamin D hormone deficiency. 19 references. •

Effects of Postmenopausal Hormone Replacement Therapy on Central Abdominal Fat, Glycemic Control, Lipid Metabolism, and Vascular Factors in Type 2 Diabetes: A Prospective Study Source: Diabetes Care. 22(9): 1401-1407. September 1999. Contact: Available from American Diabetes Association, Inc. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 806-7801. Website: www.diabetes.org. Summary: This article describes a 12-month prospective study that examined the early and longer term effects of hormone replacement therapy (HRT) on lipid metabolism, glycemic control, total body and central abdominal fat, blood pressure, and arterial pulse wave velocity (APWV) in overweight postmenopausal females who had type 2 diabetes. Participants were 14 women who were randomized to 6 months of observation or open label HRT before crossover. HRT consisted of 2 months of conjugated equine estrogen (CEE) 0.625 milligrams daily, followed by 4 months CEE and medroxyprogesterone 5 milligrams daily. The study found that 6 months of HRT induced significant reductions in waist circumference, waist to hip ratio, glycosylated hemoglobin (HbA1c), total and low density lipoprotein cholesterol, and central abdominal fat. HRT also improved physical functioning. There was a minor increase in resting energy expenditure. Total fat mass, fasting glucose, insulin, triglyceride, apolipoprotein B, nonesterified fatty acids, resting blood pressure, APWV, and physical activity were unchanged. The article concludes that postmenopausal HRT in these overweight women who had type 2 diabetes was associated with a reduction in central adiposity and improvement in lipid metabolism and glycemic control without deterioration in weight status or cardiovascular parameters measured. Further study is needed to determine whether HRT induced improvements in these cardiovascular risk factors result in lower long term cardiovascular morbidity and mortality, as observed in nondiabetic women. 3 tables. 50 references. (AA-M).

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Hormone Replacement Therapy Is Associated with Better Glycemic Control in Women with Type 2 Diabetes Source: Diabetes Care. 24(7): 1144-1150. July 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article describes a study that examined whether glycosylated hemoglobin (HbA1c) levels varied by current hormone replacement therapy (HRT) among women with type 2 diabetes. The population for the study was drawn from the Northern California Kaiser Permanente Diabetes Registry. Among women with type 2 diabetes, the 15,435 women who had HbA1c measured at least once became the final cohort for all analyses in the study. HRT and HbA1c were assessed by reviewing records in the health plan's computerized laboratory and pharmacy systems. Sociodemographic and clinical information was collected by survey. Among the cohort, 3,852 were currently using HRT before the HbA1c test. Among women currently using HRT, 62 percent were using unopposed estrogens, 36 percent were using opposed estrogen, and 2 percent were using progestins alone. Women currently using HRT were younger, leaner, better educated, and more likely to be non-Hispanic whites than women not using HRT. Mean HbA1c levels were significantly lower in women currently using HRT than in women not using HRT, and these differences increased

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after adjusting for age. No differences in HbA1c level were observed between women using unopposed estrogens and women using opposed estrogens. In a Generalized Estimating Equation model, which took into account patient clustering within physician and was adjusted for age, ethnicity, education, obesity, hypoglycemic therapy, diabetes duration, self monitoring of blood glucose, and exercise, HRT remained significantly and independently associated with decreased HBA1c levels. The article concludes that HRT was independently associated with decreased HbA1c level. Clinical trials will be necessary to understand whether HRT may improve glycemic control in women with diabetes. 1 figure. 2 tables. 37 references. (AA-M). •

Hormone Replacement Therapy and Cognition: Systematic Review and Meta-analysis Source: JAMA. Journal of the American Medical Association. 285(11): 1489- 1499. March 21, 2001. Summary: This article presents a systematic review and meta-analysis of studies examining the relationship between hormone replacement therapy (HRT) and the risk of cognitive decline and dementia. Randomized controlled trials and cohort studies were reviewed for the effects of HRT on cognitive decline; cohort and case-control studies were reviewed for dementia risk. No randomized controlled trials regarding dementia risk were found. Twenty-nine studies met inclusion criteria and were rated for quality. Studies of cognition could not be combined quantitatively because of differences in study design. However, results suggested some benefits of HRT for verbal memory, vigilance, reasoning, and motor speed in women with menopausal symptoms but not in asymptomatic women. A meta-analysis of observational studies suggested that HRT is associated with a decreased risk of dementia, but most studies had important methodological limitations. 1 figure, 5 tables, 67 references.

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Hormone Replacement Therapy, Insulin Sensitivity, and Abdominal Obesity in Postmenopausal Women Source: Diabetes Care. 25(1): 127-133. January 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reports on a study undertaken to determine whether insulin sensitivity differs between postmenopausal women taking estradiol, women on estrogen plus progesterone hormone replacement therapy (HRT), and women not on HRT and whether differences are explained by the differences in total or abdominal adiposity and fat deposition in the muscle. The authors studied 28 obese, sedentary postmenopausal Caucasian women. Women taking oral estrogen (n = 6) were matched for age, weight, and body mass index (BMI) with women not on HRT (n = 6). Eight women taking oral estrogen plus progesterone were matched with eight different women not on HRT for age, weight, and BMI. Maximal aerobic capacity, percentage of fat, total body fat mass, and fat-free mass (FFM) were similar between groups. Visceral fat, subcutaneous abdominal fat, sagittal diameter, and mid thigh low density lean tissue (intramuscular fat) did not differ by hormone status. Basal carbohydrate and fat utilization was not different among groups. Fasting plasma glucose and insulin did not differ by hormone use. Glucose utilization (M) was measured; postmenopausal women taking oral estrogen had a 31 percent lower M than women not on HRT. M was 26 percent lower in women taking estrogen plus progesterone than women not on HRT. M per I, the amount of glucose metabolized per unit of plasma insulin (I), an index of insulin sensitivity, was 36 percent lower in women taking estrogen compared with matched

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women not on HRT and 28 percent lower in women taking estrogen plus progesterone compared with matched women not on HRT. The authors conclude that postmenopausal women taking oral estrogen or those taking a combination of estrogen and HRT are more insulin-resistant than women not on HRT, even when women are of comparable total and abdominal adiposity. 1 figure. 3 tables. 49 references. •

Hormone Replacement Therapy and Its Potential Relationship to Dementia Source: Journal of the American Geriatrics Society. 44(7): 878-880. July 1996. Summary: This journal article examines the potential role of estrogen replacement therapy in the prevention of dementia and issues in designing suitable clinical trials. The author reviews current evidence of the association among estrogen and dementia and concludes that the potential effects of estrogen on vascular disease appear to have the greatest likelihood of reducing the risk of dementia, especially if there is an association between vascular disease, beta-amyloid, and the development of Alzheimer's disease (AD). However, he cautions that any role of estrogen therapy, or even high endogenous estrogen levels, in preventing dementia related to either vascular dementia or AD has not been established. The author suggests that the critical question is how best to test the hypothesis that estrogen therapy will reduce the risk or progression of dementia among older women. In designing trials of estrogen therapy, researchers must decide what population should be studied, what the necessary sample size is, how long participants should be followed, and what endpoints should be measured. In primary prevention trials, the main problem is the relatively low incidence of dementia and, especially, AD in the population. To fix this problem, larger sample sizes and a longer followup period are needed than those used in secondary prevention trials. However, the author concludes that such trials are needed and may be worth the difficulties and costs involved. 34 references.

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Hormone Replacement Therapy or Prophylaxis in Postmenopausal Women with Recurrent Urinary Tract Infection Source: Journal of Infectious Diseases. 183(Supplement 1): S74-S76. March 1, 2001. Contact: Available from Journal of Infectious Diseases. University of Chicago Press, Journals Division, P.O. Box 37005, Chicago, IL 60637. (773) 753-3347. Fax (773) 753-0811. E-mail: [email protected]. Website: www.journals.uchicago.edu. Summary: Urinary tract infection (UTI) is the most common bacterial infection in women, and it occurs with much greater frequency among elderly than among younger women and with increasing frequency among postmenopausal women. This article explores the role of hormone replacement therapy (HRT) as prophylaxis (preventive therapy) in postmenopausal women with recurrent UTI. The author reviews the related literature and concludes that estrogen replacement is effective not only in the treatment of urogynecological symptoms related to menopause but also in the prevention of recurrent UTIs. Younger postmenopausal women can benefit from oral hormonal therapy, which improves clinical symptoms related to menopause and helps avoid osteoporosis and ischemic heart disease; the use of vaginal estrogen should be limited to women older than 60 years for the treatment of atrophic vaginitis, recurrent UTIs, and urge incontinence. The use of HRT, including vaginal therapy, is contraindicated in women with active venous thromboembolism, severe active liver disease, and endometrial and breast carcinoma (cancer) but can be administered to women with diabetes, gallstones, and other relative contraindications. The author calls for additional

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studies evaluating the safety and comparative efficacy of oral and vaginal estriol. 1 figure. 10 references.

Federally Funded Research on Hormone Replacement Therapy The U.S. Government supports a variety of research studies relating to hormone replacement therapy. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to hormone replacement therapy. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore hormone replacement therapy. The following is typical of the type of information found when searching the CRISP database for hormone replacement therapy: •

Project Title: A MAYO COHORT STUDY OF MAMMOGRAPHIC BREAST DENSITY Principal Investigator & Institution: Vachon, Celine M.; Assistant Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The interindividual variability in breast tissue on mammographic images, as defined by several measures of mammographic breast density, has been shown to be a major risk factor for breast cancer. However, there are several limitations in the studies performed to date; they have involved older mammogram images from multiple institutions, using mostly subjective measures on one view of the breast. Also, none of these studies have incorporated biological samples into their analyses and very few have examined other features that may be more predictive of breast cancer risk. Our GOAL is to conduct a large-scale, prospective study at one institution with new mammography to examine the causal association of breast density with breast cancer and to identify new markers of breast cancer risk. The Mayo Mammography Clinic performs approximately 35,000 screening mammograms per year; 25,000 of these are from Minnesota, Wisconsin and Iowa. Over a three-year period, we will enroll 20,700 cancer-free women from this tri-state region into our mammography cohort study. We will collect complete risk factor information from a baseline questionnaire, modern mammogram films and biological samples and will follow participants/members for breast cancer incidence and mortality. We will use a semiautomated algorithm to estimate percent breast density, rate of change of percent density over time, dense area and regional density on members of our cohort. We propose to examine aspects of breast density with incidence of breast cancer;

2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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specifically, we will examine percent breast density, novel features of the mammogram including regional density, total dense area and longitudinal rate of change of breast density. Additionally, we will ascertain machine variability and settings (kVp, mAs, compression, thickness) from mammogram films and incorporate into the above analyses. As secondary aims, we also propose to investigate the heterogeneity of change in breast density among women who initiate hormone replacement therapy (HRT). The literature shows that approximately 30 percent of women experience increases in breast density upon HRT initiation. We propose to examine whether there is an association between this change in breast density and risk of breast cancer and also whether there is an association between this change and four functional polymorphisms in the genes SULT1A1, SULT1E1 and CYP3A5. The findings from these proposed studies have obvious translational implications: high-risk groups can be identified for intervention, more aggressive surveillance and perhaps chemoprevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A ONE YEAR ESTROGEN/PROGESTIN IMPLANT Principal Investigator & Institution: Nichols, L D.; Biotek, Inc. 21-C Olympia Ave Woburn, Ma 01801 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 28-FEB-2004 Summary: (provided by applicant): This program targets a one-year biodegradable estrogen/progestin implant for postmenopausal hormone replacement therapy. Estradiol plus levonorgestrel will be incorporated into an innovative implant design already being developed by BIOTEK for delivery of pure levonorgestrel as a maintenance contraceptive. The implant consists of a drug-free, biodegradable polymer core surrounded by a drug-containing shell, which provides efficient drug delivery. Such implants will biodegrade if left in place for more than a year, yet they can be surgically removed before the end of a year if necessary. With no need to keep track of daily pills or weekly patches, and with little reason to fear an unpleasant removal episode, such implants should provide a welcome new form of sustained hormone replacement therapy. Phase I demonstrated the feasibility of delivering estradiol and levonorgestrel at acceptable rates from the same implants. Phase II will now modify the core polymer to accelerate degradation, improve production methods, characterize promising designs in vitro, and confirm performance in rabbits. PROPOSED COMMERCIAL APPLICATION: The proposed work should lead to the development of a new kind of long lasting, highly effective, biodegradable drug delivery implant. Once fully impemented, implants of similar design should be useful for many other kinds of drug maintenance therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AGE AND CONTROL OF HUMAN SKIN BLOOD FLOW Principal Investigator & Institution: Kenney, W. L.; Professor of Physiology and Kinesiology; Noll Physiological Res Ctr; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802 Timing: Fiscal Year 2001; Project Start 30-SEP-1987; Project End 31-MAR-2004 Summary: (Adapted from the Applicant's Abstract): In men and women over the age of 65, the non-acral skin blood flow (SkBF) response to hyperthermia is significantly attenuated. The site of this age-related defect involves the active vasodilator system, a non-adrenergic efferent pathway unique to human skin. The proposed series of studies will systematically examine potential mechanisms through which the negative effects of

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aging and the positive effects of estrogen therapy are exerted. In older and younger men and women and in post-menopausal women taking various types of hormone replacement therapy or no therapy, the PI plans to (a) examine spatial distribution and heterogeneity of active cutaneous vasodilation to determine whether changes in functional capillary plexus unit density and/or flow contribute to alterations in SkBF using scanning laser-Doppler imaging; (b) examine the magnitude, spatial distribution, and heterogeneity of reflex-mediated noradrenergic cutaneous vasoconstriction during whole-body cooling and baroreceptor unloading using scanning laser-Doppler imaging; and (c) determine the role of nitric oxide (NO) in the control of active vasodilation by examining NO-dependent and independent changes in SkBF during hyperthermia using intradermal microdialysis. In addition, a fourth series of studies is proposed to quantify the upper limit of the prescriptive zone (ULPZ) and age-specific heat exchange coefficients in older versus younger healthy men and women during low-intensity activity. Data from this last proposed investigation operationalizes the SkBF decrement to allow policy-making by health organizations and for modeling biophysical and physiological responses of the elderly to extreme environments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AGE,GENDER, SEROTONIN AND RESPIRATORY CONTROL Principal Investigator & Institution: Behan, Mary; Professor; Comparative Biosciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: Serotonin (5HT) plays a major role in breathing and the control of upper airway function. The proposed research will test the hypothesis that, with increasing age, there is a gender- specific decrease in serotonergic modulation of respiratory motoneurons. Because of gender-related differences, aging males may be uniquely susceptible to breathing disorders such as obstructive sleep apnea. Our preliminary data indicate that 5HT immunoreactivity in the hypoglossal nucleus decreases with age in male rats, but increases with age in female rats. Furthermore, long term facilitation, a 5HT-dependent increase in respiratory motor output following intermittent hypoxia, decreases to older male rats, but increases to older female rats. This is the first description of age-associated change in serotonergic modulation of respiratory control, and the first description of sexual dimorphism in age-related changes in any aspect of the serotonergic nervous system. The proposed research will test the hypothesis that gonadal hormones have a neuroprotective role in the maintenance of serotonergic modulation of respiratory motoneurons in female rats with increasing age, and can potentially reverse or delay the age-associated changes that occur in male rats. Five specific aims are proposed, each corresponding to a testable hypothesis. First, we will use neurochemical and anatomical assays to detect age- and gender- related changes in key elements of the serotonergic neuromodulatory system (5HT, 5HT receptors, and the serotonin reuptake transport protein) in hypoglossal and phrenic motor nuclei. Secondly, we propose to determine if there are functional consequences of aging and gender on respiratory responses to hypoxia in awake rats. Thirdly, we will test the hypothesis that serotonin-dependent components of the hypoxic ventilatory response are decreased selectively with aging in male rats. Finally, we propose to investigate the influence of neutering and hormone replacement therapy (estrogen, progesterone, testosterone) on our anatomical and physiological indices of serotonergic modulation of respiration in male and female rats. To our knowledge, this is the first proposal to study age and gender effects on any form of plasticity in respiratory control. An understanding of these mechanisms may lead to therapeutic strategies for intervention

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in age-related breathing disorders that affect both men and women such as obstructive sleep apnea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AGING & HEMODYNAMICS OF HYPERTHERMIA IN HRT & HYDRATION IN POSTMENOPAUSE Principal Investigator & Institution: Kenney, William L.; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: The hemodynamic responses of postmenopausal women to passive heat stress have not been characterized to date. This proposal outlines two studies which seek to characterize postmenopausal women's hemodynamic responses to passive heating through an investigation of the separate roles of hormone replacement therapy and hydration. It is the purpose of the second investigation in this proposal to examine the role of hydration on postmenopausal women's responses to passive heating. It is hypothesized that: 1) hydration will increase cardiac output; and 2) hydration with a commercially available sports drink will be better than hydration with water. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AGING AND HYPERTENSION--GENDER, GENES AND RISK Principal Investigator & Institution: Fisher, Naomi D.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: (Adapted from applicant's abstract). This application is for a Mentored Clinical Scientist Development Award. The applicant states that that sexual dimorphisms in cardiovascular risk evolve with increasing age, and that women experience significantly less hypertension and heart disease than do men -- though this difference disappears with increasing age, especially among Blacks. The research plan in this proposal aims to pursue preliminary evidence which suggests that age, gender and race play a key role in modifying the ultimate expression of genetic risk. In particular, preliminary data reveal that females are protected against expression of a common intermediate phenotype of essential hypertension, marked by abnormal responsiveness to angiotensin II. And among the many genes proposed to cause human hypertension, one of the very few for which linkage has been documented is that coding for angiotensinogen (AGT), a key element of the renin-angiotensin system - yet linkage has been convincingly shown only in males. The present proposal aims to test the hypothesis that the ultimate expression of the AGT gene is strongly influenced by age, gender, and hormonal status. It will test whether female hormone replacement therapy (HRT) can confer the same protection as do endogenous sex steroid hormones; whether race influences the relationship between AGT genotype and the phenotype of AngII responsiveness; and whether nutritional factors, ultimately involving obesity, contribute. With anticipated award the applicant's plan is to continue clinical research in hypertension, applying techniques and understanding of renal and adrenal physiology to the process of aging. Controlled physiologic studies by her will be performed on the Clinical Research Center of the Brigham and Women's Hospital. As well, she will be mentored by Dr. Lewis Lipsitz who is experienced in cardiovascular function and disease in the aging populations. The applicant's stated goal is to establish for herself an independent research career path for studying cardiovascular, renal, and adrenal function in relation to the pathogenesis of hypertension in the elderly.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALTERNATIVE THERAPIES FOR MENOPAUSE: A RANDOMIZED TRIAL Principal Investigator & Institution: Newton, Katherine M.; Associate Investigator; Center for Health Studies Seattle, Wa 98101 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-NOV-2004 Summary: (Adapted from Investigator's Abstract) Hormone replacement therapy (HRT: estrogen and progestin) remains the treatment of choice for women with vasomotor symptoms, and long-term HRT has been recommended for prevention purposes. The demand for alternatives to HRT, and the availability and use of over-the-counter products including dietary phytoestrogen supplements and naturopathic medicines, has grown dramatically. Few of these products have faced the rigors of randomized trials and none have been tested to evaluate their effects on long-term outcomes. The purpose of this four-year randomized controlled trial is to evaluate the efficacy and safety of three alternative approaches utilizing phytoestrogens to treat vasomotor symptoms in peri- and postmenopausal women. The treatments were chosen because of the scientific evidence supporting a possible benefit, the availability of products with adequate quality control their frequency of use in naturopathic medicine, and our ability to blind participants to the intervention. The five proposed treatment arms are as follow: 1) esterified estrogen and micronized progesterone: 9) a single herbal product, black cohosh; 3) a multibotanical preparation; 4) a combination regimen that includes the same multibotanical preparation plus soy diet counseling; and 5) placebo. The primary aim is to compare the effects of three alternative treatments, HRT, and placebo on the frequency and intensity of vasomotor symptoms measured by The Wiklund Menopause Symptom Checklist and a daily Vasomotor Symptom Diary. The secondary aims are to compare the effects of three alternative treatments, HRT, and placebo on the following: 1) vaginal cytology (vaginal maturation index); 2) serum lipids (total cholesterol, HDL and LDL cholesterol, triglycerides); 3) bone mineral density (hip and spine dual energy x-ray absorptiometry scan); 4) glucose metabolism (insulin, fasting blood glucose); and 5) coagulation factors (fibrinogen, PAI-1). The hypotheses are that compared to placebo the three alternative treatments tested in this study will have the following effects: reduce frequency of hot flashes and night sweats, improve vaginal maturation and decrease vagina atrophy as measured by maturation index, lower total cholesterol and LDL with no effect on HDL, reduce the rate of decline in bone mineral density (BMD), and have no effect on glucose metabolism or clotting factors. To accomplish the specific aims the investigators propose to do the following: 1) recruit and randomize 400 periand post-menopausal women to one of five treatment arms for one year; 2) collect measurements of primary and secondary outcomes at baseline, three, six, and 12 months; and 3) compare changes in outcomes in the groups taking alternative treatments to those in the HRT and placebo groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ALZHEIMER'S DISEASE AND ESTROGEN REPLACEMENT Principal Investigator & Institution: Petitti, Diana B.; Director; Kaiser Foundation Research Institute 1800 Harrison St, 16Th Fl Oakland, Ca 94612 Timing: Fiscal Year 2003; Project Start 01-MAY-1998; Project End 31-JUL-2008 Summary: In 1999, 3,924 women age 75+ years who were categorized as users (N=1944) or non-users (N=1980) of hormone replacement therapy (estrogen alone--ERT; estrogen

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plus progestin--HRT) based on computer-stored prescription data were recruited to a study of the prevalence and incidence of dementia in relation to ERT/HRT use. At recruitment, cognitive status and dementia (all dementia and probable Alzheimer's Disease--AD) were assessed using the modified Telephone Interview of Cognitive Status (TICSm), the Telephone Dementia Questionnaire (TDQ) and medical record review. ApoE genotype was determined for the 2,044 women who gave blood and consented to testing. The prevalence of cognitive impairment and dementia in relation to ERT/HRT use was assessed, and the results of this analysis were published. Non-demented women who completed the TICSm at baseline have been followed annually in order to ascertain incident cases of dementia and to track changes in cognitive status based on the TICSm. To date, we have completed 2 of 4 planned years of follow-up; 182 incident cases of dementia have been identified. The study still lacks power to assess dementia in subgroups of importance. The period of follow-up to assess changes in cognitive functioning is so far short. Thus, we propose to continue follow-up of women in the cohort for an additional four years. The primary aims of continuation of the cohort study are: 1) to increase the power of the study to assess dementia and probable AD in relation to ERT/HRT use; 2) to increase the power of the study to examine dementia and probable AD risk in relation to ERT/HRT in specific subgroups; and 3) to assess rates of cognitive decline in ERT/HRT users overall and in subgroups. The study will also maintain its bank of DNA and pursue promising genetic leads in dementia and lateonset AD, although there are no specific plans to conduct additional gene tests proposed now. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIESTROGENS--MECHANISM OF ANTAGONIST ACTION Principal Investigator & Institution: Katzenellenbogen, Benita S.; Swanlund Professor; Molecular & Integrative Phys; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2001; Project Start 01-DEC-1978; Project End 29-FEB-2004 Summary: Antiestrogens (AEs) are the most widely used agents for the treatment of hormone-responsive breast cancer, and the AE tamoxifen has also proven to be effective in preventing breast cancer. AEs are also unique ligands useful for understanding the tissue selective actions of certain estrogens, an important issue in menopausal hormone replacement therapy, and for probing the intriguing pharmacology of the two estrogen receptor (ER) subtypes, ERalpha and ERbeta, and their roles in breast cancer and other estrogen target cells. In this application, we are proposing to investigate two new aspects of the action of AEs. The first aspect deals with the ability of certain proteins (denoted PAAs for "Potentiators of Antiestrogen Activity") that we have identified recently, to enhance the potency of AEs as inhibitors of estrogens. The levels and activity of these small, estrogen receptor-selective proteins could account for the differential tissue selectivity of AEs and for the ability of ER-containing breast tumors to be either highly sensitive, or resistant to AE therapy. We propose to identify and characterize PAAs, by examining their roles as modulators of AE action in target cells and determinants of hormonal resistance in breast cancer, by elucidating their interaction domains with ER, their subcellular distribution, and their interaction with other ER coregulators, and by performing structural analyses on PAA-ER complexes. The second aspect also derives from our recent work in which we have found that certain antioxidant/cytoprotective genes are upregulated by AEs and inhibited by estrogens. We propose to identify and analyze the regulation of genes selectively upregulated by AEs, by searching for other genes that are AE stimulated and estrogen suppressed, by

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analyzing the gene regulatory regions mediating the selective activation by AEs, by determining the ERalpha and ERbeta selectivity of this regulation, and by examining whether other antioxidant genes involved in cytoprotection against reactive oxygen species are upregulated by AEs. The studies we propose should provide significant new insight into how AEs act, what cellular factors determine their effectiveness and tissue selectivity, and how their gene regulating activities contribute to their beneficial antiproliferative, tumor suppressive, and cytoprotective actions in breast cancer treatment and prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BONE RESPONSE TO SOY ISOFLAVONES IN WOMEN Principal Investigator & Institution: Alekel, Lee D.; Food Science & Human Nutrition; Iowa State University of Science & Tech Ames, Ia 500112207 Timing: Fiscal Year 2002; Project Start 24-MAY-2002; Project End 30-APR-2007 Summary: (provided by applicant): Soy protein rich in isoflavones (estrogen-like compounds) has been shown to prevent bone loss in ovariectomized rats. Our shortterm preliminary study results in perimenopausal women are compelling, suggesting a bone-sparing effect. These findings have prompted great interest in isoflavones as an alternative to hormone replacement therapy, yet the long-term efficacy of isoflavones on bone in humans is unknown. Our objective is to determine the three-year efficacy of isoflavone-rich soy extract in attenuating bone loss in postmenopausal women. The central hypothesis is that soy isoflavones will attenuate bone loss in early postmenopausal women by maintaining bone formation, being modulated by growth factors and isoflavone metabolism. The rationale for this research is that current hormone therapy is fraught with side effects that adversely affect women, resulting in non-compliance. This randomized double-blind placebo controlled clinical trial will examine the effects of two doses (80 or 120 mg/d) of isoflavone-rich soy extract on bone in non-osteoporotic early postmenopausal women (N=234). Specific Aims are to: 1) Determine the bone-preserving effects of isoflavones on lumbar spine bone mass as the primary outcome; 2) Relate treatment-induced changes in bone mass to changes in biochemical markers of bone turnover; 3) Identify potential mechanisms by which isoflavones prevent or modulate bone loss by measuring endogenous estrogens, sex hormone-binding globulin, insulin-like growth factor-I (IGF-I), urinary minerals, serum 25(OH)vitamin D, plasma isoflavones and their metabolites, and customary intake of isoflavone-containing soy, thus accounting for variability in response to treatment; 4) Ascertain the safety of isoflavone-rich soy extract. Caucasian women of European descent will be recruited at two sites (117 at IA, 117 at CA). Random effects repeated measures analyses will be used to: a) characterize change in bone mass as the primary outcome, b) estimate treatment-induced effects, and c) depict change in markers of bone turnover in relation to bone mass change. We will use intent-to-treat for the primary test. We will also examine potential modulators (reproductive hormones, IGF-I, plasma isoflavones) and account for other factors that affect bone, as indicated in specific aim 3. This study will provide valuable data on whether isoflavones impact bone in early postmenopausal women and help elucidate potential mechanisms, thereby contributing to our understanding of isoflavones as an alternative to traditional hormone therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BREAST & OTHER CANCER IN THE CALIFORNIA TEACHERS COHORT Principal Investigator & Institution: Wright, William E.; Chief; Public Health Institute 555 12Th St, 10Th Fl Oakland, Ca 94607 Timing: Fiscal Year 2001; Project Start 25-SEP-1998; Project End 30-SEP-2003 Summary: (adapted from applicant's Description): A cohort of 133,000 California school teachers has been established by a collaborative group of epidemiological investigators with the goals of evaluating unresolved issues related to breast cancer risk factors and studying other important issues related to women's health. The teachers were recruited with a detailed multiple choice, optically-scanned mail survey. Scanning of the questionnaires has been completed and data editing is ongoing. Planned follow-up includes routine linkage with the California Cancer Registry and California mortality files, annual re-contact of cohort members for follow-up, and biennial contact for collecting additional risk factor exposure data and information on other health outcomes. The Specific Aims for this project are to: 1) test a series of unresolved and emerging hypotheses related to breast cancer aetiology (specifically associations with the lactation, hormone replacement therapy, abortion/miscarriage, dietary phytoestrogens, fibre, micronutrient consumption, alcohol intake, physical exercise and activities, family history of breast and other cancers, and active and passive cigarette smoke exposure); 2) conduct calibration/validation studies of the food-frequency questionnaire and self-reported information on family history of breast and other cancers reported in the baseline questionnaire; and 3) follow this cohort for five additional years, during which time, two or more questionnaires will be mailed to update initial exposure assessments, collect new exposure information, and assess additional disease outcomes for testing novel hypotheses of major importance to women's health, in a timely manner. During the next five years, 2,025 invasive incident and 390 in situ incident breast cancers are anticipated which will provide ample statistical power to address each of the proposed hypotheses in detail. The California Teachers Study presents a rare opportunity to study women's health, because of the size of the cohort, the uniformly high level of education among teachers, their experience with survey instruments, their diversity of exposures and geographic residences, and the relative ease with which they can be followed in California. This research is intended to substantially increase knowledge of preventable risk factors for cancer and other health outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BREAST CANCER ETIOLOGY Principal Investigator & Institution: Gupta, Ramesh C.; Professor of Toxicology; Prev Med & Environmental Hlth; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 06-DEC-2001; Project End 30-NOV-2005 Summary: PROVIDED BY APPLICANT) A number of risk factors, including dietary fat intake, family history, and exposure to exogenous and endogenous chemicals, have been implicated in the etiology of breast cancer incidence. Epidemiological studies have identified an association of elevated levels of estrogens with breast cancer development. In particular, the natural hormone, 17B-estradiol (E2) and its major metabolite, 4hydroxyestradiol (4-E2), which are known animal carcinogens, have been implicated in human breast cancer and it is believed that these substances cause free radical-mediated, direct and/or indirect DNA damage. Novel, polar DNA adducts have been detected in

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the mammary tissues of both rats and humans by devising new systems to employ 32Ppostlabeling/TLC. Adduct spectra between rat and human mammary DNA exhibited strong similarities. Further, the polar adducts were significantly enhanced in estrogensensitive tissues, particularly mammary, after treatment of S/D rats with estradiol. In light of the known redox-cycling activity of 4-E2, a major metabolite of estradiol, these results suggest a link between polar DNA adduct formation and metabolic processing of E2. We hypothesize that the polar DNA adducts detected in the mammary tissues originate from free radical mediation. We also hypothesize that significant inter-subject differences occur in the accumulation of pre-mutational DNA lesions, and these differences could in part explain the wide range of susceptibility seen in the induction of some cancers. Specific studies will be as follows: (1) To analyze DNA damage in mammary epithelium of rats treated with the endogenous estrogen and its metabolites, as well as the equine estrogen, equilin and equilenin. Blood lymphocytes will be included as surrogates for comparison. Antioxidant intervention experiments will be performed to support the hypothesis. Also measured will be the tissue and plasma levels of E2 and its metabolites by sensitive HPLC-CoulArray for correlating with oxidative DNA adduct burden. (2) To analyze DNA damage in epithelial cells of breast tissues of cancer-free women and breast cancer patients and surrogate blood lymphocytes, and blood lymphocytes of women receiving hormone replacement therapy. Tissue levels of E2 and its metabolites will be correlated with oxidative DNA adduct burden and breast cancer incidence. (3) To develop and apply LC-MS/MS and CE-MS/MS technology in conjunction with 32P-postlabeling for identifying DNA adducts in human breast tissues. Data resulting from this highly sensitive approach will reveal the etiological nature of exposure and will determine inter-subject differences in mammary DNA damage that may be associated with susceptibility differences. Furthermore, if tissue levels of estradiol metabolite(s) and/or oxidative burden are found to correlate positively with breast cancer incidence, then future clinical studies to reduce breast cancer risks can be planned with antioxidant intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITION AND ESTROGEN IN MIDDLE-AGED FEMALE MONKEYS Principal Investigator & Institution: Voytko, Mary L.; Associate Professor; Pathology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2003; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: (provided by applicant): This application is being submitted as a supplement to grant RO1AG19100 entitled "Cognition and Estrogen in Middle-Aged Female Monkeys". Ovarian hormone deficiency of menopause brings on changes that can have far reaching consequences on the future health and well being of women. In addition to the physical symptoms associated with menopause, postmenopausal women experience alterations in cognitive function, particularly memory and attention. However, determining the relationship between ovarian hormones and cognitive function in menopause can be difficult to study in women because of a variety of confounding factors. We have developed a monkey model of menopause that allows us to more rigorously control many of these factors and, additionally, that will permit us to identify the potential mechanisms of ovarian hormone action in the primate brain. The focus of the studies in the parent project is to determine the effects of ovariectomy and unopposed continuous estrogen replacement therapy (ERT) on cognitive abilities in a unique colony of middle-aged female rhesus monkeys at the Oregon Regional Primate Research Center (ORPRC). The purpose of this supplemental application is to expand

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the breadth of valuable information that could be obtained from the parent project by adding another group of ovariectomized monkeys that will be treated with a combined therapy of continuous estrogen and progesterone (HRT) and by performing MRI studies in all monkeys (supplemental and original groups). The addition of the new group of monkeys will permit the direct comparison between ERT and HRT treatments on cognitive function. Combined HRT is not only the most commonly prescribed ovarian hormone replacement therapy of postmenopausal women; it also represents a hormone replacement therapy that more closely mimics the natural physiological exposure to estrogen and progesterone in premenopausal women than continuous unopposed ERT alone. The MRI studies will determine the extent to which ovariectomy or ovarian hormone therapy influence measures of brain volume that decline with age, and whether there is a correlation between these volumetric changes and cognitive function. The experiments in this supplemental application will address key issues of women's health by taking advantage of the existence of the treatment and control groups already supported by the parent grant. The findings from these novel experiments in middleaged monkeys will significantly advance our understanding of the effects of different ovarian hormone therapies on cognitive and neurobiological profiles of primates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLON CANCER SURVIVORS--MEDICATIONS & RISK OF RECURRENCE Principal Investigator & Institution: Johnson, Christine C.; Ch Epidemiologist; Josephine Ford Cancer Center; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the Applicant's Abstract): Colorectal cancer will be diagnosed in over 129,000 Americans in 1999. To combat this disease, new avenues to decrease the risk of colorectal cancer, such as chemoprevention, are being explored by researchers. Non-steroidal anti-inflammatory drugs (NSAIDs) and hormone replacement therapy (HRT) have been shown to decrease incident colon cancer. Little is known of their effect on persons with a history of colon cancer which, fortunately, is a continually expanding population as survival has been significantly improving over the last twenty years. The objective of this epidemiologic study is to determine whether NSAIDs or HRT is associated with recurrence or survival among individuals diagnosed with colorectal cancer. The proposed research will establish a cohort of colorectal cancer patients treated with curative intent and create a comprehensive longitudinal database, including data on the ascertainment of subsequent adenomatous polyps, colorectal cancer and survival. The specific aims are: (1) to determine whether NSAID use deceases the risk of recurrence of colorectal cancer; (2) to determine whether HRT use deceases the risk of recurrence of colorectal cancer; (3) to determine whether NSAID use affects short-term survival; and (4) to determine whether HRT use affects short-term survival. The cohort will be established from colorectal cancer patients enrolled in two managed care organizations, Health Alliance Plan (Detroit, MI) and HealthPartners (Minneapolis, MN). Cohort subjects will be followed for at least five years for new evidence of disease, recurrence and survival outcome. Using automated pharmacy data, the timing of use and exposure to NSAIDs and HRT will be analyzed among cancer survivors, along with potentially confounding variables, in relation to these outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DECISION MAKING REGARDING HORMONE REPLACEMENT THERAPY Principal Investigator & Institution: Padonu, Georgia; None; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: The career goal of this applicant is to develop the research skills to become an independent, externally funded biomedical researcher in the field of health decision making and achieve a record of research and publication productivity. The research focus is the development and testing of decision support interventions and their adaptability in the study of decision making regarding HRT among low income menopausal African American women. To accomplish the research career goals, the following objectives are developed for the proposed award period: 1. To expand knowledge of selected concepts, measurement and analytical strategies predominately used in decision support research development and testing. 2. To build on and expand skills in developing culturally sensitive research materials, instruments and interventions. 3. To increase knowledge of select conceptual frameworks used in decision making research to including both initial and continuance decision making, and with adaptability to low income African American women. 4. To increase theoretical knowledge of risk communication in the context of decision making research, issues of communication style, format preferences, with focus on application to low income, low literacy and diversity in study populations. 5. To maintain currency in clinical competency related to menopause and HRT with special interest in health risk assessment and quality of life as health status outcome. 6. To utilize knowledge and skills gained from career development activities to conduct pilot research of decision support for community-based low-income African American women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIET, HORMONE REPLACEMENT THERAPY AND BREAST CANCER Principal Investigator & Institution: Zhang, Shumin; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 12-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): This is a resubmission of I K07 CA096619-01 "Diet, Hormone Replacement Therapy and Breast Cancer". Candidate: Shumin Zhang received her MD at the Harbin Medical University in 1986 and her ScD in epidemiology and nutrition at the Harvard School of Public Health in 1998. She then completed her post-doctoral training in 2000, and now is an Assistant Professor of Medicine at the Harvard Medical School (HMS). She applies for this Career Development Award to acquire the methodological and theoretical research skills needed to become an independent scientist in cancer and nutritional epidemiology. Sponsor and Environment: JoAnn Manson, MD, DrPH, is the Chief of the Division of Preventive Medicine at the Brigham and Women's Hospital, Professor of Medicine at the HMS and Co Principal investigator (Co-Principal Investigator) of the Women's Health Study ONHS). Julie Buring, ScD, is the Deputy Director of the Division, Professor of Ambulatory Care and Prevention at the HMS and Principal Investigator of the WHS. They have trained numerous investigators in the fields of diet, lifestyle and chronic diseases, areas in which they have published extensively. Research: We plan to conduct a prospective analysis within the WHS, an ongoing clinical trial of vitamin E and lowdose aspirin in the primary prevention of cancer and cardiovascular disease among

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39,876 women. We will test 4 dietary hypotheses that moderate alcohol intake increases risk of breast cancer, whereas high intake of folate and fiber reduces risk; and caffeine intake is not associated with risk. We will link fiber intake to plasma endogenous sex steroid hormones in a subsample of the WHS. We will also test 4 hormone replacement therapy (HRT) hypotheses that tong-term use of estrogen plus progestin increases risk of breast cancer more than estrogen alone; estrogen plus cyclic progestin increases risk more than estrogen plus continuous progestin; low-dose estrogens confer lower risk than high-dose; and use of estrogen is more strongly associated with risk among women drinking alcohol. The ongoing WHS will provide updated and repeated measures of HRT, comprehensive dietary assessment at baseline, and important covariates for breast cancer in addition to follow-up of the cohort and documentation of breast cancer cases (expected N = 1550). The findings from this project could have direct clinical application for efforts to reduce risk of breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF SOYBEANS ON BONE AND THE REPRODUCTIVE TRACT Principal Investigator & Institution: Bahr, Janice M.; Professor; Animal Sciences; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2003 Summary: (adapted from the applicant's abstract) Some postmenopausal women use hormone replacement therapy (HRT) to maintain bone. This treatment is, however, not acceptable to all women. An alternative approach is intake of foods rich in phytoestrogens - natural plant estrogens such as soybeans. The hypothesis is that soy protein protects against postmenopausal bone loss by slowing resorption and enhancing bone formation due to organ-selective estrogenic effects of the isoflavones genistein and daidzein. The applicant proposes four questions: 1. Efficacy: What is the effect of soy protein and soy isoflavones on bone formation and resorption? 2. Safety: Do soy isoflavones and estrogen have differential effects on bone and female reproductive tissues? 3. Safety: Do soy proteins or isoflavones antagonize the effects of endogenous estrogen on bone and the reproductive tract? 4. Mechanism: Do soy isoflavones differentially affect estrogen-dependent bone resorption and formation through estrogen receptor-mediated mechanisms? In vivo studies will use ovariectomized rats, an established model for osteoporosis, and intact rats. In vitro studies will use mouse calvarial explant culture and an estrogen receptor reporter system. To answer questions 1-3 ovariectomized and inteact rats will be fed diets of various concentrations of soy or isoflavones for 3 months. Measurements during and at termination of experiments are urinary deoxypyridine, an indicator of bone breakdown; bone mineral density; and bone formation by histomorphometry. The reproductive tract will be evaluated by histology and production of Complement C3 by the uterus and measurement of estradiol and luteinizing hormone in plasma. In vitro studies (question 4) will determine if isoflavones act through an ER and which subtypes, ERa or ERb. These studies are necessary to identify efficacious and safe alternative approaches to HRT readily accessible to all women. Knowledge of active agents and mechanism of action will allow standardization of soy supplements; identification of doses that maintain bone health without compromising other systems, e.g. reproductive; and assurance against interactions from like compounds in other drugs and food, including supplements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENDOGENOUS/EXOGENOUS SEX HORMONES & CHD RISK FACTORS Principal Investigator & Institution: Barrett-Connor, Elizabeth L.; Professor and Chair; Family and Preventive Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Coronary heart disease (CHD) is the most common cause of death in U.S. women. Observational studies consistently show that postmenopausal estrogen, with or without a progestin, reduces the risk of CHD, and there are several plausible mechanisms by which estrogen might protect the heart. Nevertheless, clinical trials to date have not demonstrated cardioprotection. If hormone levels play a role in determining CHD risk in postmenopausal women and HRT is to be used as a means of reducing that risk, the interactions of endogenous hormones, HRT, and CHD risk factors need further definition, in particular the effect of covariates. Individual characteristics such as basal hormone levels, body size, past hormone use, and lifestyle decisions may modify responses to HRT. This proposal focuses on four questions: 1) what factors determine circulating sex hormone levels in postmenopausal women, 2) what factors determine changes in sex hormone levels in response to hormone replacement therapy (HRT), 3) do endogenous sex hormone levels influence CHD risk factors in postmenopausal women, and 4) do changes in sex hormone levels with HRT predict the effect of HRT on CHD risk factors. These questions will be addressed by analyzing existing data from the Postmenopausal Estrogen / Progestin Interventions Trial (PEPI), a 3-year, multi-center, double-blind, placebo-controlled trial designed to compare the effect of estrogen alone and 3 estrogen/progestin HRT regimens vs placebo on selected CHD risk factors. There were 875 participants. Serum sex hormone levels, CHD risk factors, and potential covariates (including demographic characteristics, anthropometric measurements, reproductive history and lifestyle variables), determined at baseline and at 24 or 36 months of treatment, will be considered in the analyses. Results of this study will help define the differences between women with regard to endogenous sex hormone levels and responses to HRT, and the relation of sex hormones to CHD risk factors. These observations may aid in deciding whether individual women should use HRT and, if so, which regimen would provide the most benefit with the least risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY OF OVARIAN CANCER:NEW HYPOTHESES Principal Investigator & Institution: Rossing, Mary A.; Associate Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Much of the previous epidemiologic research on ovarian cancer has been conducted within the conceptual with conceptual framework of the ovulation and gonadotropin. However, additional mechanisms must be operative to account for epidemiologic findings regarding this disease. In this study, we will address the hypothesis that progesterone reduces risk of epithelial ovarian cancer. We will examine the relation of exogenous progestins administered as a component of hormone replacement therapy (HRT) with disease risk. We will further assess whether sunlight and dietary sources of vitamin D influence risk. The study will contribute to a better understanding of pathogenic mechanisms of epithelial ovarian cancer, and may provide information leading to new means of reducing the occurrence of this disease. We

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propose to conduct a population-based, case-control study of epithelial ovarian cancer among women aged 35-74 years residing in thirteen counties of Washington State. Cases will be identified through a population-based cancer registry operating as part of the Surveillance, Epidemiology and End Results Program. Controls will be identified through random digit telephone dialing, and will be selected to be similar in age and area of residence to cases. In-person interviews will be conducted and blood samples will be collected. The findings of this study will have appreciable public health importance. Study of the impact of different HRT regimens, particularly estrogen/progestin combinations, on ovarian cancer risk has been deemed an urgent task for research. Recent calls for reappraisals of the risk/benefit ratio of unopposed estrogen and combined estrogen/progestin HRT highlight the need to understand the relation of these medications with ovarian cancer risk, and to incorporate this knowledge into risk/benefit considerations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY OF VENOUS THROMBOEMBOLISM Principal Investigator & Institution: Glynn, Robert J.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2005 Summary: Venous thromboembolism (VTE) is a common condition causing substantial morbidity, cost and mortality, yet several aspects of the epidemiology of this disease remain unexplored. The major aim of this proposal is to evaluate potentially modifiable lifestyle predictors of VTE and their joint associations with biochemical and genetic determinants. Studies will identify determinants of both initial occurrence of VTE as well as recurrence among persons with a prior event. The study design is a prospective cohort study of 77,118 persons based on pooling information from four large randomized trials of US health professionals that have collected detailed risk factor information and have used common strategies to prospectively identify and validate cases of VTE. These trials are: Physicians' Health Studies I and II including 29,071 US male physicians, of whom 22,071 have been followed since the initiation of the first trial in 1982; the Women's Health Study including 39,876 female health professionals who will have an average of 10 years of follow-up; and the Women's Antioxidant Cardiovascular Study including 8,171 female health professionals with prevalent cardiovascular disease or at high risk of cardiovascular disease who will have an average of 8 years of follow-up. Archived blood samples were collected from approximately 75 percent of participants at baseline and will be used to assess biochemical and genetic markers of risk including factor V Leiden, the G20210A mutation in the prothrombin gene, hyperhomocysteinemia, and anticardiolipin antibodies. The study will assess the joint association with risk of these markers and potentially modifiable factors including body mass index, hormone replacement therapy, physical activity, and aspirin use. The study population will include over 1,000 incident cases of VTE, including 750 with blood samples. The large size, prospective design, high follow-up rates, detailed and reliable long-term exposure and outcome information, and the availability of blood specimens on a large subgroup, combined with the relatively low cost, make these cohorts a valuable and unique resource for studying determinants of risk of VTE. The results of this work may lead to new strategies for VTE preventio. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Hormone Replacement Therapy

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Project Title: EPIDEMIOLOGY OF VENOUS THROMBOSIS AND PULMONARY EMBOLISM Principal Investigator & Institution: Folsom, Aaron R.; Professor; Epidemiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-FEB-1998; Project End 31-DEC-2006 Summary: (provided by applicant): Venous thromboembolism (VTE), comprising deep venous thrombosis and pulmonary embolism, is a major contributor to morbidity and mortality in the US. We propose here a 4-year continuation of our unique and informative Longitudinal Investigation of Thromboembolism Etiology (LITE), a prospective study within the ARIC and CHS cohorts. We have several important findings from the previous project period, the three most important being (1) identification for the first time in a prospective study that plasma fibrin fragment Ddimer, a marker of fibrin turnover, is positively and strongly associated with risk of future VTE, (2) verification, again for the first time prospectively, that factor VIII and von Willebrand factor are strong risk factors for VTE, and (3) demonstration that obesity and diabetes are important VTE risk factors, but that most other arterial disease risk factors, including fibrinogen and C-reactive protein, are not. We plan to build upon these findings during LITE continuation, by adding new cases and testing new hypotheses. Our aims are 1. To extend VTE event follow-up in the LITE Study for 4 more years, which is expected to increase the current number of VTE events (n=335) by 47 percent (to n=493), and to sample 1 control per case. In the new cases and controls, we will measure analytes found to be important in LITE already (factor V Leiden, prothrombin G20210A variant, D-dimer, and TAFI), to serve as covariates in combined analyses. 2. To conduct nested case-control studies in the entire sample of 493 VTE cases and 828 controls, using prediagnosis blood and DNA specimens, to determine the prospective associations of VTE with several novel plasma hemostatic factors and genetic markers. 3. To conduct longitudinal analyses of VTE incidence and potential risk factors (or interaction) that we have not yet fully explored: diet, frailty, hormone replacement therapy, and obesity interactions. 4. To study serial blood levels of Ddimer and homocysteine, to better understand their associations with VTE occurrence. Continuation of this comprehensive prospective study will provide additional important epidemiologic insights into the etiology of VTE. This could lead to new strategies for prevention or treatment of VTE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTROGEN RECEPTOR VARIANCE AND CHD RISK IN HERS Principal Investigator & Institution: Herrington, David M.; Professor; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-MAY-2005 Summary: (provided by applicant): Estrogen raises HDL cholesterol levels - an effect that may account for the favorable association between hormone replacement therapy (HRT) and coronary heart disease (CHD) risk in postmenopausal women. Several lines of evidence suggest that genetic factors also influence HDL levels, although the precise genes involved have not yet been determined. Recent evidence from the Estrogen Replacement and Atherosclerosis (ERA) trial (N = 309) indicates that certain allelic variants in the estrogen receptor-alpha (ER-alpha) gene are associated with more than a twofold increase in estrogen's effects on HDL cholesterol. Women with the favorable genotype (ca. 20% of women) experienced a 26% increase in HDL with HRT compared with a 13% increase observed in the remaining women. However, this trial was too

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small to determine if these effects translate into an angiographic or clinical benefit. The Heart and Estrogen Replacement Study (HERS) was a large (N = 2763) randomized clinical endpoint trial of HRT for secondary prevention of CHD. This clinical trial cohort provides an ideal opportunity to confirm or refute the associations and interactions observed in the ERA trial with respect to lipids, and extend these observations to other estrogen-sensitive intermediate endpoints and clinical disease outcomes. Therefore, we propose to genotype HERS women with respect to several ER-alpha polymorphisms, and to examine the relationship between these ER-alpha genotypes, HRT use, change in HDL, and risk for CHD events. We will also examine the effects of ER-alpha polymorphisms on other plasma lipids, C-reactive protein, bone mineral density, risk for venous thromboembolic events, stroke, fractures, and all-cause mortality. Use of data and specimens from HERS is an efficient means to study the clinical impact of ER-alpha polymorphisms and possible modulation of estrogen action. If there are common polymorphisms in the ER-alpha gene that modify estrogen's effects on HDL and possibly other domains of estrogen action, this information could improve patients' and clinicians' ability to assess risks and benefits of HRT use. In addition, this information could lead to fundamentally important new knowledge about mechanisms of estrogen action, regulation of HDL cholesterol, and pathogenesis of CHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESTROGEN REGULATED GENES AND NEURAL PROTECTION Principal Investigator & Institution: Sisk, Cheryl L.; Professor and Director; Microbiology and Public Health; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2002 Summary: Epidemiological studies indicate 6that estrogen hormone replacement therapy in postmenopausal women reduces the risk of Alzheimer's Disease. One mechanisms by which estrogen may reduce risk of Alzheimer's Disease is inhibition of beta-amyloid plaque formation and ensuing cell death in hippocampus and cortex, which are among the most severely affected brain regions in Alzheimer's Disease. Using cDNA array assays to screen for estrogen-regulated genes in a mouse model of menopause, three genes were identified that are both regulated by estrogen in the hippocampus and frontal cortex and are known to be involved in amyloid precursor protein (APP) processing, plaque formation, and apoptosis. These genes encode transthyretin precursor (TTR), presenilin 1 (PS1), and presenilin 2 (PS2). Presenilins promote neural degeneration by cleaving APP into plaque-forming beta-amyloid peptide fragments (Abeta42) and inducing apoptosis. In contrast, TTR impedes plaque formation by sequestering Abeta42. The cDNA array data suggest two novel mechanisms for neural protection by estrogen: 1) inhibition of PS1 and PS2 gene expression, and 2) stimulation of TTR gene expression. The goal of the proposed project is to confirm and extend the findings based on cDNA arrays. The Specific Aims are to 1) confirm and precisely quantify estrogen regulation of TTR, PS1, and PS2 mRNA and protein are regulated by estrogen using in situ hybridization histochemistry and immunocytochemistry. The proposed studies employed a newly developed in vivo mouse model of menopause in which tissue responses to estrogen are assessed and compared when hormone replacement therapy is begin in either early or late menopause. The long-term goal of this work is to contribute to the development of hormone replacement strategies for post-menopausal women that are optimally effective in delaying or preventing the progression of Alzheimer's Disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Hormone Replacement Therapy

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Project Title: ESTROGEN, ANGINA, ACTIVITY AND QUALITY OF LIFE IN WOMEN Principal Investigator & Institution: Missik, Eugeria; None; Kent State University at Kent Research & Graduate Studies Kent, Oh 44242 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2004 Summary: Postmenopausal women comprise the largest number of female cardiac patients. Recently recognized vasoactive effects of estrogen have shown to improve coronary blood flow in postmenopausal cardiac women especially during exercise. Our recent pilot study conducted on 37 postmenopausal cardiac women identified some notable trends between women receiving hormone replacement therapy (HRT) and those women not receiving HRT. Women on HRT performed activities of higher intensity for longer periods of time, reported lower severity of angina, and higher quality of life. Studies on the relationship of hormonal status and daily physical activity of cardiac patients are not available. To what extent estrogen replacement therapy (ERT) impacts the daily physical activity of postmenopausal cardiac patients is not known. It is hypothesized that the antischemic effects of estrogen positively impact daily physical activity and quality of life of postmenopausal cardiac women. Therefore, the primary aim of this study is to test a model examining the relationship between ERT use and frequency and severity of angina, daily physical activity, and quality of life. A prospective, comparative and cohort study will be used. Data will be collected on 180 postmenopausal cardiac women at three hospital based cardiac rehabilitation centers in western Pennsylvania. Multiple measures will be used for each construct in the model. Physical activity will be measured by self-report and electronic monitoring using the Tri Trac R3D accelerometer. Angina will be measured by the supplemented Rose Questionnaire, frequency by self-report, and severity by a numerical scale. Quality of life will be measured by using the Medical Outcomes Study, Short Form 36-Items. Structural equation analysis will be used to model the impact of ERT on the dependent variables. A demonstrated positive impact on physical activity may provide an additional rationale for the prudent use of ERT in the optimum management of postmenopausal cardiac patients. Interventions to support the adoption and maintenance of physical activity recommendations by postmenopausal cardiac women are greatly needed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTROGEN, CYTOKINES AND HEART FAILURE IN WOMEN Principal Investigator & Institution: Reis, Steven E.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 10-DEC-2001; Project End 30-NOV-2006 Summary: (provided by applicant): Congestive heart failure (CHF) is a leading cause of morbidity, mortality, and hospitalization in women. The observation that women with nonischemic cardiomyopathy have an age-related increase in mortality suggests that postmenopausal estrogen loss may alter the phenotypic expression of CHF. Because estrogen is a potent in vitro inhibitor of pro-inflammatory cytokines (e.g., TNFa, IL-1B, IL-6), which are re-expressed by the failing myocardium in patients with CHF and are related to an adverse prognosis, we postulate that estrogen replacement will improve the outcome of postmenopausal women with CHF. This hypothesis is supported by our preliminary data that demonstrate 1) female sex confers a survival advantage in transgenic mice with CHF due to over-expression of TNFa, 2) female sex is associated with an attenuated pathologic response of cardiac myocytes to TNFa, 3) estrogen and

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progesterone inhibit TNFa production by rat cardiac myocytes, 4) estrogen replacement therapy in postmenopausal women with CHF abrogates an age-related increase in TNFa, and 5) estrogen therapy in women with severe CHF is associated with a significant decrease in mortality. Our proposed randomized placebo-controlled doubleblind study of hormone replacement therapy in women with CHF will evaluate the hypothesis that estrogen has a protective effect in postmenopausal women with CHF related to modulation of TNFa and associated "downstream" cytokines (i.e., IL-lB. IL-6) and/or myocardial expression of cytokine receptors. We plan to compare the effects of hormones on functional capacity, biventricular mass and function, and quality of life with their effects on circulating cytokines in postmenopausal women with CHF. To determine the degree of hormone-induced cytokine suppression that is associated with favorable outcome, we will compare post-treatment cytokine levels in women with CHF with cytokine levels in a "control" group of women from the NHLBI WISE study who have no evidence of CHF and normal ventricular function. The results of this study will define the mechanism of estrogen's beneficial effect in postmenopausal women with CHF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESTROGEN/PLATELET INTERACTION IN CEREBRAL ISCHEMIA Principal Investigator & Institution: Kearney, Marguerite L.; Associate Professor; Anesthesiology/Crit Care Med; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2005 Summary: Platelet activation in the cerebrovasculature has been implicated as a mediator of tissue injury following stroke or other ischemic events. Data suggest that pre-menopausal women are at lower risk than men for cardiovascular diseases including stroke and transient ischemic attacks, conceivably due to the effects of estrogenic hormones on platelet biology or vascular function. Many women make a choice to receive hormone replacement therapy, but controversy surrounds the risks versus the benefits of estrogen therapy. Recent studies indicate that increasing estrogen levels promotes expression of the antiaggregant vasodilator, nitric oxide (NO), while depressing platelet elaboration of the adhesion molecule, P-selectin. We propose to study the effects of elevated estrogen on platelet biology to determine if the hormone moderates alterations in pre and post-ischemic platelet function or microvascular vasodilator capacity via the expression of vasoconstrictive platelet products. In Aim 1 we will determine if chronic estrogen in two physiologic doses modulates platelet biologic via a P-selectin mediated mechanism at baseline or after global cerebral ischemia. In Aim 2 we will test if chronic estrogen in two physiologic doses modulates changes in post-ischemia pial vessel vasodilatory capacity via attenuation of the release of adhesive or vasoactive platelet products. In Aim 3 we study the interrelationship between NO and P-selectin expression. We will determine, if the effects of chronic estrogen treatment in two physiologic doses improves microvascular perfusion by depressing post-ischemic platelet and endothelial P-selectin as a result of increased nitric oxide production. We will use whole blood platelet aggregometry, intravital microscopy, immunological and biochemical techniques to ascertain how estrogen affects platelet biology and microvascular endothelial function. The studies proposed in this project will clarify the contribution of exogenous estrogen therapy in ischemic brain injury both mechanistically and according to dosage. These are important considerations which impact nursing therapeutics given the controversy surrounding the safety and efficacy of estrogen replacement regimens.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FACTORS AFFECTING SURVIVAL OF YOUNG CANCER PATIENTS Principal Investigator & Institution: Malone, Kathleen E.; Associate Program Head; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 05-JUN-1993; Project End 30-APR-2003 Summary: This application for a competitive renewal of "Factors that affec survival of young breast cancer patients", seeks to extend for five more years the follow-up for recurrence and mortality of a population-based cohort of 128 women who were diagnosed with invasive breast cancer before age 45 during the years 1983 through 1992. These women provide the investigators with a unique opportunity to investigate the interrelationships between epidemiologic risk factor data, tumor characteristics, and breast cancer occurrence and/or mortality in a population-based setting where all cases of breast cancer in a defined geographic area could be assessed, eliminating potential biases impose by studies at referral centers or clinical trials, where women may selfselect into the study and not be representative of women in general who get breast cancer. During the past five years, this cohort was followed through follow-up questionnaires and hospital chart reviews, and their tumor specimens were tested for characteristics related to aggressiveness and prognosis. It is important to extend followup of this cohort to a minimum of ten years since patient and tumor characteristics may have different relationships with short and long-term mortality. During the next five years, the investigators propose to (a) expand data collection and specimen analyses to the entire cohort (rather than the subgroup of 930 they originally proposed), (b) extend the minimum follow-up period for the entire cohort to ten years, (c) collect updated information on recurrences, treatment, the use of hormone replacement therapy and childbearing after diagnosis, (d) add apoptotic index to the laboratory analyses, and (e) conduct comprehensive analyses of all of these data in relation to mortality and diseasefree survival. Young women with many years of potential life to lose who do not fall into clear prognostic categories present a major challenge to clinicians. By gainin an understanding of the association between epidemiologic risk factors and tumor characteristics related to aggressiveness as well as actual risk of recurrence or death, it is possible to develop profiles of women at high risk for aggressive tumors who might benefit from aggressive treatment and of those with low risk tumors for whom such aggressive treatment may not be necessary. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FT-IR OSTEOPOROSIS

MICROSCOPY

OF

MINERAL

STRUCTURE

IN

Principal Investigator & Institution: Boskey, Adele L.; Starr Chair in Mineralized Tissues; Hospital for Special Surgery 535 E 70Th St New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-JAN-1993; Project End 31-JUL-2005 Summary: (provided by applicant): Osteoporosis is estimated to affect 15-20 million people (both women and men) each year, causing significant morbidity and mortality. The widely used predictors of fracture risk are bone mineral density (BMD) and incidence of a previous fracture. One of the dilemmas in the management of osteoporosis is that two individuals with the same bone density and similar life-styles can show extensive diversity in their tendency to fracture. There is little information on what, other than differences in life style and fall severity, can account for this discrepancy. The underlying hypothesis of this grant is that discrete differences in

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mineral and matrix properties contribute to the altered fracture risk in these individuals. Over the past two funding periods, we have shown that Fourier transform infrared microspectroscopy (FTIRM) and imaging (FTIRI) provide reproducible and valuable information on the mineral and matrix properties of bone. We now wish to extend this approach to two new research questions: Aim 1) Do the mineral and matrix properties differ in biopsies from patients with fracture compared with patients without fractures while controlling for age, gender, bone mineral density, and architecture? This question will be tested by assessing biopsied specimens from individuals with different fracture histories and with known age, gender, and bone mineral density. MicroCT will be used to assess architecture of the specimens, and FTIR will be used to characterize mineral and matrix properties. Under this specific aim, we will also examine associations between FTIR parameters and nanoindentation in a subset of biopsies to establish the nanoindentation technique and to test for significant correlations between mineral/matrix properties and indentation modulus and hardness. We will also develop the use of imaging ATR to establish an IR approach that does not required thin sections of embedded bone. Aim 2) Do therapeutic agents reverse the observed alterations in mineral and matrix properties? Specifically we shall examine the relative effects of a SERM (selective estrogen receptor modulator), raloxifene, Hormone Replacement Therapy, and a bisphosphonate (Risedronate) on the mineral and matrix properties in pre- and post- therapy biopsies, to identify the agent(s) that reverse(s) the observed alterations in mineral and matrix properties. Emphasis will be placed on those properties identified in Aim 1 that are most predictive of fracture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GABAPENTIN VS ESTROGEN FOR THE TREATMENT OF HOT FLUSHES Principal Investigator & Institution: Reddy, Sireesha; Obstetrics and Gynecology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Hot flashes and other climacteric symptoms affect 75% of postmenopausal women in the US and are associated with higher rates of depression and sleep disturbance. Although hormone replacement therapy (HRT) is highly effective in reducing hot flashes, there is concern that HRT is associated with an increased risk of thrombo-embolic events, breast cancer and ovarian cancer. In addition, it is poorly tolerated in clinical practice, with about 30% of women discontinuing therapy after a mean of 4.5 months. Many other women have a contraindication to HRT, such as a history of an estrogen-sensitive tumor, liver dysfunction, or a hypercoagulable state. Safe, effective, and well-tolerated alternative therapies for hot flashes are needed. Gabapentin is a gamma-aminobutyric acid (GABA)-analog approved in 1994 for the treatment of seizures. Since then, it has been shown that gabapentin is efficacious for numerous off-label indications such as neuropathic pain, anxiety, bipolar disorder, and migraine headaches. The investigators have reported that gabapentin is associated with a reduction in the frequency of hot flashes in an uncontrolled series of postmenopausal women who were taking gabapentin for other indications. The investigators also report here preliminary data from a randomized, placebo-controlled trial showing that lowdose gabapentin was associated with a greater reduction in hot flash frequency than placebo after 12 weeks of treatment. However, it is not known whether the efficacy of gabapentin in the treatment of hot flashes and other menopausal symptoms is comparable to that of estrogen, the gold standard. A randomized trial of gabapentin, estrogen and placebo is needed to inform clinicians as to whether gabapentin is an

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effective alternative to estrogen. The first major aim of this proposal is to assess the screening and recruitment of menopausal women into a randomized trial of gabapentin, estrogen and placebo in the treatment of climacteric symptoms. The second major aim is to obtain preliminary estimates of the frequency and severity of climacteric symptoms among women receiving gabapentin, estrogen and placebo. Pilot data from these two aims will permit estimates of sample-size requirements for a full-scale randomized trial, and of the overall feasibility and cost of such a trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENDER AND MENOPAUSE ON NUTRIENT AND ENERGY METABOLISM Principal Investigator & Institution: Horton, Tracy J.; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 01-MAR-1998; Project End 28-FEB-2004 Summary: The overall aim of the P.I.'s research is to better understand gender differences in energy and nutrient metabolism that related to the development and/or protection against disease. The health risks associated with a number of diseases including obesity and coronary heart disease are different between males and females. Knowledge of gender differences in energy and nutrient metabolism are required to fully understand the metabolic basis of these diseases. Studies in this proposal will begin to determine gender specific aspects of energy and nutrient metabolism and how these change at menopause. Specific aim number 1 will be to determine the sources of carbohydrate and lipid fuels utilized during exercise in males and females. This will be determined using indirect calorimetry and stable isotope techniques and muscle biopsies. Specific aim number 2 will be to determine the lipolytic response to catecholamines in males and females by using the pancreatic clamp technique in conjunction with catecholamine infusions and stable isotope measurements. Specific aim number 3 will be to determine whether males and females differ in their ability to remove exogenous lipid from the circulation and whether there are gender differences in the ability of insulin to suppress endogenous very-low density lipoprotein triglyceride (VLDL-TG) production. Triglyceride removal will be assessed in response to an intravenous fat tolerance test. Relative changes in VLDL-TG production will be measured following the radioactive labeling of VLDL-TG and measurement of VLDLTG kinetics under basal and hyperinsulinemic/euglycemic conditions. Specific aim number 4 will be to determine the effect of menopause and hormone replacement therapy on energy expenditure and resting substrate utilization. Free-living energy expenditure will be measured using the doubly labelled water technique and substrate utilization will be assessed using indirect calorimetry and stable isotope techniques. These studies will further our understanding of the metabolic basis for disease risk in males and females. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENDER, SEX STEROIDS AND DRY EYE SYNDROMES Principal Investigator & Institution: Sullivan, David A.; Schepens Eye Research Institute Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 30-SEP-1985; Project End 30-NOV-2006 Summary: (provided by applicant): The preocular tear film plays a critical role in maintaining ocular surface integrity, protecting against microbial challenge and preserving visual acuity. Tear film dysfunction, in turn, may severely impact the eye

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and lead to desiccation of the corneal epithelium, ulceration and perforation of the cornea, an increased incidence of infectious disease, and pronounced visual impairment and blindness. Countless people suffer from tear film disorders, which are termed dry eye syndromes and are classified into 2 major types: aqueous-deficient and evaporative. Aqueous-deficient dry eye is due to decreased tear secretion from the lacrimal gland. An example is Sjogren's syndrome, a common autoimmune disease that afflicts primarily women and destroys the lacrimal gland. Evaporative dry eye is typically caused by meibomian gland dysfunction and may be a major cause of dry eye during menopause, use of estrogen hormone replacement therapy (HRT) and aging. The long range objectives of this grant application are to test our hypotheses that: (1) sex steroids are extremely important in the physiological regulation of the lacrimal and meibomian glands, as well as the production of the tear film; and (2) gender, sex steroid hormones, and in particular androgen deficiency, are critical etiologic factors in the pathogenesis of both aqueous-deficient and evaporative dry eye syndromes. Experimental procedures include mouse models, DNA hybridization arrays (i.e. gene chips), RT-PCR, ribonuclease protection assays, Northern, slot and Southern blots, in situ hybridization, cell cultures, immunoassays, HPLC/mass spectrometry, enzyme assays, histology, image analysis, hormone reconstitution experiments, as well as clinical studies with humans. Our specific aims are to: (1) identify the genes and proteins that mediate the gender-related differences in, and the sex steroid control of, lacrimal glands in normal and autoimmune (i.e. Sjogren's syndrome) mice; (2) identify the genes and proteins involved in the gender-associated variations in, and the sex steroid regulation of, the mouse meibomian gland; and (3) determine the specific effects of HRT use (estrogen, or estrogen plus progesterone), with or without androgen supplementation, on the ocular surface of postmenopausal women. Results from the studies should significantly advance our understanding of the processes by which gender and sex steroids influence the anterior segment of the eye. In addition, findings may have health relatedness for the eye, because they: (1) explore the regulation of the tear film; and (2) may lead to the development of specific therapies for the clinical treatment of dry eye syndromes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENES AND THE ESTROGEN EFFECT ON ENDOMETRIAL CANCER Principal Investigator & Institution: Ross, Ronald K.; Professor; Preventive Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-DEC-2006 Summary: (provided by applicant): The etiology of endometrial cancer is relatively well understood. Estrogen stimulation of the endometrium without the modulatory effects of progestins is the major cause. Estrogen replacement therapy (ERT) in menopause and obesity are the principal risk factors. The effect of the latter is probably due to the association between postmenopausal obesity and circulating bioavailable estrogen levels. Oral contraceptives and pregnancy, both of which deliver estrogen stimulation to the endometrium but with the continuous modulatory influence of progestins, are associated with reduction in risk. Combination hormone replacement therapy in which a progestin is added to estrogen for all or part of the monthly cycle results in no increase in endometrial cancer risk over that of a non-user of hormone replacement. Despite the fact that ERT and obesity are the major risk factors, only a small proportion of women using ERT or even with extreme obesity will develop endometrial cancer. It would be important from a public health as well as from a mechanistic view to be able to predict which women those will be. We propose to evaluate a series of eight candidate genes

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Hormone Replacement Therapy

(CYP17, CYP19, HSD17B1, ER, CYP1A1, CYP1B1, COMT andPR) in the estrogen biosynthesis, transactivation and metabolism pathways to determine if the effects of these risk factors might be mediated or modified by genetic variability. We will evaluate this question in the context of a prospective epidemiologic study of 133,000 female California teachers (the California Teachers Study) using a nested case-control design. We will also examine in detail the possible impact of phytoestrogens on endometrial cancer risk reduction in conjunction with HRT, obesity and the eight candidate genes under evaluation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC EPIDEMIOLOGY OF BREAST CANCER--BRCA1 AND BRCA2 Principal Investigator & Institution: Neuhausen, Susan L.; Professor; Medical Informatics; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2001; Project Start 01-MAR-1998; Project End 28-FEB-2003 Summary: (Adapted from the Investigator's Abstract) Many environmental, reproductive, and genetic factors have been associated with an increased risk of breast and ovarian cancers. A family history of breast cancer has been identified as a major risk factor for the development of the disease. A genetic predisposition likely accounts for 5 to 10 percent of breast cancer and ovarian cancer. Approximately 80 percent of inherited early onset breast cancer is attributed to the breast cancer genes, BRCA1 and BRCA2. Among families with the same BRCA1 (BRCA2) mutations, there are differences in agespecific penetrance, lifetime penetrance, proportions of breast and ovarian cancer, and risks of other cancers. This variability suggests there are environmental and genetic factors interacting with the BRCA1 and BRCA2 genes. The identification of predictors of phenotypic expression, not only in terms of type of cancer but also in modulating age at onset, has implications for screening and prevention strategies for women at significantly increased risk of breast and ovarian cancers due to the BRCA1 and BRCA2 genes. This is a proposal to examine the effects of reproductive and genetic factors which may modulate the incidence by age and overall incidence of breast and ovarian cancers in individuals with BRCA1 and BRCA2 mutations. The cohort is composed of Caucasian and African American BRCA1 and BRCA2 mutation carriers. We have already sampled 215 BRCA1 and 141 BRCA2 mutations carriers in our Utah kindreds and will continue to sample within these families to identify all mutation carriers. Little information is available regarding prevalence of BRCA1 and BRCA2 in African Americans, although for women less than 44 years of age, their incidence of breast cancer is higher than for Caucasians. With collaborators in Dallas and Chicago, we propose to contact African American families with a history of breast and/or ovarian cancer, to identify BRCA1 and BRCA2 mutations, and sample within those families to identify all mutations carriers. The cofactors to be examined in this cohort include ages at menarche and menopause, parity, age at first pregnancy, use of oral contraceptives, and hormone replacement therapy. The genetic factors to be investigated include the hRAS VNTR and carcinogen metabolizing genes GSTT1, GSTM1, CYP2D6, CYP1A1, and EPHX. Survival analysis models will be used to estimate cumulative incidence by age and overall incidence for breast and ovarian cancers stratified by the hormone, reproductive, and genetic factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEART HEMODYNAMICS

DISEASE

IN

WOMEN:

ESTROGEN

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EFFECTS

ON

Principal Investigator & Institution: Sherwood, Andrew; Associate Professor; None; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 30-APR-2004 Summary: Coronary heart disease (CHD) has now become the leading cause of death in women. The incidence of CHD increases sharply following menopause, while estrogen levels decline. Data from observational studies suggest that higher estrogen levels may protect women from developing CHD. There is also evidence that estrogen may protect women who already have CHD. However, the cardioprotective benefits of estrogen alone may be countered by the addition of progesterone, which is typically included in hormone replacement therapy (HRT). The Heart and Estrogen/Progestin Replacement Study (HERS) recently reported that progesterone-estrogen combination therapy did not protect women with CHD from myocardial infarction and/or death. The mechanisms responsible for estrogen's cardioprotective benefits have not been fully identified. Estrogen replacement improves lipid profiles, but this mechanism alone accounts for only approximately 25 percent of the reduction in risk for mortality. Recent studies have shown that estrogen also appears to improve vascular endothelial function, which is compromised in CHD. Endothelial dysfunction simultaneously reduces myocardial oxygen supply by limiting coronary vasodilation, while increasing demand by elevating systemic vascular resistance. Depending upon the severity of this imbalance, CHD patients may experience myocardial ischemia, myocardial infarction and/or cardiac death. Several studies have shown that stress may exacerbate this pathophysiological imbalance in CHD and trigger acute events. The purpose of the proposed research is to further our understanding of estrogen and estrogen/progesterone's effects on endothelial function and its consequent impact on SVR at rest and during stress. In a randomized double-blind crossover comparison of 60 women with documented CHD and 60 age-matched healthy women, we propose to examine the acute effects of estrogen and estrogen/progesterone interventions on SVR at rest and during stress. Vascular endothelial function will be assessed using ultrasound imaging of flowmediated dilation of the brachial artery. Using recently developed ambulatory monitoring technology, blood pressure, cardiac output and SVR will be monitored noninvasively at rest, during laboratory-based mental stress, and for 24 hours during patients' normal daily routines. By these methods, the proposed research should clarify how HRT may alter risk in CHD through hemodynamic effects that are hypothesized to be secondary to alterations in endothelial function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HISTORY OF HORMONE REPLACEMENT THERAPY, 1960-2000 Principal Investigator & Institution: Watkins, Elizabeth S.; Individual Award--Watkins, Elizabeth Sie 6516 Northumberland St Pittsburgh, Pa 15217 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): The goal of this project is to produce the first sociocultural historical study of the changing rationales for prescribing hormone replacement therapy (HRT) for menopausal and post-menopausal women from the 1960s to the present. The resulting book will provide a historical perspective for contemporary debates about the health care and health policy implications of menopause, aging, and HRT. The study is driven by three main questions. 1) How and where do physicians and patients get their information about menopause, aging, and

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Hormone Replacement Therapy

medical treatments? This project investigates the interactions among scientists, physicians, drug companies, government agencies, feminist health activists, the media, and the public in the construction, dissemination, and translation of medical information for midlife and older women. 2) In what ways have the phenomena of menopause and aging been both medicalized and de-medicalized? While menopause and its sequence, like other aspects of women's health (e.g., childbirth, birth control), have increasingly come under medical control in the 20th century, there has also been a parallel trend in recent decades to re-define menopause as a "natural" event. This project will analyze the differences and similarities between these two views and set them in the larger context of health policy making and the American pursuit of health. 3) What is the relationship between the medical treatment of menopause and cultural conceptions of aging? This project locates the use of HRT in the context of changing expectations and changing roles for older women in American society. Using historical methodologies to investigate the variety of actors engaged in disseminating information about menopause, aging, and medical treatment, this study will enrich our understanding of the practices, contexts, and meanings of aging and related health-care issues among American women. The primary product will be a book written for a broad audience, including historians, health policy makers, physicians, nurses, other health care providers, and the general public. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIV: GENDER AND SEX HORMONE EFFECTS ON T CELL KINETICS Principal Investigator & Institution: Hellerstein, Marc K.; Professor of Medicine; J. David Gladstone Institutes 365 Vermont St San Francisco, Ca 94103 Timing: Fiscal Year 2001; Project Start 23-APR-2001; Project End 31-MAR-2006 Summary: (Abstract Provided by Applicant) Gender differences have been documented for many aspects of immune function and are likely mediated by the major reproductive hormones (androgens, estrogens and progesterone). Gender differences in the natural history of human immunodeficiency virus-type 1 (HIV-l) infection have also been described. In particular, a different relationship between HIV-1 viral load (VL) and progression of disease has been reported for women as compared to men. The in vivo effects of gender or reproductive hormones on proliferation and survival of T cells, including thymic production of T cells, in the setting of HIV- 1 infection have not been directly tested, however. The objectives of our proposed studies are to compare the natural history of T cell turnover in men and women with early HIV-1 disease and to establish the consequences of sex steroids on T cell turnover, including thymopoiesis, in HIV-l infection. These studies are now possible in humans because of the recent development of stable isotope-mass spectrometric techniques for directly measuring the kinetics of purified T cell subpopulations in vivo. Three clinical studies will be performed. Study #1 will compare the natural history of CD4+ and CD8+ T cell kinetics in untreated, CD4-matched men and women with early HIV-l infection (CD4 counts 500-750 cells/uL; n~l5 per group). T cell kinetics will be measured by two complementary techniques ([6,6-2H2] glucose incorporation and die-away curves, to characterize memory/effector-phenotype T cell dynamics; long term 2H2O incorporation, to characterize kinetics of naive-phenotype T cells) at baseline then every 12-18 months over a 3-4 year follow-up. Correlation between VL, CD4 count, thymic mass (by CT scan), excision circles, and blood measurements (cytokines, hormones) will be compared in men and women. Our hypothesis is that chances in T cell kinetics will track with CD4 count in both genders, but at a lower VL in women. Study #2 will

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compare the effects of puberty in HIV-1 infected pre-adolescent boys and girls (n=8 per group). The outpatient 2H2O approach will be used to measure T cell dynamics. Other parameters will be correlated as in study #1. The central hypothesis is that the rise in sex steroids will suppress thymopoiesis in both genders. perhaps greater affecting boys. Study #3 will compare the effects of reproductive hormone replacement therapy in hypogonadal adult men and women with HIV-1 infection (n=8 per group). The 2H2O method for measuring T cell dynamics will be used. with other measurements as in Studies I and 2. The hypothesis is that sex steroids will reduce production of naivephenotype T cells in both men and women, with perhaps a greater effect in men. In summary, we propose to determine directly, in vivo, whether sex steroids alter T cell kinetics (particularly thymopoiesis) in HIV-1 infected humans. and whether T cell turnover tracks better with CD4 count than VL in women, compared to men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONAL INFLUENCES ON COGNITION Principal Investigator & Institution: Luine, Victoria N.; Professor; Hunter College 695 Park Ave New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: A variety of studies show that estrogen may promote memory in females, both animal and human with low estrogen levels. Moreover, estrogen may also delay or prevent the onset of Alzheimer's Disease and improve cognition in women with the disease. Using young and aged rats as models, experiments will examine effects of gonadal hormones on memory using a spatial memory task, object recognition. First, the dose- response relationship between estrogen and enhanced memory will be determined. Whether concurrent administration of progesterone with estrogen alters the enhancing effects of estrogen on memory will be tested. Then possible enduring effects of gonadal hormones on memory will be tested, i.e., whether chronic estrogen alone or with progesterone enhances memory months after discontinuation. Effects of these hormone treatments on GABAergic and monoaminergic neurotransmission in brain areas involved in memory function will be measured by neurochemical techniques. Whether alterations in memory occur over the estrus cycle and after chronic ovariectomy will be determined and will show whether hormones exert short term effects or long term, trophic effects. Thus, proposed experiments will characterized fundamental relationships between gonadal hormones and memory function. While important for providing basic information concerning hormone actions and the neural bases for hormonal effects on memory, the studies also have significant health implications for aging and Alzheimer's disease. Concurrent estrogen and progesterone therapy is the treatment of choice for post menopausal women, but little is known about the effects of progesterone on memory. In addition, if post-menopausal hormone replacement therapy can delay dementia onset by 5 years, the incidence of dementia has been projected to decreased by 50%. Finally, if only a few years of replacement can be given with the same benefits on memory loss or in developing AD, then the risk of side effects of estrogen can be greatly minimized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONE REPLACEMENT AND AGING EFFECTS ON MEMORY Principal Investigator & Institution: Wegesin, Domonick J.; Assistant Professor of Neuropsychology; Sergiersky Center; Columbia University Health Sciences New York, Ny 10032

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Hormone Replacement Therapy

Timing: Fiscal Year 2001; Project Start 17-DEC-1998; Project End 30-NOV-2003 Summary: Memory loss is one of the main complaints of normal aging. Recent evidence suggests that hormonal changes accompanying menopause may partly account for memory-loss in aging women and that these memory effects can be tempered by the use of hormone replacement therapy (HRT) (Sherwin, 1994). The mechanism of these cognitive benefits remains unclear. The overall objective of this research is to delineate better the effects of HRT on memory in post-menopausal women. Previous studies of HRT have limited their assessment of memory to clinical measures focusing almost exclusively on recall ability. The proposed studies will extend our current understanding of HRT-mediated memory effects by examining multiple types of human memory within controlled experimental paradigms. In addition to examining the effects of HRT on memory, the proposed studies will also investigate normal age-associated memory impairment. Specifically, healthy postmenopausal women drawn from a representative community sample who have undergone long-term HRT and agematched controls who have never used HRT will be compared to younger premenopausal women on tests of implicit memory (priming) and explicit memory (recalling and recognition) for verbal and non-verbal material. Beyond proving a better description of the behavioral effects of HRT, we are interested in examining potential neural mechanisms by which estrogens modulate memory function. Specifically, we are interested in dissociating memory mediated by the frontal and medial temporal lobes. To that end, event-related brain potentials (ERPs) will be recorded from 64 scalp sites during the experimental tasks in an attempt to elucidate the electrophysiological indices of HRT-related memory enhancement. Overall, this work will serve as a mens to better elucidate the type of memory changes associated with HRT and to provide an initial examination of brain-behavior associations related to the memory effects reported in HRT-using postmenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONE CARDIOVASCULAR RISK

REPLACEMENT

AND

METABOLIC

Principal Investigator & Institution: Sites, Cynthia K.; Obstetrics and Gynecology; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2001; Project Start 02-DEC-1998; Project End 30-NOV-2003 Summary: The menopause transition is associated with a pronounced increase in risk of cardiovascular disease. Hormone replacement therapy in postmenopausal women reduces the risk of cardiovascular disease by approximately 50 percent, although the mechanisms involved are poorly understood. We will examine the impact of hormone replacement therapy on metabolic risk factors affecting cardiovascular disease and future health in aging women. Our overall hypothesis is that hormone replacement therapy in the early postmenopausal period reduces the central accumulation of body fat and improves insulin sensitivity, thereby reducing a metabolic risk factor for cardiovascular disease. A total of 88 women will be recruited for this 2-year randomized double-blinded placebo-controlled longitudinal study. We will measure outcomes of changes in body fat distribution and insulin sensitivity on 4 occasions (baseline, 6 months, 1 year and 2 years) in women taking continuous conjugated estrogens plus medroxyprogesterone acetate or placebo. Our study will provide new information on the temporal sequence of changes in outcome variables. We will use: 1) computerized tomography (CT) and dual photon x- ray absorptiometry (DEXA) scanning to measure intra-abdominal body fat and total body fat, and 2) euglycemic clamps to measure insulin sensitivity. Analysis of these data will provide an understanding of the impact of

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hormone replacement on the syndrome of central obesity and insulin resistance, which predisposes women to increased risk for cardiovascular disease. In addition, our study may allow physicians to target hormone replacement to women with specific body compositions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONE REPLACEMENT FOR PREVENTION OF VISCERAL OBESITY Principal Investigator & Institution: Cefalu, William T.; Associate Professor of Medicine; Medicine; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 31-AUG-2003 Summary: The goal of this study is to determine the therapeutic role of hormone replacement therapy (HRT) to prevent visceral obesity in postmenopausal women. The hypothesis is that HRT will augment the loss of visceral fat in postmenopausal women who undergo a 6-month weight reduction program, and that HRT will be useful in preventing visceral fat regain in women who continue HRT after a one-year follow-up. In addition, the study will examine whether changes in visceral fat are predictive of alterations in insulin sensitivity. postmenopausal women with abdominal obesity will be randomly assigned to either HRT or placebo intervention. All women will participate in a 6-month program of exercise and dietary restriction designed to induce a moderate fat loss. Women will be re-examined after a one-year follow-up period. Total abdominal and visceral fat will be measured with CT, body composition with DXA, insulin sensitivity with an euglycemic/hyperinsulinemic clamp, and energy balance with indirect calorimetry and doubly-labeled water before and after the weight reduction program, and after the one-year follow-up. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONE REPLACEMENT IN MENOPAUSAL WOMEN WITH EPILEPSY Principal Investigator & Institution: Harden, Cynthia L.; Neurology and Neuroscience; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 30-APR-2003 Summary: (Applicant's Abstract): The long-term objective is this study is to determine whether standard hormone replacement therapy is safe for menopausal women with epilepsy. The benefits of hormone replacement therapy for menopausal women are becoming widely appreciated. It is expected that hormone replacement therapy will be increasingly prescribed in a portion of the American population that is also increasing in number. Therefore, the safety of hormone replacement therapy in the settings of specific illnesses must be clear. Estrogen has neuroactive properties that are largely beneficial, that is, it can improve cerebral blood flow, promote axonal sprouting and helps to prevent protein precipitation in the brain pathognomonic of Alzheimer's Disease. However, estrogen and progesterone also have effects on increasing brain excitability which have been demonstrated in animal models of epilepsy, In these settings, estrogen, and to a lesser extent, progesterone, have been proconvulsant. Therefore, an adverse effect of hormone replacement on patients with epilepsy may be postulated. The question posed in this study is, does hormone replacement therapy adversely affect seizures or is it safe for menopausal women with epilepsy? To answer this question, women with epilepsy who are menopausal for at least one year (1 year

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Hormone Replacement Therapy

without menses) and are medically cleared to take hormone replacement therapy will be enrolled. They will be followed for a three month period while taking their usual antiepileptic medications without dosage change. During this prospective baseline period, seizure frequency will be documented. After three months, subjects will be randomized to take either placebo or one of two doses of standard hormone replacement therapy. The hormone replacement therapy used will be Prempro at doses of 1) 0.625 mg conjugated equine estrogens with 2.5 mg medroxyprogesterone and 2) 1.25 mg conjugated equine estrogens with 5 mg medroxyprogesterone. The investigators and the subjects will be blinded as to the study medication given. The subjects will then be followed for a three month prospective treatment phase and again seizure frequency will be documented. Subjects will be monitored for safety concerns regarding hormone replacement therapy and seizure frequency. The outcome of this study will be determined by comparing seizure frequency in the baseline phase with the treated phase between placebo and hormone treated groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONE REPLACEMENT THERAPY AND BREAST CANCER Principal Investigator & Institution: Carney, Patricia A.; Associate Professor; Community and Family Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2005 Summary: The long-term objective of this study is to evaluate the relationships between hormone replacement therapy (HRT) and breast cancer detection, breast cancer risk, breast tumor prognostic characteristics and health-related quality of life. Although the results of numerous case-control and follow-up studies suggest that hormone replacement therapy modestly increases breast cancer risk, most studies have been unable to adjust adequately for frequency of mammographic screening. This is an important limitation because more frequent use of mammography screening among women who maintain hormone replacement prescriptions through regular physician visits may lead to increased detection of breast cancer relative to women who do not use hormone replacement therapy. Our study design, which involves an existing cohort identified through the New Hampshire Mammography Network (NHMN) - a statewide, population-based mammography registry comprising more than 150,000 women - overcomes this limitation. Using a baseline survey, administered at the time of mammography, we have already obtained breast cancer risk factor information, including current HRT use, from all women in the NHMN registry. Through NHMN we have already identified 74,200 women who are pre- or post-menopausal including approximately 26,700 current HRT users. We will follow these women for four years prospectively to ascertain new cases of breast cancer. All NHMN enrollees have already provided permission to link medical, radiologic and pathology data, and consented to further contact for research purposes. We will implement a supplemental survey in Years 1 and 4 to obtain a detailed history of HRT use, additional risk factor information and health-related quality of life. All other data will be obtained from the well established NHMN. Our primary specific aims are to evaluate the impact of HRT on 1) mammography performance (i.e., sensitivity and specificity of screening mammography, proportion of uninterpretable mammograms and consequent use of other imaging procedures); 2) breast cancer incidence (especially combination therapies); 3) breast cancer tumor prognostic characteristics (e.g., TNM stage, tumor grade, axillary lymph node status and estrogen receptor status). As more women consider use of HRT to prevent osteoporosis and other diseases, understanding its

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impact on quality of life is imperative. Therefore, a secondary aim is to assess the impact of HRT on health- related quality of life. Results of the proposed study will benefit radiologists who interpret mammograms, and women and their health care providers, who must balance the complex issues of disease risk and health-related quality of life when deciding whether or not to use hormone replacement therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONE REPLACEMENT THERAPY AND ISCHEMIC STROKE SEVERITY Principal Investigator & Institution: Bushnell, Cheryl D.; Associate in Medicine; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Experimental studies in laboratory animals have shown that estrogen reduces stroke severity, but the impact of hormone replacement therapy (HRT) on ischemic stroke severity in humans is not known. There are 2 broad, longterm objectives of this project. The first objective is to determine whether there are differences in stroke severity and outcome between women who are HRT users and women who are nonHRT users. The second objective is to determine whether any difference in these 2 groups is related to enhanced fibrinolysis. The Specific Aims of this proposal are 1) to compare the initial stroke severity in women who are users and nonusers of HRT, 2) to measure any differences in markers of the coagulation and fibrinolytic systems in the acute stroke period, and 3) to assess stroke outcomes in women based on poststroke use or nonuse of HRTs. Subjects for this prospective, observational study will be women admitted with acute ischemic stroke to an academic medical center. In the acute stroke period, initial stroke severity will be assessed using the NIHSS and markers of coagulation (prothrombin fragment F1,2 and thrombinantithrombin III complex) and fibrinolysis (plasminogen activator inhibitor type I) will be measured. Relevant historical and demographic data will be collected. At 3 months poststroke, neurologic impairment (NIHSS), functional status (Barthel Index and Modified Rankin), and quality of life (Stroke Impact Scale) will be assessed. The differences in initial stroke severity will be analyzed accounting for co-variates, and the 3month outcomes will be adjusted for initial stroke severity. This work will provide critical information for physicians prescribing HRT for women at risk for stroke and address whether it is safe to continue these medications in the sub-acute period after stroke. As a K23 proposal, this project will not only provide important clinical information, but is a natural extension of the candidate's previous experience with coagulopathies and stroke, now combined with the commitment to study the impact of stroke in women. This proposal will also provide critical transitional support in a mentored environment leading to the candidate's complete independence as a clinical investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONE REPLACEMENT THERAPY AND LARGE BOWEL CANCER RISK Principal Investigator & Institution: Newcomb, Polly A.; Member and Acting Head; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 19-AUG-1998; Project End 31-MAY-2004

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Hormone Replacement Therapy

Summary: The benefits and risks of estrogen replacement therapy continue to confuse women and their physicians. Recent evidence suggests that estrogen replacement may be associated with reductions in large bowel cancer, a common disease among postmenopausal women. Further study of this potentially important association would provide more precise estimates of the magnitude of effect, identify salient patterns of use, and, importantly, supply insights into the biology of this tumor in women. A population-base case-control study is proposed to evaluate the association between postmenopausal hormones and the occurrence of colorectal cancer. This study will specifically assess use of estrogens with and without progestin, the duration and currency of hormone use, and inter-relationships with body mass. Additional aims of this study are to elucidate the mechanisms of this inverse association, specifically the relationship of HRT to hormone receptors and proliferation in the bowel, and to examine the modifying role of more common cancer susceptibility genes influencing the metabolism of estrogens. Over a three year period, interviews will be conducted with 1,100 women with newly diagnosed cancer of the colon or rectum selected from the population. In addition to the structured telephone interview, fixed diagnostic tissue will be obtained from 540 case in order to evaluate estrogen-receptor status and proliferation markers. Blood samples on a sample of 600 (most with diagnostic tissue) cases and 600 controls will be obtained for genetic studies of polymorphisms relevant to estrogen metabolism and function, specifically CYP17 and the estrogen receptor gene. The proposed study and its extensions should provide clear evidence for the degree to which HRT is protective against colorectal cancer and permit the determination of some of the relevant pathways for that protection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONE REPLACEMENT THERAPY WITH PROGESTERONE CREAM Principal Investigator & Institution: Hermsmeyer, Kent R.; Dimera, Llc. 2525 Nw Lovejoy St, Ste 401 Portland, or 97210 Timing: Fiscal Year 2000; Project Start 13-AUG-1998; Project End 31-AUG-2004 Summary: The objective of this project is to further develop a new progesterone formulation that is effective for hormone replacement therapy-protecting the coronary arteries against hyperreactivity. Such hyperreactivity results from the deficiency of progesterone after the cessation of ovarian function after menopause during the normal aging process. The anticipated new product will be further studied in monkeys in the catheterization laboratory and in human stress test electrocardiogram and echo cardiology protocols. These studies will determine the effectiveness of progesterone in extending treadmill stress test duration, echocardiographic cardiac wall motion, and lipid biochemical measures of coronary function. We will also explore the possible relationship of changes in blood lipids and platelet function. The new formulation is designed to be accepted sufficiently well by post- menopausal women to encourage compliance among those who initiate hormone replacement therapy-for a duration of decades in many cases. Protection of the cardiovascular system by progesterone can be expected to provide for a significant decrease in the incidence of cardiovascular disease during aging, and improved quality of life in post-menopausal women. The skin cream formulation is well accepted by women, has optimal pharmacokinetics for a once a day treatment, and is hypothesized to reduce cardiovascular risks, including coronary artery disease. Even though the risk of death due to cardiovascular causes is nearly 50% for post-menopausal women, and is far greater than any other risk, the presently available forms of hormone replacement therapy are used by only a fraction of those who would

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benefit. This leading risk of death and' available measures to minimize that risk are neither well understood nor readily accepted by post-menopausal women. This formulation has the potential to significantly improve that situation and enhance quality of life in post-menopausal women. PROPOSED COMMERCIAL APPLICATIONS: The percutaneous formulation of progesterone will produce a blood level to minimize the risk of cardiovascular disease, and thus may find widespread application in hormone replacement therapy. The number of people who would be potential consumers for the product consists of all postmenopausal women, a rapidly growing number which already exceeds 20 million. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HRT AND EXERCISE EFFECTS ON CENTRAL ARTERIAL COMPLIANCE Principal Investigator & Institution: Moreau, Kerrie L.; Integrative Physiology; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Candidate. The candidate, Kerrie L. Moreau, Ph.D., is a physiologist currently supported by an individual NRSA from NIA. Dr. Moreau's past and current research focus has been on physical activity, aging, and cardiovascular health, particularly in women. Her immediate goal is to acquire new research and professional skills to help her achieve her long-term goal of developing a successful independent extramurally-funded research program in aging. The proposed KO1 development plan should provide Dr. Moreau with the necessary training to achieve her goal. Career Development Plan. Dr. Moreau's research career development training activities consist of: 1) acquiring new research skills associated with and complimentary to (e.g., micro array gone expression analysis) the proposed research plan; and 2) structured activities including formal course work; attendance and presentation at journal clubs, seminar series, and scientific meetings; and regular interactions with her mentoring team. Environment. The environment for Dr. Moreau's training should be outstanding. The Sponsor and Co-sponsor, Drs. Douglas Seals and Wendy Kohrt, are well- established extramurally-funded scientists with strong records of successful mentoring in biomedical aging research. They are complimented by several consulting mentors who will provide guidance in specific areas of the training plan. Other faculty in aging research enhance the environment. Research. The general aim will be to determine the relative efficacy of 3 commonly used Hormone Replacement Therapy (HRT) regimens, regular aerobic exercise, and the combination of HRT and exercise for improving central (carotid) arterial compliance, the associated functional benefits, and the underlying mechanisms in healthy sedentary estrogen-deficient postmenopausal women. The general hypothesis is that HRT and exercise will, independently and additively, improve arterial compliance which will, in turn, result in functional benefits (e.g., improvements in cardiovagal baroreflex sensitivity and left-ventricular function/structure), and that these favorable adaptations will be mediated in part by a decrease in sympathetic tone (HRT only) and/or a reduced oxidative stress-associated improvement in vascular endothelium- dependent vasodilatory tone. Moreover, the amount of improvement with hormone supplementation and the additive effect of exercise will differ among HRT regimens. A 2-phase placebo controlled intervention trial employing state-of- the-art measurements of autonomic (e.g. micro neurography) and cardiovascular (e.g., high-resolution ultrasonography) function will be conducted. The expected results should provide new physiological and clinical information concerning the use of various HRT regimens and exercise for the primary prevention of

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Hormone Replacement Therapy

reduced central arterial compliance with age and estrogen deficiency, the corresponding autonomic and cardiovascular functional benefits, as well as insight into the underlying mechanisms involved. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HRT USE AND RISK OF LOBULAR AND DUCTAL BREAST CANCER Principal Investigator & Institution: Daling, Janet R.; Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 14-JUL-2000; Project End 30-JUN-2005 Summary: (Adapted from the Applicant's Abstract): Incidence rates of invasive lobular breast carcinomas (ILBC) have increased steadily in the United States since 1977, whereas the trend of increasing incidence of ductal breast cancer has plateaued since 1987. This rise in lobular tumors has occurred specifically among women over age 50. The use of combined estrogen-progestin hormone replacement therapy (CHRT) has also risen steadily over this time period, and recent analyses from two case-control investigations suggest that postmenopausal women who use CHRT may have an increased risk of ILBC, whereas there is no relationship of CHRT to ductal cancer. Few epidemiologic studies have assessed how known or suspected risk factors for breast cancer differ across different histologic types, but such investigations are important because there are likely to be multiple pathways leading to the development and progression of breast cancer of different histologic types. The primary objectives of this proposed study are to confirm recent preliminary findings that CHRT is associated with lobular breast cancer in a large population-based study, to assess this relationship in greater detail, and to explore mechanisms for this association. We propose to conduct a case-control study of 900 women aged 55-79 who have been diagnosed with breast cancer (450 lobular, 450 ductal) and 450 population-based controls who reside in the three county Seattle-Puget Sound metropolitan area of western Washington. The specific questions to be addressed are: (1) Is the use of CHRT associated with an increase in the incidence of invasive lobular breast cancer in women aged 55-79. (2) Is the use of CHRT associated with an increase in the incidence of invasive ductal breast cancer in women aged 55-79? (3) Do the duration, patterns and/or recency of CHRT use influence he size of the association? (4) Is the use of CHRT associated with alteration in the histologic characteristics, tumor cell proliferation, or expression of steroid hormone receptors, oncogenes, and cell cycle and cell death regulator proteins of lobular and ductal breast cancers? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFLUENCE ANTINOCICEPTION

OF

GONADAL

HORMONES

ON

OPIOID

Principal Investigator & Institution: Terner, Jolan M.; Psychology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2005 Summary: (provided by applicant): Previous studies indicate that male rats are more sensitive to the antinociceptive effects of opioids than their female counterparts and that males display higher nociceptive thresholds. Although the gonadal hormones appear to play a critical role in mediating these sex differences, the exact nature of this role remains elusive. The present proposal will systematically evaluate the contribution of gonadal hormones to sex differences in nociception and opioid antinociception using three well-established techniques (i.e., monitoring of the estrous cycle, gonadectomy,

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hormone replacement therapy) and a number of innovative methodological controls. A unique component of this proposal is that it will combine the use of low-efficacy opioids known to produce profound sex differences in opioid antinociception, with the use of divergent strains of rats that differ in the magnitude of their initial sex difference in nociception and opioid antinociception. Experiment I will examine the influence of estrous cycle phase on levels of nociception and opioid antinociception. Although in each phase of the cycle gonadal hormones levels change dramatically, even when hormones are at the lowest levels they may have a profound influence on both nociception and opioid antinociception. Thus, Experiment II will examine the influence of gonadectomy in male and female rats on opioid antinociception in strains that differ in their magnitude of sex differences in opioid antinociception initially observed. Finally, Experiment III will examine the specific gonadal hormones (estrogen, progesterone, and testosterone) involved in mediating nociception and opioid antinociception in male and female rats using hormone replacement therapy. By contrasting the effects of gonadal hormones using three different procedures, controlling for type of nociceptive assay, rat strain and type of opioid, this series of investigations should provide important insight into the role of gonadal hormones in mediating nociception and opioid antinociception. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTRARENAL REGULATION OF SODIUM EXCRETION Principal Investigator & Institution: Burnett, John C.; Professor of Medicine & Physiology Direc; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 01-APR-1990; Project End 30-JUN-2005 Summary: (provided by applicant): The objective of this renewal application is to elucidate the functional importance of the Natriuretic Peptide System (NPS) in the integrative control of cardiorenal homeostasis with a specific focus upon the pathophysiology and therapeutics of congestive heart failure (CHF) addressing the following working hypothesis. The NPS consisting of the cardiac hormones ANP and BNP and the endothelial cell-derived peptide CNP is activated by ventricular dysfunction representing a protective neurohumoral response that delays progressive cardiac remodeling via renal, vascular and neurohumoral mechanisms which unload the heart. This beneficial neurohumoral mechanism is progressively compromised by the development of a relative NPS deficiency and NPS resistance. Importantly, natriuretic peptide hormone replacement therapy and co-inhibition of neutral endopeptidase (NEP) and angiotensin-converting enzyme are novel strategies which delay the progression of CHF. Recognizing the increase of dietary sodium intake in the US, the hypothesis that dietary sodium excess contributes to progressive ventricular remodeling via up-regulation of NEP despite the suppression of the renin-angiotensinaldosterone system (RAAS) will also be investigated. We propose integrative physiological studies in a mouse model in which ANP is genetically absent and in a canine model of progressive left ventricular dysfunction (PLVD) with and without experimentally induced ANP deficiency. Therapeutic strategies will include the chronic administration of native natriuretic peptides, novel designer peptides and a possible fourth new member of the NPS-DNP. We will define the potential negative impact of dietary sodium excess upon cardiac remodeling and CHF and establish the role of upregulation of NEP in response to high sodium diet. We will also employ the use of biomarkers BNP and Cardiotropin-l (CT-1) to detect CHF and cardiac remodeling, The Specific Aims are: Aim 1: Establish that the genetic absence of AN? in the mouse is characterized by progressive cardiac remodeling and overt CHF which may be

42

Hormone Replacement Therapy

prevented by ANP hormone replacement therapy. Aim 2: Establish in a canine model of PLVD that the presence of an ANP deficiency is characterized by the accelerated development of cardiac remodeling and overt CHF which can be prevented by ANP hormone replacement therapy. Aim 3: Establish that novel therapies that go beyond AN? hormone replacement therapy and are based upon the properties of the NPS delay the progression and severity of progressive cardiac remodeling and overt CHF. Aim 4: Establish that dietary sodium excess accelerates the development of cardiac remodeling and overt CHF in part via up-regulation of NEP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LONG TERM OUTCOMES FOR WOMEN WITH BREAST CA IN SITU Principal Investigator & Institution: Claus, Elizabeth B.; Associate Professor; Epidemiology and Public Health; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: (Adapted from the Applicant's Abstract): This project proposes to study the long-term health and lifestyle outcomes for study participants of a population-based case/control study of female breast carcinoma in-situ (BCIS). The study population includes all cases of female BCIS diagnosed among residents of the state of Connecticut from September 15, 1994 to March 14, 1998 as well as a series of random-digit-dial controls also selected from the state of Connecticut. Cases will be between the ages of 20 and 84 years at time of diagnosis while controls are frequency matched to the cases by five-year intervals. Current response rates indicate that the final sample will include approximately 1200 cases and 1200 controls. Baseline telephone interviews have already been conducted with the study subjects and include information on family history of cancer, pregnancy and menstrual history, hormone replacement therapy, oral contraceptive use, as well as socio-demographic variables. In addition, paraffinembedded tumor tissue is being collected for each case to test for the presence of estrogen (ER), progesterone (PR), p53, and HER-2/neu using immunohistochemistry. The current application proposes to recontact study participants at five years from time of initial diagnosis/initial contact. Study subjects will again be asked to participate in a telephone interview to collect updated information on selected topic areas covered in the initial questionnaire such as medical history (breast recurrences, second cancers), family history, pregnancy and menstrual history but also to collect new information on selected measures of well-being and functioning including depression, career, sexual relations, and insurance. In addition, we will ask women to provide us with buccal specimens for BRCA1/BRCA2 testing. The goals of the study are as follows: 1) To provide annual and five-year cumulative estimates of ipsilateral and contralateral breast cancer risk, regional or distant metastatic disease risk, second cancer risk as well as death for women diagnosed with BCIS. 2) To assess the psychosocial impact of BCIS by examining differences between cases and controls on selected measures of well-being and functioning at five years after original recruitment. 3) To measure the association between clinical variables such as hormone receptor positivity and comedo necrosis on outcome for case subjects. 4) To assess the association between epidemiologic risk factors such as age and a family history of breast cancer with outcome, 5) To provide population-based estimates of BRCA1 and BRCA2 in BCIS. 6) To validate/evaluate current histopathologic classification schemes for BCIS with respect to clinical outcome. This project represents one of the first large attempts to assess the survivorship experience of women with BCIS. The data are unique in that epidemiologic, biologic and

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clinical variables will have been collected allowing us to study the relationship of these variables with long term outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LONGITUDINAL CHANGES IN HIP GEOMETRY AND SKELETAL MUSCLE Principal Investigator & Institution: Chen, Zhao; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 30-JUN-2008 Summary: (provided by applicant) This study will be conducted among a large multiethnic cohort (N = 11,432) from the nationwide Women's Health Initiative (WHI), which includes an observational study and three clinic trials. The age range of this cohort is between 50-79 years at the baseline, and it has multiple minority groups: 1583 black, 739 Hispanic and 149 Native American women. The maximal follow-up time of this cohort will be 9 years by 2005. Dual-energy x-ray absorptiometry (DXA) is used to measure bone mineral density (BMD) and body composition. The randomized clinical trials and longitudinal nature of the WHI study provide a unique opportunity to investigate: 1) treatment effects of hormone replacement therapy (HRT) and calcium and vitamin D supplementation on hip structural geometry; 2) longitudinal changes in skeletal muscle mass as a factor in hip fragility; and 3) ethnic differences of mean and rates of changes in hip geometry and muscle mass. Special computer software will be used for analyzing hip scans by dual-energy x-ray absorptiometry (DXA). Crosssectional area, subperiosteal width, estimated endocortical diameter, estimated mean cortical thickness, buckling ratio and section modulus at the femoral neck, at the intertrochanteric and the femoral shaft regions will be assessed. MRI scans will be used as references to calibrate total, appendicular and leg skeletal muscle measurements from DXA subregion analyses. Prevalence rates of sarcopenia (low muscle mass) among each age and ethnic group will be studied. Random Effects Models will be used to analyze the longitudinal data. This proposed study is not funded by the WHI program. Recourses that the WHI will provide include DXA scans, fall and fracture data, and information on covariates. Since the majority of data collection work has been or will be done by the WHI, we will be able to cost effectively test multiple important scientific hypotheses in this study. The novel approaches in this ancillary study will enhance scientific contributions of the WHI program. The significance of the proposed study is that it may demonstrate the utility of bone structural analysis in addition to bone mass measurements for understanding ethnic differences in fracture risk and/or for assessing the effect of pharmacologic therapy (i.e. HRT) on bone health. Furthermore, if the muscle variables are found to be a strong determinant of bone structure in the proximal femur and the risk of fall, then it may be important to develop interventions to increase muscle mass in this region to prevent hip fracture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LONG-TERM COMPLICATIONS OF CHILDREN/ADOLESCENTS & CANCER Principal Investigator & Institution: Green, Daniel M.; Associate Chief; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): We propose to hold a two-day conference on June 28-29, 2002 at Queen's Landing Inn (Niagara-on-the-Lake, Ontario, Canada). The

44

Hormone Replacement Therapy

program will be of interest to pediatric hematologists/oncologists, pediatric nurse practitioners, pediatric psychologists, pediatric oncology social workers, medical oncologists, fellows, residents, interns, clinical research associates and other primary care providers. The topic of bone complications following treatment of children and adolescents for cancer will be addressed. The goals of the 7th International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer will be to: 1) Review the biology of the basic multicellular unit; 2) review the role of the kidney in the regulation of calcium metabolism; 3) review the effect of cis-platinum on renal function and calcium metabolism; 4) review the late effects of ifosfamide on the kidney; 5) review the issues involved in the measurement of bone density; 6) review the effects of radiation therapy effects on bone density; 7) review the effects of glucocorticoid hormones on bone density; 8) review the roles of androgen and estrogen in skeletal physiology; 9) review the issues involved in the management of osteoporosis due to ovarian failure; 10) review the role of growth hormone in the regulation of bone density; and 11) review the issues involved in the duration of treatment with growth hormone replacement therapy. The conference will include presentations by nationally and internationally recognized experts in these areas. The conference will facilitate subsequent discussions among the investigators of the Childhood Cancer Survivor Study, most of whom attend this conference, regarding future research on bone complications among participants in the Childhood Cancer Survivor Study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF HORMONE THERAPY IN POSTMENOPAUSAL WOMEN Principal Investigator & Institution: Newby, L K.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The use of unopposed estrogen of combined estrogen/progestin therapy for primary and secondary prevention of coronary disease events in post- menopausal women is gaining favor in the United States. Support for this practice is based largely on epidemiological association of a reduction in the risk of death and non-fatal myocardial infarction in populations of women mostly without prior coronary artery disease who took estrogen for a variety of reasons. The effects of adding a progestin to estrogen are less well studied. Because the potential public health impact from treatment of postmenopausal women with hormone replacement therapy for prevention of coronary artery disease events is enormous, it is imperative to establish a fund of knowledge that supports and aids in the interpretation of clinical trials data to help establish the group or groups for whom treatment should be recommended and when it should be initiated. To accomplish these goals we propose: 1. Using non-invasive measurement of vascular reactivity, to quantify the effect on vascular endothelial function of the addition of progesterone to estrogen therapy in post-menopausal women with and without coronary artery disease. 2. To study the effect of various combinations of postmenopausal hormone therapy on the coagulation system. 3. To use accumulated clinical trials databases to study clinical factors that may influence the efficacy of hormone replacement therapy for secondary prevention of coronary artery disease in postmenopausal women. The propose work will provide additional understanding of the mechanism of estrogen action on endothelial function (which is postulated to be the major mechanism of the beneficial effects of estrogen) and the effects of adding progestins to estrogen replacement regimens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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45

Project Title: MELATONIN FOR SLEEP DISTURBANCES DURING MENOPAUSE Principal Investigator & Institution: Suhner, Andrea G.; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 16-MAR-2003 Summary: Up to half of all women going through menopause report significant sleep disturbance. A number of factors contribute to these sleep problems, with hormonal imbalance and hot flashes being the most important. Estrogen replacement therapy can alleviate these symptoms, yet side effects and contraindications make the use of this hormone replacement therapy (HRT) problematic in many women. As such, alternatives to traditional HRT are needed. Previous work in our lab has indicated that not only low levels of sex steroids but also the marked increase of gonadotropins observed during the menopause transition may play an important role in disturbed sleep experienced by peri- and postmenopausal women. In particular, our studies have shown that elevated levels of luteinizing hormone (LH) or a high ratio of LH-toestradiol were associated with low sleep- efficiency in postmenopausal women. Hormonal imbalance also induces changes in the thermoregulatory system. The result is hot flashes and sweats, which can adversely affect night-time sleep quality The proposed study will test the hypothesis that exogenous melatonin decreases LH levels and in so doing, increases sleep quality. Furthermore, we hypothesize that melatonin will reduce severity and number of hot flashes by virtue of its temperature-lowering effect. As a consequence, the number of awakenings due to nocturnal hot flashes and night sweats will be reduced, leading to improved sleep quality. To test these hypotheses, twelve symptomatic peri- or postmenopausal women between the ages of 45-55 will ingest a daily dose of 3 mg melatonin or placebo every evening at bedtime over a period of 14 days. Each subject will undergo both conditions. At the end of each treatment session, subjects will spend two consecutive nights in the sleep laboratory. Polysomnographic sleep variables and core body temperature will be recorded continuously on both nights. Hot flashes will be objectively identified by measuring distal skin temperature and proximal skin resistance. Over-night urine samples will be collected to assess LH levels. Sleep parameters, temperature data, number of hot flashes and LH levels will be compared across active and control condition. The current project is an important first step to identify and assess a promising alternative for sleep disturbances in menopause. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MENOPAUSE AND MIDLIFE AGING EFFECTS ON SLEEP DISORDERS Principal Investigator & Institution: Young, Terry B.; Professor of Prventative Medicine; Population Health Sciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 15-JAN-1997; Project End 31-DEC-2006 Summary: (provided by applicant): The long-range goals of this ongoing longitudinal study of midlife aging in women are to accurately quantify the associations of menopause with the development and progression of sleep apnea and diminished sleep quality and to identify factors that influence the associations. Understanding the role of menopause in the development of sleep apnea and diminished sleep quality has important clinical and public health significance. Sleep apnea and diminished sleep quality are associated with significant cardiovascular morbidity, depression, and decrements in daytime performance. Because menopause will become a persistent state

46

Hormone Replacement Therapy

in nearly every woman during her lifetime, even a small effect on sleep apnea and insomnia, the major sleep disorders, would translate into significant morbidity. Furthermore, if associations are causal, understanding whether hormone replacement therapy or other factors significantly modify a menopause-sleep disorder link may lead to interventions that could reduce the occurrence and severity of sleep disorders in midand later life. The proposed study is designed to: 1) Test the hypothesis that changes over the continuum of pre to post menopause increase the incidence and progression of sleep disordered breathing, adjusted for baseline age, body composition, and other potential confounders, 2) investigate the effects of change in body composition during midlife on associations of menopause and sleep apnea, 3) quantify the risk of insomnia, hypersomnia and diminished sleep quality attributable to early, middle and late perimenopause and post menopause, 4) investigate protective effects of hormone replacement therapy on sleep problems, and 5) investigate genetic vulnerability to diminished sleep quality during menopause. To accomplish these aims, we propose additional research on our unique longitudinal cohort of midlife women, with 7-15 years of previously collected polysomnographic and other data with a) new data collected from overnight in-laboratory protocols with polysomnography conducted at 4-year intervals on 621 women enrolled in the Wisconsin Sleep Cohort Study, b) new data collected semi-annually by in-home polysomnography and other procedures and monthly diaries on menstrual characteristics and sleep problems on a subset of 280 women over their pre to peri to post menopausal years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MISSING DATA, MEASUREMENT ERROR AND APPLICATIONS Principal Investigator & Institution: Wang, Ching-Yun; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 15-DEC-1997; Project End 30-NOV-2002 Summary: (Adapted from Investigator's Abstract) Missing or mismeasured regression variables are frequently encountered in the analysis of cancer research data. This problem is a major issue in dietary research, for example. The broad goal of this research is to develop statistical methods for data analysis in the presence of missing or mismeasured regression variables, and to apply these methods to epidemiologic and clinical studies. Specific areas of research include the following: 1) development of a nonparametric regression calibration method for Cox regression when validation data are available; 2) development of methods for Cox regression with reliability data; 3) development of methods for logistic regression analysis using conditional exposure mean for missing or mismeasured exposures; and 4) development of methods for characterizing associations between multiple variables. Asymptotic theory will be developed and simulation studies will be conducted. The methods will be applied to data from the Women's Health Initiative, a large disease prevention trial and observational study involving 164,500 women with the objective of evaluating the benefits and risks of dietary modification, hormone replacement therapy and supplementation with calcium and vitamin D on the overall health of postmenopausal women. The investigator states that the proposed methods will also accommodate twostage designs which are becoming popular in epidemiologic research and particular in genetic epidemiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODIFYING OXIDATIVE DAMAGE IN WAVE Principal Investigator & Institution: Steffes, Michael W.; Professor; Lab Medicine and Pathology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: Supplemental vitamin E has been associated with a reduced risk of recurrent myocardial infarctions, with efficacy related to dosage and the duration of treatment. Its effects may be enhanced by vitamin C, an antioxidant that can regenerate vitamin E activity. Theoretically vitamin E and C (VitE/C) accumulate in the vascular wall with a concurrent reduction in oxidative damage, a primary feature of atherosclerotic lesions. Estrogen/hormone replacement therapy (HRT) also may reduce oxidative damage, and it may enhance the effect of vitamin E and C. These hypotheses are supported by studies defining oxidation-dependent accumulation of lipids in developing atherosclerosis; the detection of oxidative damage products, such as oxidized-LDL particles, in human atherosclerotic lesions; and clinical studies associating antioxidant or estrogen supplementation with reductions in oxidative damage cardiovascular disease. Nevertheless, no human studies have evaluated the effect of long-term VitE/C treatment, which has been reported as being the most effective prevention factor by epidemiologic studies, on specific. biochemical markers of oxidative damage and concurrently their association with recurrent cardiovascular disease. In addition, no studies have characterized the effect of long-term HRT on markers of oxidative damage or HRT's potential synergistic effect with VitE/C therapy. We propose assaying specific biochemical measures of oxidative damage (all markers at closeout and nitrotyrosine and chlorotyrosine also at baseline) in the Women's Angiographic Vitamin and Estrogen (WAVE) Trial, which randomized 420 38-86 year old women with a prior cardiovascular disease event to placebo, VitE/C, HRT or the combination of VitE/C and HRT. WAVE will determine the efficacy of these treatments on quantitative angiographic evaluation of minimal coronary artery diameter performed at baseline and at the final visit to be completed during the first 10 months of 2001. We will measure oxidation products from several classes of compounds (lipids by F2-isoprostanes, proteins by nitrotyrosine and chlorotyrosine, and DNA by 8-hydroxy-2'-deoxyguanosine), thereby studying several major pathways that may lead to atherogenesis. In addition, inflammation with Creactive protein, platelet activation with p-selectin, altered lipid metabolism with a lipid profile and other characteristics of the study population will be integrated into the assessment of oxidative damage in WAVE. By measuring these various factors and by assessing oxidative damage in several classes of compounds, we can test the relationships among specific pathways of oxidative damage, supplemental VitE/C and/or HRT and other risk factors upon the progression of established macrovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MUTATIONS, THROMBOEMBOLISM

HORMONE

THERAPY,

AND

VENOUS

Principal Investigator & Institution: Psaty, Bruce M.; Professor, Medicine and Epidemiology; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2004 Summary: (Adapted from Investigator's Abstract) Epidemiologic studies have identified Factor V Leiden as the most common cause of heritable thrombophilia a prothrombotic mutation associated with a 5 to 7-fold increase in the risk of venous thromboembolism

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(VTE). In pre-menopausal women, the use of oral contraceptives is associated with a 4fold increase in VTE risk, and the joint effects of oral contraceptive use and Factor V Leiden carriership increase the VTE risk of by a factor of 35 (95% IC = 8 154). Recently, the results of several observational studies and randomized clinical trials suggest that in post-menopausal women, the use of hormone replacement therapy is associated with a 3-fold increase in VTE risk. Whether post-menopausal women with prothrombotic mutations experience a similar 20-fold increase in risk when they take post-menopausal hormones remains unknown. The primary aim of this ancillary study is to assess the interaction between hormone replacement therapy and the prothrombotic mutations, Factor V Leiden and the recently described prothrombin mutation (20210A) on the incidence of VTE in a population-based case-control study conducted at Group Health Cooperative of Puget Sound (GHC). The investigators state that using a variety of computerized surveillance systems at GHC will enable them to identify both in-patient and out-patient episodes of venous thromboembolism. They anticipate recruiting 300 post-menopausal women with a first episode of objectively confirmed venous thromboembolism, and 1,200 population-based controls will be identified and recruited from the GHC enrollment files. Controls will be frequency matched to the cases on age and calendar-year. Data collection includes a review of ambulatory medical record and a telephone interview. The GHC computerized pharmacy database will be used to assess exposure to hormone replacement therapy. A venous blood specimen will be obtained from consenting subjects, processed into aliquots of white cells, plasma, and red cells, and stored at 70 degrees C prior to laboratory analysis. DNA will be extracted from white cells, and molecular genotyping assays will be conducted to assess carriership of prothrombotic mutations. Data from these various sources will be entered, linked and analyzed to address the specific aims. Under an additive model, the expected joint effects of HRT and carriership of prothrombotic mutations is 7. Compared with the null hypothesis for the additive model of a joint effect of 7, the investigators have 80% power to detect a difference between the alternative hypothesis of 18 and the null hypothesis of 7. If there is an important interaction between hormone replacement therapy and prothrombotic mutations, such a finding would offer important opportunities of VTE risk reduction by pre-treatment screening in the clinical setting for the prothrombotic mutations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OVARIAN HORMONE EFFECTS OF MUSCLE INJURY AND RECOVERY Principal Investigator & Institution: Schneider, Barbara A.; None; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 30-JUN-2005 Summary: (provided by applicant): In the United States, there are about 57.6 million athletic and physically active women. More women are participating in high-intensity sports activities than ever before. Consequently, women as well as men are at risk for eccentric contraction-induced injury. Eccentric contraction-induced injury occurs when the extrinsic load on a stretched muscle exceeds the amount of force produced by that muscle. However, there are no criteria that enable health care providers to effectively predict which group(s) of women (e.g., premenopausal women and/or women taking oral contraceptives or hormone replacement therapy) have an increased susceptibility to develop eccentric contraction-induced injury. The long-term objective of our research program is to understand how personal factors, such as gender, influence eccentric contraction-induced injury and recovery. Limited study suggests that female gender

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may be one personal factor. The specific aims of the proposal are to determine the independent and interactional effects of estradiol and progesterone on 1) susceptibility to develop eccentric contraction-induced injury and 2) host defense (inflammatory) response to eccentric contraction-induced injury. The hypotheses are 1) estradiol alone increases injury susceptibility; 2) progesterone attenuates the estradiol increased injury susceptibility; and 3) a combination of estradiol and progesterone delays recovery by inhibiting and delaying the host defense response to eccentric contraction-induced injury. The hypotheses will be tested using intact mice (mice that have ovaries) and ovariectomized mice (mice that have had their ovaries surgically removed). The ovariectomized mice will be treated with placebo, estradiol alone, progesterone alone, or a combination of estradiol and progesterone. Slow-twitch and fast-twitch muscles of both intact and ovariectomized mice will undergo eccentric contraction-induced injury. Then functional and structural changes and magnitude of macrophage infiltration will be measured in injured muscles. Findings may have implications for women of varying ovarian hormone status when they engage in high-intensity eccentric contractions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHYTOESTROGENS AND PROGRESSION OF ATHEROSCLEROSIS Principal Investigator & Institution: Hodis, Howard N.; Associate Professor; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The fear and discontent with traditional hormone replacement therapy (HRT) coupled with the interest in natural products has resulted in an increased use of soy protein as a postmenopausal therapeutic alternative by both women and their physicians alike. Evidence from epidemiological and non-human primate studies indicate that isoflavone-rich soy protein has antiatherogenic activity, evidence supported by a large body of data that indicate mechanistic and biologic plausibility. No studies to our knowledge have been published or proposed to determine the long-term effects of soy protein on the progression of atherosclerosis in postmenopausal women. We propose to conduct a 2.5-year, randomized, double-blind, placebo-controlled trial of isoflavone-rich soy protein in 300 healthy postmenopausal women without clinical evidence of cardiovascular disease. We hypothesize that relative to placebo, isoflavone-rich soy protein (supplying genistein, daidzein and glycitein) will reduce the progression of subclinical atherosclerosis in healthy postmenopausal women. The primary end point will be the progression of subclinical atherosclerosis measured as the rate of change in common carotid artery intima-media thickness in computer image processed B-mode ultrasonograms, a well-established noninvasive arterial imaging end point for antiatherosclerosis trials, lsoflavone-rich soy protein may provide a safe and effective alternative approach for extending premenopausal cardioprotection afforded by endogenous estrogen into menopause without the increased risk of thromboembolic events and certain cancers associated with traditional HRT. Since many postmenopausal women are using soy products to maintain their health, it is important to understand whether soy protein has an antiatherogenic effect so that women can make a truly informed decision concerning their expectations of this form of postmenopausal therapy. The question as to whether soy protein is effective in reducing the progression of atherosclerosis in postmenopausal women is not only timely, but also of immense medical and financial importance since atherosclerosis remains the number I killer of postmenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POST ABDOMINAL FAT

MENOPAUSAL

HORMONE

THERAPY

AND

INTRA

Principal Investigator & Institution: Gower, Barbara A.; Associate Professor; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: Background: Hormonal and metabolic changes associated with the menopause may confer increased risk for cardiovascular disease (CVD). Data indicate that the postmenopausal period is associated with increases in total and central ("android") body fat; increases in the atherogenic components of the blood lipid profile; and deterioration of glucose tolerance - all risk factors for CVD. Changes in lipid and glucose metabolism may be secondary to accumulation of central fat, particularly intraabdominal fat (IAF), the compartment associated with dyslipidemia and insulin resistance. Hormone replacement therapy has positive effects on the lipid profile in postmenopausal women, and may affect regional fat deposition. However, the extent to which the beneficial effects of hormone therapy on disease risk factors are mediated by changes in fat distribution is not known. Few studies have examined the effects of hormone replacement therapy on body composition and fat distribution, and non have examined the effect of exogenous hormones on IAF, the adipose compartment most closely associated with disease risk. Objective: To test the hypothesis that hormone replacement therapy (HRT, combined estrogen-progestin) in postmenopausal women decreases risk by limiting IAF deposition. The proposed research will examine the effect of HRT on total, regional, and intra-abdominal fat deposition, and on the relationships between adiposity, the plasma lipid profile, and glucose metabolism. Design: Longitudinal cohort study of 140 early postmenopausal women using or not using HRT. A baseline assessment (within the first year of hormone use) and one 2-year follow-up assessment will be conducted. Total body fat will be assessed with dual-energy X-ray absorptiometry, hydrodensitometry, and deuterium dilution; and regional adiposity (thigh, abdominal, intra-abdominal) will be quantified with computed tomography. Circulating levels of total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides will be determined. Insulin sensitivity and glucose tolerance will be assessed with the tolbutaminde-modified, frequently-sampled, intravenous glucose tolerance test and minimal modeling. Significance: HRT reduces risk and incidence of CVD in postmenopausal women. This study will determine if HRT reduces disease risk by influencing fat distribution and decreasing IAF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY AFTER CABG Principal Investigator & Institution: Ouyang, Pamela C.; Associate Professor of Medicine; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 15-AUG-1996; Project End 31-JUL-2004 Summary: Coronary atherosclerosis is a major cause of death in women in the USA. Although coronary artery bypass surgery decreases symptomatic and clinical evidence of ischemia, it does not alter the underlying process. Patients may present several years later with recurrent symptoms that may be a result of occlusion of saphenous vein grafts, development of atherosclerotic disease in the vein grafts, or progression of underlying disease. Any intervention that can reduce the rate of progression of coronary atherosclerosis following bypass surgery would provide significant benefit for women following bypass surgery and possibly for other women with atherosclerotic disease.

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Observational studies suggest that postmenopausal estrogen replacement therapy is associated with a reduction in cardiac morbidity. However the benefit for hormone replacement therapy in women with established coronary disease has not been demonstrated. This randomized, double-blind controlled trial tests the hypothesis that postmenopausal hormone replacement therapy in women following coronary bypass surgery will reduce the occurrence of graft occlusion and delay the development of graft atherosclerosis. Women will be randomized to esnadiol with daily medroxyprogesterone or placebo within 4 weeks of bypass surgery. Graft occlusion and development of vein graft atherosclerosis will be measured by comparing quantitative coronary angiographic and intravascular ultrasonographic assessment of disease severity and extent performed at 6 months and 3.5 years after randomization. The primary outcome variables will be the occurrence of graft occlusion at 6 months and the change in severity and extent of atherosclerosis in the saphenous vein grafts over 3 years. The proposal will determine th influence of hormone replacement therapy on the primary outcome variables. The pathophysiologic mechanisms of interest in this proposal are platelet activation, fibrinogen binding to platelets, vascular reactivity, coagulation and fibrinolytic factors and lipoprotein composition. The proposal will test the hypothesis that these variables predict the occurrence of graft occlusion and rate o development of graft atherosclerosis. The proposal also tests the hypothesis that hormone replacement therapy exerts its beneficial effects by its effects on those risk factors in addition to more traditional risk factors including the lipids and lipoprotein profile. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POSTMENOPAUSE CHD RISK: PLATELET GENES & HORMONE THERAPY Principal Investigator & Institution: Bray, Paul F.; Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 27-SEP-2003; Project End 31-AUG-2007 Summary: Coronary heart disease (CHD) is the number one killer of women in the United States. Hormone replacement therapy (HRT) with estrogen (E) and progesterone (P) should probably no longer be considered cardioprotective. In fact, data from the HERS and WHI studies indicate E+P may increase myocardial infarction (MI) and stroke despite its beneficial effects on cholesterol levels. Since blood platelets play a central role in the pathophysiology of MI and stroke, these findings raise questions about the effect of HRT on platelet thrombus formation in coronary vessels. Our published and preliminary data show that 1) female platelets are hyperreactive compared to male platelets, 2) sex hormones enhance platelet reactivity, 3) platelets express estrogen receptor (ER) beta and ER alpha, 4) functional platelet polymorphisms are risks for CHD, and 5) there are pharmacogenetic interactions between functional polymorphisms of platelet genes and specific cardiovascular therapies (aspirin, statins, and GPIIb-Illa blockers). Because women are at least as predisposed as men to genetic influences on CHD development, we hypothesize that inherited platelet variants dictate which postmenopausal women are susceptible to the prothrombotic effects of HRT. Our goal in this proposal is to identify genetic predictors of CHD events in women. We will perform a case-control study on the Observational Study of the Women's Health Initiative, analyzing DNA from 1,060 women who have experienced a CHD death or documented nonfatal MI (cases) and from 2,120 controls not having a CHD event. With this large number of CHD cases and controls we will test for associations between functional platelet polymorphisms and CHD events (Aim 1) and interactions between

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these polymorphisms and HRT as a risk for CHD events (Aim 2). We have assembled an excellent group of investigators and have an extremely valuable resource, putting us in a unique position to achieve these goals and our long-term goal of optimizing the prevention and management of CHD in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGESTERONE AND SLEEP IN OLDER WOMEN Principal Investigator & Institution: Moe, Karen E.; Psychiatry and Behavioral Scis; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-DEC-2004 Summary: Sleep complaints increase significantly with age in women. Many older women experience difficulty falling asleep, more night-time awakenings, and less restful sleep. Sleep studies verify that disturbed sleep patterns are observed even in healthy older women. Sleep disturbances are associated with increased daytime drowsiness, increased accident risk, increased use of health care, and reduced quality of life. Older women receive a disproportionate number of sedative-hypnotic medications, which can exacerbate sleep apnea and have daytime carryover effects such as sedation, falls and subsequent fractures, and cognitive impairment. A better understanding of the sleep changes experienced by older women is sorely needed. One contributing factor may be menopause-related changes in sex steroids such as estrogen and progesterone. Research attention has focused on estrogen. However, progesterone may also participate in the control of sleep. Clinical reports indicate that women often feel drowsy after they take oral progesterone - an effect which is undesirable during the day, but may be positive at night. To date there are no published studies of progesterone's effect on the objectivelymeasured sleep and daytime drowsiness of older women. The proposed study will take a systematic, multi-dimensional approach to determining the effect of progesterone on the sleep and drowsiness of older women. Objective techniques (polysomnography, Multiple Sleep Latency Test) will be used to measure sleep and daytime drowsiness following evening or morning administration of 300 mg micronized progesterone, in 40 postmenopausal women who are at least 5 years past menopause and who are not experiencing hot flashes. Attention, memory, subjective sleepiness, and blood levels of progesterone and its metabolite (allopregnanolone) will also be measured. This study is part of a long-term research plan to assess (1) how the very low postmenopausal levels of estrogen and progesterone contribute to sleep difficulties of older women, and (2) how hormone replacement therapy affects the sleep of women. An ongoing placebocontrolled study is investigating the effects of estrogen on the sleep of older women. The proposed study will complement the estrogen study. It will enhance our limited understanding of the relationship between sex steroids and sleep, and the factors that contribute to sleep problems in older women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROTECTING SLEEP QUALITY IN LATER LIFE Principal Investigator & Institution: Reynolds, Charles F.; Professor; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: Good sleep quality is important to continued adaptability, physical and mental health in late life. After age 75, however, loss of sleep continuity and depth accelerates, presaging diminished adaptability and decrements in health status. Protecting sleep quality in late life therefore may be important to continued healthy

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aging. We propose to test this hypothesis by examining the ability of sleep hygiene education and restriction of time in bed: (1) to slow or reverse age-dependent loss of sleep continuity and depth and thereby (2) to promote stability or improvement in daytime wellness, mental and physical health in the later years of life. In this revision of AgeWise Project 4, we will recruit 99 elders aged 275 without sleep-wake complaints, randomly assign them (33 per cell) to one of three conditions (education in healthy sleep practices ["education"], education in healthy sleep practices plus restriction of time in bed ["education" plus "restriction"] or an attentiononly control condition) and follow them for 30 months, measuring sleep, well being, and physical and mental health at baseline (T1), six months (T2), 18 months (T3), and 30 months (T4). We predict that the combined intervention condition ("education" plus "restriction") will be associated with preservation of better sleep quality and, hence, with better adaptation and health over 2.5 years than education in sleep practices alone or an attention-only control condition. We will employ random regression analyses to model long term trajectories in outcome measures of health, well being, and functional status associated with the three intervention conditions. In these analyses we will covary for the presence/absence of hormone replacement therapy, as well as for knowledge of sleep and expectancy effects. This prediction embodies the basic premise of the AgeWise program project, namely, that continued successful aging is promoted by protecting and enhancing sleep quality in late life. Program-wide research in this project will also test that more stable sleep-wake schedules and modest reductions in time in bed will in general be associated with better sleep, mental health, physical health and well being in the final years of life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RALOXIFENE EFFECTS ON COGNITION IN EARLY MENOPAUSE Principal Investigator & Institution: Upchurch, Margaret B.; Professor; Psychology; Transylvania University 300 N Broadway Lexington, Ky 40508 Timing: Fiscal Year 2001; Project Start 15-MAY-2001; Project End 30-APR-2004 Summary: Applicant?s Hormone replacement therapy (HRT) in women is commonly used to diminish the physical symptoms of menopause and to reduce the risk of disorders such as osteoporosis, heart disease, and atherosclerosis. HRT may have by its own risks, in particular, an increased chance of developing endometrial or breast cancer. In an effort to reduce these risks, some physicians are prescribing the selective estrogen receptor modulator (SERM) raloxifene (trade name Evista) for the prevention of osteoporosis. Estrogen also has cognition-enhancing capabilities in postmenopausal women and may serve to prevent or delay the onset of Alzheimer?s disease. Because raloxifene can function as either an agonist or antagonist at estrogen receptors, it is not known whether it too may affect cognitive function. The goals of this study are to examine the cognitive function of women in the perimenopausal period and to compare the effects of estrogen replacement and raloxifene treatment on cognitive function. The women in the two replacement groups will be compared with same-aged women who are still menstruating and to same-aged postmenopausal women who are not on HRT. The research will therefore compare the function of age-matched women with cyclic variation in estrogen levels (premenopausal), consistently high estrogen levels (postmenopausal, HRT-estrogen), consistently high SERM levels (postmenopausal, HRT-raloxifene), and consistently low estrogen levels (postmenopausal, no HRT). The tests will assess verbal recall and mental rotation skills, cognitive abilities that are influenced by estrogen levels. Digit span and Trail-Making Test performance, skills for which there is little evidence of an estrogen effect, will also be measured. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REPRODUCTIVE HORMONES AND PRE-CLINICAL CVD IN WOMEN Principal Investigator & Institution: Bairey Merz, C. Noel.; Associate Professor and Medical Director; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Cardiovascular disease is the leading killer of women, yet prior research has failed to provide any clear understanding of the gender gap wherein women appear to be relatively protected from CVD while premenopausal, compared to men. Recent randomized trials of hormone replacement therapy (HRT), described below, have failed to demonstrate CVD benefit, and call into question the "estrogen protection" hypothesis. Alternative explanations for the gender gap, e.g., androgen exposure, have not been explored. This application, developed in response to the NHLBI's Innovative Research Grant Program Request for Application HL-01-016 and using existing data sets and biological specimens, is designed to support collaborative feasibility research in an innovative and high impact area relevant to CVD in women. The overall aim of this application is to use the existing data and stored blood samples from the NHLBI-sponsored Los Angeles Atherosclerosis Study (LAAS, HL-490-10) to explore new and innovative hypotheses with regard to reproductive hormones and progression of pre-clinical cardiovascular disease (CVD), measured by carotid intima-media thickness (IMT), in the 269 women (45% minority) in the Los Angeles Atherosclerosis Study (LAAS), an ongoing NHLBI-sponsored study of employed utility workers in Southern California without CVD at study entry. Hormonal assays will be performed on stored samples by a NHLBI Reproductive Hormone Core Laboratory, and subsequent analyses will characterize relationships to carotid IMT measured by the LAAS Ultrasound Core Laboratory. The following hypotheses will be test ed: 1) Reproductive hormonal profiles characterized by a relative estrogen deficiency and/or relative androgen excess will be directly correlated with increased baseline carotid IMT and predict greater carotid IMT progression over time in women; 2) Reproductive hormone effects on carotid IMT progression will be observed dominantly in situations of intimal injury, e.g. cigarette smoking, hypercholesterolemia, hypertension or diabetes in women. Innovative aspects of this application include evaluation of reproductive hormones repeatedly and prospectively in women across the spectrum of menopause (pre-, peri- and post-) using innovative methodologies including the sensitive reproductive hormonal assays used in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) core laboratory, and a newer quantitative carotid intimal media thickness (carotid IMT) protocol from the NHLBIsponsored LAAS. The current application represents an opportunity to gain feasibility pilot data in the area of the role of reproductive hormones and CVD in women using novel measures and a collaborative approach in order to plan further investigation, if warranted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REPRODUCTIVE/CONTRACEPTIVE ENDOMETRIOSIS

RISK

FACTORS

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Principal Investigator & Institution: Holt, Victoria L.; Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 01-MAY-1997; Project End 30-APR-2006

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Summary: (provided by applicant): Endometriosis affects 5-10% of reproductive-age women with chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. Medical treatment with 6 months of danazol or a GnRH agonist and surgical treatment are effective in alleviating symptoms in the short term, but the side effects of medical and surgical intervention preclude indefinite continuation or repeated treatment, and symptoms reoccur in 40-50% of women after treatment cessation. Knowledge of risk or protective factors for recurrence is of great importance, therefore, yet the effect of patient characteristics and behaviors on symptom recurrence likelihood has largely been unexamined. The main objectives of this competing continuation application are to determine the 48-84 month symptom recurrence rate in a cohort of 18-49 year old women with a first-time diagnosis of endometriosis, according to disease severity and treatment, and to assess relationships between symptom recurrence and estrogenrelated subject characteristics and behaviors. The study hypothesis is that factors associated with higher estrogen levels, including lack of regular exercise, peripheral body fat distribution, alcohol use, dietary phytoestrogen ingestion, presence of low activity alleles in genes involving estrogen metabolism, and use of hormone replacement therapy, may increase long-term risk of endometriosis symptom recurrence after treatment cessation. The proposed retrospective cohort study will utilize cases (n=337) from the principal investigator's current case-control study of endometriosis risk factors (Reproductive/Contraceptive Risk Factors & Endometriosis, R01 HD33792) conducted within a large health maintenance organization in Washington State. Information available from the cases in that study, including in-person interviews with pre-diagnosis details of medical, reproductive, menstrual, contraceptive, behavioral, and other characteristics; dietary and anthropometric measurements; and values of 4 genetic polymorphisms (GSTM1, COMT, CYP1A1, CYP1A2) will be combined with additional interview information to be collected between 48-84 months after initial diagnosis on treatment details, timing and extent of any recurrence of symptoms, and post-diagnosis estrogen-related characteristics and behaviors. Medical records and pharmacy records will be used as to supplement subject-provided diagnosis, treatment and recurrence information. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESEARCH RESOURCES CORE D--METABOLIC FUNCTION AND BODY COMPOSITION Principal Investigator & Institution: Yarasheski, Kevin E.; Associate Professor; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: This study involves two protocols: 1) the extent to which frail, old men (n=80) can respond to 9 months of exercise training with the cardiovascular, musculoskeletal, and central nervous system adaptions that have been shown to occur in younger people and 2) if hormone replacement therapy (HRT) can reduce frailty in old women (n=120) with physical frailty, and to determine if 9 months of exercise training brings about greater improvements in old women who have been on HRT for 9 months than in sex hormone deficient women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RISK FACTORS FOR CVD IN WOMEN Principal Investigator & Institution: Manson, Joann E.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115

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Timing: Fiscal Year 2002; Project Start 01-DEC-1984; Project End 31-AUG-2007 Summary: (provided by applicant): This study will examine promising but as-yetunproven biochemical, genetic, and lifestyle predictors of coronary heart disease (CHD) and stroke in a prospective cohort of 121,700 US women currently aged 55-80 years. Blood samples were collected from 32,826 participants in 1989-1990, and detailed nutritional, behavioral, and lifestyle variables have been collected for more than 25 years. A major aim is to compare the predictive capability of several biochemical and genetic markers of inflammation and endothelial activation for CHD versus stroke in women: C-reactive protein (CRP), E-selectin, intercellular adhesion molecule-1, endothelin-1, and polymorphisms of the CRP and E-selectin genes. Few studies have directly compared risk factors for both CHD and stroke, although this information is essential from public health and screening standpoints. This proposed work will also continue the investigation of lifestyle determinants of cardiovascular disease, including hormone replacement therapy (dose, formulation, and duration of use) and alcohol consumption (dose and beverage type), in the full cohort and interactions of these exposures with the above biomarkers and with novel genetic markers (prothrombin and alcohol dehydrogenase-3 gene polymorphisms). By 2004, an estimated 834 cases of CHD (nonfatal myocardial infarction and fatal CHD) and 453 cases of ischemic stroke will have been confirmed among women in the blood cohort, and 3,442 cases of CHD and 1,378 cases of ischemic stroke among women in the overall cohort. The Nurses' Health Study has a long, established record of important findings on predictors of cardiovascular disease in women. The large size, prospective design, high follow-up rates, detailed and reliable long-term exposure and outcome information, and the availability of blood specimens on a large subgroup, combined with the relatively low cost, make this cohort a valuable and unique resource for studying biochemical and genetic determinants of cardiovascular risk in women. The results of this work may lead to new strategies for identifying women at high risk of cardiovascular disease as well as new approaches for cardiovascular disease prevention and treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF ESTROGEN IN EXERCISE-INDUCED VEGF EXPRESSION Principal Investigator & Institution: Entin, Pauline L.; Northern Arizona University Department of Biological Sciences Flagstaff, Az 86011 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): A training-induced increase in muscle capillarity appears to contribute to the reduced risk of cardiovascular disease and type two diabetes associated with aerobic fitness. Vascular endothelial growth factor (VEGF), a potent initiator of angiogenesis, is upregulated in cardiac and skeletal muscle by exercise. Estrogen also enhances VEGF expression, but the interactive effect of estrogen and exercise on VEGF in muscles has not been studied. The proposed study tests the theory that estrogen status affects exercise-induced upregulation of VEGF in cardiac and skeletal muscle. Four specific hypotheses will be addressed: 1. The levels of VEGF mRNA and protein are lower in the cardiac and skeletal muscles of estrogen-depleted, sedentary female rats than sedentary females rats with normal estrogen levels; 2. Exercise-induced upregulation of VEGF mRNA and protein are attenuated in the cardiac and skeletal muscles of estrogen-depleted female rats; 3. The levels of VEGF receptor (Fit-1 and FIk-1) proteins are attenuated in the cardiac and skeletal muscles of sedentary and exercised estrogen-depleted female rats; 4. Exogenous estrogen replacement restores exercise-induced VEGF mRNA and protein upregulation to control levels in the cardiac and skeletal muscles of estrogen-depleted female rats. These

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hypotheses will be tested using six groups of 6 mo. female Fischer 344 x Brown Norway rats (n=7 per group): sedentary control; sedentary ovariectomized (OVX), exercise control, exercise OVX, sedentary OVX with estrogen replacement, and exercise OVX with estrogen replacement. Rats in the exercise groups will be run once for 45 min at 20 m/min, 10 degree incline, an intensity previously shown to induce a 4 to 6-fold increase in VEGF mRNA in 6 mo. female Fischer 344 rats. VEGF mRNA levels in the heart and gastrocnemius will be analyzed by real-time PCR. VEGF and VEGF receptor protein levels will be assessed by Western blot. Analyses will be done using two-way ANOVA (exercise status, estrogen status). The results of this study will contribute to the assessment of the risk/benefit ratio for hormone replacement therapy, particularly in the context of those at risk for cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SERUM MARKERS OF BREAST /OVARIAN CANCER RISK Principal Investigator & Institution: Modugno, Francesmary; Assistant Professor; Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 17-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Both breast and ovarian cancers are costly in terms of morbidity and mortality to women. While both diseases have some well-defined behavioral risk factors, there are few, if any, established biomarkers of risk. Moreover, there are a paucity of markers that have the possibility to be applied in a clinical setting, and there is a lack of prospectively collected data and serum samples available to researchers to explore new risk markers. Such markers, tested in a large, prospective setting, are urgently needed in order to identify women at an increased risk for these diseases, as well as to improve our models of risk assessment and to devise effective prevention strategies. We have formed a multi-institutional consortium linked to an ongoing multi-center trial in order to evaluate prospectively the utility of serum biomarkers as risk factors for breast and ovarian cancers. In particular, we will (1). determine prospectively the effects of serum markers of estrogen metabolism, body mass index (BMI), and hormone replacement therapy (HRT) on postmenopausal breast cancer risk; and (2). determine prospectively the association of insulin related serum biomarkers on postmenopausal ovarian cancer risk. To achieve our objectives, we will undertake two nested case-control studies within the Observational Study (OS) of the Women?s Health Initiative (WHI), a multi-center prospective study of women?s health funded by the NIH. The first study will compare BMI, HRT and estrogen metabolite levels in WHI banked serum between 200 confirmed cases of invasive breast cancer and 200 healthy women frequency matched by age, race and study site. The second study will compare insulin, glucose and insulin-like growth factor levels in WHI banked serum between 200 confirmed cases of epithelial ovarian cancer and 200 healthy women frequency matched by age, race, study site and HRT status. Risk factor, confounding and outcomes data has already been collected and verified by the WHI Clinical Coordinating Center and will be provided to us in a clean study database. All laboratory assays will be performed by experienced, collaborating investigators with whom we have worked in the past. Justification for our studies comes from preliminary data we have generated. Approval to undertake this collaboration has already been obtained from the WHI. By the end of this project, we will have prospectively evaluated some new and promising serum markers of risk for breast and ovarian cancer. We also expect to identify additional related research questions, which we anticipate studying further in a multi-center, collaborative fashion within the various arms of the WHI.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLEEP DISTURBANCE IN MENOPAUSE Principal Investigator & Institution: Freedman, Robert F.; Professor; Psychiatry & Behav Neuroscis; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: At present, over 35% of the women in the United States have reached the median age of menopause, 51 years. Hot flashes (HFs) are the most common symptom of the climacteric and occur in the vast majority of postmenopausal women. Sleep disturbance has also been reported to be highly prevalent in this population. Yet, the causal links, if any, between these 2 phenomena are I not known. In the studies proposed here, we will attempt to discern the relationships among Hfs and objective and subjective sleep disturbance. In Study 1, we will record sleep and HF parameters in postmenopausal women with HFs, those without HFs, and age-matched premenopausal women without HFs. We will perform quantitative EEG analyses, use an objective test of daytime sleepiness (MSLT) and assess subjective sleep quality with established instruments. HF frequency increases with ambient temperature. If HFs produce arousals and thereby disrupt sleep, then reducing ambient temperature should improve sleep and increasing temperature should worsen it (Study 2). Increased arousal frequency has been found in postmenopausal women with HFs. If this accounts for reports of poor sleep, then experimental sleep disruption in asymptomatic women should produce reports of poor sleep, as well. In Study 3, we will use yoked groups of symptomatic and asymptomatic women and disrupt sleep of the latter group based on recordings from the former group. We will do this using a stimulus specific to HFs (ambient heating). Despite the common use of hormone replacement therapy, its effects on sleep have not been established. In Study 4, we will systematically manipulate ambient temperature during sleep in symptomatic women before and during estrogen replacement and in a placebo-control group. In Study 5, we will determine the effects of elevated sympathetic activation on HFs and sleep using a stimulus that does not, by itself, disrupt sleep (orthostasis). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SLEEP DURING THE PERI-MENOPAUSE IN A MULTI-ETHNIC COHORT Principal Investigator & Institution: Gold, Ellen B.; Director; Epidemiology and Prev Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 30-SEP-2005 Summary: (provided by applicant) This interactive Research Project Grant (IRPG) will characterize the relationship between menopausal characteristics and sleep in a sample of 430 women: 200 Caucasian, 150 African-American, and 80 Chinese. Although sleep disruptions, insomnia and the incidence of sleep disordered breathing increase in midlife women, little is known about the relationship between menopause and sleep. The impact of vasomotor symptoms and hormone replacement therapy on sleep suggests that the sleep-menopause relationship is not merely a function of age. A greater understanding of the causes of sleep disturbances in mid-life women is important, given the impact of sleep on mental and physical health. Sleep disturbances are associated with a host of negative health outcomes including losses in productivity and quality of life, psychiatric morbidity, immunosuppression, and increased vulnerability to illness

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and disease. The study aims of this IRPG are to: 1) characterize sleep disturbances in a large, multi-ethnic sample of mid-life women; 2) characterize relationships among menopausal characteristics and sleep disturbances; 3) evaluate the influence of relevant psychobiological factors on the sleep-menopause relationship; and 4) establish baseline data for a future longitudinal study. Four of seven study sites from the ongoing Study of Women s Health Across the Nation (SWAN) will collaborate to recruit a sample of preand peri-menopausal women from the SWAN cohort. Once enrolled in the Sleep Study, participants will begin the protocol at the start of a new menstrual cycle. Ambulatory polysomnography will be conducted in participants homes during days 1-3 of the protocol. Sleep diary, actigraphy, and event monitor recordings of vasomotor symptom data will be collected throughout the cycle. Data will also include five years of Core SWAN study data on menopausal characteristics (bleeding patterns, vasomotor symptoms, hormone levels) and related psychobiological factors. Regression techniques will be used to model relationships among menopausal characteristics, sleep, and related psychobiological factors. The Pittsburgh site will train study personnel in the use of sleep monitoring equipment and will be responsible for processing, scoring, and archiving all sleep data. All sleep study data, as well as relevant data from the Core SWAN study, will be merged and analyzed by the Michigan site. The Chicago and UC Davis PIs will co-chair the Sleep Study Steering Committee. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLEEP DURING THE PERIMENOPAUSE IN A MULTI-ETHNIC COHORT Principal Investigator & Institution: Hall, Martica; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 30-SEP-2006 Summary: This Interactive Research Project Grant (IRPG) will characterize the relationship between menopausal characteristics and sleep in a sample of 430 women: 200 Caucasian, 150 African- American, and 80 Chinese. Although sleep disruptions, insomnia and the incidence of sleep disordered breathing increase in mid- life women, little is known about the relationship between menopause and sleep. The impact of vasomotor symptoms and hormone replacement therapy on sleep suggests that the sleep- menopause relationship is not merely a function of age. A greater understanding of the causes of sleep disturbances in mid- life women is important, given the impact of sleep on mental and physical health. Sleep disturbances are associated with a host of negative health outcomes including losses in productivity and quality of life, psychiatric morbidity, immunosuppression, and increased vulnerability to illness and disease. The study aims of this IRPG are to: 1) characterize sleep disturbances in a large, multi-ethnic sample of mid-life women; 2) characterize relationships among menopausal characteristics and sleep disturbances; 3) evaluate the influence of relevant psychobiological factors on the sleep-menopause relationship; and 4) establish baseline data for a future longitudinal study. Four of seven study sites from the ongoing Study of Women's Health Across the Nation (SWAN) will collaborate to recruit a sample of preand peri-menopausal women from the SWAN cohort. Once enrolled in the Sleep Study, participants will begin the protocol at the start of a new menstrual cycle. Ambulatory polysomnography will be conducted in participants' homes during days 1-3 of the protocol. Sleep diary, actigraphy, and event monitor recordings of vasomotor symptom data will be collected throughout the cycle. Data will also include five years of Core SWAN study data on menopausal characteristics (bleeding patterns, vasomotor symptoms, hormone levels) and related psychobiological factors. Regression techniques

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will be used to model relationships among menopausal characteristics, sleep, and related psychobiological factors. The Pittsburgh site will train study personnel in the use of sleep monitoring equipment and will be responsible for processing, scoring, and archiving all sleep data. All sleep study data, as well as relevant data from the Core SWAN study, will be merged and analyzed by the Michigan site. The Chicago and UC Davis PIS will co-chair the Sleep Study Steering Committee. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SOY AND LIPOPROTEINS IN POSTMENOPASUAL WOMEN Principal Investigator & Institution: Allen, Jerilyn K.; Associate Professor; None; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) Cardiovascular disease (CVD) remains the leading cause of mortality and disability in postmenopausal women. Menopause alters serum lipids and lipoproteins to produce a more atherogenic lipid profile that may contribute significantly to the increased risk for the development of CVD over the lifetime of women. Clinical trials have demonstrated a beneficial effect of soy protein containing isoflavones (soy) on plasma lipids and lipoproteins; however, these studies included small numbers of postmenopausal women and virtually none included sufficient African-American women. In addition, no published data exist on the impact of soy on atherogenic lipoprotein subclasses in postmenopausal women. Therefore, the primary aim of this study is to determine the effects of soy on lipids, lipoproteins and lipoprotein subclass in a sample of African-American and white postmenopausal women with lowdensity lipoprotein (LDL) cholesterol elevations that may increase their lifetime risk for CVD but would not qualify for definite pharmacotherapy under current guidelines. The secondary aims are to assess the impact of soy on menopausal quality of life, including menopausal symptoms, and to examine racial/ethnic differences in quality of life, acceptability, adherence to, and lipoprotein response to the soy supplementation. The proposed study is a double blind, parallel group, randomized clinical trial. A total of 160 healthy postmenopausal women (50 percent African-American) with LDL cholesterol between 130 mg/dL and 190 mg/dL will be enrolled. Following a pre-randomization run-in period on a NCEP Step I diet, women will be randomized to receive soy containing isoflavones or casein dietary supplements for 3 months. Major outcome variables will be assessed in both groups at baseline and again at 3 months. It is hypothesized that soy supplementation will result in significantly greater reduction in LDL cholesterol, LDL particle concentration, and prevalence of dense LDL particles and improvement in menopausal quality of life compared with placebo and that these effects will be comparable in African-Americans and whites. This will be the first study to determine whether a natural plant product can ameliorate the unfavorable changes in known and novel lipid risk factors that are a consequence of menopause in both African-American and white women. The unique transitional outcomes explored in this study will add substantially to the limited body of knowledge of the effects of soy. Evaluation of this nutritional alternative to hormone replacement therapy (HRT) that may provide a beneficial effect on lipid risk factors and menopausal symptoms but would be free of the adverse effects on triglycerides, the breast and uterus, and thrombotic events associated with HRT could have significant public health implications for postmenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE EFFECT OF BLACK COHOSH EXTRACT ON THE HUMAN BREAST Principal Investigator & Institution: Sauter, Edward R.; Surgery; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 28-FEB-2005 Summary: (provided by applicant): Over 40 million women in the US have reached menopause, and 40% will experience symptoms significant enough to seek medical attention. Hormone replacement therapy, prescribed to ameliorate menopausal symptoms, has been associated with an increased risk of developing breast cancer. Many women use herbal preparations for menopausal complaints, believing them to be safe. Black cohosh extract (BCE) is the largest selling herbal dietary supplement in the United States used to alleviate menopausal symptoms. The mechanism of action by which BCE acts to treat menopausal symptoms of estrogen deficiency is not clear, with some data supporting a central nervous system effect, while other studies demonstrate a proestrogenic effect. The primary aim of this study is to determine if BCE administered to symptomatic postmenopausal women results in estrogenic stimulation of the breast as measured by changes in nipple aspirate fluid (NAF) levels of estradiol, pS2, follicle stimulating hormone (FSH), leutenizing hormone (LH) and prostate-specific antigen (PSA), as well as NAF cytology. Secondary aims are to 1) evaluate if BCE saponins, the proposed active constituents in BCE, are detectable in the NAF of women receiving BCE, 2) determine if BCE leads to a reduction in clinical symptoms of menopause, and 3) determine if the biomarker effects persist after stopping BCE. As the American population ages there are an increasing number of menopausal women. Interest in herbal therapies is rapidly growing among these women, including breast cancer survivors, to treat the disruptive symptoms associated with menopause. BCE binds to the estrogen receptor and in some studies stimulates breast cells. It is therefore important to demonstrate that BCE does not increase the risk of estrogen-related cancers. We have chosen biomarkers proven to be estrogen responsive proteins which are readily measured in both NAF and blood. Although prior studies failed to correlate clinical response to BCE with changes in serum levels of LH, FSH, or estradiol, it is critical to measure these markers in the breast itself, not diluted by the contribution from other organs. The findings should allow us to design a high quality R01 submission involving a larger, randomized study of longer duration which should provide some answers on the potential role of BCE in breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSGENIC MODELS OF ESTROGEN RECEPTOR ACTIVITY IN BONE Principal Investigator & Institution: Alexander, Joseph M.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 17-MAY-2002; Project End 30-APR-2005 Summary: The efficacy of hormone replacement therapy (HRT) in preventing postmenopausal bone loss is well-known. However, the relative roles of the two known estrogen receptors (ERs), alpha and beta, and their bone-specific mechanisms of action continue to be debated. For example, biochemical studies outlined below agree that ERalpha has profound inhibitory effects on osteoclast-mediated bone resorption by tonically down-regulating osteoblast cytokine production. Yet, recently reported 'double knock-out' mouse animal models for both ERalpha and ERbeta so far have shown no osteoporotic phenotype, despite clear effects of estrogen (E2)-deficiency in the uterus

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and gonads. The inability to reconcile data from in vitro cell culture experiments and the mouse double ERalpha/beta knockout studies have made it difficult to formulate a hypothesis regarding ER mechanism of action in bone. This is especially true since the established animal model for post-menopausal osteoporosis (OP)-the rat- is not yet accessible to genetic manipulation by transgenic and knock-out technologies. Thus, while the rat model can continue to test the efficacy of new therapies, it cannot be adapted to functionally characterize the molecular mechanisms of ERalpha and ERbeta action and their role in OP. In an effort to shed light on ERalpha and ERbeta function in bone, re report implementation of a mouse model of ovariectomy (OVX)-induced OP as a system for further elucidating the molecular mechanisms in hormone-dependent bone homeostasis. As a 'proof of principle' experiment for testing this model system, we propose to introduce characterized, constitutively action mutant ER alpha isoform (CAM-ERalpha) as transgenes into our mice. These two ERalpha isoforms, L536P and Y537S encode adjacent single residue changes in the ERalpha ligand-binding domain, and have been previously shown to confer full gene activation to ERalpha in the absence of E2 using in vitro cell-based assays. We will confirm the activity the CAM-ERalpha (L536P) and (Y537S) on MC-3T3-E1 osteoblastic cells. We then will determine whether these receptors can prevent bone loss in the absence of HRT in vivo by expressing CAMERalpha transgenes under the transcriptional control of an inducible 'Tet On/Off promoter system designed for regulating mammalian gene expression. If this pilot transgenic study demonstrates CAM-ERalpha isoforms can rescue the OP phenotype from OVX mice in the absence of HRT, it will be a key initial experiment in: 1) elucidating the molecular mechanisms of ERalpha in bone homeostasis in an in vivo assay, and 2) developing a mouse model system for OVX-induced OP that can be manipulated to add, delete, or alter specific gene targets that are active in bone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VASCULAR REACTIVITY: GENDER AND HORMONAL INFLUENCE Principal Investigator & Institution: Duckles, Sue P.; Professor; Pharmacology; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 01-JUL-1994; Project End 30-JUN-2006 Summary: (provided by applicant): The recent explosion in understanding vascular effects of gonadal steroids includes identification of two types of estrogen receptor (ER) and both genomic and non-genomic mechanisms. Still, major questions remain concerning which receptors and which mechanisms contribute most to the actions of gonadal hormones. Therefore, we will continue to integrate both functional and biochemical approaches, using chronic hormone treatment in vivo to emphasize physiologically relevant effects in the cerebral circulation. The major hypothesis is: Estrogen and testosterone alter cerebrovascular function by influencing endothelial mechanisms. Cerebral arteries will be isolated from rats and mice chronically treated with gonadal steroids. Vascular contractility, endothelial calcium, smooth muscle membrane potential, synthetic proteins for vasoactive factors and their release will be quantified. Four specific hypotheses will be tested: 1. Estrogen, by activating ERalpha, increases endothelial-dependent cerebrovascular dilation. Estrogen may influence at least three vasodilators: NO, prostacyclin and endothelial derived hyperpolarizing factor (EDHF). We will test whether estrogen treatment increases vasodilation mediated by EDHF, whether there are significant interactions among endothelial factors that modulate estrogen effects, whether estrogen treatment increases endothelial calcium, and whether effects of estrogen on cerebrovascular endothelial function are mediated by genomic actions of ERalpha. 2. Testosterone increases cerebrovascular constriction

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through endothelial-dependent mechanisms. Since testosterone treatment increases cerebrovascular constriction, we will test whether testosterone affects endothelial vasoconstrictor and/or vasodilator factors. 3. Induction of COX-2 or iNOS will be altered by estrogen or testosterone. We will monitor iNOS and COX-2 induction and determine if gonadal steroids modulate inflammatory responses. 4. Progestins will modulate effects of estrogen. We will assess whether chronic progestin treatment alters vascular effects of estrogen. Given known sex differences in incidence of cardiovascular disease as well as the applicability of hormone replacement therapy to a large segment of the population, this work has tremendous significance for understanding physiological control of the cerebral circulation as well as improvement of hormonal therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WASHINGTON UNIVERSITY CLAUDE D PEPPER OAIC Principal Investigator & Institution: Holloszy, John O.; Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 30-SEP-1995; Project End 31-AUG-2002 Summary: A major aim of the applicant's research over the past 20 years has been to determine the extent to which exercise-training can compensate for and/or partially reverse the deterioration in cardiovascular, neuromuscular, and metabolic functions and in physical performance capacities that occur with advancing age. As a result of this research, and that of others, there is, according to the applicant, now sufficient information regarding the beneficial effects of exercise in late middle- age and early oldage to justify promotion of exercise for maintenance of functional capacity in this age group. The applicant has, therefore, decided to focus the research of the OAIC on the question of whether or not physical frailty is reversible in old women and men at risk of losing their independence. There are two intervention studies (IS) in this OAIC. The goals of IS-1 are a) to determine the extent to which trail old women and men can respond to exercise training with the adaptations that have been shown to occur in younger individuals, and b) to assess whether the adaptations to exercise in the frail elderly are sufficiently large and functionally important to result in a significant reversal of frailty. The intervention in IS-1 is a 3-phase exercise program; the first phase consists of physical therapy exercises, the second consists of weight training exercises and the third consists of endurance exercise; the second and third phases will be superimposed on maintenance programs of the preceding types of exercise. The aim is to test the hypotheses that exercise can: a) increase functional capacity and reduce physical frailty; b) improve aerobic exercise capacity and/or cardiovascular function; c) induce a sufficient increase in muscle protein synthesis and/or decrease in muscle protein breakdown to result in increases in lean body and skeletal muscle mass; d) increase bone quantity and/or quality; and e) decrease insulin resistance, improve glucose tolerance, and improve lipid and lipoprotein levels. To the extent that it is feasible, the plan is to examine the mechanisms by which improvements in function are mediated. The interventions in IS-2 are hormone replacement therapy (HRT) and exercise superimposed on HRT. The goals of IS-2 are to determine whether a) HRT can bring about a reduction of frailty in physically frail old women, and b) exercise training results in greater improvements in functional capacity, muscle mass, cardiovascular function, and bone quantity and quality, in women who have been on HRT for 9-month than in sex hormone deficient women. The research of IS-1 and IS-2, and the pilot studies will be supported by five Research Resource Cores (RRC): Recruitment/Assessment/Health Services; Functional Assessment; Clinical Physiology/ Pathophysiology; Metabolic

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Function/Body Composition; and Biostatistics/Data Management. A long-term goal is to obtain information that can be used to design practical, individualized programs of exercise that can be utilized in community settings to prevent or reverse physical frailty and maintain functional independence. To translate findings from this research into health care practice, the Demonstration and Information Dissemination Core will disseminate research findings that are relevant to the prevention and reversal of frailty to the public and health care professionals. A major goal of the Research Development Core is to utilize the OAIC research activities and RRCs to train new investigators from a variety of disciplines to perform gerontological research relevant to the goals of the OAIC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “hormone replacement therapy” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for hormone replacement therapy in the PubMed Central database: •

Changes in use of hormone replacement therapy after the report from the Women's Health Initiative: cross sectional survey of users. by Lawton B, Rose S, McLeod D, Dowell A.; 2003 Oct 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=214025

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Clinical practice guidelines for the care and treatment of breast cancer: 14. The role of hormone replacement therapy in women with a previous diagnosis of breast cancer. by Pritchard KI, Khan H, Levine M.; 2002 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100875

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Combination hormone replacement therapy and dementia. by Wooltorton E.; 2003 Jul 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164982

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Effect of hormone replacement therapy on the pathological stage of breast cancer: population based, cross sectional study. by Stallard S, Litherland JC, Cordiner CM, Dobson HM, George WD, Mallon EA, Hole D.; 2000 Feb 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27281

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Ethnic differences in use of hormone replacement therapy: community based survey. by Harris TJ, Cook DG, Wicks PD, Cappuccio FP.; 1999 Sep 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28213

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Hormone replacement therapy and prevention of vertebral fractures: a meta-analysis of randomised trials. by Torgerson DJ, Bell-Syer SE.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59898

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Hormone replacement therapy and risk of hip fracture: population based case-control study. by Michaelsson K, Baron JA, Farahmand BY, Johnell O, Magnusson C, Persson PG, Persson I, Ljunghall S.; 1998 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28583

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Hormone replacement therapy in rheumatoid arthritis is associated with lower serum levels of soluble IL-6 receptor and higher insulin-like growth factor 1. by d'Elia HF, Mattsson LA, Ohlsson C, Nordborg E, Carlsten H.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165058

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Hormone replacement therapy use dramatically increases breast oestrogen receptor expression in obese postmenopausal women. by Lawson JS, Field AS, Tran DD, Houssami N.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=57804

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Hormone replacement therapy: a time for pause. by Yusuf S, Anand S.; 2002 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117850

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Postmenopausal hormone replacement therapy for chronic disease prevention: results from the Women's Health Initiative trial. by Farquhar D.; 2002 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117857

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Pre-existing risk factor profiles in users and non-users of hormone replacement therapy: prospective cohort study in Gothenburg, Sweden. by Rodstrom K, Bengtsson C, Lissner L, Bjorkelund C.; 1999 Oct 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28245

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Randomised controlled trial of an interactive multimedia decision aid on hormone replacement therapy in primary care. by Murray E, Davis H, Tai SS, Coulter A, Gray A, Haines A.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=48137

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Relation between hormone replacement therapy and ischaemic heart disease in women: prospective observational study. by Lokkegaard E, Pedersen AT, Heitmann BL, Jovanovic Z, Keiding N, Hundrup YA, Obel EB, Ottesen B.; 2003 Feb 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149444

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Risks and benefits of hormone replacement therapy: The evidence speaks. by Humphries KH, Gill S.; 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152685

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with hormone replacement therapy, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “hormone replacement therapy” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for hormone replacement therapy (hyperlinks lead to article summaries): •

A common mutation in cholesteryl ester transfer protein gene and plasma HDL cholesterol level before and after hormone replacement therapy in Korean postmenopausal women. Author(s): Choi HS, Park JB, Han KO, Yim CH, Jung HY, Jang HC, Yoon HK, Cho DH, Shin HH, Han IK. Source: Korean J Intern Med. 2002 June; 17(2): 83-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164095&dopt=Abstract

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A comparison of two different dosages of conjugated equine estrogen in continuous combined hormone replacement therapy with progestin. Author(s): Xing S, Wu Y, Liu J, Xu R, Zhang Z, Wang Y. Source: Chinese Medical Journal. 2003 April; 116(4): 584-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875727&dopt=Abstract

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A gynecologist's view of hormone replacement therapy in light of the Women's Health Initiative. Author(s): Jelovsek FR. Source: Southern Medical Journal. 2002 September; 95(9): 955-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356131&dopt=Abstract

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A multicentre randomised trial to compare uterine safety of raloxifene with a continuous combined hormone replacement therapy containing oestradiol and norethisterone acetate. Author(s): Neven P, Lunde T, Benedetti-Panici P, Tiitinen A, Marinescu B, de Villiers T, Hillard T, Cano A, Peer E, Quail D, Nickelsen T; Eurolox 1 Study Group. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2003 February; 110(2): 157-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618160&dopt=Abstract

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A pilot study comparing the clinical effects of Jia-Wey Shiau-Yau San, a traditional Chinese herbal prescription, and a continuous combined hormone replacement therapy in postmenopausal women with climacteric symptoms. Author(s): Chen LC, Tsao YT, Yen KY, Chen YF, Chou MH, Lin MF. Source: Maturitas. 2003 January 30; 44(1): 55-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568736&dopt=Abstract

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A randomised, double-blind trial comparing raloxifene HCl and continuous combined hormone replacement therapy in postmenopausal women: effects on compliance and quality of life. Author(s): Voss S, Quail D, Dawson A, Backstrom T, Aguas F, Erenus M, The HS, Bonnar J, De Geyter C, Hunter M, Nickelsen T; Euralox Investigators Group. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 August; 109(8): 874-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197366&dopt=Abstract

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A randomized, placebo-controlled trial of the effects of continuous combined hormone replacement therapy on coagulation and fibrinolytic systems in healthy postmenopausal women. Author(s): Salobir BG, Keber I, Vrabic L. Source: Fertility and Sterility. 2002 December; 78(6): 1178-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477508&dopt=Abstract

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A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT atherosclerosis study. Author(s): Clarke SC, Kelleher J, Lloyd-Jones H, Slack M, Schofiel PM. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 September; 109(9): 1056-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269682&dopt=Abstract

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Age, menopause and hormone replacement therapy influences on cardiovascular risk factors in a cohort of middle-aged Chilean women. Author(s): Castelo-Branco C, Blumel JE, Roncagliolo ME, Haya J, Bolf D, Binfa L, Tacla X, Colodron M. Source: Maturitas. 2003 July 25; 45(3): 205-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818466&dopt=Abstract

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Age-related eye diseases: impact of hormone replacement therapy, and reproductive and other risk factors,. by K. K. Snow and J. M. Seddon. Int J Fertil Womens Med 45:301-13, 2000. Author(s): Arroyo J. Source: Survey of Ophthalmology. 2003 March-April; 48(2): 236-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686310&dopt=Abstract

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Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial. Author(s): Ascott-Evans BH, Guanabens N, Kivinen S, Stuckey BG, Magaril CH, Vandormael K, Stych B, Melton ME. Source: Archives of Internal Medicine. 2003 April 14; 163(7): 789-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695269&dopt=Abstract

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An economic analysis of hormone replacement therapy for the prevention of fracture in young postmenopausal women. Author(s): Lamy O, Krieg MA, Burckhardt P, Wasserfallen JB. Source: Expert Opinion on Pharmacotherapy. 2003 September; 4(9): 1479-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943477&dopt=Abstract

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Angiotensin-converting enzyme gene polymorphism, lipids, and apolipoproteins in menopausal women on hormone replacement therapy. Author(s): Cubrilo-Turek M, Sertic J, Durakovic Z. Source: Acta Med Croatica. 2001; 55(4-5): 161-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398019&dopt=Abstract

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Anti-aging medicine: part I. Hormone replacement therapy in women. Author(s): Kaweski S; Plastic Surgery Educational Foundation DATA Committee. Source: Plastic and Reconstructive Surgery. 2003 February; 111(2): 935-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560725&dopt=Abstract

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Antidiuretic hormone replacement therapy to prevent or ameliorate vasodilatory shock. Author(s): Singh Ranger G. Source: Medical Hypotheses. 2002 September; 59(3): 337-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208165&dopt=Abstract

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Are pharmacological considerations of relevance in hormone replacement therapy for prevention of chronic disease? Author(s): Lippert TH, Seeger H, Mueck AO. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 May; 23(3): 263-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850857&dopt=Abstract

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Are smoking-associated cancers prevented or postponed in women using hormone replacement therapy? Author(s): Olsson H, Bladstrom A, Ingvar C. Source: Obstetrics and Gynecology. 2003 September; 102(3): 565-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962944&dopt=Abstract

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Assessing benefits and harms of hormone replacement therapy: clinical applications. Author(s): Nelson HD. Source: Jama : the Journal of the American Medical Association. 2002 August 21; 288(7): 882-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186606&dopt=Abstract

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Association of hormone replacement therapy with bronchial hyper-responsiveness. Author(s): Mueller JE, Frye C, Brasche S, Heinrich J. Source: Respiratory Medicine. 2003 August; 97(8): 990-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924529&dopt=Abstract

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Attitude towards health and hormone replacement therapy among female obstetrician-gynecologists in Israel. Author(s): Kaplan B, Yogev Y, Sulkas J, Geva A, Nahum R, Fisher M. Source: Maturitas. 2002 October 25; 43(2): 113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385859&dopt=Abstract

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Basal leg blood flow in healthy women is related to age and hormone replacement therapy status. Author(s): Moreau KL, Donato AJ, Tanaka H, Jones PP, Gates PE, Seals DR. Source: The Journal of Physiology. 2003 February 15; 547(Pt 1): 309-16. Epub 2002 December 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562958&dopt=Abstract

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Bilateral carpal tunnel syndrome in a child on growth hormone replacement therapy: a case report. Author(s): Ong BC, Klugman JA, Jazrawi LM, Stutchin S. Source: Bull Hosp Jt Dis. 2001-2002; 60(2): 94-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003362&dopt=Abstract

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Bioequivalence and relative bioavailability of three estradiol and norethisterone acetate-containing hormone replacement therapy tablets. Author(s): Zdravkovic M, Muller M, Larsen S, Degenkolb J, Pabst G. Source: Int J Clin Pharmacol Ther. 2001 January; 39(1): 41-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11204938&dopt=Abstract

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Bioidentical hormone replacement therapy. A natural option for perimenopause and beyond. Author(s): Walker CR. Source: Adv Nurse Pract. 2001 May; 9(5): 39-42, 45. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400258&dopt=Abstract

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Bioidentical hormone replacement therapy. Customizing care for perimenopausal and menopausal women. Author(s): Romero M. Source: Adv Nurse Pract. 2002 November; 10(11): 47-8, 51-2. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478948&dopt=Abstract

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Biological effects of hormone replacement therapy in relation to serum estradiol levels. Author(s): Yasui T, Uemura H, Tezuka M, Yamada M, Irahara M, Miura M, Aono T. Source: Hormone Research. 2001; 56(1-2): 38-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11815726&dopt=Abstract

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Bisphosphonate addition to stable hormone replacement therapy increases bone mineral density in postmenopausal women. Author(s): Boulos P, Sebaldt RJ, Goldsmith CH. Source: The Journal of Rheumatology. 2002 May; 29(5): 1110-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022339&dopt=Abstract

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Bleeding patterns in postmenopausal women using continuous combination hormone replacement therapy with conjugated estrogen and medroxyprogesterone acetate or with 17beta-estradiol and norethindrone acetate. Author(s): Odmark IS, Jonsson B, Backstrom T. Source: American Journal of Obstetrics and Gynecology. 2001 May; 184(6): 1131-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11349178&dopt=Abstract

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Blood pressure control and hormone replacement therapy in postmenopausal women at risk for coronary heart disease. Author(s): McCubbin JA, Helfer SG, Switzer FS 3rd, Price TM. Source: American Heart Journal. 2002 April; 143(4): 711-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923810&dopt=Abstract

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Body composition and quality of life as markers of the efficacy of growth hormone replacement therapy in adults. Author(s): Svensson J, Johannsson G, Bengtsson BA. Source: Hormone Research. 2001; 55 Suppl 2: 55-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684878&dopt=Abstract

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Body composition modulates the effects of hormone replacement therapy on growth hormone and insulin-like growth factor-I levels in postmenopausal women. Author(s): Figueroa A, Going SB, Milliken LA, Blew R, Sharp S, Lohman TG. Source: Gynecologic and Obstetric Investigation. 2002; 54(4): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592062&dopt=Abstract

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Bone mass response to discontinuation of long-term hormone replacement therapy: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Safety Follow-up Study. Author(s): Greendale GA, Espeland M, Slone S, Marcus R, Barrett-Connor E; PEPI Safety Follow-Up Study (PSFS) Investigators. Source: Archives of Internal Medicine. 2002 March 25; 162(6): 665-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911720&dopt=Abstract

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Bone-resorbing cytokines from peripheral blood mononuclear cells after hormone replacement therapy: a longitudinal study. Author(s): Bernard-Poenaru O, Roux C, Blanque R, Gardner C, de Vemejoul MC, Cohen-Solal ME. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(9): 769-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11605744&dopt=Abstract

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Breast and pelvic examination in women taking hormone replacement therapy. Author(s): Harrison-Woolrych M, Purdie D. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2001 December; 108(12): 1201-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843380&dopt=Abstract

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Breast cancer survival and hormone replacement therapy: a cohort analysis. Author(s): DiSaia PJ, Brewster WR, Ziogas A, Anton-Culver H. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2000 December; 23(6): 541-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11202792&dopt=Abstract

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British-Asian women's views on and attitudes towards menopause and hormone replacement therapy. Author(s): Sethi K, Pitkin J. Source: Climacteric : the Journal of the International Menopause Society. 2000 December; 3(4): 248-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910584&dopt=Abstract

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By the way, doctor. I noticed that you listed Crinone, a vaginal progesterone, in one of your articles on products for hormone replacement therapy. Does it really offer as much protection against endometrial cancer as oral progestogens do? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 1999 December; 7(4): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10564965&dopt=Abstract

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By the way, doctor. I'm one year into menopause and really bothered by hot flashes and vaginal dryness. I'd like to take hormone replacement therapy, but I'm worried about increasing my risk of getting breast cancer. My doctor said I can take HRT at a dose longer than what's usually prescribed. What do you think? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2001 September; 9(1): 7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11572838&dopt=Abstract

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By the way, Doctor. I've seen advertisements for red clover as a treatment for menopausal symptoms. Is it an effective alternative to hormone replacement therapy (HRT)? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2001 December; 9(5): 7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751101&dopt=Abstract

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By the way, Doctor. Whenever I read about the effects of hormone replacement therapy (HRT), the researchers always seem to use 0.625 mg of Premarin. I'm taking 1 mg of Estrace daily. How does this compare to the standard dose of Premarin? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2001 December; 9(5): 7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751102&dopt=Abstract

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Can a healthy endothelium influence the cardiovascular effects of hormone replacement therapy? Author(s): Koh KK. Source: International Journal of Cardiology. 2003 January; 87(1): 1-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468049&dopt=Abstract

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Cancer recurrence and mortality in women using hormone replacement therapy: meta-analysis. Author(s): Meurer LN, Lena S. Source: The Journal of Family Practice. 2002 December; 51(12): 1056-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540332&dopt=Abstract

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Cardiac effects of low-dose growth hormone replacement therapy in growth hormone-deficient adults. An 18-month randomised, placebo-controlled, doubleblind study. Author(s): Sneppen SB, Steensgaard-Hansen F, Feldt-Rasmussen U. Source: Hormone Research. 2002; 58(1): 21-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169777&dopt=Abstract

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Cartilage turnover assessed with a newly developed assay measuring collagen type II degradation products: influence of age, sex, menopause, hormone replacement therapy, and body mass index. Author(s): Mouritzen U, Christgau S, Lehmann HJ, Tanko LB, Christiansen C. Source: Annals of the Rheumatic Diseases. 2003 April; 62(4): 332-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634232&dopt=Abstract

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Change in bone mass distribution induced by hormone replacement therapy and high-impact physical exercise in post-menopausal women. Author(s): Cheng S, Sipila S, Taaffe DR, Puolakka J, Suominen H. Source: Bone. 2002 July; 31(1): 126-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110425&dopt=Abstract

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Changes in use of hormone replacement therapy after the report from the Women's Health Initiative: cross sectional survey of users. Author(s): Lawton B, Rose S, McLeod D, Dowell A. Source: Bmj (Clinical Research Ed.). 2003 October 11; 327(7419): 845-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14551101&dopt=Abstract

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Changes in vaginal cytology after various types of hormone replacement therapy, according to body mass index and body fat distribution in postmenopausal women. Author(s): Carranza-Lira S, Barraza-Solorzano M, Fernandez RL. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 August; 78(2): 167-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175722&dopt=Abstract

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Climacteric symptoms and knowledge about hormone replacement therapy among Hong Kong Chinese women aged 40-60 years. Author(s): Lam PM, Leung TN, Haines C, Chung TK. Source: Maturitas. 2003 June 30; 45(2): 99-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787968&dopt=Abstract

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Clinical and personal relationships between oral contraceptive and hormone replacement therapy use among US women physicians. Author(s): Frank E, Elon L. Source: Menopause (New York, N.Y.). 2003 March-April; 10(2): 133-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627038&dopt=Abstract

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Clinical assessment and quality of life of postmenopausal women treated with a new intermittent progestogen combination hormone replacement therapy: a placebocontrolled study. Author(s): Gelfand MM, Moreau M, Ayotte NJ, Hilditch JR, Wong BA, Lau CY. Source: Menopause (New York, N.Y.). 2003 January-February; 10(1): 29-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544674&dopt=Abstract

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Clinical cardiovascular studies of hormone replacement therapy. Author(s): Collins P. Source: The American Journal of Cardiology. 2002 July 3; 90(1A): 30F-34F. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106638&dopt=Abstract

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Combination hormone replacement therapy and dementia. Author(s): Wooltorton E. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 July 22; 169(2): 133. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874164&dopt=Abstract

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Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women. Author(s): de Lignieres B, de Vathaire F, Fournier S, Urbinelli R, Allaert F, Le MG, Kuttenn F. Source: Climacteric : the Journal of the International Menopause Society. 2002 December; 5(4): 332-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626212&dopt=Abstract

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Comparison of hormonal activity (estrogen, androgen and progestin) of standardized plant extracts for large scale use in hormone replacement therapy. Author(s): Beck V, Unterrieder E, Krenn L, Kubelka W, Jungbauer A. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 February; 84(23): 259-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711012&dopt=Abstract

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Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause. Author(s): Woo J, Lau E, Ho SC, Cheng F, Chan C, Chan AS, Haines CJ, Chan TY, Li M, Sham A. Source: Menopause (New York, N.Y.). 2003 July-August; 10(4): 352-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851519&dopt=Abstract

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Comparison of the difference in histopathology and cell cycle kinetics among the postmenopausal endometrium treated with different progestins in sequentialcombined hormone replacement therapy. Author(s): Chang TC, Chen M, Lien YR, Chen RJ, Chow SN. Source: Menopause (New York, N.Y.). 2003 March-April; 10(2): 172-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627044&dopt=Abstract

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Compliance with hormone replacement therapy in Thai women. Author(s): Manonai J, Theppisai U, Suchartwatnachai C, Jetsawangsri T, Chittacharoen A. Source: Maturitas. 2003 March 28; 44(3): 201-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648883&dopt=Abstract

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Continuation of hormone replacement therapy after hysterectomy. Author(s): Domoney C, Studd JW, Mocroft A. Source: Climacteric : the Journal of the International Menopause Society. 2003 March; 6(1): 58-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725666&dopt=Abstract

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Cost-effectiveness of hormone replacement therapy for fracture prevention in young postmenopausal women: an economic analysis based on a prospective cohort study. Author(s): Fleurence R, Torgerson DJ, Reid DM. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 August; 13(8): 637-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181622&dopt=Abstract

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Current attitudes toward hormone replacement therapy (HRT) prescribed during menopause. Author(s): Kaplan B. Source: Clin Exp Obstet Gynecol. 2002; 29(3): 167-71. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519035&dopt=Abstract

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Decisions about hormone replacement therapy. Whose responsibility are they? Author(s): Legare F, O'Connor A. Source: Can Fam Physician. 2003 February; 49: 132-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619731&dopt=Abstract

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Description of women's personality traits and psychological vulnerability prior to choosing hormone replacement therapy. Author(s): Loekkegaard E, Eplov LF, Koster A, Garde K. Source: Archives of Women's Mental Health. 2002 August; 5(1): 23-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503071&dopt=Abstract

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Design and conduct of clinical trials in hormone replacement therapy. Author(s): Holinka CF. Source: Annals of the New York Academy of Sciences. 2001 September; 943: 89-108. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11594562&dopt=Abstract

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Designer estrogen vs. hormone replacement therapy: the menopausal woman's dilemma. Author(s): Lappe JM. Source: Orthopaedic Nursing / National Association of Orthopaedic Nurses. 2001 JulyAugust; 20(4): 66-72; Quiz 72-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12025675&dopt=Abstract

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Determinants of hormone replacement therapy duration among postmenopausal women with intact uteri. Author(s): Gavin NI, Thorp JM, Ohsfeldt RL. Source: Menopause (New York, N.Y.). 2001 September-October; 8(5): 377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528366&dopt=Abstract

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Developments in the management of menopause and hormone replacement therapy: a presentation given at the symposium to honour the retirement of Professor Martin Vessey. Author(s): Barlow DH. Source: Pharmacoepidemiology and Drug Safety. 2001 January-February; 10(1): 29-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11417063&dopt=Abstract

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Differences in hormone replacement therapy use by social class, region and psychological symptoms. Author(s): Shah S, Harris TJ, Cook DG. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2001 March; 108(3): 269-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281467&dopt=Abstract

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Differential effects of raloxifene and continuous combined hormone replacement therapy on biochemical markers of cardiovascular risk: results from the Euralox 1 study. Author(s): Nickelsen T, Creatsas G, Rechberger T, Depypere H, Erenus M, Quail D, Arndt T, Bonnar J; Euralox 1 Study Group. Source: Climacteric : the Journal of the International Menopause Society. 2001 December; 4(4): 320-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11770189&dopt=Abstract

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Differing effects of oral and transdermal hormone replacement therapy on cardiovascular risk factors in healthy postmenopausal women. Author(s): Strandberg TE, Ylikorkala O, Tikkanen MJ. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 212-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860228&dopt=Abstract

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Discussing breast cancer and hormone replacement therapy with women. Author(s): Batur P, Thacker HL, Moore HC. Source: Cleve Clin J Med. 2002 November; 69(11): 838, 840, 843-4 Passim. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430969&dopt=Abstract

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Disparities in hormone replacement therapy use by socioeconomic status in a primary care population. Author(s): Finley C, Gregg EW, Solomon LJ, Gay E. Source: Journal of Community Health. 2001 February; 26(1): 39-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297189&dopt=Abstract

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Diurnal variation in uterine artery blood flow in post-menopausal women on oestrogen hormone replacement therapy. Author(s): Jurkovic D, Ross D, Aslam N, Whitehead M. Source: Human Reproduction (Oxford, England). 1999 November; 14(11): 2716-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10548607&dopt=Abstract

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Does a better grade of tumour occurring in women under hormone replacement therapy compensate for their lower probability of detection by screening mammography. Author(s): Esteve J, Seradour B, Jacquemier J, Remontet L. Source: Journal of Medical Screening. 2002; 9(2): 70-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133926&dopt=Abstract

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Does blood pressure differ between users and non-users of hormone replacement therapy? The Women's Health In the Lund Area (WHILA) Study. Author(s): Enstrom I, Lidfeldt J, Lindholm LH, Nerbrand C, Pennert K, Samsioe G. Source: Blood Pressure. 2002; 11(4): 240-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361193&dopt=Abstract

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Does female gender or hormone replacement therapy affect early or late outcome after carotid endarterectomy? Author(s): Lane JS, Shekherdimian S, Moore WS. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2003 March; 37(3): 568-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618694&dopt=Abstract

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Does former use of hormonal contraception predispose women to accept hormone replacement therapy? Author(s): Maamari R. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2001 November 9; 3(6): 3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11965198&dopt=Abstract

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Does hormone replacement therapy (HRT) improve cognitive function or either delay or prevent dementia in postmenopausal women? Author(s): Dunne L, Seaton TL. Source: The Journal of Family Practice. 2001 June; 50(6): 547. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401745&dopt=Abstract

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Does hormone replacement therapy increase the frequency of breast atypical hyperplasia in postmenopausal women? Results from the Bouches du Rhone district screening campaign. Author(s): Gayet A, Esteve J, Seradour B, Piana L, Jacquemier J. Source: European Journal of Cancer (Oxford, England : 1990). 2003 August; 39(12): 173845. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888369&dopt=Abstract

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Does menopausal hormone replacement therapy interact with known factors to increase risk of breast cancer? Author(s): Ursin G, Tseng CC, Paganini-Hill A, Enger S, Wan PC, Formenti S, Pike MC, Ross RK. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 February 1; 20(3): 699-706. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11821451&dopt=Abstract

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Does postmenopausal hormone replacement therapy affect cardiac autonomic regulation in osteoporotic women? Author(s): Niskanen L, Laitinen T, Tuppurainen M, Saarikoski S, Kroger H, Alhava E, Hartikainen J. Source: Menopause (New York, N.Y.). 2002 January-February; 9(1): 52-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791086&dopt=Abstract

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Effect of amlodipine and hormone replacement therapy on blood pressure and bone markers in menopause. Author(s): Zacharieva S, Shigarminova R, Nachev E, Kamenov Z, Atanassova I, Orbetzova M, Stoynev A, Doncheva N, Borissova AM. Source: Methods Find Exp Clin Pharmacol. 2003 April; 25(3): 209-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743626&dopt=Abstract

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Effect of hormone replacement therapy on cardiovascular disease: current opinion. Author(s): Khan NS, Malhotra S. Source: Expert Opinion on Pharmacotherapy. 2003 May; 4(5): 667-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739992&dopt=Abstract

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Effect of hormone replacement therapy on lacrimal fluid peroxidase activity in woman. Author(s): Marcozzi G, Liberati V, Madia F, Pizzinga A, de Feo G. Source: Maturitas. 2003 July 25; 45(3): 225-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818468&dopt=Abstract

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Effect of hormone replacement therapy on plasma levels of the cardiovascular risk factor asymmetric dimethylarginine: a randomized, placebo-controlled 12-week study in healthy early postmenopausal women. Author(s): Post MS, Verhoeven MO, van der Mooren MJ, Kenemans P, Stehouwer CD, Teerlink T. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 September; 88(9): 4221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970290&dopt=Abstract

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Effect of long-term hormone replacement therapy on atherosclerosis progression in postmenopausal women relates to myeloperoxidase promoter polymorphism. Author(s): Makela R, Dastidar P, Jokela H, Saarela M, Punnonen R, Lehtimaki T. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3823-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915675&dopt=Abstract

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Effect of neighborhood social participation on individual use of hormone replacement therapy and antihypertensive medication: a multilevel analysis. Author(s): Merlo J, Lynch JW, Yang M, Lindstrom M, Ostergren PO, Rasmusen NK, Rastam L. Source: American Journal of Epidemiology. 2003 May 1; 157(9): 774-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727671&dopt=Abstract

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Effects of exercise on bone mineral density in calcium-replete postmenopausal women with and without hormone replacement therapy. Author(s): Going S, Lohman T, Houtkooper L, Metcalfe L, Flint-Wagner H, Blew R, Stanford V, Cussler E, Martin J, Teixeira P, Harris M, Milliken L, Figueroa-Galvez A, Weber J. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 August; 14(8): 637-43. Epub 2003 July 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844212&dopt=Abstract

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Effects of exercise training added to ongoing hormone replacement therapy on bone mineral density in frail elderly women. Author(s): Villareal DT, Binder EF, Yarasheski KE, Williams DB, Brown M, Sinacore DR, Kohrt WM. Source: Journal of the American Geriatrics Society. 2003 July; 51(7): 985-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834519&dopt=Abstract

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Effects of exercise training and hormone replacement therapy on lean and fat mass in postmenopausal women. Author(s): Figueroa A, Going SB, Milliken LA, Blew RM, Sharp S, Teixeira PJ, Lohman TG. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 March; 58(3): 266-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634293&dopt=Abstract

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Effects of hormone replacement therapy on mammographic findings. Author(s): Bulbul NH, Ozden S, Dayicioglu V. Source: Archives of Gynecology and Obstetrics. 2003 April; 268(1): 5-8. Epub 2002 June 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673467&dopt=Abstract

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Effects of hormone replacement therapy on platelet activation in postmenopausal women. Author(s): Gu J, Yang D, Wang L, Yin S, Kuang J. Source: Chinese Medical Journal. 2003 August; 116(8): 1134-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12935396&dopt=Abstract

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Effects of hormone replacement therapy on serum angiotensin-converting enzyme activity and plasma bradykinin in postmenopausal women according to angiotensinconverting enzyme-genotype. Author(s): Sumino H, Ichikawa S, Ohyama Y, Nakamura T, Kanda T, Sakamoto H, Sakamaki T, Mizunuma H, Kurabayashi M. Source: Hypertens Res. 2003 January; 26(1): 53-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661913&dopt=Abstract

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Effects of hormone replacement therapy on the sympathetic nervous system and blood pressure. Author(s): Wyss JM, Carlson SH. Source: Current Hypertension Reports. 2003 June; 5(3): 241-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724057&dopt=Abstract

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Effects of hormone replacement therapy on weight, abdominal fat distribution, and lipid levels in Japanese postmenopausal women. Author(s): Sumino H, Ichikawa S, Yoshida A, Murakami M, Kanda T, Mizunuma H, Sakamaki T, Kurabayashi M. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2003 September; 27(9): 1044-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917709&dopt=Abstract

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Effects of long-term estrogen replacement therapy versus combined hormone replacement therapy on nitric oxide-dependent vasomotor function. Author(s): Jokela H, Dastidar P, Rontu R, Salomaki A, Teisala K, Lehtimaki T, Punnonen R. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 September; 88(9): 4348-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970309&dopt=Abstract

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Effects of postmenopausal hormone replacement therapy on HbA(1c) levels. Author(s): Okada M, Nomura S, Ikoma Y, Yamamoto E, Ito T, Mitsui T, Tamakoshi K, Mizutani S. Source: Diabetes Care. 2003 April; 26(4): 1088-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663578&dopt=Abstract

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Effects of trimonthly progestin administration on the endometrium in elderly postmenopausal women who receive hormone replacement therapy: a pilot study. Author(s): Pinto AB, A, Binder EF, Kohrt WM, Bronder DR, Williams DB. Source: American Journal of Obstetrics and Gynecology. 2003 July; 189(1): 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861131&dopt=Abstract

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ER-alpha variants and the cardiovascular effects of hormone replacement therapy. Author(s): Herrington DM, Howard TD. Source: Pharmacogenomics. 2003 May; 4(3): 269-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718718&dopt=Abstract

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Estradiol/progesterone-releasing vaginal rings for hormone replacement therapy in postmenopausal women. Author(s): Hamada AL, Maruo T, Samoto T, Yoshida S, Nash H, Spitz IM, Johansson E. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2003 June; 17(3): 247-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857433&dopt=Abstract

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Etidronate and hormone replacement therapy (HRT) for postmenopausal women with osteoporosis despite HRT. Author(s): Morishige K, Yamamoto T, Sawada K, Ohmichi M, Tasaka K, Murata Y. Source: Archives of Gynecology and Obstetrics. 2003 June; 268(2): 105-6. Epub 2002 August 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768299&dopt=Abstract

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Factor V Leiden, hormone replacement therapy, and risk of venous thromboembolic events in women with coronary disease. Author(s): Herrington DM, Vittinghoff E, Howard TD, Major DA, Owen J, Reboussin DM, Bowden D, Bittner V, Simon JA, Grady D, Hulley SB. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2002 June 1; 22(6): 1012-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067913&dopt=Abstract

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Factors affecting a woman's intent to adopt hormone replacement therapy for menopause. Author(s): Wilhelm SL. Source: Journal of Obstetric, Gynecologic, and Neonatal Nursing : Jognn / Naacog. 2002 November-December; 31(6): 698-707. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465866&dopt=Abstract

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Factors affecting long-term adherence to hormone replacement therapy after screening for osteoporosis. Author(s): Steel SA, Albertazzi P, Howarth EM, Purdie DW. Source: Climacteric : the Journal of the International Menopause Society. 2003 June; 6(2): 96-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841879&dopt=Abstract

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Factors associated with climacteric symptoms and the use of hormone replacement therapy. Author(s): Stadberg E, Mattsson LA, Milsom I. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2000 April; 79(4): 286-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10746844&dopt=Abstract

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Factors associated with endometrial bleeding in continuous hormone replacement therapy. Author(s): Shau WY, Hsieh CC, Hsieh TT, Hung TH, Huang KE. Source: Menopause (New York, N.Y.). 2002 May-June; 9(3): 188-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973442&dopt=Abstract

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Factors determining the use of hormone replacement therapy in recent naturally postmenopausal women participating in the French SU.VI.MAX cohort. Author(s): Mohammed-Cherif S, Briancon S, Potier de Courcy G, Preziosi P, Fieux B, Zarebska M, Galan P, Hercberg S. Source: European Journal of Epidemiology. 2000 May; 16(5): 477-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997836&dopt=Abstract

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Factors of risk for breast cancer influencing post-menopausal long-term hormone replacement therapy. Author(s): Chiechi LM, Secreto G. Source: Tumori. 2000 January-February; 86(1): 12-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10778760&dopt=Abstract

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Factors predicting current use of hormone replacement therapy among menopausal Jewish women in Israel. The National Women's Health Interview Survey, 1998. Author(s): Merom D, Ifrah A, Cohen-Manheim I, Chinich A, Green MS. Source: Isr Med Assoc J. 2002 September; 4(9): 671-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440227&dopt=Abstract

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Female sex hormone replacement therapy increases serum free 1,25-dihydroxyvitamin D3: a 1-year prospective study. Author(s): van Hoof HJ, van der Mooren MJ, Swinkels LM, Sweep CG, Merkus JM, Benraad TJ. Source: Clinical Endocrinology. 1999 April; 50(4): 511-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468912&dopt=Abstract

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Fibrinolysis and lipoprotein(a) in women with coronary artery disease. Influence of hormone replacement therapy. Author(s): Falco C, Tormo G, Estelles A, Espana F, Tormo E, Gilabert J, Velasco JA, Aznar J. Source: Haematologica. 2001 January; 86(1): 92-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11146577&dopt=Abstract

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Five years of growth hormone replacement therapy in adults: age- and gender-related changes in isometric and isokinetic muscle strength. Author(s): Svensson J, Stibrant Sunnerhagen K, Johannsson G. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 May; 88(5): 2061-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727955&dopt=Abstract

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Five-year compliance with hormone replacement therapy in postmenopausal Chinese women in Hong Kong. Author(s): Leung TN, Haines CJ, Chung TK. Source: Maturitas. 2001 September 28; 39(3): 195-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11574178&dopt=Abstract

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Flaxseed dietary supplement versus hormone replacement therapy in hypercholesterolemic menopausal women. Author(s): Lemay A, Dodin S, Kadri N, Jacques H, Forest JC. Source: Obstetrics and Gynecology. 2002 September; 100(3): 495-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220769&dopt=Abstract

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Flow resistance in carotid and middle cerebral arteries in postmenopausal women: a comparative study of tibolone and continuous combined hormone replacement therapy. Author(s): Pan HA, Wang ST, Chen CH, Pai MC, Wu MH, Huang KE. Source: Climacteric : the Journal of the International Menopause Society. 2002 September; 5(3): 259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419084&dopt=Abstract

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Fluctuations of lipid and lipoprotein levels in hyperlipidemic postmenopausal women receiving hormone replacement therapy. Author(s): Weintraub MS, Grosskopf I, Charach G, Eckstein N, Ringel Y, Maharshak N, Rotmensch HH, Rubinstein A. Source: Archives of Internal Medicine. 1998 September 14; 158(16): 1803-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9738610&dopt=Abstract

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Focus on cardiovascular health: hormone replacement therapy, estrogen replacement therapy, and selective estrogen receptor modulators. Author(s): Walsh BW. Source: J Am Osteopath Assoc. 2003 February; 103(2 Suppl 2): S6-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625632&dopt=Abstract

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Follow-up study of the benefits of hormone replacement therapy on isometric muscle strength of adductor pollicis in postmenopausal women. Author(s): Onambele NG, Skelton DA, Bruce SA, Woledge RC. Source: Clinical Science (London, England : 1979). 2001 April; 100(4): 421-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11256982&dopt=Abstract

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Fractal analysis of trabecular bone texture on calcaneus radiographs: effects of age, time since menopause and hormone replacement therapy. Author(s): Lespessailles E, Poupon S, Niamane R, Loiseau-Peres S, Derommelaere G, Harba R, Courteix D, Benhamou CL. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 May; 13(5): 366-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086346&dopt=Abstract

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Frail older women's participation in a trial of hormone replacement therapy: perceived benefits and concerns. Author(s): Jeffe DB, Binder EF, Williams DB, Kohrt WM. Source: Menopause (New York, N.Y.). 2001 Summer; 8(2): 127-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11256873&dopt=Abstract

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Gauging the benefits, risks, and unknowns of hormone replacement therapy. Exploring HRT. Author(s): Valerie AM. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 2002 February-March; 6(1): 24-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913199&dopt=Abstract

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General and medical factors associated with hormone replacement therapy among women attending menopause clinics in Italy. Author(s): Progetto Menopausa Italia Study Group. Source: Menopause (New York, N.Y.). 2001 July-August; 8(4): 290-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11449088&dopt=Abstract

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Glycaemic control and hormone replacement therapy: implications of the Postmenopausal Estrogen/Progestogen Intervention (PEPI) study. Author(s): Fineberg SE. Source: Drugs & Aging. 2000 December; 17(6): 453-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11200306&dopt=Abstract

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Glycaemic control and plasma lipoproteins in menopausal women with Type 2 diabetes treated with oral and transdermal combined hormone replacement therapy. Author(s): Darko DA, Dornhorst A, Kennedy G, Mandeno RC, Seed M. Source: Diabetes Research and Clinical Practice. 2001 December; 54(3): 157-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11689270&dopt=Abstract

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GnRH analogues and uterine leiomyomas. Effect of hormone replacement therapy on cell proliferation. Author(s): Rintala S, Kujansuu E, Teisala K, Rantala I, Kivinen S, Tuimala R. Source: Gynecologic and Obstetric Investigation. 1999; 48(4): 276-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10592433&dopt=Abstract

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Gonadotropin-releasing hormone agonist plus “add-back” hormone replacement therapy for treatment of endometriosis: a prospective, randomized, placebocontrolled, double-blind trial. Author(s): Franke HR, van de Weijer PH, Pennings TM, van der Mooren MJ. Source: Fertility and Sterility. 2000 September; 74(3): 534-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10973651&dopt=Abstract

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Growth hormone replacement therapy (GHRT) in children and adolescents: skeletal impact. Author(s): Mukherjee A, Shalet SM. Source: Medical and Pediatric Oncology. 2003 September; 41(3): 235-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868125&dopt=Abstract

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Growth hormone replacement therapy and insulin sensitivity. Author(s): Svensson J, Bengtsson BA. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 April; 88(4): 1453-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679421&dopt=Abstract

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Growth hormone replacement therapy during transition of patients with childhoodonset growth hormone deficiency into adulthood: what are the issues? Author(s): Shalet SM, Rosenfeld RG. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 1998 April; 8 Suppl B: 17784. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10990158&dopt=Abstract

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Growth hormone replacement therapy for adults: into the new millennium. Author(s): Simpson H, Savine R, Sonksen P, Bengtsson BA, Carlsson L, Christiansen JS, Clemmons D, Cohen P, Hintz R, Ho K, Mullis P, Robinson I, Strasburger C, Tanaka T, Thorner M; GRS Council. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 2002 February; 12(1): 1-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127299&dopt=Abstract

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Growth hormone replacement therapy improves body composition and increases bone metabolism in elderly patients with pituitary disease. Author(s): Fernholm R, Bramnert M, Hagg E, Hilding A, Baylink DJ, Mohan S, Thoren M. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 November; 85(11): 4104-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095440&dopt=Abstract

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Growth hormone replacement therapy in adults with growth hormone deficiency improves vascular reactivity. Author(s): Christ ER, Chowienczyk PJ, Sonksen PH, Russel-Jones DL. Source: Clinical Endocrinology. 1999 July; 51(1): 21-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468961&dopt=Abstract

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Growth hormone replacement therapy in children with leukemia in remission. Author(s): Taha DR, Bastian W, Castells S. Source: Clinical Pediatrics. 2001 August; 40(8): 441-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11516051&dopt=Abstract

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Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control. Author(s): Packer RJ, Boyett JM, Janss AJ, Stavrou T, Kun L, Wisoff J, Russo C, Geyer R, Phillips P, Kieran M, Greenberg M, Goldman S, Hyder D, Heideman R, Jones-Wallace D, August GP, Smith SH, Moshang T. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 January 15; 19(2): 480-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208842&dopt=Abstract

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Growth hormone replacement therapy induces codeine clearance. Author(s): Gil Berglund E, Johannsson G, Beck O, Bengtsson BA, Rane A. Source: European Journal of Clinical Investigation. 2002 July; 32(7): 507-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153551&dopt=Abstract

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Growth hormone replacement therapy induces insulin resistance by activating the glucose-fatty acid cycle. Author(s): Bramnert M, Segerlantz M, Laurila E, Daugaard JR, Manhem P, Groop L. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 April; 88(4): 145563. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679422&dopt=Abstract

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Growth hormone replacement therapy is not associated with any increase in mortality. KIMS Study Group. Author(s): Bengtsson BA, Koppeschaar HP, Abs R, Bennmarker H, Hernberg-Stahl E, Westberg B, Wilton P, Monson JP, Feldt-Rasmussen U, Wuster C. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 November; 84(11): 4291-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10566688&dopt=Abstract

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Growth hormone replacement therapy is not associated with retinal changes. Author(s): Blank D, Riedl M, Reitner A, Schnack C, Schernthaner G, Clodi M, Frisch H, Luger A. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 February; 85(2): 634-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10690868&dopt=Abstract

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Guidelines advise against hormone replacement therapy for cardiovascular disease prevention. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2001 August 23; 12(17): 7-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296365&dopt=Abstract

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Gynecologists' trends and attitudes toward prescribing hormone replacement therapy during menopause. Author(s): Kaplan B, Aschkenazi-Steinberg S, Yogev Y, Nahum R, Sulkes J, Phisher M. Source: Menopause (New York, N.Y.). 2002 September-October; 9(5): 354-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218724&dopt=Abstract

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Hormone replacement therapy after treatment for breast cancer: physicians' attitudes towards randomized trials. Author(s): Del Giudice ME, Sawka CA, Pritchard KI, Llewellyn-Thomas HA, Trudeau ME, Lewis JE, Franssen E. Source: Breast Cancer Research and Treatment. 2003 May; 79(2): 213-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825856&dopt=Abstract

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Hormone replacement therapy and autonomic cardiovascular functions: the impact of heart rate variability analyses methods. Author(s): Kaya D. Source: American Journal of Obstetrics and Gynecology. 2003 September; 189(3): 896; Author Reply 896-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14560748&dopt=Abstract

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Hormone replacement therapy and health protection. Author(s): Chiechi LM. Source: Curr Opin Investig Drugs. 2003 April; 4(4): 439-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808884&dopt=Abstract

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Hormone replacement therapy and hypercoagulability. Results from the Prospective Collaborative Danish Climacteric Study. Author(s): Sidelmann JJ, Jespersen J, Andersen LF, Skouby SO; Prospective Collaborative Danish Climacteric Study. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2003 June; 110(6): 541-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798469&dopt=Abstract

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Hormone replacement therapy and inflammation: interactions in cardiovascular disease. Author(s): Miller AP, Chen YF, Xing D, Feng W, Oparil S. Source: Hypertension. 2003 October; 42(4): 657-63. Epub 2003 August 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913055&dopt=Abstract

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Hormone replacement therapy and menopause: a review of randomized, doubleblind, placebo-controlled trials. Author(s): Chang C, Lin CH. Source: Kaohsiung J Med Sci. 2003 June; 19(6): 257-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873034&dopt=Abstract

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Hormone replacement therapy and the risk of incident congestive heart failure: the Cardiovascular Health Study. Author(s): Rea TD, Psaty BM, Heckbert SR, Cushman M, Meilahn E, Olson JL, Lemaitre RN, Smith NL, Sotoodehnia N, Chaves PH. Source: Journal of Women's Health (2002). 2003 May; 12(4): 341-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804341&dopt=Abstract

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Hormone replacement therapy containing progestins and given continuously increases breast carcinoma risk in Sweden. Author(s): Shah NR. Source: Cancer. 2003 October 1; 98(7): 1552-3; Author Reply 1553. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508845&dopt=Abstract

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Hormone replacement therapy for postmenopausal osteoporosis. Author(s): Cranney A, Wells GA. Source: Clinics in Geriatric Medicine. 2003 May; 19(2): 361-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916291&dopt=Abstract

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Hormone replacement therapy in postmenopausal women with benign fibrocystic mastopathy. Author(s): Yenen MC, Dede M, Goktolga U, Kucuk T, Pabuccu R. Source: Climacteric : the Journal of the International Menopause Society. 2003 June; 6(2): 146-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841885&dopt=Abstract

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Hormone replacement therapy in rheumatoid arthritis is associated with lower serum levels of soluble IL-6 receptor and higher insulin-like growth factor 1. Author(s): D'Elia HF, Mattsson LA, Ohlsson C, Nordborg E, Carlsten H. Source: Arthritis Research & Therapy. 2003; 5(4): R202-9. Epub 2003 May 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823855&dopt=Abstract

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Hormone replacement therapy in the post-Women's Health Initiative era. Report a a meeting held in Funchal, Madeira, February 24-25, 2003. Author(s): Burger H. Source: Climacteric : the Journal of the International Menopause Society. 2003 May; 6 Suppl 1: 11-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12945798&dopt=Abstract

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Hormone replacement therapy is associated with improved survival in women with advanced heart failure. Author(s): Lindenfeld J, Ghali JK, Krause-Steinrauf HJ, Khan S, Adams K, Goldman S, Peberdy MA, Yancy C, Thaneemit-Chen S, Larsen RL, Young J, Lowes B, Rosenberg YD; BEST Investigators. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1238-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522488&dopt=Abstract

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Hormone replacement therapy. Author(s): Cheifitz RL. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2003 August; 93(8): 554-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14531100&dopt=Abstract

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Hormone replacement therapy: attitude and acceptance of Bangkokian women. Author(s): Taechakraichana N, Wilawan K, Wipatavit V, Maitrisathit S, Thamanavat N, Jaisamrarn U, Panyakhamlerd K, Havanond P, Limpaphayom KK. Source: J Med Assoc Thai. 2003 June; 86 Suppl 2: S385-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930015&dopt=Abstract

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Hormone replacement therapy: dilemmas in 2002. Author(s): Moore A. Source: Trans Am Clin Climatol Assoc. 2003; 114: 233-8; Discussion 238-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12813923&dopt=Abstract

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Hormone replacement therapy: primary and secondary prevention. Author(s): Penckofer S, Schwertz D. Source: The Journal of Cardiovascular Nursing. 2001 April; 15(3): 1-25; Quiz 109-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968768&dopt=Abstract

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Hormone replacement therapy: prothrombotic vs. protective effects. Author(s): Lowe GD. Source: Pathophysiology of Haemostasis and Thrombosis. 2002 September-December; 32(5-6): 329-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509584&dopt=Abstract

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Hormone replacement therapy: to use or not to use? Author(s): Baber RJ, O'Hara JL, Boyle FM. Source: The Medical Journal of Australia. 2003 June 16; 178(12): 630-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797851&dopt=Abstract

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Hormone replacement therapy--is there a place for its use in neurology? Author(s): Vukovic V, Lovrencic-Huzjan A, Solter VV, Dordevic V, Demarin V. Source: Coll Antropol. 2003 June; 27(1): 413-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974172&dopt=Abstract

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Impact of hormone replacement therapy on endogenous estradiol metabolism in postmenopausal women. Author(s): Mueck AO, Seeger H, Wallwiener D. Source: Maturitas. 2002 October 25; 43(2): 87-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385856&dopt=Abstract

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In search of the impossible dream? Thyroid hormone replacement therapy that treats all symptoms in all hypothyroid patients. Author(s): Kaplan MM, Sarne DH, Schneider AB. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 October; 88(10): 4540-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557418&dopt=Abstract

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Increased levels of C-reactive protein after oral hormone replacement therapy may not be related to an increased inflammatory response. Author(s): Silvestri A, Gebara O, Vitale C, Wajngarten M, Leonardo F, Ramires JA, Fini M, Mercuro G, Rosano GM. Source: Circulation. 2003 July 1; 107(25): 3165-9. Epub 2003 June 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796135&dopt=Abstract

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Increased resistance to activated protein C after short-term oral hormone replacement therapy in healthy post-menopausal women. Author(s): Post MS, Rosing J, Van Der Mooren MJ, Zweegman S, Van Baal WM, Kenemans P, Stehouwer CD; Ageing Women' and the Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU). Source: British Journal of Haematology. 2002 December; 119(4): 1017-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472583&dopt=Abstract

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Individual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammography. Author(s): Carney PA, Miglioretti DL, Yankaskas BC, Kerlikowske K, Rosenberg R, Rutter CM, Geller BM, Abraham LA, Taplin SH, Dignan M, Cutter G, Ballard-Barbash R. Source: Annals of Internal Medicine. 2003 February 4; 138(3): 168-75. Erratum In: Ann Intern Med. 2003 May 6; 138(9): 771. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558355&dopt=Abstract

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Individualising hormone replacement therapy. Author(s): Attilakos G, Wardle PG. Source: The Practitioner. 2002 May; 246(1634): 295-8, 302, 305 Passim. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12043347&dopt=Abstract

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Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women's Health Initiative observational study. Author(s): Pradhan AD, Manson JE, Rossouw JE, Siscovick DS, Mouton CP, Rifai N, Wallace RB, Jackson RD, Pettinger MB, Ridker PM. Source: Jama : the Journal of the American Medical Association. 2002 August 28; 288(8): 980-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190368&dopt=Abstract

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Influence of hormone replacement therapy on C-reactive protein: population-based data. Author(s): Primatesta P, Falaschetti E, Poulter NR. Source: Journal of Cardiovascular Risk. 2003 February; 10(1): 57-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569237&dopt=Abstract

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Influence of hormone replacement therapy on disease progression and bone mineral density in rheumatoid arthritis. Author(s): D'Elia HF, Larsen A, Mattsson LA, Waltbrand E, Kvist G, Mellstrom D, Saxne T, Ohlsson C, Nordborg E, Carlsten H. Source: The Journal of Rheumatology. 2003 July; 30(7): 1456-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858441&dopt=Abstract

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Influences of hormone replacement therapy on postmenopausal women's health perceptions. Author(s): Blumel JE, Castelo-Branco C, Kerrigan N, Cancelo MJ, Blumel B, Haya J, Flores M, Carvajal MC, Sarra S. Source: Menopause (New York, N.Y.). 2003 May-June; 10(3): 235-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792296&dopt=Abstract

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Inhibition of cytochrome P450 2B6 activity by hormone replacement therapy and oral contraceptive as measured by bupropion hydroxylation. Author(s): Palovaara S, Pelkonen O, Uusitalo J, Lundgren S, Laine K. Source: Clinical Pharmacology and Therapeutics. 2003 October; 74(4): 326-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14534519&dopt=Abstract

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Interaction between hormone replacement therapy preparations and oral anticoagulant therapy. Author(s): McLintock LA, Dykes A, Tait RC, Walker ID. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2003 August; 110(8): 777-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892692&dopt=Abstract

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Intermittent progestin administration as part of hormone replacement therapy: longterm comparison between estradiol 1 mg combined with intermittent norgestimate and estradiol 2 mg combined with constant norethisterone acetate. Author(s): Ylikorkala O, Wahlstrom T, Caubel P, Lane R. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 July; 81(7): 654-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190841&dopt=Abstract

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Intranasal hormone replacement therapy. Author(s): Wattanakumtornkul S, Pinto AB, Williams DB. Source: Menopause (New York, N.Y.). 2003 January-February; 10(1): 88-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544682&dopt=Abstract

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Intrauterine pathology in women with abnormal uterine bleeding taking hormone replacement therapy. Author(s): Leung PL, Tam WH, Kong WS, Yuen PM. Source: The Journal of the American Association of Gynecologic Laparoscopists. 2003 May; 10(2): 260-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732781&dopt=Abstract

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Introduction: the role of hormone replacement therapy in prevention and treatment of cardiovascular disease in postmenopausal women. Author(s): Mishell DR Jr, Mendelsohn ME. Source: The American Journal of Cardiology. 2002 June 20; 89(12A): 1E-4E. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084394&dopt=Abstract

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Is hormone replacement therapy associated with an increased risk of irritable bowel syndrome? Author(s): Ruigomez A, Garcia Rodriguez LA, Johansson S, Wallander MA. Source: Maturitas. 2003 February 25; 44(2): 133-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590009&dopt=Abstract

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Is there any rationale for prescribing hormone replacement therapy (HRT) to prevent or to treat osteoarthritis? Author(s): Reginster JY, Kvasz A, Bruyere O, Henrotin Y. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2003 February; 11(2): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554124&dopt=Abstract

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Is use of hormone replacement therapy associated with increased detection of human papillomavirus and potential risk of HPV-related genital cancers? Author(s): Smith EM, Levy BT, Ritchie JM, Jia J, Wang D, Haugen TH, Turek LP. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 2002 June; 11(3): 295-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131663&dopt=Abstract

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Issues of hormone replacement therapy and cardiovascular disease for elderly women. Author(s): Limacher MC. Source: The American Journal of Geriatric Cardiology. 2002 July-August; 11(4): 217-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091770&dopt=Abstract

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Knowledge of menopause and hormone replacement therapy use in low-income urban women. Author(s): Appling SE, Allen JK, Van Zandt S, Olsen S, Brager R, Hallerdin J. Source: Journal of Women's Health & Gender-Based Medicine. 2000 January-February; 9(1): 57-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10718507&dopt=Abstract

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Knowledge, attitudes and management strategies in Scandinavia concerning hormone replacement therapy: a comparison between gynecologists in Denmark, Norway and Sweden. Author(s): Nilsen ST, Pedersen AT, Moen MH, Milsom I, Mattsson LA, Iversen OE, Larsen PM, Andersson K. Source: Maturitas. 2001 July 25; 39(1): 83-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11451625&dopt=Abstract

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Knowledge-attitude-practice of sexual intercourse of post-menopausal women using hormone replacement therapy. Author(s): Somboonporn W, Seejorn K, Kleebkaow P, Junthathamrongwat N, Ratanasiri T. Source: J Med Assoc Thai. 2002 February; 85(2): 167-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081115&dopt=Abstract

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Landmark hormone replacement therapy study stopped after finding more harms than benefits. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2002 August 9; 13(15): 5-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553323&dopt=Abstract

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Lifestyle factors and choice of hormone replacement therapy among Danish nurses. Author(s): Hundrup YA, Thoning H, Obel EB, Rasmussen NK, Philip J. Source: Scandinavian Journal of Public Health. 2002; 30(1): 47-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11928833&dopt=Abstract

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Lipid and lipoprotein responses to oral combined hormone replacement therapy in normolipemic obese women with controlled type 2 diabetes mellitus. Author(s): Lilley SH, Spivey JM, Vadlamudi S, Otvos J, Cummings DM, Barakat H. Source: Journal of Clinical Pharmacology. 1998 December; 38(12): 1107-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11301562&dopt=Abstract

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Lipid profiles and endothelial function with low-dose hormone replacement therapy in postmenopausal women at risk for coronary artery disease: a randomized trial. Author(s): Mercuro G, Vitale C, Fini M, Zoncu S, Leonardo F, Rosano GM. Source: International Journal of Cardiology. 2003 June; 89(2-3): 257-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767550&dopt=Abstract

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Local and systemic options for hormone replacement therapy. Author(s): Gilliam ML. Source: Int J Fertil Womens Med. 2001 July-August; 46(4): 222-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11563833&dopt=Abstract

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Long term-effects of hormone replacement therapy. Author(s): Subbiah MT. Source: Lancet. 2003 January 18; 361(9353): 255. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547559&dopt=Abstract

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Long term-effects of hormone replacement therapy. Author(s): Chan NN, Tong PC, Chow CC, Chan JC. Source: Lancet. 2003 January 18; 361(9353): 254; Author Reply 254-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547557&dopt=Abstract

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Longitudinal changes in weight in perimenopausal and early postmenopausal women: effects of dietary energy intake, energy expenditure, dietary calcium intake and hormone replacement therapy. Author(s): Macdonald HM, New SA, Campbell MK, Reid DM. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2003 June; 27(6): 669-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833110&dopt=Abstract

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Long-term continuous combined hormone replacement therapy in the prevention of postmenopausal bone loss: a comparison of high- and low-dose estrogen-progestin regimens. Author(s): Heikkinen J, Vaheri R, Kainulainen P, Timonen U. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2000; 11(11): 929-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11193245&dopt=Abstract

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Long-term effects of hormone replacement therapy on bone mineral density in girls oophorectomized in adolescence. Author(s): Kanaoka Y, Honda K, Ishiko O, Hirai K, Ogita S. Source: Gynecologic and Obstetric Investigation. 2003; 55(3): 168-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865597&dopt=Abstract

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Long-term effects of hormone replacement therapy. Author(s): Stevenson JC. Source: Lancet. 2003 January 18; 361(9353): 253-4; Author Reply 254-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547556&dopt=Abstract

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Long-term effects of oral and transdermal hormone replacement therapy on plasma homocysteine levels. Author(s): Chiantera V, Sarti CD, Fornaro F, Farzati A, De Franciscis P, Sepe E, Borrelli AL, Colacurci N. Source: Menopause (New York, N.Y.). 2003 July-August; 10(4): 286-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851511&dopt=Abstract

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Long-term estrogen and hormone replacement therapy for the prevention and treatment of osteoporosis. Author(s): Levine JP. Source: Curr Womens Health Rep. 2003 June; 3(3): 181-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734027&dopt=Abstract

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Long-term growth hormone replacement therapy in hypopituitary adults. Author(s): Verhelst J, Abs R. Source: Drugs. 2002; 62(16): 2399-412. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396230&dopt=Abstract

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Long-term hormone replacement therapy in two patients with Kabuki syndrome and growth hormone deficiency. Author(s): Gabrielli O, Carloni I, Coppa GV, Bedeschi MF, Petroncini MM, Selicorni A. Source: Minerva Pediatr. 2000 January-February; 52(1-2): 47-53. English, Italian. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10829592&dopt=Abstract

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Long-term use of estrogen-only hormone replacement therapy (HRT) linked with increased risk of ovarian cancer. Author(s): American Medical Association. Source: Ginecologia Y Obstetricia De Mexico. 2002 August; 70: 409-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12448047&dopt=Abstract

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Low incidence of endometrial hyperplasia with acceptable bleeding patterns in women taking sequential hormone replacement therapy with dydrogesterone. Author(s): Bergeron C, Fox H. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2000 August; 14(4): 275-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11075299&dopt=Abstract

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Low-dose hormone replacement therapy for hot flashes. Author(s): Mikhail N. Source: Mayo Clinic Proceedings. 2003 March; 78(3): 379; Author Reply 379. Erratum In: Mayo Clin Proc. 2003 May; 78(5): 656. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630592&dopt=Abstract

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Low-dose hormone replacement therapy: effects on bone. Author(s): Gambacciani M, Monteleone P, Genazzani AR. Source: Climacteric : the Journal of the International Menopause Society. 2002 June; 5(2): 135-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051108&dopt=Abstract

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Lower diabetes risk with hormone replacement therapy: an encore for estrogen? Author(s): Wilson PW. Source: Annals of Internal Medicine. 2003 January 7; 138(1): 69-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513048&dopt=Abstract

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Making decisions about hormone replacement therapy. Author(s): Rymer J, Wilson R, Ballard K. Source: Bmj (Clinical Research Ed.). 2003 February 8; 326(7384): 322-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574048&dopt=Abstract

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Making decisions about hormone replacement therapy: bisphosphonates should not be recommended for women aged 50. Author(s): Ott SM. Source: Bmj (Clinical Research Ed.). 2003 June 21; 326(7403): 1398; Author Reply 1398-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816846&dopt=Abstract

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Making decisions about hormone replacement therapy: preparations containing oestrogen should not be given during treatment for breast cancer. Author(s): Hinton CP, Coventry C, Borrowclough B. Source: Bmj (Clinical Research Ed.). 2003 June 21; 326(7403): 1398; Author Reply 1398-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816848&dopt=Abstract

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Medical issues and hormone replacement therapy. Author(s): Harris PF. Source: Curr Womens Health Rep. 2002 October; 2(5): 373-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215310&dopt=Abstract

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Menopausal hormone replacement therapy and risk of ovarian cancer. Author(s): Lacey JV Jr, Mink PJ, Lubin JH, Sherman ME, Troisi R, Hartge P, Schatzkin A, Schairer C. Source: Jama : the Journal of the American Medical Association. 2002 July 17; 288(3): 334-41. Erratum In: Jama 2002 November 27; 288(20): 2544. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117398&dopt=Abstract

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Menopause, hormone replacement therapy and tear function. Author(s): Evans I, Millar TJ, Eden JA, Willcox MD. Source: Advances in Experimental Medicine and Biology. 2002; 506(Pt B): 1029-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614027&dopt=Abstract

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Message about hormone replacement therapy is unclear. Author(s): Dixon JM. Source: Bmj (Clinical Research Ed.). 2002 November 2; 325(7371): 1036. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411373&dopt=Abstract

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Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Author(s): Wells G, Tugwell P, Shea B, Guyatt G, Peterson J, Zytaruk N, Robinson V, Henry D, O'Connell D, Cranney A; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Source: Endocrine Reviews. 2002 August; 23(4): 529-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202468&dopt=Abstract

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Methods for evaluating the effects of new hormone replacement therapy compounds on coronary artery disease. Author(s): Ouyang P. Source: The American Journal of Cardiology. 2002 July 3; 90(1A): 44F-50F. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106640&dopt=Abstract

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Monitoring hormone replacement therapy by biochemical markers of bone metabolism in menopausal women. Author(s): Dogan E, Posaci C. Source: Postgraduate Medical Journal. 2002 December; 78(926): 727-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509689&dopt=Abstract

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Monofluorophosphate combined with hormone replacement therapy in postmenopausal osteoporosis. An open-label pilot efficacy and safety study. Author(s): Ringe JD, Setnikar I. Source: Rheumatology International. 2002 May; 22(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120908&dopt=Abstract

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Naloxone decreases insulin secretion in hyperinsulinemic postmenopausal women and may positively affect hormone replacement therapy. Author(s): Cucinelli F, Soranna L, Perri C, Romualdi D, Barini A, Mancuso S, Lanzone A. Source: Fertility and Sterility. 2002 November; 78(5): 1017-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413987&dopt=Abstract

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National differences in lipid response to postmenopausal hormone replacement therapy. Author(s): Ranta V, Oksanen H, Arrenbrecht S, Ylikorkala O. Source: Maturitas. 2002 August 30; 42(4): 259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12191848&dopt=Abstract

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Negative mood changes during hormone replacement therapy: a comparison between two progestogens. Author(s): Bjorn I, Bixo M, Nojd KS, Nyberg S, Backstrom T. Source: American Journal of Obstetrics and Gynecology. 2000 December; 183(6): 1419-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11120505&dopt=Abstract

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Neither long-term treatment with raloxifene nor hormone replacement therapy modulate cardiac function in healthy postmenopausal women: two randomized, placebo-controlled, 2-year studies. Author(s): Vogelvang TE, Mijatovic V, Kamp O, Netelenbos JC, Neele SJ, Pines A, Kenemans P, van der Mooren MJ. Source: American Journal of Obstetrics and Gynecology. 2002 April; 186(4): 729-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11967499&dopt=Abstract

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Nicotine withdrawal and depressive symptomatology during short-term smoking abstinence: a comparison of postmenopausal women using and not using hormone replacement therapy. Author(s): Allen SS, Hatsukami DK, Christianson D. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2003 February; 5(1): 49-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745506&dopt=Abstract

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Number of years since menopause: spontaneous bone loss is dependent but response to hormone replacement therapy is independent. Author(s): Bjarnason NH, Alexandersen P, Christiansen C. Source: Bone. 2002 April; 30(4): 637-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934658&dopt=Abstract

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Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy. Author(s): Sorensen MB, Rosenfalck AM, Hojgaard L, Ottesen B. Source: Obesity Research. 2001 October; 9(10): 622-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11595778&dopt=Abstract

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Observational studies and randomized trials of hormone replacement therapy: what can we learn from them? Author(s): Whittemore AS, McGuire V. Source: Epidemiology (Cambridge, Mass.). 2003 January; 14(1): 8-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500037&dopt=Abstract

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Opinion survey towards hormone replacement therapy in the prevention of coronary heart disease. Author(s): Rozenberg S, Fellemans C, Ham H. Source: Maturitas. 2001 May 30; 38(3): 273-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358644&dopt=Abstract

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Optimizing the dose of hormone replacement therapy. Author(s): Rice VM. Source: Int J Fertil Womens Med. 2002 September-October; 47(5): 205-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469707&dopt=Abstract

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Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Author(s): Vihtamaki T, Parantainen J, Koivisto AM, Metsa-Ketela T, Tuimala R. Source: Maturitas. 2002 June 25; 42(2): 129-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065172&dopt=Abstract

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Oral contraceptive use and hormone replacement therapy are associated with microalbuminuria. Author(s): Monster TB, Janssen WM, de Jong PE, de Jong-van den Berg LT; Prevention of Renal and Vascular End Stage Disease Study Group. Source: Archives of Internal Medicine. 2001 September 10; 161(16): 2000-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11525702&dopt=Abstract

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Oral contraceptives, hormone replacement therapy and thrombosis. Author(s): Rosendaal FR, Helmerhorst FM, Vandenbroucke JP. Source: Thrombosis and Haemostasis. 2001 July; 86(1): 112-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486996&dopt=Abstract

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Oral hormone replacement therapy: factors that influence the estradiol concentrations achieved in a multiracial study population. Author(s): Gavaler JS. Source: Journal of Clinical Pharmacology. 2002 February; 42(2): 137-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11831535&dopt=Abstract

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Oral symptoms at menopause--the role of hormone replacement therapy. Author(s): Tarkkila L, Linna M, Tiitinen A, Lindqvist C, Meurman JH. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2001 September; 92(3): 276-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11552144&dopt=Abstract

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Outcomes of growth hormone replacement therapy in survivors of childhood acute lymphoblastic leukemia. Author(s): Leung W, Rose SR, Zhou Y, Hancock ML, Burstein S, Schriock EA, Lustig R, Danish RK, Evans WE, Hudson MM, Pui CH. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 July 1; 20(13): 2959-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089225&dopt=Abstract

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Perspectives on the women's health initiative trial of hormone replacement therapy. Author(s): Brubaker K. Source: Obstetrics and Gynecology. 2003 April; 101(4): 813; Author Reply 813-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681893&dopt=Abstract

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Physician counseling on hormone replacement therapy and bone loss: do socioeconomic and racial characteristics of women influence counseling? Author(s): Neuner JM, McCarthy EP, Davis RB, Phillips RS. Source: Journal of Women's Health (2002). 2003 June; 12(5): 495-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869297&dopt=Abstract

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Postmenopausal femur bone loss: effects of a low dose hormone replacement therapy. Author(s): Gambacciani M, Ciaponi M, Cappagli B, Monteleone P, Benussi C, Bevilacqua G, Genazzani AR. Source: Maturitas. 2003 July 25; 45(3): 175-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818462&dopt=Abstract

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Postmenopausal hormone replacement therapy for the primary prevention of chronic conditions: recommendations and rationale. Author(s): Berg AO; U.S. Preventive Services Task Force. Source: The American Journal of Nursing. 2003 June; 103(6): 83-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802162&dopt=Abstract

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Postmenopausal hormone replacement therapy. Author(s): Grodstein F, Manson JE, Stampfer MJ. Source: Annals of Internal Medicine. 2003 April 15; 138(8): 688; Author Reply 688-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693903&dopt=Abstract

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Postmenopausal hormone replacement therapy. Author(s): Meyerson SJ. Source: Annals of Internal Medicine. 2003 April 15; 138(8): 687; Author Reply 688-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693902&dopt=Abstract

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Postmenopausal hormone replacement therapy. Author(s): Chausmer AB. Source: Annals of Internal Medicine. 2003 April 15; 138(8): 687-8; Author Reply 688-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693901&dopt=Abstract

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Prevalence of sexual dysfunction in a cohort of middle-aged women: influences of menopause and hormone replacement therapy. Author(s): Castelo-Branco C, Blumel JE, Araya H, Riquelme R, Castro G, Haya J, Gramegna G. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 July; 23(4): 426-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881088&dopt=Abstract

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Progesterone effects during sequential hormone replacement therapy. Author(s): Andreen L, Bixo M, Nyberg S, Sundstrom-Poromaa I, Backstrom T. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 May; 148(5): 571-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720542&dopt=Abstract

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Prospective association between hormone replacement therapy, heart rate, and heart rate variability. The Atherosclerosis risk in communities study. Author(s): Carnethon MR, Anthony MS, Cascio WE, Folsom AR, Rautaharju PM, Liao D, Evans GW, Heiss G. Source: Journal of Clinical Epidemiology. 2003 June; 56(6): 565-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873652&dopt=Abstract

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Quality of life and costs associated with micronized progesterone and medroxyprogesterone acetate in hormone replacement therapy for nonhysterectomized, postmenopausal women. Author(s): Ryan N, Rosner A. Source: Clinical Therapeutics. 2001 July; 23(7): 1099-115. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11519773&dopt=Abstract

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Quantification of ovarian stromal Doppler signals in postmenopausal women receiving hormone replacement therapy. Author(s): Pan HA, Li CH, Cheng YC, Wu MH, Chang FM. Source: Menopause (New York, N.Y.). 2003 July-August; 10(4): 366-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851521&dopt=Abstract

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Questions and answers about hormone replacement therapy. Author(s): Acta Obstet Gynecol Scand. 2003 Jul;82(7):335-44 Source: Geriatric Nursing (New York, N.Y.). 2003 March-April; 24(2): 126-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12790856

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Randomized clinical trials of hormone replacement therapy for treatment or prevention of cardiovascular disease: a review of the findings. Author(s): Herrington DM, Klein KP. Source: Atherosclerosis. 2003 February; 166(2): 203-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535732&dopt=Abstract

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Recurrent episodes of skin angioedema and severe attacks of abdominal pain induced by oral contraceptives or hormone replacement therapy. Author(s): Bork K, Fischer B, Dewald G. Source: The American Journal of Medicine. 2003 March; 114(4): 294-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681457&dopt=Abstract

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Regular exercise, hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women. Author(s): Moreau KL, Donato AJ, Seals DR, DeSouza CA, Tanaka H. Source: Cardiovascular Research. 2003 March; 57(3): 861-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618248&dopt=Abstract

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Relation between hormone replacement therapy and ischaemic heart disease in women: prospective observational study. Author(s): Lokkegaard E, Pedersen AT, Heitmann BL, Jovanovic Z, Keiding N, Hundrup YA, Obel EB, Ottesen B. Source: Bmj (Clinical Research Ed.). 2003 February 22; 326(7386): 426. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595383&dopt=Abstract

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Relation of androgen receptor gene polymorphism to bone mineral density and fracture risk in early postmenopausal women during a 5-year randomized hormone replacement therapy trial. Author(s): Salmen T, Heikkinen AM, Mahonen A, Kroger H, Komulainen M, Pallonen H, Saarikoski S, Honkanen R, Maenpaa PH. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2003 February; 18(2): 319-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568409&dopt=Abstract

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Relation of aromatase gene polymorphism and hormone replacement therapy to serum estradiol levels, bone mineral density, and fracture risk in early postmenopausal women. Author(s): Salmen T, Heikkinen AM, Mahonen A, Kroger H, Komulainen M, Pallonen H, Saarikoski S, Honkanen R, Maenpaa PH. Source: Annals of Medicine. 2003; 35(4): 282-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846271&dopt=Abstract

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Relationship between hormone replacement therapy, socioeconomic status, and coronary heart disease. Author(s): Grodstein F, Manson JE. Source: Jama : the Journal of the American Medical Association. 2003 January 1; 289(1): 44-5; Author Reply 45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503971&dopt=Abstract

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Reviews of hormone replacement therapy evidence support findings in recently halted trial. Author(s): Levenson D. Source: Rep Med Guidel Outcomes Res. 2002 September 6; 13(17): 7-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572547&dopt=Abstract

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Risks and benefits of hormone replacement therapy: the evidence speaks. Author(s): Humphries KH, Gill S. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 April 15; 168(8): 1001-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695385&dopt=Abstract

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Risks and benefits of long-term hormone replacement therapy. Author(s): Biscup P. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 July 15; 60(14): 1419-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892026&dopt=Abstract

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Safety of hormone replacement therapy after mastectomy. Author(s): Hitchins RN. Source: The Medical Journal of Australia. 2002 June 17; 176(12): 617; Author Reply 61820. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064965&dopt=Abstract

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Safety of hormone replacement therapy after mastectomy. Author(s): Del Mar CB, Glasziou PP, Spinks AB, Sanders SL, Hilton DJ. Source: The Medical Journal of Australia. 2002 March 18; 176(6): 285. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999265&dopt=Abstract

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Selective modulation of postmenopausal women: cutting the Gordian knot of hormone replacement therapy with breast carcinoma. Author(s): Diamanti-Kandarakis E, Sykiotis GP, Papavassiliou AG. Source: Cancer. 2003 January 1; 97(1): 12-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12491500&dopt=Abstract

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Serum leptin levels of menopausal women before and after hormone replacement therapy. Author(s): Li WL, Guo XY, Zhang JY, Peng P, Zhang YL. Source: Di Yi June Yi Da Xue Xue Bao. 2002 July; 22(7): 635-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376297&dopt=Abstract

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Sexual dysfunction in middle-aged couples: an andrological approach in relation to hormone replacement therapy of the partners. Author(s): Di Bisceglie C, Tagliabue M, Vaccari P, Giangrande R, Brocato L, Manieri C. Source: J Endocrinol Invest. 2002; 25(10 Suppl): 91-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508933&dopt=Abstract

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Significant increase of benign endometrial cells on Papanicolaou smears in women using hormone replacement therapy. Author(s): Mount SL, Wegner EK, Eltabbakh GH, Olmstead JI, Drejet AE. Source: Obstetrics and Gynecology. 2002 September; 100(3): 445-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220762&dopt=Abstract

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Smoking, estradiol metabolism and hormone replacement therapy. Author(s): Mueck AO, Seeger H. Source: Arzneimittel-Forschung. 2003; 53(1): 1-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608008&dopt=Abstract

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Soy protein has a greater effect on bone in postmenopausal women not on hormone replacement therapy, as evidenced by reducing bone resorption and urinary calcium excretion. Author(s): Arjmandi BH, Khalil DA, Smith BJ, Lucas EA, Juma S, Payton ME, Wild RA. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 March; 88(3): 104854. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629084&dopt=Abstract

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Study outlines further risks associated with hormone replacement therapy. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2003 September 5; 14(17): 1-2, 5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677336&dopt=Abstract

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Successful pregnancies after combined pentoxifylline-tocopherol treatment in women with premature ovarian failure who are resistant to hormone replacement therapy. Author(s): Letur-Konirsch H, Delanian S. Source: Fertility and Sterility. 2003 February; 79(2): 439-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568863&dopt=Abstract

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Taking hormone replacement therapy. Author(s): Griffiths F. Source: Bmj (Clinical Research Ed.). 2003 October 11; 327(7419): 820-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14551063&dopt=Abstract

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Tear function tests and conjunctival impression cytology before and after hormone replacement therapy in postmenopausal women. Author(s): Pelit A, Bagis T, Kayaselcuk F, Dursun D, Akova Y, Aydin P. Source: Eur J Ophthalmol. 2003 May; 13(4): 337-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12872789&dopt=Abstract

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The changing view of hormone replacement therapy. Author(s): Vogel RA. Source: Reviews in Cardiovascular Medicine. 2003 Spring; 4(2): 68-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776015&dopt=Abstract

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The demise of HRT? The long-term safety of hormone replacement therapy. Author(s): Fenton A. Source: Expert Opinion on Drug Safety. 2003 July; 2(4): 341-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904091&dopt=Abstract

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The effect of decision aids on the agreement between women's and physicians' decisional conflict about hormone replacement therapy. Author(s): Legare F, O'Connor AM, Graham ID, Wells GA, Jacobsen MJ, Elmslie T, Drake ER. Source: Patient Education and Counseling. 2003 June; 50(2): 211-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781936&dopt=Abstract

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The effect of various regimens of hormone replacement therapy on mammographic breast density. Author(s): Christodoulakos GE, Lambrinoudaki IV, Panoulis KP, Vourtsi AD, Vlachos L, Georgiou E, Creatsas GC. Source: Maturitas. 2003 June 30; 45(2): 109-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787969&dopt=Abstract

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The menopause and HRT. Hormone replacement therapy, cardiovascular and cerebrovascular disease. Author(s): Teede HJ. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2003 March; 17(1): 73-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763513&dopt=Abstract

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The short-term effects of different regimens of hormone replacement therapy on left ventricular structure and performance in healthy postmenopausal women. A prospective, controlled echocardiographic study. Author(s): Fenkci V, Yilmazer M, Alpaslan M, Onrat E, Fenkci S. Source: Gynecologic and Obstetric Investigation. 2003; 55(3): 139-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865592&dopt=Abstract

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Trace elements and vitamin levels in menopausal women receiving hormone replacement therapy. Author(s): Meram I, Balat O, Tamer L, Ugur MG. Source: Clin Exp Obstet Gynecol. 2003; 30(1): 32-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12731741&dopt=Abstract

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Two studies find lack of benefit from hormone replacement therapy. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2003 June 13; 14(11): 1-2, 5-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877113&dopt=Abstract

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Understanding attitudes of older women toward hormone replacement therapy. Author(s): Phelan EA, Buist DS, Anderson LA, Newton KM, Delaney KM, LaCroix AZ. Source: Preventive Medicine. 2001 January; 32(1): 49-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11162326&dopt=Abstract

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Understanding risk: women's perceived risk of menopause-related disease and the value they place on preventive hormone replacement therapy. Author(s): Ballard K. Source: Family Practice. 2002 December; 19(6): 591-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429660&dopt=Abstract

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Unscheduled bleeding during initiation of continuous combined hormone replacement therapy: a direct comparison of two combinations of norethindrone acetate and ethinyl estradiol to medroxyprogesterone acetate and conjugated equine estrogens. Author(s): Simon JA, Symons JP; femhrt Study Investigators. Source: Menopause (New York, N.Y.). 2001 September-October; 8(5): 321-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528357&dopt=Abstract

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Update: the latest on hormone replacement therapy. Author(s): Packin GS. Source: J Am Osteopath Assoc. 2000 October; 100(10 Su Pt 1): S2-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11105456&dopt=Abstract

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Use of combination hormone replacement therapy in light of recent data from the Women's Health Initiative. Author(s): Kaunitz AM; Women's Health Initiative. Source: Medscape Women's Health [electronic Resource]. 2002 July-August; 7(4): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466740&dopt=Abstract

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Use of hormone replacement therapy among Chilean women: a comparison between socioeconomic levels. Author(s): Blumel JE, Castelo-Branco C, Riquelme R, Araya H, Jaramillo P, Tacla X, Colodron M, Lavin P. Source: Menopause (New York, N.Y.). 2002 September-October; 9(5): 377-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218727&dopt=Abstract

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Use of hormone replacement therapy among Danish nurses at increased risk of osteoporosis. Author(s): Hundrup YA, Thoning H, Rasmussen NK, Obel EB, Philip J. Source: International Journal of Behavioral Medicine. 2003; 10(3): 269-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14525721&dopt=Abstract

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Use of hormone replacement therapy by menopausal women in six family-practice teaching clinics in Israel. Author(s): Vinker S, Kaplan B, Yaphe J, Cohen O, Shumla V, Shapira G, Shofty I, Kitai E. Source: Climacteric : the Journal of the International Menopause Society. 2003 March; 6(1): 75-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725667&dopt=Abstract

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Use of hormone replacement therapy: women's representations of menopause and beauty care practices. Author(s): Fauconnier A, Ringa V, Delanoe D, Falissard B, Breart G. Source: Maturitas. 2000 June 30; 35(3): 215-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10936738&dopt=Abstract

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Use of multiple providers for regular care and women's receipt of hormone replacement therapy counseling. Author(s): Gallagher TC, Geling O, Comite F. Source: Medical Care. 2001 October; 39(10): 1086-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11567171&dopt=Abstract

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Vaginal bleeding patterns in women receiving hormone replacement therapy. Impact of various progestogen regimens. Author(s): Thorneycroft IH, Gibbons WE. Source: J Reprod Med. 1999 February; 44(2 Suppl): 209-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11392034&dopt=Abstract

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Vaginal micronized progesterone in continuous hormone replacement therapy. A prospective randomized study. Author(s): Ferrero S, Gerbaldo D, Fulcheri E, Cristoforoni P. Source: Minerva Ginecol. 2002 December; 54(6): 519-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432337&dopt=Abstract

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Vaginal ring delivery of hormone replacement therapy--a review. Author(s): Dezarnaulds G, Fraser IS. Source: Expert Opinion on Pharmacotherapy. 2003 February; 4(2): 201-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562310&dopt=Abstract

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Vaginal rings delivering progesterone and estradiol may be a new method of hormone replacement therapy. Author(s): Maruo T, Mishell DR, Ben-Chetrit A, Hochner-Celnikier D, Hamada AL, Nash HA. Source: Fertility and Sterility. 2002 November; 78(5): 1010-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413986&dopt=Abstract

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Variation in the efficacy of hormone replacement therapy in the prevention of hip fracture. Swedish Hip Fracture Study Group. Author(s): Michaelsson K, Baron JA, Johnell O, Persson I, Ljunghall S. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1998; 8(6): 540-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10326058&dopt=Abstract

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Vascular function of forearm microcirculation in postmenopausal women with type 2 diabetes: potential benefit of hormone replacement therapy? Author(s): Ching HL, Watts GF, Dhaliwal SS, Barrett PH, Stuckey BG. Source: Climacteric : the Journal of the International Menopause Society. 2003 March; 6(1): 31-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725662&dopt=Abstract

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Vasomotor and vascular effects of hormone replacement therapy. Author(s): Ganz P. Source: The American Journal of Cardiology. 2002 July 3; 90(1A): 11F-16F. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106634&dopt=Abstract

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Vertebral bone mineral density, content and area in 8789 normal women aged 33-73 years who have never had hormone replacement therapy. Author(s): Shipman AJ, Guy GW, Smith I, Ostlere S, Greer W, Smith R. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1999; 9(5): 420-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10550461&dopt=Abstract

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Vertebral morphometry: repeat scan precision using the Lunar Expert-XL and the Hologic 4500A. A study for the 'WISDOM' RCT of hormone replacement therapy. Author(s): Crabtree N, Wright J, Walgrove A, Rea J, Hanratty L, Lunt M, Fogelman I, Palmer R, Vickers M, Compston JE, Reev J. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2000; 11(6): 537-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10982171&dopt=Abstract

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Visual function in menopause: the role of hormone replacement therapy. Author(s): Guaschino S, Grimaldi E, Sartore A, Mugittu R, Mangino F, Bortoli P, Pensiero S, Vinciguerra A, Perissutti P. Source: Menopause (New York, N.Y.). 2003 January-February; 10(1): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544677&dopt=Abstract

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What are the key issues women face when ending hormone replacement therapy? Author(s): Utian WH. Source: Cleve Clin J Med. 2003 February; 70(2): 93-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636339&dopt=Abstract

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What factors are associated with a woman's decision to take hormone replacement therapy? Evaluated in the context of a decision aid. Author(s): Clark HD, O'Connor AM, Graham ID, Wells GA. Source: Health Expectations : an International Journal of Public Participation in Health Care and Health Policy. 2003 June; 6(2): 110-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752739&dopt=Abstract

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What is the available evidence for hormone replacement therapy in women with stress urinary incontinence? Author(s): Al-Badr A, Ross S, Soroka D, Drutz HP. Source: J Obstet Gynaecol Can. 2003 July; 25(7): 567-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851668&dopt=Abstract

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What is the cardioprotective role of hormone replacement therapy? Author(s): Hodis HN, Mack WJ, Lobo R. Source: Current Atherosclerosis Reports. 2003 January; 5(1): 56-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562544&dopt=Abstract

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What is this thing called hormone replacement therapy? Discursive construction of medication in situated practice. Author(s): Stephens C, Budge RC, Carryer J. Source: Qualitative Health Research. 2002 March; 12(3): 347-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918100&dopt=Abstract

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What your doctor is reading. Hormone replacement therapy. Author(s): Roberts SS. Source: Diabetes Self Manag. 2002 November-December; 19(6): 78-81. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12561772&dopt=Abstract

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WHI findings another blow to hormone replacement therapy. Author(s): Traynor K. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 July 15; 60(14): 1409-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892024&dopt=Abstract

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Women & diabetes. Menopause. The latest on hormone replacement therapy. Author(s): Ross HL. Source: Diabetes Self Manag. 2002 July-August; 19(4): 90, 92, 95-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533854&dopt=Abstract

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CHAPTER 2. NUTRITION AND HORMONE REPLACEMENT THERAPY Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and hormone replacement therapy.

Finding Nutrition Studies on Hormone Replacement Therapy The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “hormone replacement therapy” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “hormone replacement therapy” (or a synonym): •

A cohort study of hormone replacement therapy given to women previously treated for breast cancer. Author(s): Women's Health Institute, Royal Hospital for Women, Barker Street, Randwick, NSW 2031, Australia. Source: Dew, J Eden, J Beller, E Magarey, C Schwartz, P Crea, P Wren, B Climacteric. 1998 June; 1(2): 137-42 1369-7137

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A comparison of tibolone and hormone replacement therapy on coronary artery and myocardial function in ovariectomized atherosclerotic monkeys. Author(s): The Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040, USA. [email protected] Source: Williams, J Koudy Hall, Jason Anthony, Mary S Register, Thomas C Reis, Steven E Clarkson, Thomas B Menopause. 2002 Jan-February; 9(1): 41-51 1072-3714

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A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT atherosclerosis study. Author(s): Papworth Hospital, Cambridge, UK. Source: Clarke, S C Kelleher, J Lloyd Jones, H Slack, M Schofiel, P M BJOG. 2002 September; 109(9): 1056-62 1470-0328

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Allopathic and complementary alternatives to hormone replacement therapy. Author(s): Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. Source: Eichholz, A C Mahavni, V Sood, A K Expert-Opin-Pharmacother. 2002 July; 3(7): 949-55 1465-6566

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Amenorrhea frequency with continuous combined hormone replacement therapy: a retrospective analysis. Menopause Study Group. Author(s): Wyeth-Ayerst Research, PO Box 8299, Philadelphia, PA 19101, USA. Source: Pickar, J H Bottiglioni, F Archer, D F Climacteric. 1998 June; 1(2): 130-6 1369-7137

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Bioidentical hormone replacement therapy. A natural option for perimenopause and beyond. Source: Walker, C R Adv-Nurse-Pract. 2001 May; 9(5): 39-42, 45 1096-6293

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Changes in coagulation factors and fibrinolytic components of postmenopausal women receiving continuous hormone replacement therapy. Author(s): Department of Gynecology and Obstetrics, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. Source: Nozaki, M Ogata, R Koera, K Hashimoto, K Nakano, H Climacteric. 1999 June; 2(2): 124-30 1369-7137

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Circadian rhythm of melatonin in postmenopausal asthmatic women with hormone replacement therapy. Author(s): Department of Pathophysiology and Endocrinology, Silesian Medical University, Zabrze, Poland. [email protected] Source: Kos Kudla, B Ostrowska, Z Marek, B Kajdaniuk, D Ciesielska Kopacz, N Kudla, M Mazur, B Glogowska Szelag, J Nasiek, M Neuroendocrinol-Lett. 2002 June; 23(3): 2438 0172-780X

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Comparison of different treatment modalities for postmenopausal patients with osteopenia: hormone replacement therapy, calcitonin and clodronate. Author(s): Department of Obstetrics and Gynecology, Gazi University School of Medicine, Besevler, Ankara, Turkey. Source: Tiras, M B Noyan, V Yildiz, A Biberoglu, K Climacteric. 2000 June; 3(2): 92-101 1369-7137

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Comparison of the efficacy and endometrial safety of two estradiol valerate/dienogest combinations and Kliogest for continuous combined hormone replacement therapy in postmenopausal women. Author(s): Clinical Research Department, Jenapharm GmbH & Co. KG, Otto-Schott-S. 15, D-07745 Jena, Germany. Source: Graser, T Koytchev, R Muller, A Oettel, M Climacteric. 2000 June; 3(2): 109-18 1369-7137

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Controversial issues in climacteric medicine I. Cardiovascular disease and hormone replacement therapy. International Menopause Society Expert Workshop. 13-16 October 2000, royal society of medicine, London, UK. Author(s): Department of Gynecology and Obstetrics, University of Pisa, Via Roma 35, 56126 Pisa, Italy. Source: Genazzani, A R Gambacciani, M Climacteric. 2000 December; 3(4): 233-40 13697137

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Differential effects of raloxifene and continuous combined hormone replacement therapy on biochemical markers of cardiovascular risk: results from the Euralox 1 study. Author(s): Eli Lilly and Company, Bad Homburg, Germany. Source: Nickelsen, T Creatsas, G Rechberger, T Depypere, H Erenus, M Quail, D Arndt, T Bonnar, J Climacteric. 2001 December; 4(4): 320-31 1369-7137

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Effect of hormone replacement therapy on self-reported cognitive symptoms: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. Author(s): Wake Forest University School of Medicine, Department of Public Health Sciences, Winston-Salem, NC 27157, USA. Source: Reboussin, B A Greendale, G A Espeland, M A Climacteric. 1998 September; 1(3): 172-9 1369-7137

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Effects of hormone replacement therapy on olfactory sensitivity: cross-sectional and longitudinal studies. Author(s): Center for Alzheimer Disease and Related Disorders, Department of Surgery, Division of Otolaryngology, Neurology, Southern Illinois University School of Medicine, PO Box 19643, Springfield, Illinois 62794-9643, USA. Source: Hughes, L F McAsey, M E Donathan, C L Smith, T Coney, P Struble, R G Climacteric. 2002 June; 5(2): 140-50 1369-7137

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Effects of tibolone and continuous combined hormone replacement therapy on bleeding rates, quality of life and tolerability in postmenopausal women. Author(s): Menox Institute, Vienna, Austria. Source: Huber, J Palacios, S Berglund, L Hanggi, W Sathanandan, S M Christau, S Helmond, F BJOG. 2002 August; 109(8): 886-93 1470-0328

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Electrocardiogram pattern in hypercholesterolemic women: the influence of hormone replacement therapy. Author(s): Department of Obstetrics and Gynecology, Lund University Hospital, Lund, Sweden.

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Source: Akerblom, M Li, C Samsioe, G Climacteric. 1998 December; 1(4): 258-63 13697137 •

Factors associated with endometrial bleeding in continuous hormone replacement therapy. Author(s): Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. Source: Shau, Wen Yi Hsieh, Ching Chang Hsieh, T'sang T'ang Hung, Tai Ho Huang, Kuo En Menopause. 2002 May-June; 9(3): 188-94 1072-3714

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Gynecologists' trends and attitudes toward prescribing hormone replacement therapy during menopause. Author(s): Department of Obstetrics and Gynecology, Rabin Medical Center, Petah Tikva, Israel. [email protected] Source: Kaplan, B Aschkenazi Steinberg, S Yogev, Y Nahum, R Sulkes, J Phisher, M Menopause. 2002 Sep-October; 9(5): 354-9 1072-3714

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Hormone replacement therapy (HRT) and ischaemic heart disease: getting to the heart of the matter. Author(s): Department of Obstetrics & Gynaecology, National University Hospital, Singapore. [email protected] Source: Chew, S Ng, S C Singapore-Med-J. 2002 January; 43(1): 041-4 0037-5675

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Hyperhomocysteinaemia and cardiovascular risk in female ovariectomized rats: role of folic acid and hormone replacement therapy. Author(s): Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Egypt. [email protected] Source: el Swefy, Sahar E Ali, Sousou I Asker, Mervat E Mohamed, Hoda E J-PharmPharmacol. 2002 March; 54(3): 391-7 0022-3573

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Intrauterine application of progestins in hormone replacement therapy: a review. Source: Riphagen, F E Climacteric. 2000 September; 3(3): 199-211 1369-7137

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Lifestyle factors and choice of hormone replacement therapy among Danish nurses. Author(s): National Institute of Public Health, Copenhagen, Denmark. [email protected] Source: Hundrup, Yrsa A Thoning, Henrik Obel, Erik B Rasmussen, Niels K Philip, John Scand-J-Public-Health. 2002; 30(1): 47-53 1403-4948

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Low-dose hormone replacement therapy: effects on bone. Author(s): Department of Obstetrics and Gynecology Piero Fioretti, University of Pisa, Via Roma 67, 56100 Pisa, Italy. Source: Gambacciani, M Monteleone, P Genazzani, A R Climacteric. 2002 June; 5(2): 1359 1369-7137

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Medical issues and hormone replacement therapy. Author(s): Washington Hospital Center, Geriatrics and Long Term Care, Room 2B-39, 110 Irving Street, NW, Washington, DC 20010, USA. [email protected] Source: Harris, P F Curr-Womens-Health-Repage 2002 October; 2(5): 373-81 1534-5874

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Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Source: Wells, G Tugwell, P Shea, B Guyatt, G Peterson, J Zytaruk, N Robinson, V Henry, D O'Connell, D Cranney, A Endocr-Revolume 2002 August; 23(4): 529-39 0163769X

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Monofluorophosphate combined with hormone replacement therapy in postmenopausal osteoporosis. An open-label pilot efficacy and safety study. Author(s): Department of Internal Med. IV, Klinikum Leverkusen, Teaching Hospital of the University of Cologne, Germany. [email protected] Source: Ringe, J D Setnikar, I Rheumatol-Int. 2002 May; 22(1): 27-32 0172-8172

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Outcomes of growth hormone replacement therapy in survivors of childhood acute lymphoblastic leukemia. Author(s): After Completion of Therapy Program and the Department of HematologyOncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA. [email protected] Source: Leung, Wing Rose, Susan R Zhou, Yinmei Hancock, Michael L Burstein, Stephen Schriock, Elizabeth A Lustig, Robert Danish, Robert K Evans, William E Hudson, Melissa M Pui, Ching Hon J-Clin-Oncol. 2002 July 1; 20(13): 2959-64 0732-183X

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Prevalence of and satisfaction with complementary therapies and hormone replacement therapy in a specialist menopause clinic. Author(s): Chelsea and Westminster Hospital, London, UK. Source: Vashisht, A Domoney, C L Cronje, W Studd, J W Climacteric. 2001 September; 4(3): 250-6 1369-7137

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Serum leptin levels of menopausal women before and after hormone replacement therapy. Author(s): Department of Gynecology and Obstetrics, General Hospital of Guangzhou Command, Guangzhou 510010, China. Source: Li, W L Guo, X Y Zhang, J Y Peng, P Zhang, Y L Di-Yi-Jun-Yi-Da-Xue-Xue-Bao. 2002 July; 22(7): 635-6 1000-2588

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Sex hormone replacement therapy reverses altered venous contractility in rats after pharmacological ovariectomy. Author(s): Second Department of Obstetrics and Gynecology, Semmelweis University, Faculty of Medicine, Budapest, Hungary. Source: Varbiro, Szabolcs Vajo, Zoltan Nadasy, Gyorgy L Monos, Emil Acs, Nandor Lorant, Miklos Felicetta, James V Sze, Bela Menopause. 2002 Mar-April; 9(2): 122-6 10723714

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Tamoxifen, hormone receptors and hormone replacement therapy in women previously treated for breast cancer: a cohort study. Author(s): School of Women's and Children's Health, University of New South Wales, Royal Hospital for Women, Randwick, Australia. Source: Dew, J E Wren, B G Eden, J A Climacteric. 2002 June; 5(2): 151-5 1369-7137

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The association of hormone replacement therapy and coronary calcium as determined by electron beam tomography. Author(s): Departments of Imaging (Division of Nuclear Medicine), Burns & Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Source: Schisterman, E F Gallagher, A M Bairey Merz, C N Whitcomb, B W Faraggi, D Moysich, K B Lewin, H J-Womens-Health-Gend-Based-Med. 2002 September; 11(7): 6318 1524-6094

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The effect of hormone replacement therapy on appendicular lean tissue mass in early postmenopausal women. Author(s): Center for Clinical and Basic Research, Ballerup, Denmark. [email protected] Source: Tanko, Laszlo B Movsesyan, Lusine Svendsen, Ole L Christiansen, Claus Menopause. 2002 Mar-April; 9(2): 117-21 1072-3714

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The effects of growth hormone replacement therapy on bone metabolism in adultonset growth hormone deficiency: a 2-year open randomized controlled multicenter trial. Author(s): Department of Endocrinology, University Hospital Gasthuisberg, Leuven, Belgium. Source: Bex, M Abs, R Maiter, D Beckers, A Lamberigts, G Bouillon, R J-Bone-Miner-Res. 2002 June; 17(6): 1081-94 0884-0431

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Which is the appropriate hormone replacement therapy after sub-total hysterectomy? Author(s): Department of Obstetrics and Gynaecology, Farnborough Hospital, Kent, UK. Source: Imoh Ita, F Morgan, P Rymer, J Climacteric. 2000 March; 3(1): 65-7 1369-7137

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMD®Health: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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The following is a specific Web list relating to hormone replacement therapy; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Vitamin D Source: Healthnotes, Inc.; www.healthnotes.com Vitamin D Alternative names: Calciferol Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Alternative names: Alpha-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com

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Minerals Alpha-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Beta-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: Integrative Medicine Communications; www.drkoop.com D-alpha-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Delta-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Gamma-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com

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Magnesium Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Integrative Medicine Communications; www.drkoop.com •

Food and Diet High Cholesterol Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND HORMONE REPLACEMENT THERAPY Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to hormone replacement therapy. At the conclusion of this chapter, we will provide additional sources.

The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “hormone replacement therapy” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •

Informed Choices: Your Most Valuable Role in Menopause Care is Education Source: Advance for Nurse Practitioners. 10(1): 65-68. January 2002. Summary: This article provides information for nurse practitioners on menopause and how to treat its symptoms. It lists recommendations from the North American Menopause Society about how to help women achieve optimum health through the menopause transition, and discusses the pharmacologic treatment of menopause and post menopause. Alternative treatments for women who are reluctant or unable to take hormone replacement therapy are also covered. The article includes tables of the most common menopausal symptoms and the most commonly used hormone replacement therapies. 11 references.

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Alternative Therapies for Managing Menopausal Symptoms Source: Gaithersburg, MD: National Center for Complementary and Alternative Medicine. 2002. 3 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL: [email protected]. PRICE: Free. Publication Number: D169. Summary: This consumer advisory alerts consumers about recent research demonstrating that long-term use of estrogen in combination with progestin results in more risks than benefits. It discusses the use of alternative therapies for managing menopausal symptoms, provides information on the current scientific evidence of the effectiveness and safety of these therapies, and offers advice to consumers about using hormone replacement therapy and alternative therapies for menopausal symptoms. The advisory also provides a list of sources for further information.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to hormone replacement therapy and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “hormone replacement therapy” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to hormone replacement therapy: •

“Natural” hormone replacement therapy and dietary supplements used in the treatment of menopausal symptoms. Author(s): Taffe AM, Cauffield J. Source: Lippincott's Primary Care Practice. 1998 May-June; 2(3): 292-302. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9644444&dopt=Abstract

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A novel concept to preserve the beneficial effects of hormone replacement therapy in bilaterally female ovariectomized rats: role of lovastatin therapy. Author(s): El-Swefy SE, Asker ME, Ali SI, Mohammed HE. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 2002 March; 45(3): 167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11884211&dopt=Abstract

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A nurse's guide to hormone replacement therapy. Author(s): Moore AA, Noonan MD. Source: Journal of Obstetric, Gynecologic, and Neonatal Nursing : Jognn / Naacog. 1999; 28(6 Suppl 1): 13-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10608492&dopt=Abstract

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A nurse's guide to hormone replacement therapy. Author(s): Moore AA, Noonan MD. Source: Journal of Obstetric, Gynecologic, and Neonatal Nursing : Jognn / Naacog. 1996 January; 25(1): 24-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8627399&dopt=Abstract

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A pilot study comparing the clinical effects of Jia-Wey Shiau-Yau San, a traditional Chinese herbal prescription, and a continuous combined hormone replacement therapy in postmenopausal women with climacteric symptoms. Author(s): Chen LC, Tsao YT, Yen KY, Chen YF, Chou MH, Lin MF. Source: Maturitas. 2003 January 30; 44(1): 55-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568736&dopt=Abstract

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A practical guide to prescribing hormone replacement therapy. Author(s): McKinney KA, Thompson W. Source: Drugs. 1998 July; 56(1): 49-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9664198&dopt=Abstract

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Additive effect of alfacalcidol on bone mineral density of the lumbar spine in Taiwanese postmenopausal women treated with hormone replacement therapy and calcium supplementation: a randomized 2-year study. Author(s): Chen M, Chow SN. Source: Clinical Endocrinology. 2001 August; 55(2): 253-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11531934&dopt=Abstract

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Allopathic and complementary alternatives to hormone replacement therapy. Author(s): Eichholz AC, Mahavni V, Sood AK. Source: Expert Opinion on Pharmacotherapy. 2002 July; 3(7): 949-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083994&dopt=Abstract

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Alternatives to conventional hormone replacement therapy. Author(s): Taylor M. Source: Compr Ther. 1997 August; 23(8): 514-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9283741&dopt=Abstract

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Alternatives to hormone replacement therapy. Do they measure up to estrogen? Author(s): Cornell S. Source: Adv Nurse Pract. 1997 July; 5(7): 45-6, 49, 72. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9459944&dopt=Abstract

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Ascorbic acid status in postmenopausal women with hormone replacement therapy. Author(s): Kuo SM, Stout A, Wactawski-Wende J, Leppert PC.

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Source: Maturitas. 2002 January 30; 41(1): 45-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11809342&dopt=Abstract •

Bioidentical hormone replacement therapy. A natural option for perimenopause and beyond. Author(s): Walker CR. Source: Adv Nurse Pract. 2001 May; 9(5): 39-42, 45. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400258&dopt=Abstract

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Bioidentical hormone replacement therapy. Customizing care for perimenopausal and menopausal women. Author(s): Romero M. Source: Adv Nurse Pract. 2002 November; 10(11): 47-8, 51-2. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478948&dopt=Abstract

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Bone effects of transdermal hormone replacement therapy in postmenopausal women as evaluated by means of ultrasound: an open one-year prospective study. Author(s): de Aloysio D, Rovati LC, Cadossi R, Paltrinieri F, Mauloni M, Mura M, Penacchioni P, Ventura V. Source: Maturitas. 1997 May; 27(1): 61-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9158079&dopt=Abstract

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By the way, Doctor. I've seen advertisements for red clover as a treatment for menopausal symptoms. Is it an effective alternative to hormone replacement therapy (HRT)? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2001 December; 9(5): 7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751101&dopt=Abstract

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Calcium supplementation with and without hormone replacement therapy to prevent postmenopausal bone loss. Author(s): Aloia JF, Vaswani A, Yeh JK, Ross PL, Flaster E, Dilmanian FA. Source: Annals of Internal Medicine. 1994 January 15; 120(2): 97-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8256988&dopt=Abstract

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Carcinoma of the breast and hormone replacement therapy for osteoporosis. Author(s): Crawshaw A. Source: Int J Clin Pract. 2000 March; 54(2): 99-103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10824364&dopt=Abstract

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Comparison of hormonal activity (estrogen, androgen and progestin) of standardized plant extracts for large scale use in hormone replacement therapy. Author(s): Beck V, Unterrieder E, Krenn L, Kubelka W, Jungbauer A. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 February; 84(23): 259-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711012&dopt=Abstract

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Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause. Author(s): Woo J, Lau E, Ho SC, Cheng F, Chan C, Chan AS, Haines CJ, Chan TY, Li M, Sham A. Source: Menopause (New York, N.Y.). 2003 July-August; 10(4): 352-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851519&dopt=Abstract

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Cutting through the hype. Hormone replacement therapy with DHEA. Author(s): Ricchini W. Source: Adv Nurse Pract. 1998 November; 6(11): 73-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9919066&dopt=Abstract

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Disputes definition of 'hormone replacement therapy'. Author(s): Wright JV. Source: Alternative Therapies in Health and Medicine. 1996 July; 2(4): 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8795910&dopt=Abstract

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Effect of a fish-oil concentrate on serum lipids in postmenopausal women receiving and not receiving hormone replacement therapy in a placebo-controlled, doubleblind trial. Author(s): Stark KD, Park EJ, Maines VA, Holub BJ. Source: The American Journal of Clinical Nutrition. 2000 August; 72(2): 389-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10919932&dopt=Abstract

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Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. Author(s): Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers WJ, Ouyang P, Thompson P, Tardif JC, Higginson L, Bittner V, Steffes M, Gordon DJ, Proschan M, Younes N, Verter JI. Source: Jama : the Journal of the American Medical Association. 2002 November 20; 288(19): 2432-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435256&dopt=Abstract

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Effects of hormone replacement therapy on sexual psychophysiology and behavior in postmenopause. Author(s): Sarrel PM.

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Source: Journal of Women's Health & Gender-Based Medicine. 2000; 9 Suppl 1: S25-32. Review. Erratum In: J Womens Health Gend Based Med 2001 January-February; 10(1): 91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695871&dopt=Abstract •

Estrogenic activity of two standardized red clover extracts (Menoflavon) intended for large scale use in hormone replacement therapy. Author(s): Dornstauder E, Jisa E, Unterrieder I, Krenn L, Kubelka W, Jungbauer A. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2001 July; 78(1): 6775. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11530286&dopt=Abstract

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Evaluation of combining kava extract with hormone replacement therapy in the treatment of postmenopausal anxiety. Author(s): De Leo V, la Marca A, Morgante G, Lanzetta D, Florio P, Petraglia F. Source: Maturitas. 2001 August 25; 39(2): 185-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11514117&dopt=Abstract

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Flaxseed dietary supplement versus hormone replacement therapy in hypercholesterolemic menopausal women. Author(s): Lemay A, Dodin S, Kadri N, Jacques H, Forest JC. Source: Obstetrics and Gynecology. 2002 September; 100(3): 495-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220769&dopt=Abstract

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Genistein appears to prevent early postmenopausal bone loss as effectively as hormone replacement therapy. Author(s): Cotter A, Cashman KD. Source: Nutrition Reviews. 2003 October; 61(10): 346-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14604267&dopt=Abstract

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Gynecologists' trends and attitudes toward prescribing hormone replacement therapy during menopause. Author(s): Kaplan B, Aschkenazi-Steinberg S, Yogev Y, Nahum R, Sulkes J, Phisher M. Source: Menopause (New York, N.Y.). 2002 September-October; 9(5): 354-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218724&dopt=Abstract

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Hormone replacement therapy and coronary artery disease: buried alive? Author(s): Bahl VK, Naik N. Source: Indian Heart J. 2002 January-February; 54(1): 23-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999084&dopt=Abstract

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Hormone replacement therapy in women with a history of breast cancer. Author(s): Ylikorkala O, Metsa-Heikkila M.

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Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2002 December; 16(6): 469-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626034&dopt=Abstract •

Hormone replacement therapy trials: an update. Author(s): Duvernoy CS, Mosca L. Source: Current Atherosclerosis Reports. 2002 March; 4(2): 156-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11822980&dopt=Abstract

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Hormone replacement therapy: all a woman could desire? Author(s): Adams S. Source: J Fam Health Care. 2002; 12(4): 105-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416018&dopt=Abstract

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Hormone replacement therapy: current controversies. Author(s): Davison S, Davis SR. Source: Clinical Endocrinology. 2003 March; 58(3): 249-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608928&dopt=Abstract

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Hormone replacement therapy: I. A pharmacoeconomic appraisal of its therapeutic use in menopausal symptoms and urogenital estrogen deficiency. Author(s): Whittington R, Faulds D. Source: Pharmacoeconomics. 1994 May; 5(5): 419-45. Review. Erratum In: Pharmacoeconomics 1995 September; 8(3): 244. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10147233&dopt=Abstract

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Hormone replacement therapy: separating fact from fallacy. Author(s): Shepherd JE. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 2002 January-February; 42(1): 122-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833505&dopt=Abstract

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Long-term vitamin D3 supplementation may have adverse effects on serum lipids during postmenopausal hormone replacement therapy. Author(s): Heikkinen AM, Tuppurainen MT, Niskanen L, Komulainen M, Penttila I, Saarikoski S. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1997 November; 137(5): 495-502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9405029&dopt=Abstract

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Management of surgically hypogonadal patients unable to take sex hormone replacement therapy. Author(s): Nieman LK.

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Source: Endocrinology and Metabolism Clinics of North America. 2003 June; 32(2): 32536. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800534&dopt=Abstract •

Managing the menopause: phyto-oestrogens or hormone replacement therapy? Author(s): Eden JA. Source: Annals of Medicine. 2001 February; 33(1): 4-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11310938&dopt=Abstract

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Menopause and hormone replacement therapy from holistic and medical perspectives. Author(s): Herrick CA, Douglas V, Carlson JH. Source: Issues in Mental Health Nursing. 1996 March-April; 17(2): 153-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8707535&dopt=Abstract

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Menopause and hormone replacement therapy: an overview. Author(s): Hammond CB. Source: Obstetrics and Gynecology. 1996 February; 87(2 Suppl): 2S-15S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8559549&dopt=Abstract

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Menopause, naturally. Exploring alternatives to traditional hormone replacement therapy. Author(s): Lindsay SH. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 1999 October-November; 3(5): 32-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10827581&dopt=Abstract

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More on oral contraceptives, drug interactions, herbal medicines, and hormone replacement therapy. Author(s): Shader RI, Greenblatt DJ. Source: Journal of Clinical Psychopharmacology. 2000 August; 20(4): 397-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10917398&dopt=Abstract

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Myocardial blood flow and flow reserve in response to short-term cyclical hormone replacement therapy in postmenopausal women. Author(s): Duvernoy CS, Rattenhuber J, Seifert-Klauss V, Bengel F, Meyer C, Schwaiger M. Source: J Gend Specif Med. 2001; 4(3): 21-7, 47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11605352&dopt=Abstract

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Perimenopausal and postmenopausal hormone replacement therapy. Part 1. An update of the literature on benefits and risks. Author(s): Lichtman R.

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Source: Journal of Nurse-Midwifery. 1996 January-February; 41(1): 3-28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8820754&dopt=Abstract •

Perimenopausal and postmenopausal hormone replacement therapy. Part 2. Hormonal regimens and complementary and alternative therapies. Author(s): Lichtman R. Source: Journal of Nurse-Midwifery. 1996 May-June; 41(3): 195-210. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8708803&dopt=Abstract

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Phytoestrogens as hormone replacement therapy: an evidence-based approach. Author(s): Carusi D. Source: Prim. Care Update Ob Gyns. 2000 November 1; 7(6): 253-259. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11077239&dopt=Abstract

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Phytoestrogens for hormone replacement therapy? Author(s): Wuttke W, Jarry H, Westphalen S, Christoffel V, Seidlova-Wuttke D. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 December; 83(1-5): 133-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650710&dopt=Abstract

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Phytoestrogens: endocrine disrupters or replacement for hormone replacement therapy? Author(s): Wuttke W, Jarry H, Becker T, Schultens A, Christoffel V, Gorkow C, SeidlovaWuttke D. Source: Maturitas. 2003 March 14; 44 Suppl 1: S9-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609555&dopt=Abstract

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Postmenopausal hormone replacement therapy for primary prevention of chronic conditions: recommendations and rationale. Author(s): U.S. Preventive Services Task Force. Source: Annals of Internal Medicine. 2002 November 19; 137(10): 834-9. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435221&dopt=Abstract

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Prescribing hormone replacement therapy for menopausal symptoms. Author(s): McNagny SE. Source: Annals of Internal Medicine. 1999 October 19; 131(8): 605-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10523222&dopt=Abstract

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Prevalence of and satisfaction with complementary therapies and hormone replacement therapy in a specialist menopause clinic. Author(s): Vashisht A, Domoney CL, Cronje W, Studd JW.

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Source: Climacteric : the Journal of the International Menopause Society. 2001 September; 4(3): 250-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588949&dopt=Abstract •

Soy phytoestrogens: an adjunct to hormone replacement therapy? Author(s): Birge SJ. Source: Menopause (New York, N.Y.). 2000 July-August; 7(4): 209-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914612&dopt=Abstract

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Soy phytoestrogens: what will be their role in postmenopausal hormone replacement therapy? Author(s): Clarkson TB. Source: Menopause (New York, N.Y.). 2000 March-April; 7(2): 71-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10746888&dopt=Abstract

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Soy protein has a greater effect on bone in postmenopausal women not on hormone replacement therapy, as evidenced by reducing bone resorption and urinary calcium excretion. Author(s): Arjmandi BH, Khalil DA, Smith BJ, Lucas EA, Juma S, Payton ME, Wild RA. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 March; 88(3): 104854. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629084&dopt=Abstract

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Soybean isoflavones as an alternative to traditional hormone replacement therapy: are we there yet? Author(s): Burke GL, Vitolins MZ, Bland D. Source: The Journal of Nutrition. 2000 March; 130(3): 664S-5S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10702606&dopt=Abstract

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Soyfoods and soybean phyto-oestrogens (isoflavones) as possible alternatives to hormone replacement therapy (HRT). Author(s): Messina M. Source: European Journal of Cancer (Oxford, England : 1990). 2000 September; 36 Suppl 4: S71-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11056326&dopt=Abstract

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Supplemental and complementary alternatives to hormone replacement therapy. Author(s): Keller C, Fullerton J, Mobley C. Source: Journal of the American Academy of Nurse Practitioners. 1999 May; 11(5): 18798. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10504933&dopt=Abstract

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The potential of soybean phytoestrogens for postmenopausal hormone replacement therapy. Author(s): Clarkson TB, Anthony MS, Williams JK, Honore EK, Cline JM. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1998 March; 217(3): 365-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9492349&dopt=Abstract

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Therapeutic options: hormone replacement therapy-soy therapy. Author(s): Merritt JC. Source: Journal of the National Medical Association. 2001 July-August; 93(7-8): 288-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11491281&dopt=Abstract

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Treating hot flushes without hormone replacement therapy. Author(s): Seibel MM. Source: The Journal of Family Practice. 2003 April; 52(4): 291-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681090&dopt=Abstract

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Women's beliefs about “natural” hormones and natural hormone replacement therapy. Author(s): Adams C, Cannell S. Source: Menopause (New York, N.Y.). 2001 November-December; 8(6): 433-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723417&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMD®Health: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to hormone replacement therapy; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com Breast Cancer Source: Integrative Medicine Communications; www.drkoop.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Erectile Dysfunction Source: Healthnotes, Inc.; www.healthnotes.com Fibrocystic Breast Disease Source: Healthnotes, Inc.; www.healthnotes.com Heart Attack Source: Healthnotes, Inc.; www.healthnotes.com Heart Attack Source: Integrative Medicine Communications; www.drkoop.com High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com Hirsuitism Source: Integrative Medicine Communications; www.drkoop.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Hypothyroidism Source: Integrative Medicine Communications; www.drkoop.com

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Menopause Source: Healthnotes, Inc.; www.healthnotes.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Myocardial Infarction Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Healthnotes, Inc.; www.healthnotes.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Transient Ischemic Attacks Source: Integrative Medicine Communications; www.drkoop.com Urinary Incontinence Source: Integrative Medicine Communications; www.drkoop.com •

Herbs and Supplements Black Cohosh Alternative names: Cimicifuga racemosa Source: Healthnotes, Inc.; www.healthnotes.com Black Cohosh Alternative names: Cimicifuga racemosa (actea), Black Snakeroot Source: Integrative Medicine Communications; www.drkoop.com Black Cohosh Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10009,00.html Black Snakeroot Source: Integrative Medicine Communications; www.drkoop.com Calciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Calcitrol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Carotenoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,763,00.html

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Cholecalciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Cimicifuga Racemosa (ACTEA) Source: Integrative Medicine Communications; www.drkoop.com Erocalciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Estradiol Source: Healthnotes, Inc.; www.healthnotes.com Estrogens (Combined) Source: Healthnotes, Inc.; www.healthnotes.com Forskolin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10025,00.html Licorice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,801,00.html Natural Progesterone Cream Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10099,00.html Progesterone Source: Healthnotes, Inc.; www.healthnotes.com Red Clover Source: Integrative Medicine Communications; www.drkoop.com Wild Yam Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10070,00.html

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html.

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This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS REPLACEMENT THERAPY

ON

HORMONE

Overview In this chapter, we will give you a bibliography on recent dissertations relating to hormone replacement therapy. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “hormone replacement therapy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hormone replacement therapy, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Hormone Replacement Therapy ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to hormone replacement therapy. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Are Perimenopausal and Postmenopausal Women More Apt to Choose Hormone Replacement Therapy If They Are More Knowledgeable about the Effects of Said Therapy? by Pineda, Cleo C.; MS from California State University, Long Beach, 2002, 58 pages http://wwwlib.umi.com/dissertations/fullcit/1410331

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Coverage of Hormone Replacement Therapy in Popular Periodicals and Professional Journals by Badie, Homa Baher, PhD from Texas Woman's University, 1997, 125 pages http://wwwlib.umi.com/dissertations/fullcit/9804893

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Effect of Web-based Computer-tailoring on Women's Intention to Continue or Begin to Use Hormone Replacement Therapy to Lower Their Risk for Osteoporosis by McGinley, Anne Marie; PhD from University of Pennsylvania, 2002, 166 pages http://wwwlib.umi.com/dissertations/fullcit/3043913

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Effects of Hormone Replacement Therapy on Insulin Resistance in Cynomolgus Monkeys by Shadoan, Melanie Kimbrell; PhD from Wake Forest University, 2002, 134 pages http://wwwlib.umi.com/dissertations/fullcit/3082973

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Effects of N-3 Supplementation in Postmenopausal Women Receiving and Not Receiving Hormone Replacement Therapy by Stark, Kenneth Douglas; PhD from University of Guelph (canada), 2002, 163 pages http://wwwlib.umi.com/dissertations/fullcit/NQ67237

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Enhancing Women's Decision-making Concerning the Use of Hormone Replacement Therapy by Katra, Jane Elizabeth, PhD from University of Oregon, 1993, 211 pages http://wwwlib.umi.com/dissertations/fullcit/9405189

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Exploratory Research of the Factors That Influence a Woman's Decision Regarding Hormone Replacement Therapy by Prue, Christine Ellen, PhD from University of Maryland College Park, 1998, 183 pages http://wwwlib.umi.com/dissertations/fullcit/9836466

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Factors Associated with the Utilization of Hormone Replacement Therapy among Postmenopausal Women: a Case Study of a Suburban Philadelphia Retirement Community (Pennsylvania) by Powers, Barbara L., PhD from Temple University, 1996, 94 pages http://wwwlib.umi.com/dissertations/fullcit/9623796

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Factors That Influence a Woman's Decision to Initiate or Decline the Use of Hormone Replacement Therapy by Arruda, Judy Ann; MS from University of Nevada, Reno, 2002, 47 pages http://wwwlib.umi.com/dissertations/fullcit/1410208

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Hormone Replacement Therapy: Health State Preference Measurement and Markov Model Based Decision-Making Regarding Its Use by Datta, Santanu Kumar; PhD from The University of North Carolina at Chapel Hill, 2002, 141 pages http://wwwlib.umi.com/dissertations/fullcit/3070838

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Menopausal Women Receiving and Not Receiving Hormone Replacement Therapy: Generalized Contentment, Marital Satisfaction, Sexual Satisfaction, Health Locus of Control, and Sex Role Identity Self-reports by St. Hillier, Donna Jones, PhD from The Florida State University, 1989, 178 pages http://wwwlib.umi.com/dissertations/fullcit/8916205

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Physical Activity, Hormone Replacement Therapy, and Atherosclerotic Risk in Midlife Women by Hunter, Carol J.; PhD from The University of New Mexico, 1999, 157 pages http://wwwlib.umi.com/dissertations/fullcit/9938979

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Physical Activity, Hormone Replacement Therapy, and Insulin-resistant Coronary Artery Disease Risk Factors in Postmenopausal Women by Manns, Patricia Janine; PhD from Oregon State University, 2002, 99 pages http://wwwlib.umi.com/dissertations/fullcit/3044340

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Understanding Factors Associated with Intention to Use Hormone Replacement Therapy among Thai Middle-aged Women by Burusanont, Montarat; PhD from University of Minnesota, 2002, 192 pages http://wwwlib.umi.com/dissertations/fullcit/3039636

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Women's Ways of Speaking about Menopause and Hormone Replacement Therapy: an American Discourse on Personhood by Suopis, Cynthia Anne; PhD from University of Massachusetts Amherst, 2002, 274 pages http://wwwlib.umi.com/dissertations/fullcit/3056283

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL REPLACEMENT THERAPY

TRIALS

AND

HORMONE

Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning hormone replacement therapy.

Recent Trials on Hormone Replacement Therapy The following is a list of recent trials dedicated to hormone replacement therapy.8 Further information on a trial is available at the Web site indicated. •

Development and Evaluation of a Hormone Replacement Therapy Decision-Aid Condition(s): Menopause Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service Purpose - Excerpt: The decision regarding the use of post-menopausal estrogen hormone replacement therapy (HRT) is complex because patients must balance the short- and long-term risks and benefits. Information from new and important clinical trials must also be considered. The purpose of this research is to develop and evaluate the efficacy of a HRT CD-ROM decision-aid in improving the decision-making process for women considering the use of estrogen HRT. The objectives of the study are to: 1) develop a model of the decision-making process for women considering estrogen hormone replacement therapy (HRT), based on Multi-Attribute Utility Theory (MAUT); 2) produce an interactive CD-ROM decision-aid for HRT; 3) evaluate the effect of the interactive CD-ROM decision-aid on patient satisfaction with decision (SWD) and knowledge about menopause and HRT; and 4) test the effect of the interactive CD-ROM decision-aid on women's decisions regarding initiation of HRT. Phase I (completed) used structured interviews and surveys in the development of a decision model for HRT. In phase II, an interactive CD-ROM decision-aid was developed and a randomized controlled trial (RCT) of its effect on decision processes was initiated. Postmenopausal

8

These are listed at www.ClinicalTrials.gov.

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women, aged 45-74, are being recruited from the primary care clinics of the four participating Veterans Affairs hospitals: Milwaukee, Madison, Chicago-Hines, and Chicago-Westside. The primary hypothesis is that women who use the CD-ROM decision-aid will demonstrate increased satisfaction with their decision regarding hormone replacement therapy use compared to women receiving the control intervention. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012909 •

Hormone Replacement Therapy and the Risk of Breast Cancer Recurrence in Women With Previous Early Stage Breast Cancer Condition(s): menopausal symptoms; stage I breast cancer; stage II breast cancer; breast cancer in situ Study Status: This study is currently recruiting patients. Sponsor(s): Regional Oncologic Center; Scandinavian Breast Group; International Breast Cancer Study Group; EORTC Breast Cancer Cooperative Group Purpose - Excerpt: RATIONALE: Hormone replacement therapy is effective for relieving symptoms of menopause. It is not yet known if hormone replacement therapy increases the risk of breast cancer recurrence in women previously treated for early stage breast cancer. PURPOSE: Randomized phase III trial to determine the risk of breast cancer recurrence in women with previous early stage breast cancer who are receiving hormone replacement therapy for menopause symptoms. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003771

•

Randomized Study of Oral Contraceptives or Hormone Replacement Therapy in Women With Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); UAB Comprehensive Cancer Center Purpose - Excerpt: Objectives: I. Determine the effect of oral contraceptives containing low-dose synthetic estrogens and progestins on disease activity in premenopausal women with inactive, stable, or moderate systemic lupus erythematosus (SLE). II. Determine the effect of hormone replacement therapy with conjugated estrogens and progestins on disease activity in postmenopausal women with inactive, stable, or moderate SLE. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006133

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•

Hormone Replacement Therapy and Prothrombotic Variants Condition(s): Cardiovascular Diseases; Heart Diseases; Cerebrovascular Accident; Myocardial Infarction; Hypertension Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine in postmenopausal women the potential interactions of hormone replacement therapy with other blood clotting factors on the risk of cardiovascular diseases such as heart attack or stroke. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049933

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “hormone replacement therapy” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

•

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

•

For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

•

For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

•

For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

146 Hormone Replacement Therapy

•

For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

•

For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

•

For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

•

For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

•

For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

147

CHAPTER 6. PATENTS ON HORMONE REPLACEMENT THERAPY Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “hormone replacement therapy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hormone replacement therapy, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Hormone Replacement Therapy By performing a patent search focusing on hormone replacement therapy, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on hormone replacement therapy: •

11.beta.-aryl substituted 14,17-ethanoestratriens, method for the production of these compounds and their use in the production of medicaments Inventor(s): Bohlmann; Rolf (Berlin, DE), Fritzemeier; Karl Heinrich (Berlin, DE), Hegele-Hartung; Christa (Berlin, DE), Knauthe; Rudolf (Berlin, DE), Parzcyk; Karsten (Berlin, DE) Assignee(s): Schering Aktiengesellschaft (Berlin, DE) Patent Number: 6,229,029 Date filed: June 9, 2000 Abstract: This invention describes 11.beta.-aryl-substituted 14,17-ethanoestratrienes of general formula (I). The new compounds are selective estrogens whose action occurs in a tissue-selective manner. The estrogenic action occurs in particular on bone, in the cardiovascular system and in the CNS (central nervous system). Only a slight estrogenic action or no estrogenic action occurs in the uterus and in the liver, however. The compounds are suitable for the production of pharmaceutical agents for use in numerous indications (for example for hormone replacement therapy, prevention and treatment of osteoporosis). Excerpt(s): This application is a 371 of PCT/EP98/03243 filed Jun. 2, 1998. R.sup.6 has the meaning of R.sup.4 or R.sup.5 or is an optionally substituted aryl or arylalkyl radical, whereby the alkyl radical can have up to 6 carbon atoms in it and the aryl radical alone or in the arylalkyl radical is a 5- or 6-membered monocyclic ring or a condensed 8- to 10-membered ring system, and the aryl radical can have one or more heteroatoms that are selected from among oxygen, nitrogen and sulfur. Alkyl groups that are mentioned within the scope of this invention as R.sup.4 and R.sup.5 are, for example, the methyl, ethyl, n- or iso-propyl, n-, iso- or tert-butyl, pentyl, neo-pentyl, hexyl, heptyl or octyl group. Web site: http://www.delphion.com/details?pn=US06229029__

•

Administration system for estradiol Inventor(s): Gonella; Jacques (Muttenz, CH) Assignee(s): Giapharma SA (Zug, CH) Patent Number: 5,665,377 Date filed: December 19, 1994 Abstract: The adhesive plaster for the transdermal administration of estradiol or mixture estradiol/progestin is composed of an impermeable carrier film and of an adhesive composition. The latter represents a matrix or reservoir layer and is composed of a solvent-based polyacrylate or polyisobutylene adhesive which contains a saturated or unsaturated fatty acid with 6 to 18 C atoms as permeability enhancer, estradiol or mixture estradiol/progestin as active substance and optionally propylene glycol as solvent.The adhesive plaster is used for the systemic administration of hormones in hormone replacement therapy for a time of at least 3 days.

Patents 149

Excerpt(s): The present invention relates to a percutaneous (or transdermal) administration system for estradiol, alone or in combination with a progestin. This administration system is an adhesive plaster which contains an adhesive composition which contains the active substance and which is applied to an impermeable carrier film. Sticking on the adhesive plaster results in a virtually constant rate of release of the hormone for a period of at least 3 days. The system additionally contains a permeability enhancer which reduces the resistance of the skin to diffusion of the active substance. Estradiol is the main estrogen secreted by the female gonad during the fertile years of life. At an age of 45 to 50 years the menses cease owing to a decrease in ovarian function, and women enter the so-called climacterium. The deficiency of hormone secretion leads in many women to development of vasomotor signs and symptoms (hot flushes, sweating) as well as sleep distrubances, anxiety states and atrophy of hormonecontrolled organs, such as in the mammary glands and the vaginal epithelium. These symptoms and signs are called the menopausal syndrome. In addition to this, the low level of hormone secretion likewise leads to an increase in cardiovascular disorders and the development of osteoporosis. Web site: http://www.delphion.com/details?pn=US05665377__ •

Antiprogestin cyclophasic hormonal regimen Inventor(s): Grubb; Gary S. (Bridgewater, NJ) Assignee(s): Ortho Pharmaceitical Corporation (Raritan, NJ) Patent Number: 5,521,166 Date filed: December 19, 1994 Abstract: The present invention is directed to cyclophasic hormonal regimens which comprise antiprogestin and progestin for human contraception whereby progestin is administered in the alternating presence and absence of an antiprogestin in effective amounts to upregulate steroid receptor levels or is alternatively dosed with effective amounts of antiprogestin to upregulate steroid receptor levels. The present invention also provides an estrogen containing cyclophasic hormonal regimen for climacteric or menopausal hormone replacement therapy comprising the administration of an effective hormone replacement amount of estrogen in alternating doses with a combined amount of estrogen and an effective amount of antiprogestin to inhibit proliferation of endometrial tissue caused by the administration of the estrogen. Excerpt(s): The present invention is directed to cyclophasic hormonal regimens for contraception and hormone replacement therapy. More particularly, the present invention is directed to cyclophasic hormonal regimens which comprise antiprogestin and progestin for human contraception whereby progestin is continuously administered in the alternating addition and absence of an antiprogestin in effective amounts to upregulate steroid receptor levels or progestin is administered in alternating doses with effective amounts of antiprogestin to upregulate steroid receptor levels. The present invention also provides an estrogen containing cyclophasic hormonal regimen for climacteric or menopausal hormone replacement therapy comprising the administration of an effective hormone replacement amount of estrogen in alternating doses with a combined amount of estrogen and an effective amount of antiprogestin to inhibit proliferation of endometrial tissue caused by the administration of the estrogen. The concept of cyclophasic hormonal regimens comprising estrogens and progestins is disclosed by Robert Casper in U.S. Pat. Nos. 5,108,995; 5,256,421; and 5,276,022. The disclosures of these three U.S. Patents are hereby incorporated herein by reference. The

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primary aim of both the oral contraception (OC) hormone replacement therapy (HRT) and cyclophasic regimens disclosed by Casper is to induce higher levels of progestin and estrogen receptors by an estrogen-induced increase in receptor production. The greater concentration of steroid receptors increases the sensitivity of the target organs to progestin and estrogen and allows the use of lower doses of exogenous steroids. The cyclophasic regimens of Casper upregulate the estrogen and progestin receptors in an estrogen-dominant phase of 2-4 days and then down-regulate the same receptors in a progestin-dominant phase in the next 2-4 days. In contrast to conventional oral contraception regimens which are continuously progestin-dominant, the levels of the estrogen and progestin receptors are continuously down-regulated. In both phases of the cyclophasic regimen, the estrogen dose is constant while the progestin dose is varied to produce relatively progestin-dominant or estrogen-dominant effects. These alternating phases continue without interruption for HRT but with OC, they are interrupted periodically for 4-7 days to allow menstrual bleeding to occur. Web site: http://www.delphion.com/details?pn=US05521166__ •

COMBINATION OF PROSTACYCLIN WITH AN ESTROGEN OR PROGESTIN FOR THE PREVENTION AND TREATMENT OF ATHEROSCLEROTIC VASCULAR DISEASE INCLUDING PREECLAMPSIA AND FOR THE TREATMENT OF HYPERTENSION, AND FOR HORMONE REPLACEMENT THERAPY Inventor(s): Chwalisz; Kristof (Berlin, DE), Garfield; Robert E. (Friendswood, TX) Assignee(s): Board of Regents, The University of Texas System (Austin, TX) Patent Number: 6,613,757 Date filed: September 22, 1994 Abstract: Cardiovascular disease, including preeclampsia in pregnant women and hypertension in both women and men, are prevented or treated by administering thereto prostacyclin or a prostacyclin analog in combination with one or both of an estrogen and a progestin, which combination is also useful for HRT in peri- and postmenopausal women. Excerpt(s): This invention relates to a method for the prevention and treatment of atherosclerotic vascular disease (cardiovascular disease); for the prevention and treatment preeclampsia in pregnant women and for hormone replacement therapy in peri- and post-menopausal women, and for the treatment of hypertension in women and men. Epidemiological data indicate that approximately one half of the deaths in economically developed countries are attributable to a single major cause, viz., cardiovascular disease, including coronary heart disease, stroke and other forms of vascular disease (Green, A., Bain, C., 1993). The commonest and most lethal form of cardiovascular disease is coronary heart disease. In men, there is a continuous increase in the prevalence of cardiovascular disease after the age of 30-40 years. On the other hand, the rate of cardiovascular disease, especially coronary heart disease, is relatively low among premenopausal women but rises sharply with increasing age, suggesting that sex steroids (estrogens and progesterone) have a protective effect in women. The increased risk of coronary heart disease among women with bilateral oophorectomy further supports the view that steroid hormones may play a protective role with regard to cardiovascular disease. Cardiovascular disease can be prevented in postmenopausal women by hormone replacement therapy (HRT) with estrogens. The recently performed meta-analysis of 29 studies has demonstrated a reduced cardiovascular

Patents 151

disease risk among estrogen users in 23 of these studies (Stampfer et al., 1991). There is also experimental evidence from studies in monkeys that the development of coronary atherosclerosis induced by oophorectomy and diet may be reversed by estrogen supplementation (Adams et al., 1992). On the other hand, there are no effective methods for the prevention of cardiovascular disease in man, since estrogen cannot be used because of side-effects. Web site: http://www.delphion.com/details?pn=US06613757__ •

Combined pharmaceutical estrogen-androgen-progestin Inventor(s): Hughes, Jr.; Claude L. (Simi Valley, CA), Jayo; Manuel J. (Advance, NC) Assignee(s): Cedars-Sinai Medical Center (Los Angeles, CA), Wake Forest University (Winston-Salem, NC) Patent Number: 6,139,873 Date filed: October 23, 1998 Abstract: Disclosed are methods and compositions for oral contraception and for hormone replacement therapy. Certain compositions of the invention contain androgens, preferably methyltestosterone to be taken in conjunction with estrogens and progestins. Excerpt(s): The present invention relates generally to the field of pharmaceutical preparations and in particular to the field of oral contraceptives and hormone replacement therapy. In particular the present invention addresses the field of peak bone mass accrual in young oral contraceptive users and restoration of normal hormonal balance in women of any age in need thereof. Due to the relatively high rate of teenage pregnancy in the United States, pediatric and adolescent gynecologists often recommend that young women take some form of contraception to prevent unwanted pregnancies (The Contraception Report, 1995). The most common method of contraception among adolescents is oral contraceptives, taken by approximately 46% of the sexually active population. Consequently, almost half of all premenopausal women (<44 years) are potentially taking oral contraceptives while their skeleton is still maturing and before reaching peak bone mass, which occurs at about age 30-35. Peak bone mass is a term that describes a point at which the maximum bone density is reached. For a woman, bone density increases until about age 30-35, and then slowly decreases for the remainder of her life. This peak is known as the peak bone mass. As the bone density decreases in later years, osteopenia and osteoporosis with bone fractures are more likely to occur. It is important, therefore, to forestall these problems by attaining as high a peak as possible. Although estrogen is necessary for maintaining bone density in premenopausal women, the role of androgens or their combined effect is unclear. It is generally accepted that low-dose estrogens are potent bone growth promoters and probably provide the major growth stimulus in girls, while in boys, estrogens may be involved in the growth spurt along with testosterone (Kulin, 1991). However, some recent evidence suggests that androgens play an important role in building and maintaining bone in the female as well as in the male. During puberty, androgens influence bone growth and peak bone mass, but after puberty, during adolescence and early adulthood, androgens are also involved in the maintenance of bone mass. Peak bone mass is acquired by age 30-35 (Recker, et al., 1992), but 15% of the adult height and 48% of the skeletal mass are attained during adolescence. Web site: http://www.delphion.com/details?pn=US06139873__

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•

Drug dosage unit for buccal administration of steroidal active agents Inventor(s): Place; Virgil A. (P.O. Box 44555 - 10 Ala Kahua, Kawaihae, HI 96743) Assignee(s): none reported Patent Number: 6,117,446 Date filed: January 26, 1999 Abstract: A buccal dosage unit is provided for administering a combination of steroidal active agents to a female individual. The novel buccal drug delivery systems may be used in female hormone replacement therapy, in female contraception, to treat female sexual dysfunction, and to treat or prevent a variety of conditions and disorders which are responsive to the active agents discussed herein. The buccal dosage unit comprises a progestin, an estrogen and optionally an androgenic agent, as well as a polymeric carrier that bioerodes and provides for delivery of the active agents throughout a predetermined drug delivery period. Excerpt(s): This invention relates generally to pharmaceutical compositions and methods for administering pharmacologically active agents. More particularly, the invention relates to buccal drug delivery, and to a buccal dosage unit and method for administering a combination of steroidal active agents, e.g., for female hormone replacement therapy, female contraception, treatment of female sexual dysfunction, and the like. Androgens are the hormones that cause most of the masculinizing changes that occur in males during puberty. Harrison 's Principles of internal Medicine, 12.sup.th Edition (New York, N.Y.: McGraw Hill, Inc., 1991). However, low levels of androgens are also present in normal females. Testosterone and other androgens are secreted by the ovary and the adrenal cortex. See, e.g., Goodman & Gilman's The Pharmacological Basis of Therapeutics, 9.sup.th Edition (New York, N.Y.: McGraw Hill, Inc., 1996). Dehydroepiandrosterone (DHEA) and androstenedione are also synthesized by both the adrenal gland and the ovary and can be converted to testosterone or estrogen in peripheral tissues. The daily rate of production of testosterone in women is on the order of 0.25 mg, about half of which is derived from the metabolic conversion of androstenedione to testosterone at extraglandular sites. The plasma concentration of testosterone in women alters with the menstrual cycle and ranges from 15 to 65 nanogram/deciliter (ng/dl). As with estrogen, testosterone levels peak at the preovulatory and luteal phases of the cycle. At menopause, plasma androgen and estrogen levels are reduced but not completely absent in women. Alteration in the hormone profile is believed to be an underlying cause of menopausal symptoms in women, including vasomotor instability ("hot flash"), atrophy of the urogenital epithelium and skin, decreased size of the breasts and osteoporosis. See, e.g., Harrison's Principles of Internal Medicine, supra. Alteration in normal hormonal levels can also cause sexual dysfunction. For example, estrogen deficiency, causing vaginal atrophy and dyspareunia, is a common cause of sexual dysfunction. Dyspareunia is thought to affect approximately 40% of women; it has been estimated that over 40 million female individuals will suffer dyspareunia at some time in their lives. On the order of twentyfive million women will experience dyspareunia in the peri- and postmenopausal periods (Kelly (1992) Clinical Practice and Sexuality 8(8):2; and Sato et al. (1992) Clinical Practices in Sexuality 8(5):1. Web site: http://www.delphion.com/details?pn=US06117446__

Patents 153

•

Endothelin antagonist and/or endothelin synthase inhibitor in combination with a progestin, an estrogen, a cyclooxygenase inhibitor, or a nitric acid donor or substrate Inventor(s): Chwalisz; Kristof (Berlin, DE), Garfield; Robert E. (Friendswood, TX) Assignee(s): Board of Regents The University of Texas System (Austin, TX), Schering Aktiengesellschaft (Berlin, DE) Patent Number: 5,811,416 Date filed: May 8, 1995 Abstract: A pharmaceutical composition for and methods of treatment of menstrual disorders, e.g., dysmenorrhea, in a non-pregnant female, preterm labor, preeclampsia and/or fetal growth retardation in a pregnant female mammal, treatment of atherosclerotic vascular disease and hypertension in males as well as females, and for hormone replacement therapy in peri- and post-menopausal females, comprising administering effective amounts of an endothelin antagonist and/or an endothelin synthase inhibitor or both, in combination witha progestin, and/or an estrogen, and/ora cyclooxygenase inhibitor, and/ora nitric oxide donor and/or nitric oxide substrate,to prevent and/or ameliorate said conditions, are disclosed. In the method aspects, the endothelin antagonist and/or endothelin synthase inhibitor can be administered alone for treatment of menstrual disorders, e.g., dysmenorrhea, in a non-pregnant female, preterm labor, preeclampsia and/or fetal growth retardation in a pregnant female mammal. Further, methods for screening compounds for such treatments are disclosed. Excerpt(s): This invention relates to a method for the treatment of uterine contractility disorders, such as preterm labor, abortion, dysmenorrhea and menstrual disorders and to the treatment of preeclampsia with an endothelin antagonist, an endothelin synthase inhibitor, or both, alone or further in combination with a progesterone or a cyclooxygenase inhibitor. In addition, the invention relates to the treatment of atherosclerotic vascular disease and hypertension in males as well as females with an endothelin antagonist and/or an endothelin synthase inhibitor in combination with estrogens and/or progestins, and as a component of hormone replacement therapy in peri- and post-menopausal females. Preterm labor, and subsequent preterm birth is a major problem of perinatology in general. By definition, a term gestation in human is one that is completed between 38 and 42 weeks. However, in approximately 5 to 15% of women, birth occurs prematurely, i.e., before 37 completed weeks. In humans, premature birth is responsible for 75% of infant mortality and 50% of long-term neurological handicaps (Creasy, 1989). To date, there are no effective methods of treatment and prevention for either preterm labor or preterm birth. The current use of.beta.-mimetics in the treatment of preterm labor is only of limited value. The metaanalyses of the results of controlled trials show little or no effect of.beta.-mimetics on the frequency of the respiratory distress syndrome or on perinatal mortality (King et al., 1988). There is growing evidence that preterm labor is syndrome which can be induced by a variety of factors. Moreover, preterm labor has to be considered a chronic pathological condition of the uterus in response to a variety of etiological factors. In some clinical situations, decrease in progesterone levels or in progesterone action at the receptor level may result in preterm labor. In many species, preterm labor can be induced with progesterone antagonists (e.g., RU 486, onapristone) or progesterone synthase inhibitors (epostane, trilostane). There is growing evidence, however, that intrauterine or systemic infections play a key role in the etiology and pathogenesis of preterm labor in humans (for review see Romero et al.). In 20-40% of pre-term labor, there is clinical and/or biochemical evidence of the intrauterine infection such as hyperthermia, positive bacterial cultures, increase in cytokines such as IL-1b,

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TNF.alpha., IL-8 in the amniotic fluid (Romero et al., 1991, 1992). It is well established that the cytokines are released from uterine macrophages, activated lymphocytes and other white blood cells in response to a lipopolysaccharide (LPS) which is a major constituent of outer bacterial membrane. The cytokines stimulate in turn the release of prostaglandins from the decidual and amnion cells which directly induce uterine contractions leading to preterm labor and subsequently to preterm birth. Web site: http://www.delphion.com/details?pn=US05811416__ •

Estra-1,3,5(10)-trien derivatives, processes for their preparation and pharmaceutical compositions containing these compounds Inventor(s): Elger; Walter (Berlin, DE), Lucas, heir; by Margit (Mettmann, DE), Reddersen; Gudrun (Jena, DE), Schneider; Birgitt (Jena, DE), Schwarz; Sigfrid (Jena, DE), Siemann, deceased; Hans-Joachim (late of Jena, DE), Siemann, heir; by Frank (Mitweida, DE) Assignee(s): Jenapharm GmbH & Co. KG (Jena, DE) Patent Number: 6,080,735 Date filed: February 2, 1998 Abstract: This invention is relating to new estra-1,3,5(10)-trien-sulfamates carrying at the 3-position an R--SO.sub.2 --O--group, with R being an R.sup.1 R.sup.2 N--group in which R.sup.1 and R.sup.2, independently of each other, represent a hydrogen atom, an alkyl residue with 1-5 C atoms or, together with the N atom, a polymethylene-imino residue with 4-6 C atoms or a morpholino residue.The compounds, according to this invention, are suitable for hormonal contraception and climacteric hormone replacement therapy (HRT) as well as for treatment of gynecological and andrological diseases. Hence, only low hepatic estrogenicity is exhibited by the compounds according to this invention.Also described are processes for preparation of the compounds according to this invention and for preparation of pharmaceutical compositions. Excerpt(s): This invention relates to new estra-1,3,5(10)-trien sulfamates. Estrogens play a major role in hormonal contraception and climacteric hormone replacement therapy (HRT) as well as in the treatment of gynecological (e.g. mammary carcinoma) and andrological (e.g. prostate carcinoma) diseases. In HRT and for contraception, estrogens are predominantly used in combination with a gestagen, e.g. levonorgestrel, desogestrel, gestodene, drospirorenone, norethisterone, cyproterone acetate, chlormadinone acetate and dienogest. Web site: http://www.delphion.com/details?pn=US06080735__

•

Hormone replacement therapy drug formulations for topical application to the skin Inventor(s): Gyurik; Robert J. (Exeter, NH), Krauser; Scott F. (Tyngsboro, MA), Samour; Carlos M. (Bedford, MA) Assignee(s): MacroChem Corporation (Lexington, MA) Patent Number: 5,968,919 Date filed: October 16, 1997

Patents 155

Abstract: Topical alcoholic or aqueous alcoholic gels containing testosterone, progesterone, estradiol or other hormones have enhanced penetration through skin by including in the formulation 2-n-nonyl-1,3-dioxolane or other hydrocarbyl derivative of 1,3-dioxolane or 1,3-dioxane or acetal, as skin penetration enhancing compound. Excerpt(s): This invention relates to topical compositions for transdermal administration of a hormone through the skin of a patient and to the method for transdermally administering the hormone using the topical composition. All drugs must be administered in such a manner that they reach the intended site in the body in an optimal concentration (e.g., amount of drug per unit volume of blood) to achieve the desired effect at the proper time, and for an appropriate length of time. Customarily, drugs are taken orally, injected, inhaled, or applied topically. These conventional routes of administration often fail to meet the stated objectives, however. For example, when drugs are absorbed into the blood stream by whatever route, peaks and valleys in the blood concentration of the drug occur and may cause undesirable effects (e.g., peak levels), or loss of activities (e.g., valleys). To meet these problems, a variety of approaches have been investigated. These include, for example, special drug coatings, combining the drug with other materials, suspensions or emulsions, and compressed tablets. Although these formulations attempt to control the release of drugs from their carriers, the desired effects are often not reproducible, may be subject to patient-topatient variations, and may not be suitable for prolonged periods of delivery, such as days or even months. Recent research has produced systems in which a drug is implanted in the body, released from skin sites, introduced in to the body by minipumps, and/or released in minute quantities through the skin. These innovative drug-delivery systems are improving drug effectiveness and also are opening opportunities for new pharmaceuticals. Web site: http://www.delphion.com/details?pn=US05968919__ •

Hormone replacement therapy method and hormone dispenser Inventor(s): Elliesen; Jorg (Berlin, DE), Riedl; Jutta (Berlin, DE) Assignee(s): Schering Aktiengesellschaft (DE) Patent Number: 5,897,539 Date filed: September 27, 1996 Abstract: Varying the daily dose of either or both of the estrogen and the progestogen administered for hormone replacement therapy (HRT) is readily and inexpensively accomplished, without the necessity of the physician prescribing a new product each time the daily dose of the estrogen or progestogen is changed, by administering preferably transdermally the estrogen and progestogen contained in separate extrudable pharmaceutical compositions from a dispenser which contains means, preferably adjustable only by the attending physician or dispensing pharmacist, for varying the volume of either or both of the respective compositions which is dispensed as a single dose from the dispenser in response to a defined digital dispensing manipulation of the dispenser. Excerpt(s): This invention relates to a method of conducting hormone replacement therapy (HRT) and to dispensers and kits adapted to practice the method. Thus, a fixed combination of an estrogen dosage and a progestogen dosage that is suitable for all menopausal women is impossible to design, for a variety of reasons. One reason is the wide variation from individual to individual in the resorption rate which exists with all

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modes of administration except intraveneous, which is not practiced in HRT. These differences in bioavailability can reach 100% or more. For example, the bioavailability of estradiol orally averages 5% of the oral dose, which means that in an individual it can be as low as 3% or as high as 6%. Another reason why a fixed combination is not suitable is because of variations in body weight and fat mass proportion, which has an endrocrine function because it contains enzymes to transform hormonal precursors intro estrogens. A third reason is the interaction between estrogens and progestogens, i.e., progestogens may only become effective in the presence of estrogens because they stimulate the production of progestogen recepton. Although some of these transdermal dosage forms have been commercialized for contraception purposes, for HRT use they suffer even more than separate tablets of the estrogen and of the progestogen from the lack of flexibility with respect to the ability of the physician to change the dosage of only one of the estrogen and the progestogen or the dosage of both by only a small amount. Web site: http://www.delphion.com/details?pn=US05897539__ •

Hormone replacement therapy monitoring Inventor(s): Dullien; Vivian (Boulder, CO) Assignee(s): Biex, Inc. (Dublin, CA) Patent Number: 6,174,665 Date filed: September 10, 1999 Abstract: The present invention provides methods for monitoring the effectiveness of hormone replacement therapy in a perimenopausal, early menopausal, or late menopausal woman, comprising testing for hormonal levels in a body fluid of the woman at intervals depending on the stage of menopause, and adjusting levels of replacement hormone administered to the woman based on the test results. Excerpt(s): The invention relates to methods for monitoring the effectiveness of hormone replacement therapy in various stages of menopause. Menopause is a natural event in a woman's life that designates the end of fertility, and results from decreased ovarian production of estrogen and progesterone. In its strictest sense, menopause refers to a one-day event occurring one year after the last menstrual period. While the majority of women experience "natural" menopause, some women undergo "induced" menopause, due to any one of a number of medical interventions, such as surgical removal of the ovaries, or ovarian damage by radiation or chemotherapy. Perimenopause refers to a period of up to 7 years wherein the woman has wide fluctuations in estrogen levels from month to month. Perimenopause generally starts when a woman is in her forties, and ends one year after menstruation stops. During perimenopause, a woman may be in estrogen deprivation one month but not the next. She may experience symptoms of menopause, such as hot flashes and insomnia, which also may fluctuate from month to month. During perimenopause, a diagnosis of estrogen deprivation may be accurate one month and proper hormone replacement therapy ("HRT") prescribed, while the next month the HRT dosage may be too much or not enough. Web site: http://www.delphion.com/details?pn=US06174665__

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Intravaginal rings with insertable drug-containing core Inventor(s): Bardin; C. Wayne (New York, NY), Harmon; Troy (Lansdale, PA), Nash; Harold A. (Harrington Park, NJ), Saleh; Saleh Ismail (Assuit, EG) Assignee(s): The Population Council, Inc. (New York, NY) Patent Number: 5,972,372 Date filed: May 2, 1997 Abstract: Disclosed is a vaginal ring intended for the release of at least one drug over a prolonged time period. The vaginal ring contains a ring body made of a first polymeric material having at least one hollow internal channel defining an opening to the exterior of the ring body and which channel is adapted to receive a, drug-containing core through the opening, and an intravaginally administerable drug-containing core disposed in the channel. The core is positioned in the vaginal ring body suitably prior to use in order to substantially avoid initial bursts of drug into the tissues of the subject and resultant side effects such as nausea and vomiting. The core contains a pharmaceutically effective amount of at least one intravaginally administerable drug dispersed in a second polymeric material. The first and second polymeric materials may be the same or different. Representative drugs include contraceptive agents and other steroidal substances for use in hormone replacement therapy. Also disclosed are methods for preparing the vaginal rings, kits for assembling the vaginal rings, and methods of using the vaginal rings to achieve intravaginal delivery of drugs to a female. Excerpt(s): The present invention is directed to intravaginal drug delivery devices and methods for the intravaginal administration of drugs, and more particularly, the intravaginal administration of contraceptive agents and agents for hormone replacement therapy. Vaginal rings are torous shaped devices designed to deliver a relatively constant dose of drug to the vagina usually over a period of weeks to months. Typically, they are made of a silicone elastomer and contain a drug released by diffusion though the elastomer. The most common commercial applications have been to deliver low doses of steroids for post-menopausal vaginal conditions. They have also been under development for use in contraception and hormone replacement therapy. Vaginal rings have also been used to administer spermicides, as well as a variety of locally or systematically active medicaments. Vaginal rings have provided several advantages in that their use is controlled by the female; they allow for a better regulated dose of drug without attention by the user; and they avoid the destruction (by the intestine and by first pass through the liver) of an appreciable portion of the daily dosage of some steroids compared to their orally delivered counterparts. The use of a vaginal ring to deliver drugs requires a ring design that regulates the release rate so as to provide the user with the appropriate daily dose. Among the important factors governing release are the solubility of the drug in the ring elastomer, the surface area of the drug reservoir, the distance the drug must diffuse through the ring body to reach its surface and the molecular weight of the drug. If very high release rates are desired, they can be attained by a drug load at the ring surface as is characteristic of the homogeneous matrix ring design. This design, however, suffers from rapidly declining release rates as the distance the drug must travel to reach the ring surface increases as the drug load near the surface is depleted. If moderately high release rates are needed to provide the appropriate dose, a design which modulates release rate by imposing a layer of drugfree elastomer between the drug reservoir and the ring exterior is appropriate. This may be attained by coating a homogeneous ring, or to conserve drug, by incorporating a drug-free core, a shell design may be used. If an even lower release rate is desired, the drug may be confined to a small diameter at the center of the ring ("core ring"). Finally,

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the drug-loaded core may not encircle the ring but instead be of short length. Numerous types of vaginal rings have been described in the patent and non-patent literature alike. See, e.g., U.S. Pat. Nos. 4,012,496 and 4,155,991 (both to Schopflin et al.), 4,292,965 (Nash), 3,545,439 (Duncan), 3,920,805 (Roseman), 3,991,760 and 3,995,634 (both to Drobish et al.), 3,995,633 (Gougen), 4,250,611 and 4,286,587 (both to Wong), 4,596,576 (de Nijs); W095/00199 (Lehtinen et al.), NL 8500-470-A; and Apter et al., Contraception 42:285-295 (1990), Burton et al., Contraception 17:221-230 (1978), Burton et al., contraception 19:507-516 (1979), Jackanicz, Contraception 24:323-339 (1981), Sivin et al., Contraception 24:341-358 (1981), Timmer et al., Contraception 43:629-642 (1990), and Toivonen, Contraception 20:511-518 (1979). Web site: http://www.delphion.com/details?pn=US05972372__ •

Method for diagnosing estrogen responsiveness Inventor(s): Bishop; Jean (Jacksonville, FL), Simpkins; James W. (Gainesville, FL) Assignee(s): University of Florida (Gainesville, FL) Patent Number: 5,550,029 Date filed: September 8, 1994 Abstract: A method and diagnostic kit is provided for diagnosing responsiveness to a hormone in a human subject that includes determining the amount of glucose utilized by a sample taken from the subject in the presence of the hormone. The sample taken from the subject may include body fluid or body tissue such as blood or skin. The glucose utilized in the test may be labelled for example, with a radioactive label. The diagnostic test may be used to determine responsiveness to estrogen in a human subject prior to treatment with hormone replacement therapy. Excerpt(s): Methods for diagnosing responsiveness to estrogen in subjects are disclosed. One of the most prevalent forms of hormone therapy today is that of estrogen replacement therapy in women. Estrogen therapy is prescribed widely not only for the alleviation of menopausal symptoms but also for the prevention of osteoporosis and cardiovascular disease. Furthermore, estrogen may have utility as a therapeutic treatment for chronic neurodegenerative diseases such as Alzheimer's disease. Estrogen therapy is still very much a "hit-or-miss" treatment. Doses are increased for a patient until symptoms are observed to subside. Some women respond to this approach and others do not. In addition, the treatment protocol may be adversely affected by transient side effects which can be short term (such as nausea or bloating) or long term (such as increased susceptibility to cancer). There is no way to predict, in advance, whether a woman will respond in the long term to estrogen therapy; whether alternative versions of the drug will work better; or whether life-long therapy is for naught. Web site: http://www.delphion.com/details?pn=US05550029__

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Monoglyceride/lactate ester permeation enhancer for codelivery of steroids Inventor(s): Crisologo; Nieves Marzan (Sunnyvale, CA), Taskovich; Lina Tormen (Palo Alto, CA), Yum; Su Il (Los Altos, CA) Assignee(s): Alza Corporation (Palo Alto, CA) Patent Number: 5,686,097 Date filed: March 9, 1995 Abstract: A composition of matter for application to a body surface or membrane to coadminister an estrogen and progesterone by permeation through the body surface or membrane, the composition comprising, in combination, the estrogen and progesterone to be administered, in a therapeutically effective amount; and a permeation-enhancing mixture comprising a monoglyceride or a mixture of monoglycerides, and a lactate ester or a mixture of lactate esters at specific concentrations. The composition of matter is used to provide hormone replacement therapy to a woman. Excerpt(s): This invention relates to the transdermal codelivery of drugs and other biologically active agents. More particularly, this invention relates to novel methods and compositions for enhancing the percutaneous coabsorption of steroids when incorporated in transdermal drug delivery systems. More particularly, but without limitation thereto, this invention relates to the transdermal codelivery of steroids utilizing a permeation-enhancing mixture of a monoglyceride and a lactate ester. Still more particularly, but without limitation thereto, this invention relates to the transdermal codelivery of steroids such as estradiol and progesterone utilizing a permeation-enhancing mixture of a monoglyceride and a lactate ester, wherein the monoglyceride and lactate ester are present in the composition in specific weight percentages. The transdermal route of parenteral delivery of drugs provides many advantages over other administrative routes. Transdermal systems for delivering a wide variety of drugs or other beneficial agents are described in U.S. Pat. Nos. 3,598,122; 3,598,123; 3,731,683; 3,797,494; 4,031,894; 4,201,211; 4,286,592; 4,314,557; 4,379,454; 4,435,180; 4,559,222; 4,568,343; 4,573,995; 4,588,580; 4,645,502; 4,704,282; 4,788,062; 4,816,258; 4,849,226; 4,908,027; 4,943,435; and 5,004,610. The disclosures of the above patents are incorporated herein by reference. Estrogen replacement therapy is warranted in menopausal women for several reasons. Estrogen replacement will relieve hot flushes and this relief of flushes and night sweats improves sleep patterns and contributes to the patient's general feeling of well-being. (See Campbell S., Whitehead M. I. Estrogen therapy and the menopausal syndrome. In Clinics in Obstetrics and Gynecology: Volume 4. The Menopause, Edited by R. B. Greenblatt, J. W. W. Studd, London, W. B. Saunders, 1977, pages 31-47; Erlik Y., Tataryn I. V., Meldrum D. R. et al. Association of waking episodes with menopausal hot flushes. JAMA 24:1741, 1981). Estrogen replacement protects against postmenopausal loss of calcium from the skeleton, especially from vertebral bodies, preventing crush fractures and loss of body height. (See Lindsay R., Hart D. M., Forrest, C. et al. Prevention of spinal osteoporosis in oophorectomized women. Lancet 2:1151,1980). Several studies have now reported that long-term estrogen therapy is also associated with a reduction in the incidence of classical osteoporotic fractures of the forearm and hip. (See Hutchinson, T. A., Polansky, S. M., Finestein, A. Post-menopausal estrogens protect against fractures of hip and distal radius. Lancet 2:706, 1979; Paganini-Hill, A., Ross, R. K., Gerkins, V. R., et al. A case control study of menopausal estrogen therapy in hip fractures. Annals of Internal Medicine 95:28, 1981; Weiss N. S., Ure C. L, Ballard J. H. et al. Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen. New England Journal of Medicine 303:1195, 1980). Another beneficial effect of long-term estrogen use

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is the reduction of the risk of death from ischemic heart disease probably mediated by changes in blood lipoprotein concentrations. (See Ross R. K., Paganini-Hill A., Mack T. M. et al. Menopausal estrogen therapy and protection from ischemic heart disease. Lancet 1:858, 1981). Estrogen replacement has also been shown to improve the vascularity and health of the vaginal mucosa and urinary tract. The only major risk factor associated with estrogen administration in the doses required to relieve menopausal symptoms, is hyperstimulation of the endometrium and an increased risk of endometrial cancer. (See Cramer D. W., Knapp R. C. Review of epidemiologic studies of endometrial cancer and exogenous estrogen. Obstetrics and Gynecology 54:521, 1979; Shapiro S., Coughman D. W., Sloan D., et al. Recent and past use of conjugated estrogens in relation to adenocarcinoma of the endometrium. New England Journal of Medicine 303:485, 1980). Web site: http://www.delphion.com/details?pn=US05686097__ •

Progestin tablet Inventor(s): Dong; Liang C. (Mountain View, CA), Espinal; Steven (Sunnyvale, CA), Wong; Patrick S.-L. (Palo Alto, CA) Assignee(s): ALZA Corporation (Palo Alto, CA) Patent Number: 5,620,705 Date filed: May 16, 1995 Abstract: A hormone replacement composition, a hormone replacement dosage form, and a method of hormone replacement are disclosed and indicated for the management of hormone replacement therapy. Excerpt(s): This invention pertains to a novel therapeutic composition comprising a progesterone. The invention concerns also a novel dosage form comprising a progesterone. The invention relates further to a method of progesterone replacement therapy by administering the composition, or by administering the dosage form for delivering progesterone for the indicated therapy. Progesterone is the active, natural progestin secreted by the ovary, mainly from the corpus luteum, from the placenta, and from the adrenal cortex. Progesterone released during the luteal phase of the normal female cycle leads to development of a secretary endometrium. Progesterone influences the endocervical glands, and progesterone is very important for the maintenance of pregnancy as progesterone suppresses menstruation and uterine contractility. Progesterone has application in the management of ovarian disorders, in dysfunctional irregular menstrual cycles, in dysmenorrhea, in premenstrual and post menopausal symptoms, especially in the latter where menopause is an endocrine deficiency state. The medical and pharmaceutical prior arts administered progesterone as replacement therapy to provide progesterone for the physiological and therapeutic purposes indicated above, and more specifically for postmeno-pausal hormone replacement therapy. The medical and pharmaceutical prior arts administered progesterone for these therapies by injection with progesterone supplied in vegetable oil, progesterone in a suppository for vaginal or for rectal administration, progesterone in an intrauterine or vaginal device, and progesterone in a topical cream. The prior art dispensing of progesterone in oils, suppositories and creams lacked controlled delivery, and the prior art dispensing of progesterone in an intrauterine or vaginal device frequently lead to bleeding and infection of the uterus and the vagina. The prior art has not provided an acceptable oral means for administering progesterone at a controlled dose over time, even though patients are more comfortable taking compositions and dosage forms by

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mouth. The properties of progesterone are reported in The Pharmacological Basis of Therapeutics, by Gilman and Rall, 8th ed, pp 1384-1412 (1990), published by Pergamon Press, Inc. Web site: http://www.delphion.com/details?pn=US05620705__ •

Sustained release thyroactive composition Inventor(s): Hennemann; Georg (Rotterdam, NL), Krenning; Eric P. (Rotterdam, NL) Assignee(s): Akzo N.V. (Arnhem, NL) Patent Number: 5,324,522 Date filed: December 28, 1992 Abstract: Disclosed are sustained release dosage forms of liothyronine, in combination with normal or sustained release of thyroxine in a molar ratio of about 1 to 50:1, especially 5 to 20:1, useful in thyroid hormone replacement therapy. Surprisingly, it is found that by incorporating liothyronine and optionally thyroxine into a prolonged action dosage form in the described ratios, that the side effects associated with thyroid hormone replacement therapy are greatly reduced or eliminated. The preparation can be a dosage form containing salts of both thyroxine and liothyronine which release in a sustained manner. The preparations will typically contain 5 to 25.mu.g of liothryronine. Also disclosed are processes of manufacturing the pharmaceutical preparations. The compositions are useful in treating disease states such as hypothyroidism, hyperthyroidism (in combination with thyrostatic drugs), so-called "TSH" suppressive therapy, and depression. Excerpt(s): The invention relates to pharmaceutical preparations generally, and more specifically to a preparation useful in replacement therapy for thyroactive material normally supplied by the thyroid gland. The thyroid gland, among other things, modulates a body's energy metabolism. It does so by releasing various iodinated thyronines. Two of these iodinated thyronines are thyroxine (3,5,3',5'-tetraiodothyronine or "T-4") and liothyronine (3,5,3'-triiodothyronine or "T-3"). Various diseases affecting the thyroid or pituitary gland can result in hypothyroidism. Hypothyroidism can also result from thyroid surgery or treatment with radioactive iodine. In a "hypothyroid" state, the body's basal metabolic state drops, and growth and development may be impaired. Web site: http://www.delphion.com/details?pn=US05324522__

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Total hormone replacement therapy Inventor(s): Chein; Edmund Y. M. (1100 Maytok Pl., Beverly Hills, CA 90210) Assignee(s): none reported Patent Number: 5,855,920 Date filed: December 13, 1996 Abstract: A hormone replenishment method particularly useful in maintaining the body's neuroendocrine clock at optimal levels and combating conditions associated with advancing age is disclosed. The method includes determining that the level of human growth hormone and at least two other supplemental hormones are below optimal or pre-determined physiological levels for an adult human. Once it has been established

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that the level of human growth hormone and at least two of certain supplemental hormones are below pre-determined physiological levels, the method includes establishing a regimen for the replenishment of the level of the deficient hormones to optimal or pre-determined physiological levels. The supplements hormones include the sex hormones, namely testosterone, progesterone, and estrogen, the pineal hormone melatonin, the adrenal hormones, namely DHEA and pregnenolone, the thyroid hormone, and the thymus hormone. A method of increasing life expectancy and life span by determining the level of human growth hormone and at least two of the supplemental hormones and establishing a regimen for the maintenance of the level of human growth hormone and supplemental hormones at optimal or pre-determined physiological levels is also disclosed. Excerpt(s): The invention relates to hormone therapy and more particularly to the restoration and balance of a select group of hormones to maintain optimal physiological levels. It is known that the levels of a variety of hormones drop substantially with age. These include human growth hormone, sex hormones, pineal, adrenal, thyroid, and thymus hormones. The following sections describe various hormones that decline with age. The major secretion of HGH occurs at night, one to two hours after the onset of deep REAM sleep. Peek secretion levels are between 10-50 ng/ml. Web site: http://www.delphion.com/details?pn=US05855920__ •

Transdermal application of naturally occurring steroid hormones Inventor(s): Shaak; Carolyn V. (1093 Beacon St., Brookline, MA 02146) Assignee(s): none reported Patent Number: 6,228,852 Date filed: July 8, 1997 Abstract: The invention features a physiologically acceptable cream that contains estrogen, progesterone, and testosterone molecules that are identical to the estrogen, progesterone, and testosterone molecules naturally produced by the human body. The cream may be self-administered to the skin and is useful as a means of hormone replacement therapy, which may begin at around the time of menopause. Excerpt(s): This invention relates to hormone replacement therapy. Progesterone is a steroid hormone that is produced by the ovaries during a woman's child-bearing years. Progesterone is also made, although in smaller amounts, by the adrenal glands in both sexes and by the testes in males. An astonishing variety of physiological functions are mediated by progesterone (See e.g., Lee, 1993, Natural Progesterone, BLL Publishing, Sebastopol, Calif.). For example, progesterone, which surges following ovulation, maintains the secretory endometrium and thus, helps to ensure the survival of the embryo and fetus. It also acts as a diuretic, an antidepressant, and as a precursor of corticosteroids and of other sex hormones, notably estrogen and testosterone. There is also evidence that progesterone affords protection against loss of libido, osteoporosis, endometrial cancer, breast cancer, and fibrotic cysts. When the child-bearing years draw to a close, every woman experiences a decline in the production of progesterone, and consequently, a decline in all of the hormones that are synthesized from progesterone. This decline significantly and negatively affects both life-span and quality of life (Ettinger, 1996, Obst. and Gyne. 87:6-12; Karlberg et al., 1995, Acta. Obstet. Gynecol. Scand. 74:367-372). In addition to the uncomfortable symptoms, such as hot flashes, that are frequently experienced at around the time of menopause, there is an increase in the

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prevalence of life-threatening conditions, including heart disease, osteoporosis, and brain ischemia (more commonly called a "stroke"; Hunt et al., 1990, Br. J. Obstet. Gynecol. 97:1080-1086). These conditions exact a high personal price and consume significant medical resources. Postmenopausal osteoporosis, the most common metabolic bone disorder in the United States, is the underlying cause of over 1.3 million fractures, at an estimated cost of over $10 billion annually. Web site: http://www.delphion.com/details?pn=US06228852__ •

Transdermal hormone replacement therapy Inventor(s): Casper; Robert F. (Toronto, CA) Assignee(s): Jencap Research Ltd. (Toronto, CA) Patent Number: 5,422,119 Date filed: January 3, 1994 Abstract: The present invention provides a method of treating a female in need of hormone replacement therapy comprising transdermally administering to said female a series of alternating phases of from about one to about four days of estrogen dominant activity and phases of from about one to about four days of progestin dominant activity, with the estrogen dominant activity phase consisting of administering a transdermal estrogen substance alone or administering a transdermal estrogen substance and a transdermal progestin substance and the progestin dominant activity phase consisting of administering a transdermal progestin substance and a transdermal estrogen substance, the amount of progestin substance being alternately increased in the progestin dominant activity phase and decreased in the estrogen dominant activity phase to provide the required dominant activity. Excerpt(s): This invention relates to hormone replacement therapy for menopausal or castrate women. In particular, this invention relates to a form of a preparation and method which involves transdermal delivery. Estrogen replacement therapy is warranted in menopausal women for several reasons. Estrogen :replacement is known to relieve hot flushes and this relief of flushes and night sweats improves sleep patterns and contributes to the patient's general feeling of well-being. Estrogen replacement protects against postmenopausal loss of calcium from the skeleton, especially from vertebral bodies, preventing crush fractures and loss of body height. Several studies have now reported that long-term estrogen therapy is also associated with a reduction in the incidence of classical osteoporotic fractures of the forearm and hip. Another beneficial effect of long-term estrogen use is the reduction of the risk of death from ischemic heart disease probably mediated by changes in blood lipoprotein concentrations. Estrogen replacement has also been shown to improve the vascularity and health of the vaginal mucosa and urinary tract. The only major risk factor associated with estrogen administration in the doses required to relieve menopausal symptoms, is hyperstimulation of the endometrium and an increased risk of endometrial cancer. The addition of a progestin for 13 days each month has been demonstrated to protect the endometrium from these stimulatory effects of estrogen. Progestin protects the endometrium by reducing nuclear estradiol receptor concentration and thereby decreasing nuclear estrogen bioavailability resulting in an antimitotic effect and lowering DNA synthesis. Progestins also increase the activity of endometrial estradiol17.beta.-dehydrogenase, an enzyme which metabolizes estradiol to estrone, a less potent estrogen. However, concerns have been expressed about the potential adverse effects of progestin in suppressing high density lipoprotein cholesterol concentrations. This

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cholesterol fraction appears to have a protective effect against ischemic heart disease and atherosclerosis. The lowering of HDL cholesterol by progestin could negate the long-term beneficial effects of estrogen in reducing the incidence of myocardial infraction. Other side effects of progestins include acne, breast tenderness, depression and irritability. Since the side effects of progestins appear to be dose dependent, the dose of progestin used with postmenopausal estrogen replacement should be the minimum necessary to achieve endometrial protection. Web site: http://www.delphion.com/details?pn=US05422119__ •

Unsaturated 14, 15-cyclopropanoandrostanes, method for the production thereof and pharmaceutical preparations containing said compounds Inventor(s): Elger; Walter (Berlin, DE), Kaufmann; Gunter (Jena, DE), Ring; Sven (Jena, DE), Schneider; Birgitt (Jena, DE), Schwarz; Sigfrid (Jena, DE), Sobek; Lothar (Jena, DE) Assignee(s): Jenapharm GmbH & Co. KG. (Jena, DE) Patent Number: 6,534,490 Date filed: December 21, 2000 Abstract: Described are new, unsaturated 14,15-cyclopropano-androstanes of general formula (I) and their pharmaceutically acceptable salts, a process for their production and pharmaceutical preparations that contain these compounds. The compounds are characterized by hormonal (gestagenic and/or androgenic) activity and may be used for hormone replacement therapy. Excerpt(s): The invention relates to new, unsaturated 14,15-cyclopropano-androstanes, their production and pharmaceutical preparations that contain these compounds. are described. R.sub.5 stands for an alkyl group with 1-3 carbon atoms. Web site: http://www.delphion.com/details?pn=US06534490__

Patent Applications on Hormone Replacement Therapy As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to hormone replacement therapy: •

Combination of drospirenone and an estrogen sulphamate for HRT Inventor(s): Schuermann, Rolf; (Berlin, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030050289 Date filed: July 15, 2002 Abstract: A pharmaceutical dosage unit comprising drospirenone and an estrogen sulphamate, such as an estradiol sulphamate or an estriol sulphamate for use in hormone replacement therapy is disclosed. This, combination therapy may comprise

10

This has been a common practice outside the United States prior to December 2000.

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continuous or discontinuous administration of drospirenone and/or the estrogen sulphamate, such as weekly administration of both agents or weekly administration of the estrogen sulphamate and daily administration of the drospirenone. Excerpt(s): This application claims the benefit of the filing date of U.S. Provisional Application Serial No. 60/304,760, filed Jul. 13, 2001. The present invention relates to a pharmaceutical dosage unit comprising drospirenone and an estrogen sulphamate, such as an estradiol sulphamate or an estriol sulphamate, and to methods of hormone replacement therapy by administration of drospirenone and an estrogen sulphamate to estrogen-deficient women. Estrogen plays an important role in protecting the health of women such as protecting and maintaining cardiovascular health, bone mass, and mental cognition. However, normal ageing process results in lower levels of estrogen in women and the estrogen level may be significantly reduced upon entering menopause or upon surgical removal of the uterus and/or ovaries, for which reason those women risk the development of cardiovasculary diseases, bone mineralisation and/or poor mental cognition. Loss of bone mineral density is the key indicator of osteoporosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Combinations of hormone replacement therapy composition(s) and sterol absorption inhibitor(s) and treatments for vascular conditions in post-menopausal women Inventor(s): Strony, John T.; (Lebanon, NJ) Correspondence: Schering-plough Corporation; Patent Department (k-6-1, 1990); 2000 Galloping Hill Road; Kenilworth; NJ; 07033-0530; US Patent Application Number: 20030119796 Date filed: September 19, 2002 Abstract: The present invention provides compositions, therapeutic combinations and methods including: (a) at least one hormone replacement therapy composition; and (b) at least one sterol absorption inhibitor which can be useful for treating vascular conditions in post-menopausal women and lowering plasma levels of sterols or 5.alpha.stanols. Excerpt(s): This application claims the benefit of priority from U.S. Provisional Patent Application Serial No. 60/324,118, filed Sep. 21, 2001, and is a continuation-in-part of U.S. patent application Ser. No.10/166,942, filed Jun. 11, 2002, each incorporated herein by reference. The present invention relates to compositions, therapeutic combinations and methods for treating vascular conditions in post-menopausal women comprising at least one hormone replacement therapy composition and at least one sterol and/or 5.alpha.-stanol absorption inhibitor. Cardiovascular diseases, such as coronary artery disease, arteriosclerosis, atherosclerosis, hypertension, hypercholesterolemia, hyperlipidemia, congestive heart failure and other cerebro- or peripheral vascular diseases are a leading risk factor and a major cause of death worldwide. Recently, trends have shown post-menopausal women to be at a greater risk than previously thought. It is now generally acknowledged that after menopause, protection from vascular disease slowly dwindles over time and by the seventh and eighth decade of life even approaches the frequency found in men. A number of ongoing studies have and are in the process of evaluating this aspect of women's health and determining recommended courses of therapy which may be effective in preventing or treating post-menopausal women who suffer from vascular diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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CRYSTALLINE PROGESTAGENS Inventor(s): BOOY, CORNELIUS J.; (OSS, NL), BRANDS, FRANCISCUS T. L.; (HAREN, NL), DE WILDT, WILHELMUS P. H. M.; (WYCHEN, NL), VAN DER SCHANS, MARIA J. A.; (SPRANG-CAPELLE, NL) Correspondence: Rothwell, Figg, Ernst & Manbeck, P.C.,; 555 13th Street, N.W.; Suite 701-east; Washington; DC; 20004; US Patent Application Number: 20020010166 Date filed: August 4, 1998 Abstract: The disclosed invention resides in the polymorphism found with the progestagenic steroidal compound (17.alpha.)-17-hydroxy-11-methylene-19-norpregna-4,15-diene-20-yn-3-one. More particularly, the invention resides in crystalline forms of said compound having unexpectedly favorable thermodynamic stability. These crystalline compounds, which can be suitably described with reference to spectral data, can advantageously be employed as an active ingredient in solid pharmaceutical compositions. The crystalline compounds can be used in oral contraceptives and in hormone replacement therapy (HRT). Excerpt(s): The invention pertains to crystalline (17.alpha.)-17-hydroxy-11-met- hylene19-norpregna-4,15-diene-20-yn-3-one, hereinafter referred to as Org 30659. Org 30659 is a progestational steroid with high progestagenic activity and with low estrogenic and low androgenic activity. Org 30659 is suitable for being utilised in hormone replacement therapy (HRT) and in contraception. Org 30659 as a crystalline chemical compound is known from EP 210 678. A drawback to the Org 30659 produced therein is that it is not obtained in one single, reproducible crystalline form. Further, the thermodynamic stability of the crystals obtainable needs to be improved. Another background disclosure on Org 30659 is WO 96/09056, which pertains to a process of making dosage units comprising e.g. Org 30659 in a relatively low amount, which process involves wet granulation. WO 96/09056 refers to Org 30569 as a known compound without specifically teaching its crystallinity or the selection of a particular preparation method. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Drospirenone for hormone replacement therapy Inventor(s): Heil, Wolfgang; (Berlin, DE), Hilmann, Juergen; (Berlin, DE), Lipp, Ralph; (Berlin, DE), Schuermann, Rolf; (Berlin, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030144258 Date filed: February 6, 2003 Abstract: A pharmaceutical composition comprising as a first active ingredient an estrogen, such as estradiol or estradiol valerate, in sufficient amounts to treat disorders and symptoms associated with deficient endogenous levels of estrogen in women, and as a second active ingredient 6.beta.,7.beta.; 15.beta.; 16.beta.-dimethylene-3-oxo17.alpha.-preg-4-en- e-21,17-carbolactone (drospirenone, DRSP) in sufficient amounts to protect the endometrium from the adverse effects of estrogen is useful for, amongst others, treating peri-menopausal, menopausal and post-menopausal women. This

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composition may be used for hormone replacement therapy and may be administered as a multi-phased pharmaceutical preparation. This combination therapy may comprise continuous, sequential or interrupted administration, or combinations thereof, of DRSP and estrogen, each optionally in micronized form. Excerpt(s): The present invention relates to a pharmaceutical composition comprising drospirenone and estrogen, and to methods of hormone replacement therapy by administration of drospirenone and estrogen for estrogen-deficient women. The rise in life expectancy and consequent rise in the number of peri- and post-menopausal women has led to an increase in public and medical awareness of the climacteric period of transition in the reproduction phase of women. Menopause, the last menstruation, occurs between the ages of 45 and 55 in most women. Many factors, including race, genetics, nutrition, altitude, smoking, number of live births, the use of hormonal contraception, length of menstrual cycle and the age of onset of puberty have all been attributed, rightly or wrongly, to affect the age of the last menstrual period. During these phases of life, female endocrine activity undergoes a series of changes, with the result that the physical and psychological well being of many women is adversely affected. Hormone replacement therapy has aimed to improve the quality of life of women during this natural ageing process to alleviate symptoms associated with this time of transition and to reduce the likelihood or slow the progression of disorders and diseases associated with reduced hormonal activity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Genetic polymorphisms of estrogen receptor alpha associated with favorable HDL cholesterol response to hormone replacement therapy Inventor(s): Hawkins, Gregory A.; (High Point, NC), Herrington, David M.; (WinstonSalem, NC), Howard, Timothy D.; (Clemmons, NC), Meyers, Deborah A.; (Mocksville, NC) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20020187495 Date filed: February 22, 2002 Abstract: A method of screening a subject for increased likelihood of having a favorable response to estrogen replacement therapy comprises detecting the presence of the rare form of at least one estrogen receptor alpha polymorphism in the subject, the presence of the estrogen receptor alpha polymorphism indicating the subject is more likely to have a favorable response to estrogen replacement therapy (e.g., with respect to cardiovascular health, heart disease, and/or HDL levels). Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/270,700, filed on Feb. 22, 2001, the disclosure of which is incorporated herein by reference in its entirety. The present invention concerns methods for beneficially increasing HDL cholesterol levels in subjects. Endogenous estrogen prior to menopause, and exogenous estrogen use after menopause, results in elevations of HDL cholesterol in women. This effect is often cited as a potential explanation for lower rates of heart disease in premenopausal women and postmenopausal women taking estrogen replacement. Sullivan et al., Ann Intern Med1988; 108:358-363; and Gerhard et al., Circulation1995; 92:5-8. However, there is considerable variability among women in terms of premenopausal HDL levels and changes in HDL in response to postmenopausal estrogen replacement. A significant portion of this variability has been

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attributed to genetic factors. Mahaney et al., Arterioscler Thromb Vasc Biol1995; 15:17301739; and Austin et al., Am J Hum Genet1998; 62:406-419. Allelic variants of the estrogen receptor alpha (ER-.alpha.) gene that alter the expression, function, or stability of the expressed receptor protein may account for some of this variation. Functionally significant mutations in other steroid receptor genes including receptors for androgens, mineralocorticoids, vitamin D, and glucocorticoids have already been described. Being able to identify women who are likely to have a more favorable lipid response to estrogen would be useful for patients and their physicians as they weigh the risks and benefits of estrogen replacement therapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

HMG-CoA reductase inhibitors and method Inventor(s): Chen, Bang-Chi; (Plainsboro, NJ), Robl, Jeffrey A.; (Newtown, PA), Sun, Chong-Qing; (East Windsor, NJ) Correspondence: Marla J Mathias; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20020028826 Date filed: June 6, 2001 Abstract: Compounds of the following structure are HMG CoA reductase inhibitors and thus are active in inhibiting cholesterol biosynthesis, modulating blood serum lipids, for example, lowering LDL cholesterol and/or increasing HDL cholesterol, and treating hyperlipidemia, dyslipidemia, hormone replacement therapy, hypercholesterolemia, hypertriglyceridemia and atherosclerosis as well as Alzheimer's disease and osteoporosis 1and pharmaceutically acceptable salts thereof, 2n is 0 or 1;x is 0, 1, 2, 3 or 4;y is 0, 1, 2, 3 or 4, provided that at least one of x and y is other than 0; and optionally one or more carbons of (CH.sub.2), and/or (CH.sub.2).sub.y together with additional carbons form a 3 to 7 membered spirocyclic ring;R.sub.1 and R.sub.2 are the same or different and are independently selected from alkyl, arylalkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, heteroaryl or cycloheteroalkyl;R.sub.3 is H or lower alkyl;R.sub.4 and R.sub.7 are as defined herein. Excerpt(s): This application claims priority from U.S. provisional application No. 60/211,594, filed Jun. 15, 2000. The present invention relates to compounds and pharmaceutical compositions useful as hypocholesterolemic and hypolipidemic agents. More particularly, this invention concerns (1) certain inhibitors of the enzyme 3hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) that include a pyridine containing nucleus attached by means of a linker to an HMG-binding domain sidechain, (2) pharmaceutical compositions containing such compounds and (3) a method of lowering blood serum cholesterol levels and modulating blood serum lipids employing such pharmaceutical compositions. r is 0, 1, 2, or 3. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Hormone replacement therapy Inventor(s): Pickar, James H.; (Springfield, PA) Correspondence: Cozen O' Connor, P. C.; 1900 Market Street; Philadelphia; PA; 191033508; US Patent Application Number: 20030216367 Date filed: May 15, 2003 Abstract: This invention relates to methods for providing hormone replacement therapy in perimenopausal, menopausal, and postmenopausal women through the sequential administration of combinations of conjugated estrogens and trimegestone. Excerpt(s): This application claims priority from copending provisional application Serial No. 60/381,257, filed May 17, 2002, the entire disclosure of which is hereby incorporated by reference. This invention relates to methods and pharmaceutical compositions for providing hormone replacement therapy in perimenopausal, menopausal, and postmenopausal women through the administration of combinations of conjugated estrogens and trimegestone. Menopause is generally defined as the last natural menstrual period and is characterized by the cessation of ovarian function, leading to the substantial diminution of circulating estrogen in the bloodstream. Menopause is usually identified, in retrospect, after 12 months of amenorrhea. It is usually not a sudden event, but is often preceded by a time of irregular menstrual cycles prior to eventual cessation of menses. Following the cessation of menstruation, the decline in endogenous estrogen concentrations is typically rapid. There is a decrease in serum estrogens from circulating levels ranging from 40-250 pg/mL of estradiol and 40170 pg/mL of estrone during ovulatory cycles to less than 15 pg/mL of estradiol and 30 pg/mL of estrone in postmenopausal women. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Hormone replacement therapy method Inventor(s): Elliesen, Jorg; (Berlin, DE), Riedl, Jutta; (Berlin, DE) Correspondence: John R Moses; Millen White Zeland & Branigan P C; 2200 Clarendon Boulevard Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20020142028 Date filed: May 1, 2000 Abstract: Varying the daily dose of either or both of the estrogen and the progestogen administered for hormone replacement therapy (HRT) is readily and inexpensively accomplished, without the necessity of the physician prescribing a new product each time the daily dose of the estrogen or progestogen is changed, by administering preferably transdermally the estrogen and the progestogen contained in separate extrudable pharmaceutical compositions from a dispenser which contains means, preferably adjustable only by the attending physician or dispensing pharmacist, for varying the volume of either or both of the respective compositions which is dispensed as a single dose from the dispenser in response to a defined digital dispensing manipulation of the dispenser thereby facilitating optimal compliance to a combination of HRT with individually adjusted dosages of the estrogen and progestogen. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 08/535,402, filed Sep. 28, 1995, which is hereby incorporated by reference. This

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invention relates to a method of conducting hormone replacement therapy (HRT) and to dispensers and kits adapted to practice the method. HRT in women during the menopausal and post-menopausal period of their lives to prevent or at least diminish the adverse physiological effects thereof, such as bone loss and resultant structural deformation, is now conventional therapy, irrespective of whether the menopause is surgically induced or is the result of the normal aging process. HRT usually involves either the concurrent administration of both an estrogen and a progestogen on a constant, e.g., daily, basis or constant administration of an estrogen and intermittent, e.g., on the 10th to 14th days of a 28 day cycle, administration of the progestogen, at respective dosages which often are changed during the period of HRT, depending on the symptoms currently being displayed by an individual as a result of the menopausal state, the HRT or both. Those doses may be changed infrequently, e.g., every six months or longer at the time the individual visits her doctor for a routine examination, or more often, e.g., from month to month or even more frequently, if the individual is experiencing undesirable menstrual symptoms, e.g., irregular menses, break through bleeding, which is a common consequence of an imbalace of estrogens and progestogens in a continuous combined HRT regimin, excessive blood flow, severe bleeding pain or cramps or a number of other symptoms consistent with the dosage of one or both of the estrogen and the progestogen being too high and thereby creating hormonal side effects, e.g., breast tenderness, nausea, edema, menstrual disorders, etc., or too low and thereby limiting the efficacy of the HRT or creating other side effects. Moreover, because menopause involves a gradual reduction in circulating serum estrogen and progestogen levels, it is usually desirable to initiate HRT during the peri-menopausal period at lower dosages of the estrogen and/or progestogen and gradually increase the dosage thereof as menopause progresses. In addition, a full replacement dosage of estrogens may not be tolerable in a postmenopausal woman whose body has been adapting to estrogen deficiency over a certain period and who may experience breast tension, nausea, oedema and other typical side-effects when receiving the full dosage. In these women, one may wish to start with a very small dosage and increase it only gradually until symptoms have disappeared or plasma levels have reached premenopausal values. Modifying the progesterone dosage level also is frequently necessary during menopause to deal with menses irregularities. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Identifying, monitoring, and treating women for breast precancer or cancer Inventor(s): Cen, Hui; (Oakland, CA), Hung, David; (Belmont, CA), Love, Susan; (Pacific Palisades, CA) Correspondence: Banner & Witcoff, LTD.; 1001 G. Street, N.W. Eleventh Floor; Washington; DC; 20001-4597; US Patent Application Number: 20030022161 Date filed: February 10, 2000 Abstract: The invention is to methods for screening women for breast cancer and precancer by determining a level of an estrogen-related marker. The invention further provides methods of treating such patients identified as having one or more abnormal ductal epithelial cells and an estrogen-related marker. The invention provides methods for screening patient for hormone replacement therapy (HRT), and of monitoring such patients once they begin HRT. The invention provides methods of treating peri-, menopausal or postmenopausal women for both cancer risk reduction and menopausal

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symptoms (or other conditions related to lowered systemic estrogen levels). The invention also provides kits for the screening, monitoring, and treating methods described. Excerpt(s): The present application is a continuation-in-part of U.S. application Ser. No. 09/313,463, filed on May 17, 1999, which claimed the benefit and priority of Provisional U.S. Application No. 60/117,281 filed on Jan. 26, 1999, under 37 CFR.sctn.1.78, the full disclosures of which are incorporated herein by reference. The field of this invention is identifying, treating and monitoring women at risk for or having breast precancer or cancer. Although the role of hormone replacement therapy (HRT) using estrogen or an estrogen/progestin combination in the etiology of breast cancer continues to be debated (Colditz, G A J. Women 's Health 8(3): 347-57 (1999), the magnitude of increase in breast cancer risk per year of hormone use is comparable to that associated with delaying menopause by a year (Colditz, G A J. Nat'l Cancer Inst 90(11): 814-23 (1998). Adding support to these conclusions is other research concluding that experimental and clinical evidence currently underway and recently completed suggests that breast neoplasia is a hormone-dependent process (Newman et al., J. Surg. Oncol. 71(4): 250-260 (1999)) and as such a postmenopausal patient may be placed at increased risk of breast neoplasia with prolonged HRT. Studies conducted by at least one group in Tavani and Vecchia, Drugs Aging 14(5): 347-57 (1999) indicate that there is a 2.3% risk of breast cancer for women on HRT for from 5 to 15 years if the women start the therapy at age 50. Estrogens and estrogen/progestin combination are most frequently prescribed to patients experiencing menopausal symptoms, and generally the duration of treatment is about a year but sometimes up to 5 years for these patients. Less frequently, estrogen is prescribed to postmenopausal women experiencing osteoporosis (bone density loss). The treatment duration for osteoporosis, a potentially serious and life threatening condition, can be prolonged. Osteoporosis is associated with increased mortality due to increased fractures, particularly hip fractures and affects millions of people worldwide. Women of postmenopausal age (i.e., approximately over 50 years of age) are one category prone to the development of low bone density associated with osteoporosis. See, Watts, Obstet Gynecol Surv 54(8): 532-8 (1999). Osteoporosis is reduced with estrogen administration. See, for example Shoupe D, Hosp Pract (OffEd) 34(8): 97-103, 107-8, 113-4 (1999). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Low dose estrogen interrupted hormone replacement therapy Inventor(s): Ausmanas, Militza K.; (Lake Forest, IL), Casper, Robert F.; (Toronto, CA), Shangold, Gary A.; (Califon, NJ) Correspondence: Crowell & Moring Llp; Intellectual Property Group; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20020165209 Date filed: April 30, 2002 Abstract: A hormone replacement therapy, comprising a plurality of daily doses of a pharmaceutical preparation, the doses being administered continuously and consecutively in alternating phases of three daily doses, a relatively dominant estrogenic activity phase comprising three daily doses of a substance exhibiting estrogenic activity equivalent to about 1 mg per day of 17.beta.-estradiol per day, and a relatively dominant progestagenic activity phase of a combination of a substance exhibiting estrogenic activity equivalent to about 1 mg per day of 17.beta.-estradiol and a substance exhibiting progestogenic activity equivalent to about 90.mu.g per day of norgestimate.

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Excerpt(s): This application claims the benefit of priority from U.S. Provisional Application No. 60/126,970 filed Mar. 30, 1999, the disclosure of which is incorporated herein by reference. The present invention relates to hormone replacement therapy (HRT) for administration to menopausal or castrate women. More specifically, the present invention relates to a hormone replacement therapy regimen comprising a specific dosage combination that includes a reduced amount of estrogen, which provides a reduced risk of cancer, while providing a regimen with vasomotor symptom relief that is usually only available at higher estrogen levels. There are a number of patents relating to hormone replacement therapy and many different formulations available in the marketplace. Many formulations involve the administration of continuous estrogen and progestogen, while other regimens can be characterized as interrupted or cyclophasic. Examples of patents covering interrupted regimens include Robert F. Casper's U.S. Pat. No. 5,108,995 issued Aug. 28, 1992, for a method of HRT; U.S. Pat. No. 5,256,421 issued Oct. 26, 1993 for an HRT method; U.S. Pat. No. 5,422,119 issued Jun. 6, 1995 for a transdermal HRT method, preparation and package; and U.S. Pat. No. 5,382,573 issued Jan. 17, 1995, which relates to an HRT preparation and package. Casper is also the holder of U.S. Pat. No. 5,276,022 issued Jan. 4, 1994 and U.S. Pat. No. 5,585,370 issued Dec. 17, 1996 both of which relate to contraceptive therapy. The disclosures of all of these patents are incorporated herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for preventing hormone induced adverse effects Inventor(s): Levy, Joseph; (Omer, IL), Sharoni, Yoav; (Omer, IL) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20010027216 Date filed: March 5, 2001 Abstract: The present invention provides a method for preventing the adverse effects which may be associated with the administration of at least one hormone to a subject without detectable cancer comprising administering to such subject at least one carotenoid. The invention further provides a method for preventing a variety of adverse effects associated with the administration of hormones, including, for example, an increased risk for developing cancer. The invention further provides a method for preventing adverse effects without inhibiting the beneficial activity of the hormone. The invention further provides a method for preventing the adverse effects associated with administration of estrogen and/or progestin in hormone replacement therapy without inhibiting the beneficial activity of such hormone. The invention further provides a method for preventing the adverse effects associated with the administration of phytoestrogens. The invention further provides a method for preventing adverse effects associated with the administration of phytoestrogens without inhibiting the beneficial activity of such hormone. Excerpt(s): The present invention provides a method for preventing adverse effects associated with the administration of hormones such as phytoestrogens and steroidal estrogens. Hormone intake by humans can occur through, inter alia, consumption of pharmaceutical compositions, foodstuffs, nutritional supplements, and nutraceuticals. Such hormones include phytoestrogens, or nonsteroidal estrogens, steroidal estrogens and progestins. Phytoestrogens comprise, for example, genistein, daidzein and glycitein, and their respective glucoside, malonylglucoside and acetylglucoside derivatives. Estrogens and progestins are known to be used for hormone replacement therapy

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(HRT) and in contraceptive medications. HRT with estrogens or with estrogen/progestin combinations has been the standard method for treating symptoms associated with menopause (Emster V L et al. (1988) Benefits and Risks of Menopausal Estrogen and/or Progestin Hormone Use, Prev. Med. 17:201-223). The onset of menopause in mature adult women, which is accompanied by reduced estrogen production, is associated with an array of symptoms. These symptoms include hot and cold flashes, palpitations, dizziness, headaches, altered secretions as well as weight loss and gain. Reduced levels of circulating estrogen in post-menopausal women are also associated with increased risks of osteoporosis and coronary heart disease. Treatment protocols using estrogen alone significantly reduce the risks of cardiovascular disease and osteoporosis, if treatment begins at menopause. The protective effect of estrogen against heart disease is related to its ability to raise levels of circulating HDL and lower levels of LDL. In contrast with this beneficial effect, long-term use of estrogens is positively correlated with an increased risk for endometrial cancer development. This risk may be reduced by simultaneous administration of a progestin, which prevents overgrowth of endometrial cells. Hence, an estrogen/progestin combined HRT protocol is recommended for a woman with an intact uterus. This form of combination therapy however, apparently diminishes the beneficial effects of estrogen on the plasma lipid profile (Lobo R. 1992. The Role of Progestins in Hormone Replacement Therapy; Am. J Obstet. Gynecol. 166:1997-2004). Furthermore, some progestins are associated with an increased risk of mammary cancer development (Staffa J. A. et al. 1991. Progestins and Breast Cancer: An Epidemiologic Review, 57: 473-491; King R. J. B. 1991. A Discussion of the Roles of Estrogen and Progestin in Human Mammary Carcinogenesis, J. Ster. Biochem. Molec. Bio. 39:8111-8118). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for treating or preventing cardiovascular disease via administration of an ace inhibitor Inventor(s): Vaughan, Douglas E.; (Nashville, TN) Correspondence: Jenkins & Wilson, PA; 3100 Tower Blvd; Suite 1400; Durham; NC; 27707; US Patent Application Number: 20020142970 Date filed: October 10, 2001 Abstract: A method for preventing or reducing a risk of cardiovascular disease in a healthy subject via administration of an ACE inhibitor. Also provided is a method for reducing a plasma level of PAI-1 in a healthy subject via administration of an ACE inhibitor. The methods can be combined with hormone replacement therapy for improved effectiveness. Representative healthy subjects include post-menopausal women. Excerpt(s): This application is based on and claims priority to U.S. Provisional Application Serial No. 60/239,324, filed Oct. 10, 2000, the entire contents of which are herein incorporated by reference. The present invention relates generally to therapeutic methods for cardiovascular disease. More particularly, the present invention relates to the modulation of plasminogen activator inhibitor--type 1 (PAI-1) levels via administration of an angiotensin converting enzyme (ACE) inhibitor to a subject in need thereof. Preferred subjects comprise post-menopausal women. Cardiovascular disease is the most common cause of death and disability in the United States. While the incidence of cardiovascular disease, and in particular coronary artery disease and acute

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myocardial infarction, is reduced in pre-menopausal women compared to that of age marked men, the incidence of cardiovascular disease increases rapidly in women following menopause. See Mendelsohn & Karas (1999) N Engl J Med 340:1801-1811. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of diagnosing and monitoring endometrial glandular development Inventor(s): Dubowy, Rebecca L.; (Chicago, IL), Kliman, Harvey J.; (New Haven, CT) Correspondence: Woodcock Washburn Kurtz; Mackiewicz & Norris Llp; 46th Floor; One Liberty Place; Philadelphia; PA; 19103; US Patent Application Number: 20020006628 Date filed: March 8, 2001 Abstract: Methods of diagnosing an abnormality in endometrial glandular development in a woman suspected of being infertile are disclosed. Methods of predicting abnormal endometrial glandular development are also disclosed. In addition, methods of assessing the suitability of the endometrium for embryo implantation in a woman undergoing ovulation induction are disclosed. Further, methods of evaluating the effect of a hormonal protocol on endometrial glandular development in a woman undergoing a hormonal protocol to produce a mock cycle are disclosed. Methods of evaluating a hormone replacement therapy protocol in a woman undergoing hormone replacement therapy are disclosed. Further, methods of diagnosing endometrial glandular mitotic arrest in a woman suspected of having endometrial hyperplasia are disclosed. Excerpt(s): The present application claims priority of application Ser. No. 60/187,682, filed Mar. 8, 2000, which is hereby incorporated by reference in its entirety. The present invention relates generally to the fields of infertility, endometrial hyperplasia, assisted reproduction, and hormone replacement therapy for women, and methods of assessing and monitoring endometrial development in connection with diagnoses and therapies related to the same. Over 10% of reproductive age couples suffer from infertility. While many of these couples are successfully diagnosed and treated for their underlying conditions, nearly 20-25% are found to have no proven cause for their difficulties in achieving a successful pregnancy. Many of these couples further pursue costly procedures using assisted reproductive technology (ART) in an attempt to overcome their unidentified problems. The ART procedures used in the United States are IVF (in vitro fertilization), GIFT (gamete intrafallopian transfer), and ZIFT (zygote intrafallopian transfer). Yet, even with ART, only 29.5% of fresh, nondonor cycles result in pregnancies and only 24% result in live births. Rates vary between 19% and 25% depending on the cause of the infertility and older women generally have lower rates of success. Also, the live birth rate decreases to 18.6% when frozen embryos are used. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Multi-vitamin and hormone replacement supplement Inventor(s): Fox, Dorothy Jean; (Chesapeake, VA), Schloss, Caroline Maxine; (Knotts Island, NC) Correspondence: Kimberly A Chasteen; Williams Mullen Clark & Dobbins; One Iod Oyster Point Road; Suite 210; Newport News; VA; 23602 Patent Application Number: 20030096018 Date filed: September 23, 2002 Abstract: A supplement is disclosed for use by naturally or surgically menopausal women. The supplement includes: Estrogen, Selenium, Zinc, Chromium, Calcium, Copper, Phosphorus, Magnesium, Molybdenum, Iodine, Beta Carotene, Ascorbic Acid, Vitamin D, Vitamin E, Vitamin K, Thiamin, Riboflavin, Vitamin B6, Vitamin B12, Folic Acid, Iron, Pantothenic Acid, and Biotin. The supplement provides hormone replacement therapy along with nutritional supplements. Excerpt(s): The present invention relates generally to a pharmaceutical supplement for menopausal women and more specifically to a pharmaceutical supplement which combines the hormone estrogen with daily supplemental vitamins to treat menopausal women and women who have undergone complete hysterectomies as more fully set forth in the below specifications, drawings and claims. It is well known that estrogen is critical to a woman's health in that it helps to protect the cardiovascular system, helps protect against bone loss and aids mental sharpness. At menopause or subsequent to a complete hysterectomy, the estrogen levels decline significantly thus, the protective aspects of estrogen are significantly reduced for these women. Because heart disease is a major cause of death in women, this creates an increased risk for menopausal and posthysterectomy women. Further, loss of the protection against bone loss can lead to osteoporosis, another major problem for these women. The impairment of cognitive abilities can be another side effect of the significant estrogen loss suffered in menopause or post-hysterectomy. Additional side effects have been linked to reduced estrogen levels such as urinary incontinence and weight gain. Many women are treated with hormone replacement therapy to help reduce these symptoms. The treatment generally consists of supplemental estrogen. This reduces the problems noted above, heart disease, bone loss, loss of cognitive ability, urinary incontinence, weight gain, as well as other well-known symptoms such as hot flashes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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New antiestrogens, process for their production and their pharmaceutical use Inventor(s): Bohlmann, Rolf; (Berlin, DE), Fritzemeier, Karl-Heinrich; (Berlin, DE), Klar, Ulrich; (Berlin, DE), Lessl, Monika; (Berlin, DE), Lichtner, Rosemarie; (Berlin, DE), Parczyk, Karsten; (Berlin, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030162830 Date filed: February 21, 2003 Abstract: This invention relates to new antiestrogens of the general formula 1in which the substituents have the meanings that are explained in more detail in the description.The new compounds are a) pure antiestrogens or b) antiestrogens with

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partial estrogenic action (tissue-selective estrogens).Based on these properties, the new compounds are suitable for the production of pharmaceutical agents: in the case of a), for example, for the treatment of breast cancer; in the case of b), for example, for hormone replacement therapy. Excerpt(s): Z stands for hydrogen, halogen, OH, N.sub.3, NH.sub.2, CO.sub.2H, CO.sub.2--(C.sub.1-C.sub.20)-alkyl, C.sub.1-C.sub.20 alkoxy, --NO.sub.2, --CN or C.sub.1-C.sub.20 acyloxy. As used throughout this application (e.g., with respect to Y, R.sup.4 or R.sup.5 groups as defined above), the term heteroaryl means, e.g., a C.sub.4C.sub.10 ring which optionally contains one or more (e.g., 1-3) N, S or O atoms in place of C. Also, as used throughout (e.g., with respect to substituents E, R.sup.3, R.sup.4a or R.sup.5 as defined above), an alkenyene or alkynylene typically contains 1-3 unsaturated bonds. The invention relates to the diastereomers and/or enantiomers of these derivatives and also their mixtures. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel methods and compositions to upregulate, redirect or limit immune responses to peptides, proteins and other bioactive compounds and vectors expressing the saMen Inventor(s): Bot, Adrian; (San Diego, CA), Dellamary, Luis; (San Marcos, CA), Smith, Dan J.; (San Diego, CA), Woods, Catherine M.; (La Jolla, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 620 Newport Center Drive; Sixteenth Floor; Newport Beach; CA; 92660; US Patent Application Number: 20020106368 Date filed: July 30, 2001 Abstract: Novel compositions are disclosed which can induce or enhance an immune response against foreign or self antigens (microbial or parasitic) or modulate (that can lead to suppression) the activity of pathogenic cells in inflammatory or autoimmune diseases. Compositions and methods are taught in how to limit the generation of an immune response against formulated peptides and proteins with application in antibody therapy or hormone replacement therapy. Methods of suppressing autoimmunity are also disclosed which use ligands for cellular receptors expressed on cells of the innate immune system and more specifically for down-regulation of autoimmune processes by either deletion or induction of anergy at the level of autoreactive T cells or by triggering active-suppressor T cells that down-regulate the activity of pathogenic cells. Excerpt(s): The present application claims priority to U.S. Provisional Patent Application Serial No. 60/221,544, filed Jul. 28, 2000, the disclosure of which is incorporated herein by reference in its entirety. The present invention is generally related to various microparticle formulations and methods to control an immune response. More specifically, the present invention is directed to administration of formulated peptides or proteins formulated in microparticles which control (upregulate, redirect or limit) an immune response in a subject. Novel compositions are disclosed which can induce or enhance an immune response against foreign antigens (microbial or parasitic) or modulate (that can lead to suppression) the activity of pathogenic cells in inflammatory or autoimmune diseases. Compositions and methods are disclosed in how to limit the generation of an immune response against formulated peptides and proteins with application in antibody or hormone replacement therapy. Methods of suppressing

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autoimmunity are also disclosed which use ligands for cellular receptors expressed on cells of the innate immune system and more specifically for down-regulation of autoimmune processes by either deletion or induction of anergy at the level of autoreactive T cells or by triggering active-suppressor T cells that down-regulate the activity of pathogenic cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

ONCE-A-MONTH INJECTION AS A DEPOT CONTRACEPTIVE AND FOR HORMONE REPLACEMENT THERAPY FOR PERIMENOPAUSAL AND PREMENOPAUSAL WOMEN Inventor(s): AYDINLIK, SEMIRAMIS; (BERLIN, DE), LACHNIT-FIXSON, URSULA; (BERLIN, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20010006963 Date filed: July 6, 1999 Abstract: This invention describes the use of a once-a-month injection (once-a-month injectable) that contains an estrogenic and gestagenic component as an active ingredient for the production of a pharmaceutical agent for contraception and simultaneous hormone replacement therapy for perimenopausal and premenopausal women.With this pharmaceutical agent, a more reliable contraceptive effect with a "natural" estrogen (without ethinylestradiol) with accompanying active therapy of the beginning estrogenloss symptoms, as well as prevention of osteoporosis, is achieved. Excerpt(s): This invention relates to the use of a once-a-month injection (once-a-month injectable composition) that contains an estrogenic and gestagenic component as an active ingredient for the production of a pharmaceutical agent for contraception and simultaneous hormone replacement therapy for perimenopausal and premenopausal women. A once-a-month injection as defined by this invention means a hormone preparation that is injected in women of child-bearing age once a month for contraception. In this hormone preparation, a gestagenic as well as an estrogenic component are contained as active substances, each with a sufficiently long action to achieve a contraceptive effect for a one-month period. So-called progestogen-only injectables are also available, which ensure longer-lasting contraceptive protection, but with poor cycle control. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Patient compliance and monitoring system Inventor(s): Leonard, Thomas W.; (Wilmington, NC), Waldon, R. Forrest; (Wilmington, NC) Correspondence: Allen R. Baum; Burns, Doane, Swecker & Matthis, L.L.P.; P. O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030036923 Date filed: May 18, 2001

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Abstract: This invention is directed to methods and systems for monitoring compliance with or effectiveness of hormone replacement therapy. The methods and systems of the invention provide an efficient means of communication between medical professionals and patients for between visit monitoring of patient compliance with a prescribed hormone therapy and the effectiveness of the treatment recommended. Excerpt(s): The present invention relates to methods of monitoring patient symptoms, side effects and compliance with administration of prescribed therapeutic agents that are prophylactic or used to treat slow onset or chronic conditions. The present invention further provides systems for remotely assessing patient symptoms, side effects, and compliance with chronic therapeutic agents. There are significant problems with patient compliance monitoring and communication in prophylactic therapies or in the treatment of slow onset conditions or diseases or chronic conditions, such as osteoporosis, vasomotor symptoms associated with menopause, vulvar/vagina atrophy associated with menopause, cardiovascular prophylaxis, neurodegenerative disease and hypertension. Symptoms resulting from these types of conditions may be difficult for the patient to accurately describe in a short office visit with medical professionals and may change as therapy is ongoing. These changes may require a review of the patient's symptoms over time to ascertain therapy effectiveness and side effects profiles. In addition, the symptoms may be difficult for medical professionals to adequately detect, diagnose, and address in the small amount of time devoted to each patient during an office visit. In addition to addressing patient symptoms and side effects in therapies for prophylaxis, in slow onset diseases or other conditions, there is often a problem with patient compliance with the administration of recommended or prescribed therapeutic agents. In some cases the patients may discontinue therapy because acute symptoms subside. Others may stop therapy because side effects of the therapy become more pronounced or troubling than the symptoms of the disease or condition. Additionally patients may discontinue therapy because of a perceived lack of benefit or overexaggeration of risk related to therapies. In many cases patients may take the therapy sporadically or not as regularly as recommended for optimum benefit. The patient's physician may not become aware of cessation of therapy or sporadic continuation of therapy in time to address problems that may result and encourage compliance, or modify the therapy to optimize results. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Progestin therapy for maintaining amenorrhea Inventor(s): Bologna, William J.; (Paris, FR), deZiegler, Dominique; (Paris, FR), Levine, Howard L.; (Oceanside, NY) Correspondence: Lyon & Lyon Llp; Suite 4700; 633 West Fifth Street; Los Angeles; CA; 90071-2066; US Patent Application Number: 20010031747 Date filed: April 3, 2001 Abstract: The present invention teaches that daily, cyclical vaginal delivery of progestin may be used to provide regular, predictable withdrawal bleeding during hormone replacement therapy. The present invention also teaches that constant administration of progestin in a water-insoluble, water-swellable cross-linked polycarboxylic acid polymer may be used to maintain amenorrhea. Either regimen is accompanied by a significant decrease in adverse side effects.

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Excerpt(s): This invention relates to a method of administering progestin therapy in a manner that promotes controlled bleeding, rather than the irregular and unpredictable bleeding that normally accompanies progestin administration. Progesterone is a naturally occurring steroid which is the main steroid secreted by women during their reproductive years. This steroid has been studied extensively and has been found to be a major precursor in the biosynthesis of most other steroids, particularly glucocorticoids, androgens and estrogens. Progesterone also stimulates the growth of the uterus and a number of specific changes in the endometrium and myometrium. It is essential for the development of decidual tissue and the differentiation of luminal and glandular epithelial tissue. Progesterone also plays several roles in gestation, including breast enlargement, inhibition of uterine contractility, maintenance of gestation, immunological protection of the embryo, and inhibition of prostaglandin synthesis. Progestins include the natural progestin, progesterone, as well as the synthetic progestins, such as medroxyprogesterone acetate (MPA). Progestins have been used pharmaceutically in the treatment of a number of clinical disorders such as luteal phase deficiency, dysfunctional uterine bleeding, endometriosis, endometrial carcinoma, benign breast disease, pre-eclampsia, and assisting in vitro fertilization, preventing early abortion and reducing the occurrence of endometrial hyperplasia in estrogen replacement therapy (ERT). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Progestogen-anti-progestogen regimens Inventor(s): Bennink, Herman Jan Tijmen Coelingh; (Driebergen, NL), Verbost, Pieter M.; (Et Heesch, NL) Correspondence: Michael G. Sullivan; Akzo Nobel Patent Department; Suite 206; 1300 Piccard Drive; Rockville; MD; 20850; US Patent Application Number: 20010027189 Date filed: January 8, 2001 Abstract: Disclosed is a contraceptive and/or HRT (hormone replacement therapy) kit comprising sequential daily dosage units each containing as the sole contraceptively effective ingredient of a progestogen, or as effective ingredient for HRT a progestogen with or without an estrogen or an estrogen only, and further two or more dosage units comprising an anti-progestogen. One of the anti-progestogen is administered at the beginning and the others regularly divided throughout the cycle, preferably one only in the middle of the cycle. Excerpt(s): The invention relates generally to progestogen-anti-progestogen regimens for use in contraception and hormone replacement therapy, and more specifically for contraception to progestogen-anti-progestogen regimens involving only the administration of a progestogen and an anti-progestogen. It has been known for some time that contraception can be achieved by the oral administration of sufficient quantities of a progestogen to a female of child-bearing age. Contraceptive preparations that minimize the incidence of menstrual spotting, break through bleeding, variations in menstrual cycle length and amenorrhea are preferred. It is further preferred to use contraceptive regimens that minimize the amounts of estrogens and progestogens used. Preparations that fulfil many of these requirements are disclosed in WO 93/21927, wherein a contraceptive regimen free from estrogens is described, the active ingredient being a progestational agent and intermittently an anti-progestogen. The regimen used is a regimen wherein only levonorgestel is administered as the progestogen, except that

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on days 1, 30, 60, 90, 120, 150, and 180 a dosage of the anti-progestogen RU 486 is administered. In fact the regimen is a progestogen-only regimen, interrupted by antiprogestogen administration at the beginning of each cycle. Although this regimen is a considerable improvement over existing regimens comprising estrogens, the bleeding profile is still not perfect since it recurs slowly after an almost bleeding-free interval, and further improvement is therefor desirable. "Progestogen-only pills" are a preferred method of contraception for breast-feeding mothers, older women, women for whom estrogen is contraindicated, women who are hypertensive, and women who develop migraine headaches when taking a combined pill (i.e. one containing an estrogen and progestogen component). See, e.g. "Contraception for women over the age of 35", IPPF Medical Bulletin, 22: 3-4 (1988) and P. W. Howie "The progestogen-only pill", Brit. J. Obstet. Gynaecol., 92: 1001-2 (1985). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Progestogen-anti-progestogen regimens Inventor(s): Bennink, Herman Jan Tijmen Coelingh; (Driebergen, NL), Verbost, Pieter M.; (Heesch, NL) Correspondence: Intervet Inc; 405 State Street; PO Box 318; Millsboro; DE; 19966; US Patent Application Number: 20030078245 Date filed: November 25, 2002 Abstract: A contraceptive and/or HRT (hormone replacement therapy) kit comprising sequential daily dosage units each containing as the sole contraceptively effective ingredient a progestogen, or as the effective ingredient for HRT a progestogen with or without an estrogen or an estrogen only, and further two or more dosage units comprising an anti-progestogen. The present invention also provides contraceptive and HRT methods comprising administering daily dosage units of a progestogen and antiprogestogen. Excerpt(s): This application is a continuation of U.S. Ser. No. 09/194,134, filed Nov. 20, 1998, which is the U.S. National Phase of PCT/EP97/03288, filed Jun. 23, 1997. The invention relates generally to progestogen-anti-progestogen regimens for use in contraception and hormone replacement therapy, and more specifically for contraception to progestogen-anti-progestogen regimens involving only the administration of a progestogen and an anti-progestogen. It has been known for some time that contraception can be achieved by the oral administration of sufficient quantities of a progestogen to a female of child-bearing age. Contraceptive preparations that minimize the incidence of menstrual spotting, break through bleeding, variations in menstrual cycle length and amenorrhea are preferred. It is further preferred to use contraceptive regimens that minimize the amounts of estrogens and progestogens used. Preparations that fulfill many of these requirements are disclosed in WO 93/21927, wherein a contraceptive regimen free from estrogens is described, the active ingredient being a progestational agent and intermittently an anti-progestogen. The regimen used is a regimen wherein only levonorgestel is administered as the progestogen, except that on days 1, 30, 60, 90, 120, 150, and 180 a dosage of the anti-progestogen RU 486 is administered. In fact the regimen is a progestogen-only regimen, interrupted by antiprogestogen administration at the beginning of each cycle. Although this regimen is a considerable improvement over existing regimens comprising estrogens, the bleeding profile is still not perfect since it recurs slowly after an almost bleeding-free interval, and further improvement is therefor desirable.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Thio-oxindole derivatives Inventor(s): Edwards, James P.; (San Diego, CA), Fensome, Andrew; (Wayne, PA), Jones, Todd K.; (Solana Beach, CA), Koko, Marci C.; (Bethlehem, PA), Melenski, Edward G.; (Woodlyn, PA), Tegley, Christopher M.; (Thousand Oaks, CA), Wrobel, Jay E.; (Lawrenceville, NJ), Zhang, Puwen; (Audubon, PA), Zhi, Lin; (San Diego, CA) Correspondence: Howson And Howson; One Spring House Corporation Center; Box 457; 321 Norristown Road; Spring House; PA; 19477; US Patent Application Number: 20020169198 Date filed: April 5, 2002 Abstract: This invention relates to methods of co-administering compounds of formula 1 which are agonists of the progesterone receptor which have the general structure: 1wherein:R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and Q.sup.1 are as defined herein, or a pharmaceutically acceptable salt thereof, with estrogen, an estrogen, or an estrogen receptor agonist for contraception, hormone replacement therapy, or treating progesterone-related carcinomas and adenocarcinomas. Excerpt(s): This application is a continuation of U.S. patent application Ser. No. 10/022,467, filed Oct. 30, 2001, which is a divisional of U.S. patent application Ser. No. 09/552,033, filed Apr. 19, 2000, now U.S. Pat. No. 6,355,648, issued Mar. 12, 2002, which claims the benefit of the priority of U.S. Provisional Patent Application No. 60/172,259, filed May 4, 1999, now abandoned. This invention relates to compounds which are agonists of the progesterone receptor, their preparation and utility. Intracellular receptors (IR) form a class of structurally related gene regulators known as "ligand dependent transcription factors" (R. M. Evans, Science, 240, 889, 1988). The steroid receptor family is a subset of the IR family, including progesterone receptor (PR), estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Transdermal administration of steroid drugs using hydroxide-releasing agents as permeation enhancers Inventor(s): Hsu, Tsung-Min; (San Diego, CA), Luo, Eric C.; (Plano, TX) Correspondence: Reed & Associates; 800 Menlo Avenue; Suite 210; Menlo Park; CA; 94025; US Patent Application Number: 20010033870 Date filed: December 14, 2000 Abstract: A method is provided for increasing the permeability of skin or mucosal tissue to transdermally administered steroid drugs. The method involves use of a specified amount of a hydroxide-releasing agent, the amount optimized to increase the flux of the drug through a body surface while minimizing the likelihood of skin damage, irritation or sensitization. Formulations and drug delivery systems for co-administering a hydroxide-releasing agent with a steroid drug are provided as well. Optimally, the

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steroid drugs are a combination of an estrogen and progestin that may be administered in female hormone replacement therapy, to provide female contraception, and the like. Excerpt(s): This is a continuation-in-part of U.S. Ser. No.09/569,889, filed May 11, 2000 which is a continuation-in part of U.S. Ser. No. 09/465,098, filed Dec. 16, 1999, the disclosures of which are incorporated by reference. This invention relates generally to transdermal administration of pharmacologically active agents, and more particularly relates to methods and compositions for transdermally administering steroid drugs, particularly progestins and estrogens. The delivery of drugs through the skin provides many advantages; primarily, such a means of delivery is a comfortable, convenient and noninvasive way of administering drugs. The variable rates of absorption and metabolism encountered in oral treatment are avoided, and other inherent inconveniences--e.g., gastrointestinal irritation and the like--are eliminated as well. Transdermal drug delivery also makes possible a high degree of control over blood concentrations of any particular drug. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with hormone replacement therapy, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “hormone replacement therapy” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on hormone replacement therapy. You can also use this procedure to view pending patent applications concerning hormone replacement therapy. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. THERAPY

BOOKS ON HORMONE REPLACEMENT

Overview This chapter provides bibliographic book references relating to hormone replacement therapy. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on hormone replacement therapy include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “hormone replacement therapy” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on hormone replacement therapy: •

New dimensions in women's health. (2nd ed.) Source: Boston, MA: Jones and Bartlett. 2001. 531 pp. Contact: Available from Jones and Bartlett Publishers, 40 Tall Pine Drive, Sudbury, MA 01776. Telephone: (800) 832-0034 or (508) 443-5000 / e- mail: [email protected]. $56.95. Summary: Presented in four parts, this book discusses women's health issues over the full life cycle. Part one includes an introduction into the study of women's health including developmental issues over the lifespan, mental health, and occupational health. Part two focuses on lifestyle and social health, including nutrition, weight, exercise and fitness, substance abuse, violence, abuse, and sexual harassment. The third part discusses personal and sexual health, including contraception and abortion, pregnancy and childbirth, and reproductive tract infections. Finally, part four covers

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lifespan dimensions such as menopause and hormone replacement therapy, cardiovascular disease, and other chronic conditions. References and a glossary are included. •

Beyond Viagra: Plain Talk About Treating Male and Female Sexual Dysfunction Source: Montgomery, AL: Starrhill Press. 1999. 196 p. Contact: Available from Black Belt Press. P.O. Box 551, Montgomery, AL 36101. (800) 959-3245 or (334) 265-6753. Fax (334) 265-8880. PRICE: $13.95 plus shipping and handling. ISBN: 1573590142. Summary: This book discusses the drug sildenafil (Viagra) in the context of a larger discussion about sexuality and sexual dysfunction. Twenty-four chapters cover normal male sexual function, an overview of male sexual dysfunction, the causes of male erectile dysfunction, evaluating the male with erectile dysfunction, treatment strategies for metabolic disorders (including diabetes and prolactinoma), hormone replacement therapy, penile injections with vasoactive drugs, urethral suppository with vasoactive drugs, vacuum erection devices, vascular surgery for impotence, an overview of penile implants, treatment of Peyronie's disease, treatment of psychological impotence, the role of impotence support groups, herbal medicine for males, Viagra for male erectile dysfunction, Viagra in combination with injections or vacuum erection devices, Viagra in combination with penile implants, future treatments for erectile dysfunction, normal female sexual function, the causes and treatment of female sexual dysfunction, Viagra and apomorphine for females, herbal medicine for females, and healthy relationships and sexual function. The chapters are written in nontechnical language but include enough medical information to be of use to medical professionals wishing to learn more about sexual dysfunction. The book concludes with a list of resources and a subject index. 10 figures. 5 tables. 237 references.

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Coronary artery disease in women: What all physicians need to know Source: Philadelphia, PA: American College of Physicians: American Society of Internal Medicine. 1999. 615 pp. Contact: Available from American College of Physicians-American Society of Internal Medicine, 190 North Independence Mall West, Philadelphia, PA 19106. Telephone: (215) 351-2400 or (800) 523-1546 / fax: (215) 351- 2799 / e-mail: [email protected] / Web site: http://www.acponline.org. $43 for nonmembers, $32 for members; plus shipping and handling. Summary: This book for health care practitioners reviews all important aspects of coronary artery disease, with an emphasis on gender differences, age, and race. It contains five parts: the introduction, prevention, diagnosis, management, and conclusion. The section on prevention discusses smoking; diabetes and insulin resistance; the history and pharmacologic management of lipids/cholesterol; nutrition; hypertension; obesity; exercise as prevention; aspirin, antioxidants, and alcohol; and issues in hormone replacement therapy. The diagnosis section provides information on the differential diagnosis of chest pain, noninvasive testing techniques, and influence of gender in coronary angiography. Topics in the the section on management include angina pectoris, acute coronary syndromes, bypass grafting risks, angioplasty, congestive heart failure, psychosocial issues, and pharmacologic secondary prevention. The concluding section discusses future trends in treatment and research. Each chapter contains a summary and list of references. Numerous charts and graphs present statistical information. The book concludes with an index.

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Today and tomorrow's woman: Menopause: Before and after (Girls of 16 to women of 99) Source: Potomac, MD: Health Leadership Associates. 1996. 279 pp. Contact: Available from Health Leadership Associates, Inc, P.O. Box 59153, Potomac, MD 20854. Telephone: (800) 435-4775 / fax: (301) 983-2693. $10.00. Summary: This book is written for women 16 and older, and discusses ways menopause can be managed and controlled with proper planning and healthy activities. Topics include understanding the myths and realities of menopause, osteoporosis, cardiovascular disease in women, management through hormone replacement therapy, and starting and maintaining a healthy lifestyle. The final chapter centers on research in the area of women's health and menopause. Appendices include a glossary, a resource directory, references, and an index.

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Mayo Clinic on Managing Diabetes Source: Rochester, MN: Mayo Clinic. 2001. 194 p. Contact: Available from Mayo Clinic Health Information. 200 First Street, S.W., Fifth Floor Centerplace Building, Rochester, MN 55905. (800) 430-9699. Website: www.mayoclinic.com. PRICE: $14.95 plus shipping and handling. ISBN: 1893005062. Summary: This book provides practical and easy to understand information on controlling diabetes and preventing complications of the disease. Part one provides facts about diabetes. Topics include types of diabetes, the signs and symptoms of diabetes, the risk factors for diabetes, and the criteria and tests for diagnosing diabetes. In addition, the issue of diabetic complications is addressed, focusing on hypoglycemia, diabetic hyperosmolar syndrome, diabetic ketoacidosis, neuropathy, nephropathy, retinopathy, heart and blood vessel disease, and increased risk of infection. Part two deals with the components involved in controlling the disease. Chapters discuss monitoring blood glucose, eating a healthy diet, getting daily exercise, and maintaining a healthy weight. Part three examines medical therapies for managing diabetes. Chapters provide information on the use of insulin to manage type 1 and type 2 diabetes; the use of sulfonylureas, meglinitides, biguanides, alpha glucosidase inhibitors, thiazolidinediones, and drug combinations to manage type 2 diabetes; and pancreas and islet cell transplantation as possible cures for diabetes. Part four addresses issues related to living well with diabetes. One chapter focuses on important tests every person who has diabetes should be getting, including the glycosylated hemoglobin test, lipid tests, the serum creatinine test, and the urine microalbumin test. Another chapter discusses self care issues, including having annual physical examinations, visiting a dentist regularly, caring for feet, avoiding smoking, monitoring blood pressure, and managing stress. A third chapter explores sexual health issues for both men and women. Topics include the affect of the menstrual cycle and menopause on blood glucose, hormone replacement therapy, pregnancy, and impotence. Each chapter concludes with a question and answer section. The book also includes a list of additional resources. 17 figures. 1 table.

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Boning Up on Osteoporosis: A Guide to Prevention and Treatment Source: Washington, DC: National Osteoporosis Foundation (NOF). 1998. 75 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: $3.00; bulk orders available at cost.

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Summary: This book provides the general public and people who have osteoporosis with information on preventing and treating this disease. It is characterized by a loss of bone mass and by poor bone quality, leading to reduced bone strength and increased risk of fractures. The first section explains how bones grow and change through the process of bone remodeling. A description of risk factors for osteoporosis follows. Risk factors that people cannot change are gender, age, family history, body size, and ethnicity. Risk factors that people can change are hormone levels, diet, exercise, and lifestyle choices. A description of other factors that influence bone health and a discussion of osteoporosis and arthritis are included. The next section focuses on preventing bone loss at all ages. Building and maintaining strong bones involves attaining peak bone mass during childhood, adolescence, and young adulthood; maintaining peak bone mass; and preventing bone loss in later life. In addition, this section discusses the prevention of osteoporosis by consuming enough calcium and vitamin D, exercising, and taking medications such as estrogen and hormone replacement therapy and alendronate sodium. The occurrence of osteoporosis in children and men is also discussed. The third section uses a question and answer format to provide information on using bone mineral density tests to diagnose osteoporosis. In addition, this section discusses other methods of diagnosis such as detecting biochemical markers and using laboratory and other tests. The next section deals with treatment. Approved medications are estrogen, calcitonin, alendronate sodium, and etridronate. In addition, many experimental treatments may prevent bone breakdown or stimulate the formation of new bone. The section also presents strategies for recovering from fractures and managing pain, discusses osteoporosis support groups, provides tips on moving safely, and describes exercises designed to promote and maintain good posture. A final section presents suggestions on finding better fitting clothing, remaining sexually active, and preventing falls. Numerous figures, 7 tables, and 3 references. •

Good Bones: The Complete Guide To Building and Maintaining the Healthiest Bones Source: Palo Alto, CA: Bull Publishing Company. 1999. 184 p. Contact: Available from Bull Publishing Company. P.O. Box 208, Palo Alto, CA 943020208. (650) 322-2855. Fax (650) 327-3300. Website: www.bullpub.com. PRICE: $14.95 plus shipping and handling. ISBN 0923521445. Summary: This book provides women with guidelines on building and maintaining healthy bones. By examining 17 major risk factors for bone health, the book helps women assess their overall risk for osteoporosis. A chapter on normal bone physiology is followed by a chapter that discusses risk factors in the prenatal and infancy periods, childhood, adolescence, young adulthood, middle age, and older adulthood. Chapter three examines hereditary risk factors: race, ethnicity, and family history. The next chapter is devoted to factors affecting women: age at menarche, menstrual cycles, age at menopause, and total reproductive years. Other topics include oral contraceptives, treatments for endometriosis, pregnancy and breast feeding, and hysterectomy. The fifth chapter evaluates the role of body build, weight, and fat in bone health. Chapter six focuses on the effect of exercise and physical activity on bone health and presents an example of an exercise routine that includes both endurance and strength training. The next chapter discusses the impact of hormones, prescription medications, and calcium supplements on bone health, and presents the advantages and disadvantages of hormone replacement therapy (HRT), highlights alternatives to HRT, and explains how to select the best calcium supplements and use them most effectively. Other chapters examine lifestyle factors, such as alcohol and caffeine consumption and smoking that

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affects bone health; identify factors influencing calcium absorption; present calcium requirements for various age groups; and discuss the importance of good nutrition in building strong bones. The final chapter applies the 17 risk factors to case studies presented in the previous chapters. A glossary of terms and a list of suggested readings and resources are included. 15 figures, 21 tables, and numerous references. •

Women and Diabetes: Staying Healthy in Body, Mind, and Spirit. 2nd ed Source: Alexandria, VA: American Diabetes Association. 2000. 230 p. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $14.95 plus shipping and handling. ISBN: 1580400582. Summary: This newly revised and updated book presents an approach to diabetes designed exclusively for women. The book explores different times of a woman's life and ways to deal with the situations and emotions likely to be encountered. The book includes stories of women who encountered dilemmas and made choices that are involved in living as a woman with diabetes. Chapter one asks readers to determine whether they are treating their diabetes as separate from themselves, as the dominant force in their life, or as part of their life and explains how women can develop a healthy relationship with diabetes. Chapter two helps readers become more aware of the choices they have already made and reveals some other choices that they can make for themselves. Chapter three helps women who have diabetes discover where they are on their journey in dealing with diabetes, handling life challenges, and coping with overall health issues. The chapter also helps the reader weave these three pathways of a life journey together to see how they interact to shape her life experience as a woman with diabetes. Chapter four focuses on relationships. Topics include understanding the impact of one's personality on relationships, dealing with other people, using social skills for maintaining health and wellness, and negotiating for agreements that meet one's needs. Chapter five discusses the impact of diabetes on the mind, body, and soul and offers tips on having a healthy relationship with one's mind, body, and soul. Chapter six explains how diabetes and one's physical health are interconnected, focusing on issues that are common to all women and some that are unique to women who have diabetes. Topics include sexuality, menses, contraception, pregnancy, breastfeeding, menopause, hormone replacement therapy, breast health, osteoporosis, and heart disease. Chapter seven focuses on life practices and explains how women can bring new practices into their life. Personal accounts are presented throughout the book to illustrate the topics being discussed. 1 table.

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Female Pelvic Health and Reconstructive Surgery Source: New York, NY: Marcel Dekker, Inc. 2003. 503 p. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $185.00 plus shipping and handling. ISBN: 0824708229. Summary: This textbook provides comprehensive, authoritative coverage of female pelvic health and reconstructive surgery. The editors compiled contributions from many experts who specialize in the treatment of pelvic floor disorders. The text includes 27 chapters on the epidemiology and etiology of incontinence and voiding dysfunction; diagnostic evaluation of the female patient; bladder physiology and neurophysiological evaluation; diagnosis and assessment of female voiding function; radiological

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evaluation; urodynamic evaluation of pelvic floor dysfunction; injectable agents for the treatment of stress urinary incontinence in females; transabdominal procedures for the treatment of stress urinary incontinence; transvaginal surgery for stress urinary incontinence; laparoscopic approaches to female incontinence, voiding dysfunction, and prolapse; diagnosis and management of obstruction following anti-incontinence surgery; pediatric dysfunctional voiding in females; nonsurgical treatment of urinary incontinence; sacral nerve root neuromodulation or electrical stimulation; musculoskeletal evaluation for pelvic pain; diagnosis and management of interstitial cystitis (IC); abdominal approach to apical prolapse; the types and choice of operation for repair of vaginal prolapse; colpocleisis for the treatment of vaginal vault prolapse; technique of vaginal hysterectomy; urethral diverticulum; evaluation and management of urinary fistulas; iatrogenic urological trauma; surgical treatment of rectovaginal fistulas and complex perineal defects; pessaries; menopause and hormone replacement therapy; and diagnosis of female sexual dysfunction. Each chapter includes black and white photographs and charts and concludes with a list of references. A subject index concludes the volume.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “hormone replacement therapy” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “hormone replacement therapy” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “hormone replacement therapy” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

A Woman's Guide to Menopause and Hormone Replacement Therapy by Lorraine Dennerstein (Editor), et al; ISBN: 0880487828; http://www.amazon.com/exec/obidos/ASIN/0880487828/icongroupinterna

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Effectiveness and costs of osteoporosis screening and hormone replacement therapy; ISBN: 0160482089; http://www.amazon.com/exec/obidos/ASIN/0160482089/icongroupinterna

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Effectiveness and Costs of Osteoporosis Screening and Hormone Replacement Therapy by United States; ISBN: 0160482070; http://www.amazon.com/exec/obidos/ASIN/0160482070/icongroupinterna

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Ernst Schering Research Foundation Workshop, Supplement 4: Hormone Replacement Therapy and Osteoporosis by Junzo Kato (Editor), et al; ISBN: 3540664807; http://www.amazon.com/exec/obidos/ASIN/3540664807/icongroupinterna

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Estrogen: Answers to All Your Questions About Hormone Replacement Therapy and Natural Alternatives by Mark W. Stolar; ISBN: 0380790769; http://www.amazon.com/exec/obidos/ASIN/0380790769/icongroupinterna

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Hormone Replacement Therapy by Khaw (1997); ISBN: 0443047170; http://www.amazon.com/exec/obidos/ASIN/0443047170/icongroupinterna

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Hormone Replacement Therapy by R. Don, Jr Gambrell (1997); ISBN: 0929240812; http://www.amazon.com/exec/obidos/ASIN/0929240812/icongroupinterna

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Hormone Replacement Therapy by Donald P. Swartz (Editor) (1992); ISBN: 0683080350; http://www.amazon.com/exec/obidos/ASIN/0683080350/icongroupinterna

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Hormone Replacement Therapy by A. Wayne Meikle (Editor); ISBN: 0896036014; http://www.amazon.com/exec/obidos/ASIN/0896036014/icongroupinterna

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Hormone Replacement Therapy by Patricia T. Kelly Ph.D.; ISBN: 1581110529; http://www.amazon.com/exec/obidos/ASIN/1581110529/icongroupinterna

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Hormone Replacement Therapy (Clinical Series) by Jean Coope (1993); ISBN: 0850841844; http://www.amazon.com/exec/obidos/ASIN/0850841844/icongroupinterna

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Hormone Replacement Therapy (DK Healthcare) by Miriam Stoppard; ISBN: 0789437562; http://www.amazon.com/exec/obidos/ASIN/0789437562/icongroupinterna

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Hormone Replacement Therapy (What You Really Need to Know About.) by Wendy Dear; ISBN: 1840282495; http://www.amazon.com/exec/obidos/ASIN/1840282495/icongroupinterna

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Hormone Replacement Therapy : an Option for Women at Menopause by Spellacy, Sturdee; ISBN: 1885274181; http://www.amazon.com/exec/obidos/ASIN/1885274181/icongroupinterna

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Hormone replacement therapy : is it for you? (SuDoc HE 20.3861:H 78/999) by U.S. Dept of Health and Human Services; ISBN: B000111VHO; http://www.amazon.com/exec/obidos/ASIN/B000111VHO/icongroupinterna

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Hormone Replacement Therapy and Cancer: The Current Status of Research and Practice by Andrea R. Genazzani (Editor), A.R. Genazzani; ISBN: 1842140795; http://www.amazon.com/exec/obidos/ASIN/1842140795/icongroupinterna

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Hormone Replacement Therapy and Cardiovascular Disease: The Current Status of Research and Practice by Andrea R. Genazzani (Editor); ISBN: 1842140388; http://www.amazon.com/exec/obidos/ASIN/1842140388/icongroupinterna

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Hormone Replacement Therapy and Osteoporosis by M. Kleerekoper, Michael Kleerekoper; ISBN: 1842140302; http://www.amazon.com/exec/obidos/ASIN/1842140302/icongroupinterna

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Hormone Replacement Therapy and Quality of Life by H. P. G. Schneider (Editor); ISBN: 1842140140; http://www.amazon.com/exec/obidos/ASIN/1842140140/icongroupinterna

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Hormone Replacement Therapy and the Brain: The Current Status of Research and Practice (Controversial Issues in Climacteric Medicine Series) by A. R. Genazzani (Editor); ISBN: 1842141686; http://www.amazon.com/exec/obidos/ASIN/1842141686/icongroupinterna

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Hormone Replacement Therapy and the Endometrium by Farook, Ma, Phd, Frcog AlAzzawi (Editor), May, Md, Mrcog Wahab (Editor); ISBN: 1850700923; http://www.amazon.com/exec/obidos/ASIN/1850700923/icongroupinterna

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Hormone Replacement Therapy and the Skin by Mark P. Brincat (Editor); ISBN: 185070810X; http://www.amazon.com/exec/obidos/ASIN/185070810X/icongroupinterna

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Hormone Replacement Therapy and Urogenital Aging by L. Cardozo; ISBN: 1842140299; http://www.amazon.com/exec/obidos/ASIN/1842140299/icongroupinterna

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Hormone Replacement Therapy for Endocrine Deficiencies by J. Wass (Editor), J. Ahlquist (Editor); ISBN: 1860161154; http://www.amazon.com/exec/obidos/ASIN/1860161154/icongroupinterna

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Hormone Replacement Therapy for Menopausal Women: A Clinical Appraisal by J. P. Thomas; ISBN: 9057024772; http://www.amazon.com/exec/obidos/ASIN/9057024772/icongroupinterna

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Hormone Replacement Therapy in the Male by L. Tenover (2004); ISBN: 1842140426; http://www.amazon.com/exec/obidos/ASIN/1842140426/icongroupinterna

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Hormone Replacement Therapy Studies: A Reference Guide by Sara T. Goulden; ISBN: 0786416831; http://www.amazon.com/exec/obidos/ASIN/0786416831/icongroupinterna

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Hormone Replacement Therapy Yes or No?: How to Make an Informed Decision About Estrogen, Progesterone, & Other Strategies for Dealing With Pms, Menopause, & Osteoporosis by Betty Kamen (1996); ISBN: 0944501109; http://www.amazon.com/exec/obidos/ASIN/0944501109/icongroupinterna

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Hormone Replacement Therapy: A Guide for Primary Care by Sally Hope (Editor), et al (1999); ISBN: 0192629565; http://www.amazon.com/exec/obidos/ASIN/0192629565/icongroupinterna

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Hormone Replacement Therapy: Conventional Medicine and Natural Alternates, Your Guide to Menopausal Health Care Choices by Linda Laucella; ISBN: 1565651545; http://www.amazon.com/exec/obidos/ASIN/1565651545/icongroupinterna

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Hormone Replacement Therapy: Standardized or Individually Adapted Doses? by B. Von Schoultz (Editor), et al; ISBN: 1850705453; http://www.amazon.com/exec/obidos/ASIN/1850705453/icongroupinterna

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Hormone Replacement Therapy: Your Questions Answered by Malcolm I. Whitehead (2004); ISBN: 0443050449; http://www.amazon.com/exec/obidos/ASIN/0443050449/icongroupinterna

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Hrt-- The Answers: A Concise Guide for Solving the Hormone Replacement Therapy Puzzle by Pamela Wartian Smith (2003); ISBN: 0972976736; http://www.amazon.com/exec/obidos/ASIN/0972976736/icongroupinterna

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Medical-Economic Aspects of Hormone Replacement Therapy: Proceedings of a Workshop Held at Ciba-Geigy, Basel, Switzerland, 9th March 1993 (Internati) by J.-M. Cossery (Editor) (1993); ISBN: 1850705194; http://www.amazon.com/exec/obidos/ASIN/1850705194/icongroupinterna

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Menopause and Hormone Replacement Therapy: A Simple but Complete Guide for Today's Busy Woman by Sharon Lunz, Dr. Sharon Lunz; ISBN: 0966998502; http://www.amazon.com/exec/obidos/ASIN/0966998502/icongroupinterna

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Menopause and Hormone Replacement Therapy: Effective Patient Care by Isaac Schiff, et al (1998); ISBN: 1572760400; http://www.amazon.com/exec/obidos/ASIN/1572760400/icongroupinterna

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Menopause Myths & Facts : What Every Woman Should Know about Hormone Replacement Therapy by Lorraine Rothman, Marcia Wexler; ISBN: 0962994561; http://www.amazon.com/exec/obidos/ASIN/0962994561/icongroupinterna

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Molecular Basis of Hormone Replacement Therapy by Malcolm I. Whitehead; ISBN: 1842141465; http://www.amazon.com/exec/obidos/ASIN/1842141465/icongroupinterna

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Natural Alternatives to HRT (Hormone Replacement Therapy) Cookbook : Understanding Estrogen and Food that Benefits Your Health by Marilyn Glenville (2001); ISBN: 1587610256; http://www.amazon.com/exec/obidos/ASIN/1587610256/icongroupinterna

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Physiological Hormone Replacement Therapy by N Duitsin (Editor); ISBN: 1850703612; http://www.amazon.com/exec/obidos/ASIN/1850703612/icongroupinterna

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Prescription Charges (Hormone Replacement Therapy): [HC]: [1998-99]: House of Commons Bills: [1998-99] by Great Britain (1999); ISBN: 0103080996; http://www.amazon.com/exec/obidos/ASIN/0103080996/icongroupinterna

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Progesterone in Hormone Replacement Therapy by R.A. Lobo, F. Naftolin; ISBN: 1850704406; http://www.amazon.com/exec/obidos/ASIN/1850704406/icongroupinterna

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Restoring Balance: An Individualized Approach to Hormone Replacement Therapy by R.Ph., Marla Ahlgrimm, John Kells; ISBN: 1890694037; http://www.amazon.com/exec/obidos/ASIN/1890694037/icongroupinterna

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Sex Hormone Replacement Therapy by H. G. Burger (Editor); ISBN: 0792379659; http://www.amazon.com/exec/obidos/ASIN/0792379659/icongroupinterna

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Sex, Lies, and Menopause : The Shocking Truth About Hormone Replacement Therapy by T. S. Wiley (Author), et al (2003); ISBN: 0060542330; http://www.amazon.com/exec/obidos/ASIN/0060542330/icongroupinterna

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Smart Medicine for Menopause: Hormone Replacement Therapy and Its Natural Alternatives by Sandra Cabot M.D. (1998); ISBN: 0895296284; http://www.amazon.com/exec/obidos/ASIN/0895296284/icongroupinterna

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The Amarant Book of Hormone Replacement Therapy: How Hrt Can Dramatically Reduce All the Symptoms Connected with the Menopause and Protect Against Hea by Teresa Gorman, Malcolm Whitehead (1989); ISBN: 0330310224; http://www.amazon.com/exec/obidos/ASIN/0330310224/icongroupinterna

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The Estrogen Alternative: What Every Woman Needs to Know About Hormone Replacement Therapy and Serms, the New Estrogen Substitutes by Steven R. Goldstein, Laurie Ashner; ISBN: 0399144536; http://www.amazon.com/exec/obidos/ASIN/0399144536/icongroupinterna

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The Hormone Decision : 7 Questions To Ask Yourself and Your Doctor About Hormone Replacement Therapy and Other Options by Linda Laucella; ISBN: 0071416153; http://www.amazon.com/exec/obidos/ASIN/0071416153/icongroupinterna

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The Hormone Replacement Handbook: Everything a Woman Needs to Know to Make an Informed Decision About Hormone Replacement Therapy by Paula Brisco, et al; ISBN: 1882606205; http://www.amazon.com/exec/obidos/ASIN/1882606205/icongroupinterna

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The Menopause and Hormone Replacement Therapy by Roger Smith, John Studd (1998); ISBN: 1853176192; http://www.amazon.com/exec/obidos/ASIN/1853176192/icongroupinterna

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The Natural Woman's Guide to Hormone Replacement Therapy: An Alternative Approach by M. Sara, Ph.D. Rosenthal (2003); ISBN: 1564146812; http://www.amazon.com/exec/obidos/ASIN/1564146812/icongroupinterna

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The Prescriber's Guide to Hormone Replacement Therapy by Malcolm I. Whitehead (Editor); ISBN: 1850709742; http://www.amazon.com/exec/obidos/ASIN/1850709742/icongroupinterna

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The role of menopause and gender difference in aging on the development of disease in mid-life and older women : hearing before the Subcommittee on Aging of the Committee on Labor and Human Resources, United States Senate, One Hundred Second Congress, first session, on examining the health of mid-life and older women, focusing on the health effects of menopause and its treatment (hormone replacement therapy or HRT), April 19, 1991 (SuDoc Y 4.L 11/4:S.HRG.102-1197); ISBN: 0160446481; http://www.amazon.com/exec/obidos/ASIN/0160446481/icongroupinterna

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The Seville Hgh Symposium: Clinical Aspects of Growth Hormone Replacement Therapy, Proceedings, Seville, Spain, April 1990 (Hormone Research Vol. 33) by J. Girard (Editor), J.S. Christiansen (Editor) (1990); ISBN: 3805552904; http://www.amazon.com/exec/obidos/ASIN/3805552904/icongroupinterna

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The Truth About Hormone Replacement Therapy: How to Break Free from the Medical Myths of Menopause by National Women's Health Network (Editor) (2002); ISBN: 0761534784; http://www.amazon.com/exec/obidos/ASIN/0761534784/icongroupinterna

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Venous Thrombosis in Women: Pregnancy, the Contraceptive Pill and Hormone Replacement Therapy by I. A. Greer; ISBN: 1842142283; http://www.amazon.com/exec/obidos/ASIN/1842142283/icongroupinterna

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What You Really Need To Know About Hormone Replacement Therapy by Rob Buckman, et al; ISBN: 0867307986; http://www.amazon.com/exec/obidos/ASIN/0867307986/icongroupinterna

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Women's Health Alert: What Most Doctors Won't Tell You About Birth Control, CSections, Weight Control Products, Hormone Replacement Therapy, Osteop by Sidney M. Wolfe, et al; ISBN: 0201550415; http://www.amazon.com/exec/obidos/ASIN/0201550415/icongroupinterna

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Women's Health in Menopause: Behaviour, Cancer, Cardiovascular Disease, Hormone Replacement Therapy (Medical Science Symposia Series, Vol 7) by P. G. Crosignani, et al (1994); ISBN: 0792330684; http://www.amazon.com/exec/obidos/ASIN/0792330684/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “hormone replacement therapy” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 11 In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed

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A critical look at hormone replacement therapy: Healthsharing Women, papers and proceedings, April 1992. Author: Healthsharing Women.; Year: 1994; Melbourne, Vic.: Healthsharing Productions, 1992; ISBN: 0646125648

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Hormone replacement therapy: a consensus development conference report to the National Advisory Committee on Core Health and Disability Support Services. Author: New Zealand. National Advisory Committee on Core Health and Disability Support Services; Year: 1995; Wellington, N.Z.: National Advisory Committee on Core Health and Disability Support Services, 1993; ISBN: 0477016820

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Hormone replacement therapy and breast cancer risk Author: Mann, Ronald D. (Ronald David),; Year: 1990; Carnforth, Lancs, UK; Park Ridge, N.J., USA: Parthenon Pub. Group, 1992; ISBN: 185070399X http://www.amazon.com/exec/obidos/ASIN/185070399X/icongroupinterna

Chapters on Hormone Replacement Therapy In order to find chapters that specifically relate to hormone replacement therapy, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and hormone replacement therapy using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “hormone replacement therapy” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on hormone replacement therapy: •

Menopause and Hormone Replacement Therapy Source: in Carlin, B.I. and Leong, F.C., eds. Female Pelvic Health and Reconstructive Surgery. New York, NY: Marcel Dekker, Inc. 2003. p. 417-474. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $185.00 plus shipping and handling. ISBN: 0824708229. Summary: This chapter on menopause and hormone replacement therapy (HRT) is from a textbook that provides comprehensive, authoritative coverage of female pelvic health and reconstructive surgery. The authors introduce menopause and discuss the factors that influence the age of menopause onset. They also discuss the transition to menopause; symptoms of menopause, including those of the central nervous system, skin, and genitourinary tract, osteoporosis, and cardiovascular disease; the use of estrogen in menopausal women for both primary and secondary prevention of cardiovascular disease; the risks of HRT, including endometrial cancer, breast cancer, venous thromboembolic events, and alternative benefits of HRT; regimens for HRT, including the supplementation with calcium and vitamin D; and alternative therapies for symptoms of menopause. The authors conclude that the menopause is a normal life

in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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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. 5 figures. 11 tables. 266 references. •

Testosterone Effect: Hormone Replacement Therapy Source: in Newman, A.J. Beyond Viagra: Plain Talk About Treating Male and Female Sexual Dysfunction. Montgomery, AL: Starrhill Press. 1999. p. 64-66. Contact: Available from Black Belt Press. P.O. Box 551, Montgomery, AL 36101. (800) 959-3245 or (334) 265-6753. Fax (334) 265-8880. PRICE: $13.95 plus shipping and handling. ISBN: 1573590142. Summary: This chapter, from a book that discusses the drug sildenafil (Viagra) in the context of a larger discussion about sexuality and sexual dysfunction, discusses hormone replacement therapy (namely, testosterone). Testosterone replacement is currently used today in both primary and secondary hypogonadism (decreased testicular production of testosterone). The current methods of androgen replacement available for human use include oral preparations, the long acting esters of testosterone, and the transdermal preparations. The author describes how each of these preparations is used, and then discusses how low serum testosterone contributes to erectile dysfunction. Testosterone therapy is contraindicated in men with prostate cancer. It is relatively contraindicated in older men with bladder neck obstruction from prostate enlargement. The author recommends that all men over the age of 50 receiving testosterone first have a prostate specific antigen (PSA) level measurement and a digital rectal exam. In addition, because oral testosterone preparations definitely increase the risk of liver problems, requiring close monitoring of liver function. The chapter is written in nontechnical language but includes enough medical information to be of use to medical professionals wishing to learn more about sexuality and sexual dysfunction.

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CHAPTER 8. MULTIMEDIA ON HORMONE REPLACEMENT THERAPY Overview In this chapter, we show you how to keep current on multimedia sources of information on hormone replacement therapy. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on hormone replacement therapy is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “hormone replacement therapy” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “hormone replacement therapy” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on hormone replacement therapy: •

Exploring Your Brain: Memory Source: New York, NY: Dana Foundation. 1998. Contact: Available from Films for the Humanities and Sciences. PO Box 2053, Princeton, NJ 08543-2053. (800) 257-5126, (609) 275-1400; FAX: (609) 275-3767. Internet: http://www.films.com. PRICE: $89.95. Item number: BVL8644. Summary: This video is one in a series about the brain, broadcast by the Public Broadcasting System. This show discussed the biology of memory and memory loss. The first segment of the program discussed types of memory such as explicit and implicit, and short and long term memory. The panelists then discussed the aging brain and the prospect of losing memory. Factors which can prevent or slow memory loss may include education, physical and mental activity, and a feeling of control over one's life. Current research into treating memory loss includes cholinesterase inhibitors,

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Vitamin E, and hormone replacement therapy. The next section of the show discussed memory distortion and recovered memory. Following a question and answer time with the audience, the panelists expressed their thoughts on future research into memory and the brain.

Bibliography: Multimedia on Hormone Replacement Therapy The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in hormone replacement therapy (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on hormone replacement therapy: •

Hormone replacement therapy [videorecording]: the benefits and the concerns Source: the American Academy of Family Physicians; Year: 2000; Format: Videorecording; Leawood, KS: American Academy of Family Physicians, c2000

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Menopause and hormone replacement therapy [electronic resource]: effective patient care Source: New England Research Institutes; Year: 1998; Format: Electronic resource; Newton, MA: SilverPlatter Education, 1998

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Menopause and hormone replacement therapy [videorecording] Source: [presented by] the Cleveland Clinic Foundation; Year: 1996; Format: Videorecording; Cleveland, Ohio: Cleveland Clinic Foundation: Unitech Communications, 1996

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Menopause and hormone replacement therapy [videorecording] Source: Marshfield Clinic, Saint Joseph's Hospital; a presentation of the Marshfield Video Network; Year: 1994; Format: Videorecording; Marshfield, WI: The Clinic, [1994]

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Prescribing hormone replacement therapy [videorecording] Source: [presented by] the Emory Medical Television Network, Emory University School of Medicine of the Robert W. Woodruff Health Sciences Center; Year: 1994; Format: Videorecording; Atlanta, GA: The University, c1994

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CHAPTER 9. PERIODICALS AND NEWS ON HORMONE REPLACEMENT THERAPY Overview In this chapter, we suggest a number of news sources and present various periodicals that cover hormone replacement therapy.

News Services and Press Releases One of the simplest ways of tracking press releases on hormone replacement therapy is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “hormone replacement therapy” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to hormone replacement therapy. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “hormone replacement therapy” (or synonyms). The following was recently listed in this archive for hormone replacement therapy: •

Growth hormone replacement therapy may benefit diabetics Source: Reuters Industry Breifing Date: March 25, 2003

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Hormone replacement therapy reduces diabetes risk in women with heart disease Source: Reuters Industry Breifing Date: January 06, 2003

•

Combination hormone replacement therapy increases mammographic density Source: Reuters Industry Breifing Date: January 03, 2003 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “hormone replacement therapy” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “hormone replacement therapy” (or synonyms). If you know the name of a company that is relevant to hormone replacement therapy, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “hormone replacement therapy” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “hormone replacement therapy” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on hormone replacement therapy: •

Menopausal Weight Gain Source: Mayo Clinic Women's HealthSource. December 1998. Contact: Mayo Clinic Women's HealthSource, P.O. Box 56931, Boulder, CO 80322-6931. Summary: This article discusses the changes a woman can expect to go through during perimenopause and menopause. The author points out the changes of puberty and pregnancy as models for the change of menopause. According to the author, lowered estrogen production contributes to the mood swings, sleep disturbances, and hot flashes of menopause. For most women, their metabolism also slows down, and their lean muscle mass diminishes. This can lead to weight gain. A starvation diet is not the answer, according to the author, who says that exercise is a better choice. Exercise boosts the metabolism, burns fat, and can strengthen bones. All forms of exercise are potentially beneficial, including aerobic exercise to burn fat, stretching to increase flexibility, and strength training to improve muscle mass and strengthen bones. Other topics discussed include hormone replacement therapy and a healthy diet.

•

Glucocorticoid-Induced Osteoporosis in SLE Source: Lupus News. 23(1): 24-25. Spring 2003. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9486. Website: www.lupus.org/lupus. Summary: This newsletter article discusses glucocorticoid-induced osteoporosis (GIOP), a less recognized but serious side effect of glucocorticoids, in patients with systemic lupus erythematosus (SLE). Glucocorticoids (steroids) have long been used in the treatment of patients with SLE. Steroids lower bone mass by slowing the function of osteoblasts which leads to a reduction of bone formation, increasing bone resorption, disrupting the metabolism of calcium, and affecting the hormones which lead to bone loss. To prevent GIOP, patients should take the lowest dosage of steroids that is effective or stop taking steroids altogether, consume 1500 mg of calcium per day, supplement vitamin D consumption to 800 IU per day, take biphosphonates such as alendronate, risedronate, and pamidronate to prevent bone resorption, use hormone replacement

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therapy if female, start an exercise program, stop smoking, and use alcohol and caffeine in moderation or not at all. •

Does Excess Vitamin A Cause Hip Fracture? Source: Harvard Women's Health Watch. 9(7): 1-3. March 2000. Contact: Available from Harvard Women's Health Watch. Department SR, P.O. Box 380, Boston, MA 02117. (800) 829-5921. E-mail: [email protected]. Summary: This newsletter article provides women with information on the role of excess vitamin A in hip fracture. Researchers at Harvard Medical School who were studying the relationship between postmenopausal hip fracture and vitamin A intake found that women with an intake of 3,000 micrograms (mcg) or more per day had a 48 percent greater risk for hip fracture compared to women with an intake of 1,250 mcg or less per day. The increased risk was mainly due to a form of vitamin A known as retinol. In contrast, consumption of high levels of beta carotene, also a source of vitamin A, had a negligible impact on hip fracture risk. Women taking hormone replacement therapy were somewhat protected from the effects of too much retinol. A Swedish study also found a higher occurrence of hip fracture among women who consumed more than 1,500 mcg of retinol per day than women whose intake was less than 500 mcg daily. The study also found a consistent association between bone mineral density loss and retinol intake. No significant relationship was found between beta carotene intake and hip fracture. The article suggests some simple precautions women can take to prevent excess vitamin A in the body, including learning the source of vitamin A in fortified foods and multivitamins, avoiding exceeding the recommended dietary allowance of vitamin A, and eating fruits and vegetables. 2 figures and 1 table.

Academic Periodicals covering Hormone Replacement Therapy Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to hormone replacement therapy. In addition to these sources, you can search for articles covering hormone replacement therapy that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for hormone replacement therapy. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with hormone replacement therapy. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-

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interaction risks, etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to hormone replacement therapy: Progestins for Noncontraceptive Use •

Systemic - U.S. Brands: Amen; Aygestin; Crinone; Curretab; Cycrin; DepoProvera; Gesterol 50; Gesterol LA 250; Hy/Gestrone; Hylutin; Megace; Prodrox; Prometrium; Pro-Span; Provera http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202758.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “hormone replacement therapy” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 12575 108 867 33 9 13592

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “hormone replacement therapy” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

15

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

16

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

20 Adapted 21

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on hormone replacement therapy can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to hormone replacement therapy. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to hormone replacement therapy. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “hormone replacement therapy”:

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•

Guides on hormone replacement therapy Hormone Replacement Therapy http://www.nlm.nih.gov/medlineplus/hormonereplacementtherapy.html

•

Other guides Breast Cancer http://www.nlm.nih.gov/medlineplus/breastcancer.html Hormones http://www.nlm.nih.gov/medlineplus/hormones.html Menopause http://www.nlm.nih.gov/medlineplus/menopause.html Pituitary Disorders http://www.nlm.nih.gov/medlineplus/pituitarydisorders.html

Within the health topic page dedicated to hormone replacement therapy, the following was listed: •

General/Overviews Hormone Therapy Source: American College of Obstetricians and Gynecologists http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZMIM8U5FD &sub_cat=2002 Hormones After Menopause Source: National Institute on Aging http://www.niapublications.org/engagepages/hormonesafter.asp Latest on Hormone Replacement Therapy Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=WO00037 Menopause and Hormones Source: Food and Drug Administration http://www.fda.gov/womens/menopause/mht-FS.html

•

Treatment FDA Approves Estrasorb for Treatment of Menopausal Hot Flashes Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01255.html

•

Alternative Therapy Hormone Replacement Therapy: Who Should Take It and What Are the Alternatives? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=WO00046

Patient Resources

•

213

Specific Conditions/Aspects American Heart Association President Responds to New Findings From Women's Health Initiative Trial Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3003700 Estrogen and Progestin Dilemma: New Advice, Labeling Guidelines Source: Food and Drug Administration http://www.fda.gov/fdac/features/2003/203_estrogen.html FDA Approves Lower Dose of Prempro, a Combination Estrogen and Progestin Drug for Postmenopausal Women Source: Food and Drug Administration http://www.fda.gov/bbs/topics/NEWS/2003/NEW00878.html FDA Approves New Labeling and Provides New Advice to Postmenopausal Women Who Use or Who Are Considering Using Estrogen and Estrogen With Progestin Source: Food and Drug Administration http://www.fda.gov/oc/factsheets/WHI.html Phytoestrogens and Bone Health Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r618i&doctitle=Phytoestrogens%2Band%2 BBone%2BHealth&doctype=HTML%2BFact%2BSheet Pill Revisited: Benefits Beyond Birth Control Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01522 Questions and Answers for Estrogen and Estrogen with Progestin Therapies for Postmenopausal Women Source: Center for Drug Evaluation and Research http://www.fda.gov/cder/drug/infopage/estrogens_progestins/Q&A.htm

•

From the National Institutes of Health Facts About Postmenopausal Hormone Therapy Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/women/pht_facts.htm Menopausal Hormone Use: Questions and Answers Source: National Cancer Institute http://www.cancer.gov/newscenter/estrogenplus

•

Latest News FDA Approves Estrasorb for Treatment of Menopausal Hot Flashes Source: 10/10/2003, Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01255.html

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•

Law and Policy Task Force Issues Caution on Combined Hormone Therapy Source: Agency for Healthcare Research and Quality http://www.ahrq.gov/news/press/pr2002/hrtrecpr.htm

•

Organizations American Society for Reproductive Medicine http://www.asrm.org/ Hormone Foundation http://www.hormone.org/ National Institute on Aging http://www.nia.nih.gov/ National Women's Health Information Center Source: Dept. of Health and Human Services http://www.4woman.gov/ North American Menopause Society http://www.menopause.org/

•

Prevention/Screening Postmenopausal Hormone Replacement Therapy to Prevent Chronic Conditions: Recommendations from the U.S. Preventive Services Task Force Source: American College of Physicians http://www.annals.org/cgi/content/full/137/10/I-48

•

Research Alcohol, Postmenopausal Hormone Therapy, and Breast Cancer Source: American College of Physicians http://www.annals.org/cgi/content/full/137/10/I-43 Bone Loss after Stopping Estrogen or Alendronate Therapy Source: American College of Physicians http://www.annals.org/cgi/content/full/137/11/I-31 Cancer Risk May Vary by Hormone Regimen and How Recently Used Source: American College of Obstetricians and Gynecologists http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZWP40L19D& sub_cat=2 Combination Hormone Therapy Raises Women's Stroke Risk Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3008846 Effects of Age, Breast Density, and Hormone Therapy on the Accuracy of Screening Mammograms Source: American College of Physicians http://www.annals.org/cgi/content/full/138/3/I-28

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Ending Hormone Therapy Leads to Rapid Bone Loss in Elderly Women Source: Endocrine Society http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZW7Z7LL9D& sub_cat=2 Hormone Replacement Therapy Does Not Appear to Influence Breast Cancer Detection Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZVXZAO66D &sub_cat=2 Hormone Therapy Can Relieve Menopause-Type Symptoms Common in Elderly Women: HERS Study Report Source: American College of Obstetricians and Gynecologists http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZRMBOL19D &sub_cat=2 Increased Risk of Ovarian Cancer Is Linked to Estrogen Replacement Therapy Source: National Cancer Institute http://www.cancer.gov/newscenter/Laceyovarian Long-Term Use of Estrogen Replacement Therapy (ERT) Associated With Increased Risk of Ovarian Cancer Death Among Postmenopausal Women Source: American Medical Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZ8VKGSIKC &sub_cat=638 NHLBI Stops Trial of Estrogen Plus Progestin Due to Increased Breast Cancer Risk, Lack of Overall Benefit Source: National Heart, Lung, and Blood Institute http://www.nih.gov/news/pr/jul2002/nhlbi-09.htm Postmenopausal Hormone Therapy and Blood Sugar Source: American College of Physicians http://www.annals.org/cgi/content/full/138/1/I-10 Rates of Dementia Increase among Older Women on Combination Hormone Therapy Source: National Institute on Aging http://www.nih.gov/news/pr/may2003/nia-27.htm Reduced Risk of Alzheimer Disease Associated With Prior Use of Hormone Therapy in Older Women Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZ68RHO78D& sub_cat=2 Risedronate and Hormone Replacement Therapy Improve Bone Mineral Density in Postmenopausal Women Source: Endocrine Society http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZVDIQNQM C&sub_cat=638 Statement on Hormone Therapy for the Prevention and Treatment of Postmenopausal Osteoporosis Source: American College of Obstetricians and Gynecologists http://medem.com/medlb/article_detaillb.cfm?article_ID=ZZZJLS9PJLD&sub_cat

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=2009 Study Confirms Breast Cancer Risk in Continuous Combined Hormone Therapy Risk Begins to Return to Normal After Women Stop Taking Hormones Source: National Institute of Child Health and Human Development http://www.nih.gov/news/pr/nov2002/nichd-29.htm Study of Menopausal Women with Heart Disease Finds No Benefit, Potential for Harm from Hormone Therapy and Antioxidant Vitamins Source: National Heart, Lung, and Blood Institute http://www.nih.gov/news/pr/nov2002/nhlbi-19.htm WHIMS Study on Estrogen/Progestin Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01226.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on hormone replacement therapy. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Hormone Replacement Therapy and Tinnitus Source: London, England: Royal National Institute for Deaf People. 1998. [2 p.]. Contact: Available from RNID Helpline. P.O. Box 16464, London EC1Y 8TT, United Kingdom. 0870 60 50 123. Fax 0171-296 8199. E-mail: [email protected]. Website: www.rnid.org.uk. Also available from RNID Tinnitus Helpline. Castle Cavendish Works, Norton Street, Radford, Nottingham NG7 5PN, United Kingdom. 0345 090210. Fax 0115-978 5012. E-mail: [email protected]. PRICE: Single copy free. Summary: This fact sheet from the Royal National Institute for Deaf People (RNID) discusses the relationship between hormone replacement therapy (HRT) and tinnitus (ringing or other sounds in the ears). A number of women callers to the RNID helpline have reported that their tinnitus either started, or became more noticeable, following HRT taken to alleviate menopausal symptoms and to reduce the future risk of osteoporosis and cardiovascular disease. The fact sheet reviews the factors that may result in tinnitus being associated with the menopause or HRT and also describes a research study presently underway in London on this topic. The fact sheet concludes with information on the RNID Tinnitus Helpline (in Nottingham, UK), which is also

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accessible online at [email protected]. The RNID website is at www.rnid.org.uk. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “hormone replacement therapy” (or synonyms). The following was recently posted: •

(1) Best practice evidence-based guideline for the appropriate prescribing of hormone replacement therapy. (2) Guideline update: hormone replacement therapy Source: Effective Practice Institute, University of Auckland - Academic Institution; 2001 May (revised information released on 2002 September 30); 185 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3107&nbr=2333&a mp;string=hormone+AND+replacement+AND+therapy

•

Perimenopausal and postmenopausal hormone replacement therapy Source: American College of Preventive Medicine - Medical Specialty Society; 1999 October; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2120&nbr=1346&a mp;string=hormone+AND+replacement+AND+therapy

•

Postmenopausal hormone replacement therapy for the primary prevention of chronic conditions: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2002); 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3455&nbr=2681&a mp;string=hormone+AND+replacement+AND+therapy Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

American Indian and Alaska Native Women's Health: Mature Women Summary: This page features links to information about osteoporosis and hormone replacement therapy. Source: Indian Health Service http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6882

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•

Evolution of Estrogen Summary: This timeline is a compilation of events that traces the evolution of estrogen in women's health and its role in hormone replacement therapy. Source: Hormone Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7163

•

Hormone Replacement Therapy for Primary Prevention of Chronic Conditions: Recommendations and Rationale Summary: The U.S. Preventive Services Task Force (USPSTF) recommends against the routine use of estrogen and progestin for the prevention of chronic conditions in postmenopausal women. Source: Agency for Healthcare Research and Quality http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6952

•

Questions and Answers: Use of Hormones After Menopause Summary: Postmenopausal hormone use usually involves hormone replacement therapy (HRT) with either estrogen alone or in combination with progestin to compensate for the decrease in natural hormones that occurs Source: National Cancer Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6794 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to hormone replacement therapy. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

Patient Resources

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMD®Health: http://my.webmd.com/health_topics

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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to hormone replacement therapy. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with hormone replacement therapy. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about hormone replacement therapy. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “hormone replacement therapy” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “hormone replacement therapy”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred

220 Hormone Replacement Therapy

language and the format option “Organization Resource Sheet.” Type “hormone replacement therapy” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “hormone replacement therapy” (or a synonym) into the search box, and click “Submit Query.”

221

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.23

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

23

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)24: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

24

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

226 Hormone Replacement Therapy

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

227

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

229

HORMONE REPLACEMENT THERAPY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [NIH]

ACE Inhibitor: A type of drug used to lower blood pressure. Studies indicate that it may also help prevent or slow the progression of kidney disease in people with diabetes. [NIH] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing

230 Hormone Replacement Therapy

of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the

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stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Alcohol Dehydrogenase: An enzyme that catalyzes reversibly the final step of alcoholic fermentation by reducing an aldehyde to an alcohol. In the case of ethanol, acetaldehyde is reduced to ethanol in the presence of NADH and hydrogen. The enzyme is a zinc protein which acts on primary and secondary alcohols or hemiacetals. EC 1.1.1.1. [NIH] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] Alendronate Sodium: A drug that affects bone metabolism. It is used in treating osteoporosis and Paget's disease, and is being studied in the treatment of hypercalcemia (abnormally high levels of calcium in the blood) and in treating and reducing the risk of bone pain caused by cancer. Alendronate sodium belongs to the family of drugs called bisphosphonates. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU]

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Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amlodipine: 2-((2-Aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylic acid 3-ethyl 5-methyl ester. A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in

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the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgen-Binding Protein: Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. They participate in the transport of androgens. Androgen-binding protein has the same amino acid sequence as sex hormone binding-globulin. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Androgenic: Producing masculine characteristics. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Androstanes: The family of steroids from which the androgens are derived. [NIH] Androstenedione: A steroid with androgenic properties that is produced in the testis, ovary, and adrenal cortex. It is a precursor to testosterone and other androgenic hormones. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another

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living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthropometric measurements: Measurements of human body height, weight, and size of component parts, including skinfold measurement. Used to study and compare the relative proportions under normal and abnormal conditions. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antiepileptic: An agent that combats epilepsy. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimitotic: Inhibiting or preventing mitosis. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Anus: The opening of the rectum to the outside of the body. [NIH]

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Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition

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(arteriolosclerosis). [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Articular: Of or pertaining to a joint. [EU] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspirate: Fluid withdrawn from a lump, often a cyst, or a nipple. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atherectomy: Endovascular procedure in which atheromatous plaque is excised by a cutting or rotating catheter. It differs from balloon and laser angioplasty procedures which enlarge vessels by dilation but frequently do not remove much plaque. If the plaque is removed by surgical excision under general anesthesia rather than by an endovascular procedure through a catheter, it is called endarterectomy. [NIH] Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Atypical hyperplasia: A benign (noncancerous) condition in which cells have abnormal features and are increased in number. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here)

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considered to be part of the autonomic nervous system itself. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axillary Artery: The continuation of the subclavian artery; it distributes over the upper limb, axilla, chest and shoulder. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Baroreflex: A negative feedback system which buffers short-term changes in blood pressure. Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in the vessel walls. The net response of the central nervous system is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [NIH]

Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Beta carotene: A vitamin A precursor. Beta carotene belongs to the family of fat-soluble vitamins called carotenoids. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the

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target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Birth Rate: The number of births in a given population per year or other unit of time. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose.

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[NIH]

Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]

Bone Remodeling: The continuous turnover of bone matrix and mineral that involves first, an increase in resorption (osteoclastic activity) and later, reactive bone formation (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium homeostasis. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as osteoporosis. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Artery: The continuation of the axillary artery; it branches into the radial and ulnar arteries. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH]

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Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breast Feeding: The nursing of an infant at the mother's breast. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]

Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcaneus: The largest of the tarsal bones and is situated at the lower and back part of the foot forming the heel. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing

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pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [NIH]

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Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the

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relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chlormadinone Acetate: An orally active synthetic progestational hormone used often in combinations as an oral contraceptive. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Civil Rights: Legal guarantee protecting the individual from attack on personal liberties, right to fair trial, right to vote, and freedom from discrimination on the basis of race, religion, national origin, age, or gender. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH]

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Climacteric: Physiologic period, characterized by endocrine, somatic, and psychic changes with the termination of ovarian function in the female. It may also accompany the normal diminution of sexual activity in the male. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clodronate: A drug used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). It may decrease pain, the risk of fractures, and the development of new bone metastases. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the

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high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Comedo: A plug of keratin and sebum within the dilated orifice of a hair follicle, frequently containing the bacteria Propionibacterium acnes, Staphylococcus albus, and Pityrosporon ovale; called also blackhead. [EU] Competency: The capacity of the bacterium to take up DNA from its surroundings. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH]

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Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraceptive Agents: Chemical substances that prevent or reduce the probability of

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conception. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Angiography: Radiography of the vascular system of the heart muscle after injection of a contrast medium. [NIH] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Corpus: The body of the uterus. [NIH]

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Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyproterone: An anti-androgen that, in the form of its acetate, also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. [NIH] Cyproterone Acetate: An agent with anti-androgen and progestational properties. It shows competitive binding with dihydrotestosterone at androgen receptor sites. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cystathionine beta-Synthase: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to hyperhomocysteinemia and homocystinuria. EC 4.2.1.22. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and

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cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents. [NIH] Danazol: A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose. [NIH]

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Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Desiccation: Removal of moisture from a substance (chemical, food, tissue, etc.). [NIH] Desogestrel: A synthetic progestational hormone used often as the progestogenic component of combined oral contraceptive agents. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Ketoacidosis: Complication of diabetes resulting from severe insulin deficiency coupled with an absolute or relative increase in glucagon concentration. The metabolic acidosis is caused by the breakdown of adipose stores and resulting increased levels of free fatty acids. Glucagon accelerates the oxidation of the free fatty acids producing excess ketone bodies (ketosis). [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease. [NIH] Dispenser: Glass, metal or plastic shell fitted with valve from which a pressurized

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formulation is dispensed; an instrument for atomizing. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Dry Eye Syndrome: A common condition that occurs when the eyes do not produce enough tears to keep the eye moist and comfortable. Common symptoms of dry eye include pain, stinging, burning, scratchiness, and intermittent blurring of vision. [NIH] Duct: A tube through which body fluids pass. [NIH]

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Dydrogesterone: A synthetic progestational hormone with no androgenic or estrogenic properties. Unlike many other progestational compounds, dydrogesterone produces no increase in temperature and does not inhibit ovulation. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]

Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emetic: An agent that causes vomiting. [EU]

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Emulsions: Colloids of two immiscible liquids where either phase may be either fatty or aqueous; lipid-in-water emulsions are usually liquid, like milk or lotion and water-in-lipid emulsions tend to be creams. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory

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systems. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelial ovarian cancer: Cancer that occurs in the cells lining the ovaries. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Equilenin: 3-Hydroxyestra-1,3,5(10),6,8-pentaen-17-one. A naturally occurring steroid with estrogenic activity obtained from the urine of pregnant mares. [NIH] Equilin: 3-Hydroxyestra-1,3,5(10)7-tetraen-17-one. A naturally occurring steroid with estrogenic activity obtained from the urine of pregnant mares. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estriol: (16 alpha,17 beta)-Estra-1,3,5(10)-triene-3,16,17-triol. A metabolite of estradiol and usually the predominant estrogenic metabolite in urine. During pregnancy, large amounts of estriol are produced by the placenta. It has also been obtained from plant sources. The 16 beta-isomer has also been isolated from the urine of pregnant women. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach.

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[NIH]

Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]

Estrone: 3-Hydroxyestra-1,3,5(10)-trien-17-one. A metabolite of estradiol but possessing less biological activity. It is found in the urine of pregnant women and mares, in the human placenta, and in the urine of bulls and stallions. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), estrone may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethinyl Estradiol: A semisynthetic estrogen with high oral estrogenic potency. It is often used as the estrogenic component in oral contraceptives. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extreme obesity: A body mass index [NIH] Fallopian Tubes: Two long muscular tubes that transport ova from the ovaries to the uterus. They extend from the horn of the uterus to the ovaries and consist of an ampulla, an infundibulum, an isthmus, two ostia, and a pars uterina. The walls of the tubes are composed of three layers: mucosal, muscular, and serosal. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.

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[NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Neck Fractures: Fractures of the short, constricted portion of the thigh bone between the femur head and the trochanters. It excludes intertrochanteric fractures which are hip fractures. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetal Growth Retardation: The failure of a fetus to attain its expected growth potential at any gestational stage. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Foetoplacental: Pertaining to the fetus and placenta. [EU] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH]

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Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]

Forearm: The part between the elbow and the wrist. [NIH] Frail Elderly: Older adults or aged individuals who are lacking in general strength and are unusually susceptible to disease or to other infirmity. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gamete Intrafallopian Transfer: A technique that came into use in the mid-1980's for assisted conception in infertile women with normal fallopian tubes. The protocol consists of hormonal stimulation of the ovaries, followed by laparoscopic follicular aspiration of oocytes, and then the transfer of sperm and oocytes by catheterization into the fallopian tubes. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

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Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH]

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Gonadal: Pertaining to a gonad. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Government Agencies: Administrative units of government responsible for policy making and management of governmental activities in the U.S. and abroad. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Gravidity: Pregnancy; the condition of being pregnant, without regard to the outcome. [EU] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of

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glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Hip Fractures: Fractures of the femur head, the femur neck, the trochanters, or the inter- or subtrochanteric region. Excludes fractures of the acetabulum and fractures of the femoral shaft below the subtrochanteric region. For the fractures of the femur neck the specific term femoral neck fractures is available. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]

Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH]

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Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydration: Combining with water. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperhomocysteinemia: An inborn error of methionone metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine betasynthase and is a risk factor for coronary vascular disease. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hyperreactive: Describes a situation in which a body tissue is especially likely to have an exaggerated reaction to a particular situation. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hyperstimulation: Excessive stimulation. [EU] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to

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damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]

Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypolipidemic: A drug that lowers abnormally high plasma concentrations of cholesterol or triglycerides or both. [NIH] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysterectomy: Excision of the uterus. [NIH] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Ifosfamide: Positional isomer of cyclophosphamide which is active as an alkylating agent and an immunosuppressive agent. [NIH] Ileum: The lower end of the small intestine. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH]

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Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant Mortality: Perinatal, neonatal, and infant deaths in a given population. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized,

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subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Intercellular Adhesion Molecule-1: A cell-surface ligand with a role in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue. [NIH] Interindividual: Occurring between two or more individuals. [EU] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU]

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Intracellular: Inside a cell. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ipsilateral: Having to do with the same side of the body. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH]

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Islet: Cell producing insulin in pancreas. [NIH] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kava: Dried rhizome and roots of Piper methysticum, a shrub native to Oceania and known for its anti-anxiety and sedative properties. Heavy usage results in some adverse effects. It contains alkaloids, lactones, kawain, methysticin, mucilage, starch, and yangonin. Kava is also the name of the pungent beverage prepared from the plant's roots. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacrimal: Pertaining to the tears. [EU] Lacrimal gland: The small almond-shaped structure that produces tears; located just above the outer corner of the eye. [NIH] Lactation: The period of the secretion of milk. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH]

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Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Levonorgestrel: A progestational hormone with actions similar to those of progesterone and about twice as potent as its racemic or (+-)-isomer (norgestrel). It is used for contraception, control of menstrual disorders, and treatment of endometriosis. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU]

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Lipoprotein(a): A family of lipoprotein particles varying in density and size depending on the protein-lipid ratio and the protein composition. These particles consist of apolipoprotein B-100 covalently linked to apolipoprotein-a by one or two disulfide bonds. There is a correlation between high plasma levels of this lipoprotein and increased risk for atherosclerotic cardiovascular disease. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Luteal Phase: The period of the menstrual cycle that begins with ovulation and ends with menstruation. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along

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lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mammography: Radiographic examination of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Marital Status: A demographic parameter indicating a person's status with respect to marriage, divorce, widowhood, singleness, etc. [NIH] Mastectomy: Surgery to remove the breast (or as much of the breast tissue as possible). [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of

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the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical oncologist: A doctor who specializes in diagnosing and treating cancer using chemotherapy, hormonal therapy, and biological therapy. A medical oncologist often serves as the main caretaker of someone who has cancer and coordinates treatment provided by other specialists. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medroxyprogesterone: (6 alpha)-17-Hydroxy-6-methylpregn-4-ene-3,20-dione. A synthetic progestational hormone used in veterinary practice as an estrus regulator. [NIH] Medroxyprogesterone Acetate: An injectable contraceptive, generally marketed under the name Depo-Provera. [NIH] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meibomian: A series of simple, branched, alveolar, sebaceous glands, located in the tarso of the eyelids, whose ducts empty into the eyelid margins in line with and lateral to the lacrimal puncta. [NIH] Meibomian Glands: The sebaceous glands situated on the inner surface of the eyelids between the tarsal plates and conjunctiva. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other

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career development situations. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methyltestosterone: A synthetic hormone used for androgen replacement therapy and as an hormonal antineoplastic agent. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Midaxillary line: An imaginary vertical line that passes midway between the anterior and posterior axillary (armpit) folds. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mineralocorticoid: 1. Any of the group of C21 corticosteroids, principally aldosterone, predominantly involved in the regulation of electrolyte and water balance through their effect on ion transport in epithelial cells of the renal tubules, resulting in retention of sodium

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and loss of potassium; some also possess varying degrees of glucocorticoid activity. Their secretion is regulated principally by plasma volume, serum potassium concentration and angiotensin II, and to a lesser extent by anterior pituitary ACTH. 2. Of, pertaining to, having the properties of, or resembling a mineralocorticoid. [EU] Minority Groups: A subgroup having special characteristics within a larger group, often bound together by special ties which distinguish it from the larger group. [NIH] Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary

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arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myometrium: The smooth muscle coat of the uterus, which forms the main mass of the organ. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH]

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Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Norethindrone: A synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. [NIH] Norgestrel: (+-)-13-Ethyl-17-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one. A progestational agent with actions similar to those of progesterone. This racemic or (+-)-form has about half the potency of the levo form (levonorgestrel). Norgestrel is used as a contraceptive and ovulation inhibitor and for the control of menstrual disorders and endometriosis. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the

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information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Occupational Health: The promotion and maintenance of physical and mental health in the work environment. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Oestradiol: Growth hormone. [NIH] Oestrogen: A generic term for oestrus-producing steroid compounds; the female sex hormones. In humans, oestrogen is formed in the ovary, possibly the adrenal cortex, the testis, and the foetoplacental unit; it has various functions in both sexes. It is responsible for the development of the female secondary sex characteristics, and during the menstrual cycle it acts on the female genitalia to produce an environment suitable for the fertilization, implantation, and nutrition of the early embryo. Oestrogen is used in oral contraceptives and as a palliative in cancer of the breast after menopause and cancer of the prostate; other uses include the relief of the discomforts of menopause, inhibition of lactation, and treatment of osteoporosis, threatened abortion, and various functional ovarian disorders. [EU]

Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oncogenes: Genes which can potentially induce neoplastic transformation. They include genes for growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. When these genes are constitutively expressed after structural and/or regulatory changes, uncontrolled cell proliferation may result. Viral oncogenes have prefix "v-" before the gene symbol; cellular oncogenes (protooncogenes) have the prefix "c-" before the gene symbol. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in

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treating cancer with radiation. [NIH] Oncology: The study of cancer. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Oophorectomy: Surgery to remove one or both ovaries. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opsin: A visual pigment protein found in the retinal rods. It combines with retinaldehyde to form rhodopsin. [NIH] Osteoarthritis: Degeneration of articular cartilage. Primary osteoarthritis is very common in older persons, especially affecting weight-bearing joints. Articular cartilage becomes soft, frayed and thinned. [NIH] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovariectomy: The surgical removal of one or both ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovulation Induction: Techniques for the artifical induction of ovulation. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pamidronate: A drug that belongs to the family of drugs called bisphosphonates.

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Pamidronate is used as treatment for abnormally high levels of calcium in the blood. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parity: The number of offspring a female has borne. It is contrasted with gravidity, which refers to the number of pregnancies, regardless of outcome. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Satisfaction: The degree to which the individual regards the health care service or product or the manner in which it is delivered by the provider as useful, effective, or beneficial. [NIH] Pelvic: Pertaining to the pelvis. [EU]

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Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Perceived risk: Estimate or evaluation of risk as observed through personal experience or personal study, and personal evaluation of consequences. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perimenopausal: The time of a woman's life when menstrual periods become irregular. Refers to the time near menopause. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH]

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Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacist: A person trained to prepare and distribute medicines and to give information about them. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]

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Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness,

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aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Policy Making: The decision process by which individuals, groups or institutions establish policies pertaining to plans, programs or procedures. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postmenopause: The physiological period following the menopause, the permanent cessation of the menstrual life. Since in the United States the age of the menopause ranges between 48 and 55 years, generally conceived as middle age, the postmenopause often refers to women considerably older. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of

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the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Pre-Eclampsia: Development of hypertension with proteinuria, edema, or both, due to pregnancy or the influence of a recent pregnancy. It occurs after the 20th week of gestation, but it may develop before this time in the presence of trophoblastic disease. [NIH] Pregnenolone: Steroid hormone. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Premenstrual: Occurring before menstruation. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle (shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal tumor. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progestogen: A term applied to any substance possessing progestational activity. [EU] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU]

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Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Prolactinoma: A pituitary adenoma which secretes prolactin, leading to hyperprolactinemia. Clinical manifestations include amenorrhea; galactorrhea; impotence; headache; visual disturbances; and cerebrospinal fluid rhinorrhea. [NIH] Prolapse: The protrusion of an organ or part of an organ into a natural or artificial orifice. [NIH]

Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propylene Glycol: A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally

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occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate-Specific Antigen: Kallikrein-like serine proteinase produced by epithelial cells of both benign and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. EC 3.4.21.77. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Protooncogenes have names of the form c-onc. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] P-Selectin: Cell adhesion molecule and CD antigen that mediates the adhesion of neutrophils and monocytes to activated platelets and endothelial cells. [NIH]

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Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]

Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH]

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Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Radius: The lateral bone of the forearm. [NIH] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in

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crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectovaginal Fistula: Abnormal communication between the rectum and the vagina. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Rehabilitation Centers: Facilities which provide programs for rehabilitating the mentally or physically disabled individuals. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the

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most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although

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infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinorrhea: The free discharge of a thin nasal mucus. [EU] Ribonuclease: RNA-digesting enzyme. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Sagittal: The line of direction passing through the body from back to front, or any vertical plane parallel to the medial plane of the body and inclusive of that plane; often restricted to the medial plane, the plane of the sagittal suture. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH]

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Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH] Second cancer: Refers to a new primary cancer that is caused by previous cancer treatment, or a new primary cancer in a person with a history of cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to

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reproduction. [NIH] Sex Hormone-Binding Globulin: A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Sexual Harassment: A form of discrimination in the workplace which violates the Civil Rights Act of 1964. Sexual harassment takes two forms: quid pro quo, where the employee must submit to sexual advances in exchange for job benefits or be penalized for refusing; or a hostile environment, where the atmosphere of the workplace is offensive and affects the employee's well-being. Offensive sexual conduct may include unwelcome advances, comments, touching, questions about marital status and sex practices, etc. Both men and women may be aggressors or victims. (Slee and Slee, Health Care Terms, 2d ed, p.404). While civil rights legislation deals with sexual harassment in the workplace, the behavior is not restricted to this; it may take place outside the work environment: in schools and colleges, athletics, and other social milieus and activities. [NIH] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Class: A stratum of people with similar position and prestige; includes social stratification. Social class is measured by criteria such as education, occupation, and income. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH]

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Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Soy Proteins: Proteins which are present in or isolated from soybeans. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spotting: A slight discharge of blood via the vagina, especially as a side-effect of oral contraceptives. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body,

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especially whether the disease has spread from the original site to other parts of the body. [NIH]

Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress urinary: Leakage of urine caused by actions--such as coughing, laughing, sneezing, running, or lifting--that place pressure on the bladder from inside the body. Stress urinary incontinence can result from either a fallen bladder or weak sphincter muscles. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Subtrochanteric: Below a trochanter. [NIH]

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Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Tarsal Bones: The seven bones which form the tarsus - namely, calcaneus, talus, cuboid, navicular, and first, second and third cuneiforms. The tarsus is a skeletal part of the foot. [NIH]

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Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombophilia: A disorder of hemostasis in which there is a tendency for the occurrence of thrombosis. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thymus Gland: A single, unpaired primary lymphoid organ situated in the mediastinum, extending superiorly into the neck to the lower edge of the thyroid gland and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. [NIH] Thymus Hormones: Humoral factors secreted by the thymus gland. They participate in the development of the lymphoid system and the maturation of the cellular immune response. [NIH]

Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either

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side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrostatic: Antithyroid agent. [EU] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Total hysterectomy: Surgery to remove the entire uterus. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH]

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Traction: The act of pulling. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Transient Ischemic Attacks: Focal neurologic abnormalities of sudden onset and brief duration that reflect dysfunction in the distribution of the internal carotid-middle cerebral or the vertebrobasilar arterial system. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica Intima: The innermost coat of blood vessels, consisting of a thin lining of endothelial cells longitudinally oriented and continuous with the endothelium of capillaries on the one hand and the endocardium of the heart on the other. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH]

298 Hormone Replacement Therapy

Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Fistula: An abnormal passage in any organ of the urinary tract or between urinary organs and other organs. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urodynamic: Measures of the bladder's ability to hold and release urine. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH]

Dictionary 299

Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

Ventricular Remodeling: The geometric and structural changes that the ventricle undergoes, usually following myocardial infarction. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral fat: One of the three compartments of abdominal fat. Retroperitoneal and subcutaneous are the other two compartments. [NIH] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is

300 Hormone Replacement Therapy

dependent mainly on the sharpness of the retinal focus. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Waist circumference: To define the level at which the waist circumference is measured, a bony landmark is first located and marked. The subject stands, and the technician, positioned to the right of the subject, palpates the upper hip bone to locate the right ileum. Just above the uppermost lateral border of the right ileum, a horizontal mark is drawn and then crossed with a vertical mark on the midaxillary line. The measuring tape is then placed around the trunk, at the level of the mark on the right side, making sure that it is on a level horizontal plane on all sides. The tape is then tightened slightly without compressing the skin and underlying subcutaneous tissues. The measure is recorded in centimeters to the nearest millimeter. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zygote: The fertilized ovum. [NIH] Zygote Intrafallopian Transfer: An assisted reproduction technique consisting of hormonal stimulation of the ovaries, laparoscopic follicular aspiration of oocytes, in-vitro fertilization, and intrafallopian transfer of the zygote by transabdominal cannulation at the pronuclear stage (before cleavage). [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

301

INDEX A Abdomen, 229, 238, 239, 254, 264, 268, 278, 288, 293, 295 Abdominal, 5, 6, 34, 35, 50, 81, 104, 188, 229, 230, 265, 277, 278, 288, 299 Abdominal fat, 5, 6, 50, 81, 229, 299 Abdominal Pain, 104, 229, 265 Acceptor, 229, 267, 276 ACE, 173, 229 ACE Inhibitor, 173, 229 Acetaldehyde, 229, 231 Acetylcholine, 229, 243, 274 Acidosis, 229, 250 Acne, 164, 229, 248, 288 Acute lymphoblastic leukemia, 102, 119, 229 Acute lymphocytic leukemia, 229 Adaptability, 18, 52, 229, 242 Adaptation, 53, 229, 280 Adduct, 16, 230 Adenocarcinoma, 160, 230 Adenoma, 230, 283 Adenosine, 230, 236, 240, 279 Adipocytes, 230, 267 Adipose Tissue, 229, 230 Adjustment, 229, 230 Adolescence, 96, 151, 186, 230 Adrenal Cortex, 152, 160, 230, 231, 233, 254, 275, 282, 288 Adrenal Glands, 162, 230 Adrenal Medulla, 230, 242, 254, 274 Adrenergic, 9, 230, 251, 254 Adverse Effect, 35, 60, 129, 163, 166, 172, 230, 235, 266, 291 Aerobic, 6, 39, 56, 63, 199, 230 Aerobic Exercise, 39, 63, 199, 230 Aerosol, 230, 294 Aetiology, 15, 230 Afferent, 230, 267 Affinity, 230, 231, 292 Agar, 231, 280 Age Groups, 187, 231 Age of Onset, 167, 231, 297 Aged, 80 and Over, 231 Ageing, 92, 165, 167, 231 Aggressiveness, 26, 231 Agonist, 53, 55, 86, 181, 231, 235, 251, 286, 294

Airway, 10, 231, 291 Alcohol Dehydrogenase, 56, 231 Aldosterone, 41, 231, 271 Alendronate, 67, 186, 199, 214, 231 Alendronate Sodium, 186, 231 Alertness, 231, 240 Algorithms, 231, 238 Alimentary, 231, 277 Alkaline, 229, 231, 240 Alleles, 55, 232 Allergen, 232, 290 Alpha Particles, 232, 285 Alternative medicine, 198, 232 Alveolar Process, 232, 288 Amenorrhea, 116, 169, 178, 179, 180, 232, 274, 283 Amino Acid Sequence, 232, 233, 234, 291 Amino Acids, 232, 233, 278, 281, 284, 289, 290, 294, 297 Amlodipine, 78, 232 Amnion, 154, 232 Amniotic Fluid, 154, 232 Amyloid, 7, 23, 232 Anaesthesia, 232, 263 Anal, 232, 254, 256, 268 Analgesic, 232, 244, 272 Analog, 27, 150, 232 Analytes, 22, 232 Anaphylatoxins, 232, 245 Anatomical, 10, 233, 246, 250, 263, 289 Androgen-Binding Protein, 233, 291 Androgenic, 152, 164, 166, 233, 249, 252, 274 Androgens, 32, 151, 152, 168, 179, 230, 233, 235 Androstanes, 164, 233 Androstenedione, 152, 233 Anemia, 233, 257 Anergy, 176, 177, 233 Anesthesia, 231, 233, 236, 253 Aneurysm, 233, 298 Angina, 24, 184, 232, 233 Angina Pectoris, 184, 232, 233 Angiogenesis, 56, 233 Angioplasty, 184, 233, 236 Angiotensinogen, 11, 233, 287 Animal model, 35, 61, 233 Antagonism, 233, 240

302 Hormone Replacement Therapy

Anthropometric measurements, 20, 55, 234 Antibacterial, 234, 292 Antibiotic, 234, 292 Antibodies, 21, 234, 263, 269, 280 Antibody, 176, 231, 234, 245, 260, 263, 270, 272, 285, 286, 290, 292 Antibody therapy, 176, 234 Anticoagulant, 93, 234, 284 Antidepressant, 162, 234, 240 Antiepileptic, 36, 234 Antigen, 194, 230, 234, 245, 260, 261, 263, 270, 284, 290 Antigen-Antibody Complex, 234, 245 Antihypertensive, 79, 234 Anti-infective, 234, 265 Anti-inflammatory, 17, 234, 236, 258, 277 Anti-Inflammatory Agents, 234, 236 Antimitotic, 163, 234 Antineoplastic, 234, 248, 257, 258, 271 Antioxidant, 13, 16, 21, 47, 127, 216, 234, 236, 276 Antiproliferative, 14, 234 Anus, 232, 234, 239, 278, 287 Anxiety, 27, 128, 149, 235, 266 Aorta, 235, 247, 282, 299 Apnea, 11, 45, 235 Apolipoproteins, 68, 235, 267 Apomorphine, 184, 235 Apoptosis, 23, 235 Applicability, 63, 235 Aqueous, 29, 155, 235, 237, 249, 253 Arachidonic Acid, 235, 283 Arginine, 232, 235, 274 Aromatase, 105, 235 Arterial, 5, 22, 39, 49, 104, 235, 236, 239, 240, 243, 261, 284, 294, 297 Arteries, 38, 62, 235, 236, 238, 239, 242, 247, 265, 268, 271, 273 Arteriolar, 235, 239, 288 Arterioles, 235, 238, 241, 271, 273, 298 Arteriolosclerosis, 235, 236 Arteriosclerosis, 82, 165, 235, 262 Arteriovenous, 236, 271 Articular, 236, 276 Ascites, 236, 275 Ascorbic Acid, 101, 175, 236, 261 Aspirate, 61, 236 Aspiration, 236, 257, 300 Aspirin, 18, 21, 51, 184, 236 Assay, 41, 62, 73, 236 Asymptomatic, 6, 58, 236

Atherectomy, 236, 253 Atherogenic, 50, 60, 236 ATP, 236, 251, 258, 265, 279, 284 Atrophy, 12, 149, 152, 178, 236, 273 Attenuated, 9, 24, 56, 236, 250 Attenuation, 25, 236 Atypical, 78, 236 Atypical hyperplasia, 78, 236 Autoimmune disease, 29, 176, 236 Autoimmunity, 176, 177, 236 Autonomic, 39, 78, 88, 229, 236, 274, 278, 294 Autonomic Nervous System, 236, 278, 294 Autosuggestion, 237, 262 Axillary, 36, 237, 239, 271 Axillary Artery, 237, 239 Axonal, 35, 237 B Bacteria, 234, 237, 245, 252, 253, 261, 271, 286, 292, 298 Bacterial Physiology, 230, 237 Bacteriophage, 237, 280 Bacterium, 237, 245 Baroreflex, 39, 237 Base, 38, 237, 249, 266, 295 Benign, 90, 106, 179, 230, 235, 236, 237, 249, 259, 273, 284, 286, 300 Benzene, 237, 266 Beta carotene, 200, 237 Beta-pleated, 232, 237 Bilateral, 69, 150, 237 Bile, 237, 257, 268, 293 Bile Ducts, 237, 257 Bilirubin, 237, 257 Bioavailability, 69, 156, 163, 237 Bioavailable, 29, 238 Biochemical, 14, 21, 25, 38, 47, 56, 61, 62, 76, 99, 117, 153, 186, 232, 238, 290 Biological therapy, 238, 259, 270 Biological Transport, 238, 250 Biomarkers, 41, 56, 57, 61, 92, 238 Biopsy, 238, 278 Biosynthesis, 30, 168, 179, 235, 238, 248, 268, 290 Biotechnology, 64, 65, 192, 198, 207, 238 Bipolar Disorder, 27, 238 Birth Rate, 174, 238 Bladder, 187, 194, 238, 243, 248, 263, 284, 293, 298 Blastocyst, 238, 246, 280 Bloating, 158, 238, 265 Blood Coagulation, 238, 240, 295

Index 303

Blood Glucose, 6, 12, 185, 238, 259, 262, 264 Blood Platelets, 51, 238, 290 Blood pressure, 5, 31, 70, 77, 78, 80, 185, 229, 234, 237, 238, 241, 261, 272, 278, 292 Blood vessel, 185, 229, 233, 237, 238, 239, 240, 241, 242, 253, 265, 268, 269, 278, 279, 291, 292, 293, 295, 297, 298 Blot, 57, 238 Body Composition, 35, 43, 46, 50, 64, 87, 239 Body Fluids, 238, 239, 240, 251, 292, 297 Body Mass Index, 6, 21, 57, 73, 239, 255, 276 Bone Density, 26, 44, 67, 151, 171, 239 Bone Marrow, 229, 237, 239, 263, 269, 272, 292, 293 Bone metastases, 239, 244 Bone Remodeling, 186, 239 Bone Resorption, 19, 61, 107, 132, 199, 239 Bone scan, 239, 289 Bowel, 38, 232, 239, 250, 264, 293 Bowel Movement, 239, 250, 293 Brachial, 31, 239, 269 Brachial Artery, 31, 239 Brachytherapy, 239, 264, 285 Bradykinin, 80, 239, 266, 274, 280 Brain Hypoxia, 239, 240 Brain Infarction, 239, 240 Brain Ischemia, 163, 240 Branch, 225, 240, 252, 269, 277, 285, 292, 294, 295 Breakdown, 19, 63, 186, 240, 250, 257 Breast Feeding, 186, 240 Bronchi, 240, 254, 296 Bronchial, 69, 240, 284 Buccal, 42, 152, 240, 268 Buffers, 237, 240 Bupropion, 93, 240 Burns, 119, 199, 240 Burns, Electric, 240 Bypass, 50, 184, 240 C Caffeine, 19, 186, 200, 240 Calcaneus, 85, 240, 294 Calcification, 235, 240 Calcium channel blocker, 232, 240 Capillary, 10, 239, 241, 299 Capillary Permeability, 239, 241 Capsules, 241, 251, 257 Carbohydrate, 6, 28, 241, 258, 281

Carbon Dioxide, 241, 256, 257, 280, 288, 299 Carcinogen, 30, 230, 241, 255 Carcinogenic, 237, 241, 264, 283, 293 Carcinoma, 7, 42, 89, 106, 126, 154, 179, 241, 248 Cardiac, 11, 24, 31, 38, 41, 51, 56, 72, 78, 100, 237, 240, 241, 247, 254, 255, 273, 293 Cardiac Output, 11, 31, 237, 241, 293 Cardiology, 38, 72, 74, 77, 90, 94, 96, 99, 111, 241 Cardiomyopathy, 24, 241 Cardiorespiratory, 230, 241 Cardiovascular System, 38, 148, 175, 241 Carotene, 175, 200, 237, 241, 288 Carotenoids, 135, 237, 241 Carpal Tunnel Syndrome, 69, 241 Case report, 69, 242, 244 Case-Control Studies, 6, 22, 57, 242, 254 Catecholamine, 28, 242, 251, 279 Catheterization, 38, 233, 242, 257, 265 Causal, 8, 46, 58, 242, 254, 264 Cause of Death, 20, 31, 50, 165, 173, 175, 242 Cell Cycle, 40, 75, 242, 284 Cell Death, 23, 40, 235, 242, 273 Cell Division, 237, 242, 259, 272, 280 Cell proliferation, 40, 86, 235, 242, 275 Cell Respiration, 242, 288 Cell Survival, 242, 259 Cell Transplantation, 185, 242 Central Nervous System, 55, 61, 148, 193, 229, 236, 237, 240, 242, 243, 257, 258, 259, 272, 290 Cerebral, 25, 35, 62, 84, 239, 242, 247, 254, 255, 292, 295, 297 Cerebral Arteries, 84, 242 Cerebrospinal, 242, 283 Cerebrospinal fluid, 242, 283 Cerebrovascular, 62, 108, 145, 241, 242 Cerebrum, 242 Character, 233, 242, 249 Chemoprevention, 9, 17, 243 Chemotactic Factors, 243, 245 Chemotherapy, 156, 243, 270 Chest Pain, 184, 243 Chlormadinone Acetate, 154, 243 Cholesterol Esters, 243, 267 Cholinergic, 243 Cholinesterase Inhibitors, 195, 243 Chromatin, 235, 243 Chromosome, 243, 267

304 Hormone Replacement Therapy

Chronic Disease, 18, 65, 68, 243 Chronic renal, 4, 243 Chylomicrons, 243, 267 CIS, 44, 243, 288 Citrus, 236, 243 Civil Rights, 243, 291 Clamp, 28, 35, 243 Clinical Medicine, 118, 244, 282 Clinical study, 244, 247 Clinical trial, 6, 7, 8, 18, 20, 23, 26, 44, 60, 76, 143, 145, 207, 244, 247, 251, 284, 286 Clodronate, 117, 244 Cloning, 238, 244 Coagulation, 12, 37, 44, 51, 67, 116, 238, 244, 260, 280, 295 Cochlear, 244, 296, 299 Cochlear Diseases, 244, 296 Codeine, 87, 244 Coenzyme, 168, 236, 244, 268 Cofactor, 244, 284, 295 Cognition, 6, 16, 33, 53, 165, 244 Cohort Studies, 6, 244, 254 Colitis, 244, 265 Collagen, 73, 244, 257, 281, 283 Collapse, 240, 245, 291 Colloidal, 245, 294 Colorectal, 17, 38, 134, 245 Colorectal Cancer, 17, 38, 134, 245 Combination Therapy, 31, 164, 167, 173, 245, 255 Comedo, 42, 245 Competency, 18, 245 Complement, 19, 52, 233, 245, 280, 290 Complementary and alternative medicine, 123, 124, 136, 245 Complementary medicine, 124, 245 Complete remission, 245, 287 Computational Biology, 207, 246 Computed tomography, 50, 239, 246, 289 Computerized axial tomography, 246, 289 Computerized tomography, 34, 246 Conception, 246, 247, 256, 257, 293 Cone, 246, 294 Confounding, 16, 17, 57, 246 Congestive heart failure, 24, 41, 89, 165, 184, 246 Conjugated, 5, 34, 36, 66, 70, 109, 144, 160, 169, 246, 249 Conjunctiva, 246, 270 Connective Tissue, 236, 239, 244, 246, 257, 268, 288, 294 Consciousness, 232, 246, 249

Constipation, 246, 265 Constriction, 62, 246, 265, 298 Constriction, Pathologic, 246, 298 Consumption, 15, 56, 172, 186, 199, 200, 246, 250, 276 Continuum, 46, 246 Contraceptive Agents, 157, 246, 250 Contractility, 62, 119, 153, 160, 179, 247 Contraindications, ii, 7, 45, 247 Contralateral, 42, 247 Control group, 17, 58, 247, 286 Controlled clinical trial, 14, 247, 286 Controlled study, 52, 74, 247 Conventional therapy, 170, 247 Conventional treatment, 247 Convulsions, 247, 252, 282 Cornea, 29, 247 Coronary Angiography, 184, 247 Coronary Arteriosclerosis, 247, 273 Coronary Artery Bypass, 50, 247 Coronary Circulation, 233, 247 Coronary Disease, 44, 51, 82, 247 Coronary heart disease, 20, 22, 28, 31, 51, 56, 70, 92, 101, 105, 150, 173, 241, 247 Coronary Thrombosis, 247, 271, 273 Coronary Vessels, 51, 247 Corpus, 160, 247, 248, 282 Corpus Luteum, 160, 248, 282 Cortex, 23, 242, 248, 253, 255 Cortical, 43, 248, 290 Corticosteroids, 162, 248, 258, 271 Craniocerebral Trauma, 248, 259, 296 Creatinine, 185, 248 Cross-Sectional Studies, 248, 254 Curative, 17, 248, 295 Cutaneous, 10, 248, 268 Cyclic, 19, 53, 240, 248, 259, 274, 279, 283 Cyclophosphamide, 248, 262 Cyproterone, 154, 248 Cyproterone Acetate, 154, 248 Cyst, 236, 248 Cystathionine beta-Synthase, 248, 261 Cysteine, 248, 294 Cystitis, 188, 248 Cytochrome, 93, 235, 248 Cytokine, 25, 61, 249, 278 Cytoplasm, 235, 249, 253, 259, 272, 289 Cytoprotection, 14, 249 D Danazol, 55, 249 Data Collection, 26, 43, 249 Databases, Bibliographic, 207, 249

Index 305

Decidua, 249, 280 Decision Making, 18, 249 Degenerative, 249, 288 Deletion, 176, 177, 235, 249 Dementia, 6, 7, 13, 33, 64, 74, 78, 215, 249 Dentate Gyrus, 249, 260 Deoxyguanosine, 47, 249 Deprivation, 156, 250 Desiccation, 29, 250 Desogestrel, 154, 250 Deuterium, 50, 250, 261 Developed Countries, 150, 250 Diabetes Mellitus, 250, 259 Diabetic Ketoacidosis, 185, 250 Diagnostic procedure, 147, 198, 250 Diarrhea, 250, 265 Diastolic, 250, 261 Diffusion, 149, 157, 238, 241, 250, 264, 265 Digestion, 231, 237, 239, 250, 264, 268, 293 Digestive system, 146, 250 Dihydrotestosterone, 248, 250, 287, 291 Dilatation, 233, 250, 282, 298, 299 Dilatation, Pathologic, 250, 298 Dilation, 31, 62, 236, 239, 250, 298 Dilution, 50, 250, 280 Direct, iii, 15, 17, 19, 109, 201, 244, 250, 251, 287, 294 Discrimination, 243, 250, 291 Disease Progression, 93, 250, 299 Disease-Free Survival, 26, 250 Dispenser, 155, 169, 250 Distal, 45, 159, 237, 247, 251, 284 Diuresis, 240, 251 Diuretic, 162, 251 Diverticulum, 188, 251 Dizziness, 173, 251 DNA Topoisomerase, 251, 258 Dopamine, 235, 240, 251 Dosage Forms, 156, 160, 161, 251 Double-blinded, 34, 251 Drive, ii, vi, 115, 183, 199, 251, 265, 267 Drug Delivery Systems, 152, 159, 181, 251 Drug Interactions, 130, 202, 251 Drug Tolerance, 251, 296 Dry Eye Syndrome, 29, 251 Duct, 242, 251, 255, 289 Dydrogesterone, 97, 252 Dyes, 232, 252, 274 Dyslipidemia, 4, 50, 168, 252 Dysmenorrhea, 55, 153, 160, 252 Dyspareunia, 55, 152, 252, 255

E Eclampsia, 252, 282 Edema, 170, 252, 265, 275, 282 Effector, 32, 229, 245, 252, 279 Elasticity, 235, 247, 252 Elastin, 244, 252 Elective, 106, 252 Electrocardiogram, 38, 117, 252 Electrocoagulation, 244, 252 Electrolyte, 231, 252, 271, 281, 292 Electrons, 234, 237, 252, 265, 276, 285, 286 Electrophysiological, 34, 252, 299 Embolus, 252, 263 Embryo, 162, 174, 179, 232, 238, 252, 263, 275 Emetic, 235, 252 Emulsions, 155, 231, 253 Endarterectomy, 77, 233, 236, 253 Endemic, 253, 292 Endocrine System, 253, 273 Endometriosis, 55, 86, 179, 186, 249, 253, 267, 274 Endometrium, 29, 75, 81, 160, 162, 163, 166, 174, 179, 189, 249, 253, 270 Endothelial cell, 41, 253, 284, 295, 297 Endothelium, 39, 72, 253, 274, 280, 297 Endothelium, Lymphatic, 253 Endothelium, Vascular, 253 Endothelium-derived, 253, 274 Endotoxic, 253, 267 Endotoxins, 245, 253 End-stage renal, 243, 253 Energy balance, 35, 253, 267 Energy Intake, 96, 253 Enhancer, 148, 149, 159, 253 Entorhinal Cortex, 253, 260 Environmental Health, 206, 208, 254 Enzymatic, 240, 241, 245, 254, 256, 288 Epidemic, 254, 292 Epidemiologic Studies, 40, 47, 160, 254 Epidemiological, 15, 23, 44, 49, 150, 254 Epigastric, 254, 277 Epinephrine, 230, 251, 254, 274 Epithelial, 16, 20, 57, 170, 179, 230, 238, 249, 254, 271, 284 Epithelial Cells, 16, 170, 254, 271, 284 Epithelial ovarian cancer, 20, 57, 254 Epithelium, 16, 29, 149, 152, 253, 254, 265, 277 Equilenin, 16, 254 Equilin, 16, 254 Erectile, 134, 184, 194, 254

306 Hormone Replacement Therapy

Erection, 184, 254 Erythrocytes, 233, 239, 254, 287, 290 Esophagus, 250, 254, 293 Estriol, 8, 164, 165, 254 Estrogen receptor, 13, 19, 22, 36, 38, 51, 53, 61, 62, 150, 167, 168, 181, 254 Estrogen Replacement Therapy, 7, 16, 24, 25, 38, 51, 81, 84, 158, 167, 168, 179, 215, 255 Estrone, 163, 169, 255 Ethanol, 231, 255, 256 Ethinyl Estradiol, 109, 255 Eukaryotic Cells, 255, 263 Evoke, 255, 293 Excitability, 35, 255 Exocrine, 255, 277 Exogenous, 15, 20, 25, 28, 45, 50, 56, 150, 160, 167, 255, 297 Expiration, 255, 288 External-beam radiation, 255, 285 Extracellular, 232, 246, 255, 271, 276, 292 Extracellular Matrix, 246, 255, 276 Extracellular Space, 255, 271 Extreme obesity, 29, 255 F Fallopian Tubes, 255, 257 Family Planning, 207, 255 Fatigue, 255, 259 Fatty acids, 5, 250, 256, 283 Femoral, 43, 256, 260 Femoral Neck Fractures, 256, 260 Femur, 43, 102, 256, 260 Fermentation, 231, 256 Fertilizers, 256, 274 Fetal Growth Retardation, 153, 256 Fetus, 162, 256, 280, 282, 298 Fibrin, 22, 238, 256, 280, 295 Fibrinogen, 4, 12, 22, 51, 256, 280, 295 Fibrinolysis, 37, 83, 256 Fibrinolytic, 37, 51, 67, 116, 256 Fixation, 256, 290 Foetoplacental, 256, 275 Folate, 19, 256, 257 Fold, 47, 57, 256 Folic Acid, 118, 175, 256, 257 Follow-Up Studies, 36, 257 Forearm, 111, 159, 163, 238, 257, 269, 286 Frail Elderly, 63, 80, 257 G Gallbladder, 229, 237, 250, 257 Gallstones, 7, 257 Gamete Intrafallopian Transfer, 174, 257

Gamma Rays, 257, 285, 286 Gamma-interferon, 257, 264 Ganglia, 229, 239, 257, 273, 278, 294 Gas, 241, 250, 257, 261, 265, 274, 294, 298, 299 Gas exchange, 257, 299 Gastric, 251, 257 Gastrin, 257, 260 Gastrointestinal, 182, 239, 243, 254, 255, 257, 290, 293, 297 Gastrointestinal tract, 243, 255, 257, 290, 297 Gelatin, 257, 294 Gels, 155, 257 Gene Expression, 23, 62, 258 Genetic Markers, 21, 22, 56, 258 Genetics, 167, 258 Genistein, 19, 49, 128, 172, 258 Genital, 94, 258, 298 Genitourinary, 193, 258, 298 Genotype, 11, 13, 22, 80, 258, 279 Germ Cells, 258, 276, 295 Gestation, 153, 179, 258, 278, 280, 282 Gestational, 256, 258 Gland, 29, 152, 161, 230, 258, 268, 277, 280, 284, 286, 289, 290, 293, 295, 296 Glucocorticoid, 44, 181, 199, 258, 272 Glucose, 3, 5, 6, 12, 32, 50, 57, 63, 87, 158, 185, 236, 238, 250, 258, 259, 264, 289 Glucose tolerance, 4, 50, 63, 258 Glucose Tolerance Test, 4, 50, 258 Glutamic Acid, 257, 258, 283 Glycoprotein, 256, 258, 291, 295 Glycoside, 258, 289 Gonad, 149, 258, 259 Gonadal, 10, 33, 40, 62, 259, 293 Gonadotropin, 20, 86, 259 Governing Board, 259, 282 Government Agencies, 32, 259, 282 Grade, 36, 77, 259 Graft, 51, 259, 260 Grafting, 184, 247, 259, 263 Granulocytes, 259, 300 Grasses, 257, 259 Gravidity, 259, 277 Growth, 14, 44, 56, 57, 65, 69, 70, 72, 83, 86, 87, 88, 90, 97, 102, 119, 120, 151, 153, 161, 162, 179, 192, 197, 230, 231, 233, 234, 235, 242, 256, 259, 261, 262, 264, 269, 273, 275, 280, 295, 296, 297 Growth factors, 14, 259, 275 Guanylate Cyclase, 259, 274

Index 307

H Headache, 240, 259, 283 Health Policy, 31, 112, 259 Health Status, 18, 52, 259 Heart attack, 145, 241, 259 Heart failure, 90, 259, 275 Heme, 237, 248, 259 Hemoglobin, 4, 5, 185, 233, 254, 259 Hemorrhage, 248, 252, 259, 260, 293 Hemostasis, 260, 290, 295 Hepatic, 154, 258, 260 Hereditary, 186, 260, 273, 278 Heredity, 257, 258, 260 Heterogeneity, 9, 10, 231, 260 Hip Fractures, 159, 171, 256, 260 Hippocampus, 23, 249, 260, 293 Hirsutism, 248, 260 Histology, 19, 29, 260, 277 Homeostasis, 41, 62, 239, 260 Homogeneous, 157, 235, 246, 260, 279 Homologous, 232, 260, 284, 290 Hormonal therapy, 7, 63, 260, 270 Hormone therapy, 260 Host, 49, 58, 59, 237, 260, 263, 299 Human growth hormone, 161, 162, 261 Human papillomavirus, 94, 261 Hybrid, 261 Hybridization, 29, 261 Hydration, 11, 261 Hydrogen, 154, 176, 229, 231, 237, 240, 241, 250, 261, 267, 272, 274, 275, 276, 279, 284 Hydrolysis, 261, 265, 278, 281, 284 Hydrophobic, 261, 267 Hydroxylation, 93, 261 Hydroxylysine, 244, 261 Hydroxyproline, 244, 261 Hypercalcemia, 231, 244, 261 Hypercholesterolemia, 54, 134, 165, 168, 252, 261 Hyperhomocysteinemia, 21, 248, 261 Hyperlipidemia, 165, 168, 252, 261 Hyperlipoproteinemia, 261, 262 Hyperplasia, 97, 174, 179, 261 Hyperreactive, 51, 261 Hypersensitivity, 232, 261, 289, 290 Hyperstimulation, 160, 163, 261 Hypertension, 11, 54, 80, 89, 134, 145, 150, 153, 165, 178, 184, 232, 235, 241, 261, 265, 282 Hyperthermia, 9, 153, 261 Hyperthyroidism, 161, 262

Hypertriglyceridemia, 168, 252, 262 Hypertrophy, 261, 262 Hypnotic, 52, 262 Hypoglycemia, 185, 262 Hypoglycemic, 6, 262 Hypogonadism, 194, 262 Hypolipidemic, 168, 262 Hypothalamus, 236, 262, 280 Hypothyroidism, 134, 161, 262 Hypoxia, 10, 262 Hysterectomy, 75, 175, 186, 188, 262 I Iatrogenic, 188, 262 Id, 31, 120, 133, 212, 213, 217, 218, 224, 226, 262 Ifosfamide, 44, 262 Ileum, 262, 300 Imaging procedures, 36, 262 Immune function, 32, 262 Immune response, 176, 233, 234, 236, 262, 263, 290, 293, 295, 299 Immune system, 176, 177, 234, 236, 238, 262, 263, 269, 273, 298, 300 Immunization, 263, 282, 290 Immunodeficiency, 32, 263 Immunogenic, 263, 267 Immunohistochemistry, 42, 263 Immunologic, 243, 263, 278, 286, 295 Immunosuppressive, 248, 258, 262, 263 Impairment, 13, 29, 34, 37, 52, 175, 263, 270 Implant radiation, 263, 264, 285 Implantation, 174, 246, 263, 275 Impotence, 184, 185, 254, 263, 283 In situ, 15, 23, 29, 54, 112, 144, 263 In Situ Hybridization, 23, 29, 263 In vitro, 9, 19, 24, 62, 174, 179, 263 In vivo, 19, 23, 32, 62, 263, 271 Incision, 263, 265 Incontinence, 7, 112, 135, 175, 187, 263, 293 Indicative, 188, 263, 277, 298 Induction, 16, 63, 176, 177, 233, 263, 276, 283 Infancy, 186, 263 Infant Mortality, 153, 263 Infant, Newborn, 231, 263 Infarction, 31, 135, 145, 239, 263 Infection, 7, 32, 153, 160, 185, 238, 243, 262, 263, 268, 269, 274, 289, 293, 300 Infertility, 55, 174, 264 Infiltration, 49, 264

308 Hormone Replacement Therapy

Inflammation, 47, 56, 89, 229, 234, 236, 244, 248, 264, 288, 294, 298 Ingestion, 55, 258, 264, 281 Initiation, 9, 21, 109, 143, 264, 297 Initiator, 56, 264 Inlay, 264, 288 Insight, 14, 40, 41, 264 Insomnia, 46, 58, 59, 156, 264 Insulin-dependent diabetes mellitus, 264 Insulin-like, 14, 57, 65, 70, 90, 264 Intercellular Adhesion Molecule-1, 56, 264 Interindividual, 8, 264 Intermittent, 10, 74, 93, 170, 251, 264 Internal radiation, 264, 285 Interstitial, 188, 239, 255, 264 Intervention Studies, 63, 264 Intestinal, 241, 258, 264 Intestine, 157, 239, 245, 264, 266 Intoxication, 264, 300 Intracellular, 181, 240, 263, 265, 274, 281, 283, 286 Intracranial Hypertension, 259, 265, 296 Intramuscular, 6, 265, 277 Intravascular, 51, 265 Intravenous, 28, 50, 265, 277 Intubation, 242, 265 Invasive, 15, 26, 40, 44, 57, 265, 269 Involuntary, 265, 273, 287, 291 Iodine, 161, 175, 265 Ion Transport, 265, 271 Ions, 237, 240, 252, 261, 265, 284 Ipsilateral, 42, 265 Iris, 247, 265, 285 Irritable Bowel Syndrome, 94, 265 Ischemia, 25, 50, 54, 236, 240, 265 Ischemic stroke, 37, 56, 265 Islet, 185, 266 Isoflavones, 14, 19, 60, 132, 266 J Joint, 21, 48, 236, 266, 294 K Kallidin, 239, 266 Kava, 128, 266 Kb, 206, 266 Keratin, 245, 266, 290 Ketone Bodies, 250, 266 Ketosis, 250, 266 Kinetics, 28, 32, 75, 266 L Labile, 245, 266 Lacrimal, 29, 79, 266, 270 Lacrimal gland, 29, 266

Lactation, 15, 266, 275, 283 Large Intestine, 245, 250, 264, 266, 287, 291 Latent, 266, 282 Least-Squares Analysis, 266, 287 Leptin, 106, 119, 267 Lesion, 247, 267, 268, 297 Lethal, 150, 267 Lethargy, 262, 267 Leukemia, 87, 267 Leukocytes, 239, 243, 259, 267, 272, 278 Levonorgestrel, 9, 154, 267, 274 Libido, 162, 233, 267 Library Services, 224, 267 Life cycle, 183, 267 Life Expectancy, 162, 167, 267 Ligament, 267, 284 Ligands, 13, 176, 177, 267 Likelihood Functions, 267, 287 Linear Models, 267, 287 Linkage, 11, 15, 258, 267 Lipid A, 3, 50, 63, 84, 267 Lipid Peroxidation, 267, 276 Lipopolysaccharide, 154, 267 Lipoprotein, 4, 5, 28, 51, 60, 63, 83, 84, 95, 160, 163, 252, 267, 268 Lipoprotein(a), 83, 268 Liver, 4, 7, 27, 148, 157, 194, 229, 235, 237, 248, 250, 257, 258, 260, 268, 287, 289 Liver scan, 268, 289 Lobe, 261, 268 Localization, 263, 268 Localized, 240, 256, 260, 263, 268, 275, 280, 297 Logistic Models, 268, 287 Longitudinal Studies, 117, 248, 268 Longitudinal study, 34, 45, 59, 71, 268 Lovastatin, 124, 268 Low-density lipoprotein, 50, 60, 252, 267, 268 Lumbar, 14, 125, 268 Lupus, 144, 199, 268, 294 Luteal Phase, 152, 160, 179, 268 Lymph, 36, 237, 253, 268, 269 Lymph node, 36, 237, 268, 269 Lymphatic, 253, 264, 268, 269, 275, 281, 292, 295 Lymphatic system, 268, 269, 292, 295 Lymphoblastic, 269 Lymphoblasts, 229, 269 Lymphocyte, 234, 269, 270 Lymphoid, 234, 248, 269, 295

Index 309

M Macrophage, 49, 269 Magnetic Resonance Imaging, 269, 289 Maintenance therapy, 9, 269 Malignant, 230, 234, 235, 269, 270, 273, 284, 286 Malnutrition, 236, 269 Mammary, 16, 149, 154, 173, 247, 269, 286, 294 Mammogram, 8, 240, 269 Mammography, 8, 36, 77, 92, 269 Mandible, 232, 269, 288 Manic, 238, 269 Manifest, 237, 269 Marital Status, 269, 291 Mastectomy, 106, 269 Medial, 34, 235, 269, 289 Median Nerve, 241, 269 Mediate, 19, 29, 251, 269 Mediator, 25, 269, 290 Medical oncologist, 44, 270 Medical Staff, 251, 270 Medicament, 270, 294 MEDLINE, 207, 270 Medroxyprogesterone, 5, 34, 36, 51, 70, 103, 109, 179, 270 Medroxyprogesterone Acetate, 34, 70, 103, 109, 179, 270 Medulloblastoma, 87, 270 Megaloblastic, 257, 270 Meibomian, 29, 270 Meibomian Glands, 29, 270 Membrane, 62, 154, 159, 232, 245, 246, 253, 255, 270, 271, 272, 279, 281, 288, 294, 297 Memory, 6, 16, 32, 33, 34, 52, 195, 249, 270 Menarche, 30, 186, 270 Meninges, 242, 248, 270 Menstrual Cycle, 59, 152, 160, 167, 169, 179, 180, 185, 186, 268, 270, 275, 282 Menstruation, 156, 160, 167, 169, 232, 249, 252, 268, 270, 282 Mental Disorders, 146, 270, 282, 285 Mental Health, iv, 8, 52, 75, 130, 146, 183, 206, 208, 270, 275, 282, 285 Mentors, 39, 270 Meta-Analysis, 6, 65, 72, 150, 271 Metabolic disorder, 184, 271 Metabolite, 15, 52, 57, 254, 255, 268, 271 Metastasis, 271 Metastatic, 42, 271 Methionine, 271, 294 Methyltestosterone, 151, 271

MI, 6, 17, 51, 57, 227, 271 Microbiology, 23, 230, 236, 271 Microcirculation, 111, 271, 280 Microdialysis, 10, 271 Microorganism, 244, 271, 300 Microscopy, 25, 271 Midaxillary line, 271, 300 Migration, 264, 271 Milliliter, 239, 271 Millimeter, 271, 300 Mineralocorticoid, 181, 271 Minority Groups, 43, 272 Miscarriage, 15, 272 Mitochondrial Swelling, 272, 273 Mitosis, 234, 235, 272 Mitotic, 174, 272 Modeling, 10, 50, 272 Modification, 46, 272, 285 Modulator, 272 Molecule, 25, 234, 237, 241, 244, 245, 252, 253, 258, 261, 272, 275, 276, 284, 286 Monitor, 59, 63, 248, 272, 274 Monoclonal, 272, 285 Monocytes, 267, 272, 284 Mononuclear, 71, 272 Morphine, 235, 244, 272 Morphological, 231, 252, 272 Motility, 272, 290 Motion Sickness, 272, 273 Mucosa, 160, 163, 268, 272, 283 Mydriatic, 250, 272 Myocardial infarction, 31, 44, 47, 51, 56, 174, 247, 271, 272, 273, 299 Myocardial Ischemia, 31, 233, 247, 273 Myocardium, 24, 233, 271, 272, 273 Myometrium, 179, 273 N Naive, 32, 273 Nausea, 157, 158, 170, 251, 266, 273 NCI, 1, 145, 205, 243, 273 Necrosis, 42, 235, 239, 263, 271, 272, 273 Need, 3, 4, 9, 20, 21, 151, 163, 173, 183, 184, 189, 192, 193, 195, 199, 219, 230, 243, 273, 296 Neonatal, 82, 85, 124, 125, 130, 263, 273 Neoplasia, 171, 273 Neoplasm, 273, 297 Neoplastic, 273, 275 Nephropathy, 185, 273 Nerve, 188, 230, 233, 237, 269, 270, 273, 288, 289, 293, 297, 299

310 Hormone Replacement Therapy

Nervous System, 10, 230, 236, 242, 270, 273, 274, 278, 294 Neural, 23, 33, 34, 230, 232, 273 Neurodegenerative Diseases, 158, 273 Neuroendocrine, 161, 273 Neurologic, 37, 273, 297 Neurology, 35, 91, 117, 274 Neuromuscular, 63, 229, 274 Neurons, 249, 257, 274, 294, 299 Neuropathy, 185, 274 Neutrons, 232, 274, 285 Neutrophil, 264, 274 Nitric acid, 153, 274 Nitric Oxide, 10, 25, 81, 153, 274 Nitrogen, 148, 233, 248, 256, 274, 297 Norepinephrine, 230, 251, 274 Norethindrone, 70, 109, 274 Norgestrel, 267, 274 Nuclear, 119, 163, 252, 255, 257, 273, 274, 275 Nuclei, 10, 232, 252, 269, 272, 274, 284, 299 Nucleic acid, 261, 263, 274 Nucleic Acid Hybridization, 261, 275 Nucleus, 10, 168, 235, 236, 243, 248, 249, 250, 255, 257, 272, 274, 275, 284, 299 Nurse Practitioners, 44, 123, 132, 275 O Observational study, 37, 43, 46, 65, 92, 104, 275 Occupational Health, 183, 275 Ocular, 28, 275 Oedema, 170, 275 Oestradiol, 66, 101, 275 Oestrogen, 65, 77, 98, 275 Ointments, 251, 275, 277 Oncogenes, 40, 275, 284 Oncologist, 270, 275 Oncology, 44, 71, 78, 86, 87, 102, 116, 119, 276 Oocytes, 257, 276, 300 Oophorectomy, 150, 276 Opacity, 249, 276 Opsin, 276, 288 Osteoarthritis, 94, 276 Osteoblasts, 199, 276 Outpatient, 33, 276 Ovarian Follicle, 248, 276 Ovariectomy, 16, 33, 62, 119, 276 Ovaries, 49, 156, 162, 165, 235, 254, 255, 257, 276, 290, 300 Ovary, 152, 160, 233, 248, 254, 258, 275, 276

Overweight, 5, 120, 276 Ovulation, 20, 162, 174, 252, 268, 274, 276 Ovulation Induction, 174, 276 Ovum, 248, 249, 258, 267, 276, 282, 283, 300 Oxidation, 47, 229, 234, 248, 250, 267, 276 Oxidative Stress, 39, 276 Oxygen Consumption, 276, 288 P Palliative, 248, 275, 276, 295 Pamidronate, 199, 276 Pancreas, 185, 229, 238, 250, 264, 266, 277, 297 Pancreatic, 28, 277 Papillomavirus, 277 Paraffin, 42, 277 Parasite, 277 Parasitic, 176, 277 Parenteral, 159, 253, 277 Parity, 30, 277 Parkinsonism, 235, 277 Paroxysmal, 233, 277 Partial remission, 277, 287 Particle, 60, 277 Patch, 277, 297 Pathogenesis, 11, 23, 29, 153, 277 Pathologic, 24, 229, 235, 238, 247, 261, 277, 288 Pathologic Processes, 235, 277 Pathophysiology, 41, 51, 63, 91, 116, 277 Patient Compliance, 178, 277 Patient Education, 108, 216, 222, 224, 227, 277 Patient Satisfaction, 143, 277 Pelvic, 55, 71, 187, 193, 253, 277, 284 Pentoxifylline, 107, 278 Peptide, 23, 41, 266, 267, 278, 281, 284, 296 Peptide Fragments, 23, 278 Perceived risk, 109, 278 Percutaneous, 39, 149, 159, 278 Perforation, 29, 278 Perfusion, 25, 262, 278 Pericardium, 278, 294 Perimenopausal, 14, 53, 69, 96, 126, 130, 131, 139, 156, 169, 177, 217, 278 Perinatal, 153, 263, 278 Perineal, 188, 278 Perineum, 278 Peripheral blood, 71, 278 Peripheral Nervous System, 273, 278, 293 Peripheral Vascular Disease, 165, 278 Peritoneal, 236, 275, 278

Index 311

Peritoneal Cavity, 236, 275, 278 Peroxidase, 79, 267, 278 Peroxide, 267, 278, 279 Petroleum, 277, 279 PH, 34, 86, 87, 89, 105, 111, 239, 279 Pharmaceutical Preparations, 151, 161, 164, 255, 257, 279, 283 Pharmaceutical Solutions, 251, 279 Pharmacist, 155, 169, 279 Pharmacokinetic, 4, 279 Pharmacologic, 43, 123, 184, 233, 279, 296 Pharmacotherapy, 60, 68, 79, 110, 125, 279 Phenotype, 11, 32, 61, 279 Phosphodiesterase, 278, 279 Phospholipids, 255, 267, 279 Phosphorus, 175, 240, 279 Phosphorylated, 244, 279 Photocoagulation, 244, 279 Physical Examination, 185, 279 Physical Therapy, 63, 279 Physiologic, 4, 11, 25, 231, 238, 244, 270, 280, 283, 286, 288 Physiology, 9, 11, 39, 41, 44, 63, 69, 186, 187, 241, 252, 280 Pigments, 241, 280, 288 Pilot study, 24, 66, 81, 125, 280 Pituitary Gland, 161, 280 Placenta, 160, 235, 254, 255, 256, 280, 282 Plants, 241, 243, 258, 274, 280, 289, 296 Plaque, 23, 233, 236, 280 Plasma cells, 234, 280 Plasma protein, 253, 280, 284 Plasma Volume, 272, 280 Plasmin, 280 Plasminogen, 37, 173, 280 Plasminogen Activators, 280 Plasticity, 10, 280 Platelet Activation, 47, 51, 80, 280 Platelet Aggregation, 233, 274, 278, 281 Platelets, 51, 274, 280, 281, 284, 295 Platinum, 44, 281 Pleural, 275, 281 Pleural cavity, 275, 281 Plexus, 10, 269, 281 Poisoning, 235, 264, 273, 281 Policy Making, 32, 259, 281 Polymorphism, 68, 79, 105, 166, 167, 281 Polypeptide, 232, 244, 256, 261, 280, 281, 283, 300 Polyposis, 245, 281 Polysaccharide, 234, 281 Posterior, 232, 265, 271, 277, 281

Postmenopause, 127, 281 Post-translational, 233, 281, 291 Potassium, 231, 272, 281 Potentiation, 243, 281 Practice Guidelines, 64, 208, 217, 282 Precipitation, 35, 282 Precursor, 23, 162, 179, 233, 235, 237, 248, 251, 252, 254, 274, 280, 282, 284, 297 Predisposition, 30, 282 Preeclampsia, 150, 153, 282 Pre-Eclampsia, 179, 282 Pregnenolone, 162, 282 Premenopausal, 17, 34, 48, 49, 53, 54, 58, 144, 150, 151, 167, 170, 177, 282 Premenstrual, 160, 282 Prenatal, 186, 252, 282 Pressoreceptors, 237, 282 Prevalence, 13, 30, 43, 60, 103, 119, 131, 150, 163, 282 Primary Prevention, 7, 18, 39, 102, 131, 217, 218, 282 Primitive neuroectodermal tumors, 270, 282 Probe, 271, 282 Progesterone, 6, 10, 12, 17, 20, 25, 29, 31, 32, 33, 35, 38, 41, 42, 44, 49, 51, 52, 71, 81, 103, 110, 136, 150, 153, 155, 156, 159, 160, 162, 170, 179, 181, 190, 191, 267, 274, 282, 283, 293 Progestogen, 74, 85, 110, 155, 169, 170, 172, 177, 179, 180, 282 Progression, 7, 23, 32, 40, 41, 45, 47, 49, 50, 54, 79, 167, 229, 233, 282 Progressive, 41, 235, 243, 249, 251, 255, 259, 273, 280, 282, 297 Prolactin, 283 Prolactinoma, 184, 283 Prolapse, 188, 283 Proline, 244, 261, 283 Promoter, 62, 79, 283 Prone, 171, 283 Prophylaxis, 7, 178, 283, 288 Propylene Glycol, 148, 283 Prospective study, 5, 8, 22, 57, 83, 126, 268, 283 Prostaglandin, 179, 283 Prostaglandins A, 283 Prostaglandins F, 154, 283 Prostate, 61, 154, 194, 238, 275, 284, 297 Prostate-Specific Antigen, 61, 284 Protease, 245, 284

312 Hormone Replacement Therapy

Protein C, 60, 232, 235, 237, 266, 267, 268, 284 Protein Kinases, 275, 284 Protein S, 63, 192, 238, 261, 284, 289 Protein-Tyrosine Kinase, 258, 284 Proteinuria, 282, 284 Proteolytic, 245, 256, 280, 284 Prothrombin, 21, 22, 37, 48, 56, 284, 295 Protocol, 54, 59, 158, 173, 174, 257, 284 Protons, 232, 261, 284, 285 Proto-Oncogenes, 275, 284 Proximal, 43, 45, 251, 284 P-Selectin, 47, 284 Psychiatric, 58, 59, 270, 285 Psychiatry, 52, 58, 59, 256, 285 Psychic, 244, 267, 285, 290 Psychophysiology, 127, 285 Puberty, 33, 151, 152, 167, 199, 285, 295 Public Health, 15, 18, 21, 23, 29, 42, 44, 45, 56, 60, 95, 117, 118, 208, 285 Public Policy, 207, 285 Publishing, 4, 64, 162, 186, 285 Pulmonary, 22, 238, 246, 285, 299 Pulmonary Artery, 238, 285, 299 Pulmonary Embolism, 22, 285 Pulse, 5, 272, 285 Pupil, 247, 250, 272, 285 Purulent, 285, 298 Q Quality of Life, 18, 24, 25, 36, 37, 38, 52, 58, 59, 60, 67, 70, 74, 117, 162, 167, 189, 285 R Race, 11, 57, 108, 167, 184, 186, 243, 267, 271, 274, 285 Radiation, 44, 156, 233, 255, 257, 262, 264, 275, 285, 286, 289, 300 Radiation therapy, 44, 255, 264, 285 Radioactive, 28, 158, 161, 239, 261, 263, 264, 268, 274, 285, 289 Radiolabeled, 285 Radiological, 187, 278, 285 Radiology, 102, 285, 286 Radiotherapy, 239, 285, 286 Radius, 159, 286 Raloxifene, 27, 53, 66, 67, 76, 100, 117, 286, 290 Random Allocation, 286 Randomization, 51, 60, 286 Randomized clinical trial, 43, 48, 60, 104, 286 Randomized Controlled Trials, 6, 286 Reactive Oxygen Species, 14, 286

Receptor, 13, 19, 38, 42, 56, 65, 90, 105, 149, 153, 163, 167, 168, 181, 230, 234, 246, 248, 251, 286, 290 Receptors, Serotonin, 286, 290 Recombination, 258, 286 Reconstitution, 29, 287 Rectal, 160, 194, 287 Rectovaginal Fistula, 188, 287 Rectum, 38, 234, 239, 245, 250, 257, 263, 266, 284, 287, 294 Recurrence, 17, 21, 26, 55, 72, 144, 238, 243, 287 Red blood cells, 254, 287, 289 Reductase, 168, 235, 268, 287 Refer, 1, 240, 245, 251, 256, 268, 273, 274, 287 Reflex, 10, 287 Refraction, 287, 292 Regeneration, 287 Regimen, 12, 20, 149, 162, 172, 178, 179, 180, 214, 252, 277, 279, 287 Regression Analysis, 46, 287 Rehabilitation Centers, 24, 287 Reliability, 46, 287 Remission, 87, 238, 269, 287 Renin, 11, 41, 233, 287 Renin-Angiotensin System, 11, 287 Resorption, 19, 155, 199, 239, 288 Respiration, 10, 235, 241, 272, 288 Respiratory distress syndrome, 153, 288 Response rate, 42, 288 Restoration, 151, 162, 279, 287, 288 Retina, 288, 289 Retinal, 88, 246, 276, 288, 300 Retinoids, 288, 300 Retinol, 200, 288 Retinopathy, 185, 279, 288 Retroperitoneal, 230, 288, 299 Retrospective, 55, 116, 288 Rheology, 278, 288 Rheumatism, 288 Rheumatoid, 65, 90, 93, 288 Rheumatoid arthritis, 65, 90, 93, 288 Rhinorrhea, 283, 289 Ribonuclease, 29, 289 Ribosome, 289, 297 Rod, 237, 243, 289 S Sagittal, 6, 289 Salivary, 250, 289 Salivary glands, 250, 289 Saphenous, 50, 247, 289

Index 313

Saphenous Vein, 50, 247, 289 Saponins, 61, 289, 293 Scans, 43, 289 Schizoid, 289, 300 Schizophrenia, 289, 300 Schizotypal Personality Disorder, 289, 300 Sclerosis, 235, 289 Screening, 8, 28, 30, 36, 48, 56, 77, 78, 82, 92, 153, 167, 170, 188, 214, 244, 289 Sebaceous, 270, 289, 290 Sebaceous gland, 270, 289, 290 Sebum, 245, 289, 290 Second cancer, 42, 290 Secretion, 29, 100, 149, 162, 262, 264, 266, 272, 290 Secretory, 162, 290, 294 Sedative, 52, 244, 266, 290 Sedentary, 6, 39, 56, 290 Seizures, 27, 35, 277, 290 Selective estrogen receptor modulator, 27, 53, 84, 286, 290, 294 Self Care, 185, 290 Sella, 280, 290 Semen, 284, 290 Semisynthetic, 255, 290 Senile, 276, 290 Sensitization, 181, 290 Serine, 248, 284, 290 Serotonin, 10, 279, 286, 290, 297 Serous, 253, 290 Sex Characteristics, 230, 233, 275, 285, 290, 295 Sex Hormone-Binding Globulin, 14, 291 Sexual Harassment, 183, 291 Sharpness, 175, 291, 300 Shock, 68, 291, 297 Side effect, 14, 33, 45, 55, 157, 158, 161, 164, 170, 175, 178, 199, 201, 230, 238, 248, 291, 296 Signs and Symptoms, 149, 185, 287, 291 Skeletal, 43, 44, 56, 63, 86, 151, 233, 243, 291, 294 Skeleton, 151, 159, 163, 239, 256, 266, 283, 291 Skull, 248, 291, 295 Sleep apnea, 10, 45, 52, 291 Small intestine, 237, 243, 260, 262, 264, 291 Smooth muscle, 62, 233, 240, 272, 273, 284, 288, 291, 293 Sneezing, 291, 293 Social Class, 76, 291 Social Environment, 285, 291

Social Work, 44, 292 Sodium, 41, 186, 231, 271, 292 Soft tissue, 239, 291, 292 Solid tumor, 233, 292 Solvent, 148, 237, 255, 279, 283, 292 Somatic, 230, 244, 272, 278, 292 Soy Proteins, 19, 292 Spastic, 265, 292 Spatial disorientation, 251, 292 Specialist, 119, 131, 219, 250, 292 Species, 153, 242, 254, 261, 271, 272, 277, 285, 286, 292, 293, 297, 299, 300 Specificity, 36, 231, 292 Spectrum, 54, 292 Sperm, 157, 233, 243, 257, 292 Sphincter, 292, 293 Spinal cord, 239, 242, 243, 269, 270, 273, 274, 278, 287, 292, 294 Sporadic, 178, 273, 292 Spotting, 179, 180, 292 Staging, 289, 292 Steel, 82, 243, 293 Sterility, 67, 86, 100, 107, 110, 248, 264, 293 Stimulant, 240, 266, 293 Stimulus, 58, 151, 247, 251, 287, 293, 295 Stomach, 229, 250, 254, 257, 258, 260, 266, 273, 278, 291, 293 Stool, 263, 265, 266, 293 Stress, 11, 31, 38, 112, 185, 188, 236, 242, 265, 273, 276, 282, 289, 293 Stress urinary, 112, 188, 293 Stroke, 23, 25, 37, 51, 56, 145, 146, 150, 163, 206, 214, 241, 265, 293 Stroke Volume, 241, 293 Stromal, 104, 253, 293 Subacute, 264, 293 Subclinical, 49, 264, 290, 293 Subcutaneous, 6, 230, 252, 275, 277, 293, 299, 300 Subiculum, 260, 293 Subspecies, 292, 293 Substance P, 271, 282, 287, 290, 293 Substrate, 28, 153, 293 Subtrochanteric, 260, 293 Sulfur, 148, 271, 294 Supplementation, 29, 39, 43, 46, 47, 60, 125, 126, 129, 140, 151, 193, 294 Support group, 184, 186, 294 Suppositories, 160, 257, 294 Suppression, 25, 41, 176, 294 Suppressive, 14, 161, 294 Suspensions, 155, 294

314 Hormone Replacement Therapy

Sympathetic Nervous System, 80, 236, 294 Symphysis, 284, 294 Symptomatic, 45, 50, 58, 61, 294 Symptomatology, 100, 294 Synapses, 243, 294 Synergistic, 47, 283, 294 Systemic lupus erythematosus, 144, 199, 294 Systolic, 261, 294 T Tamoxifen, 13, 119, 290, 294 Tarsal Bones, 240, 294 Temporal, 34, 260, 295 Temporal Lobe, 34, 295 Testicular, 194, 235, 295 Testis, 233, 254, 275, 295 Testosterone, 10, 41, 62, 151, 152, 155, 162, 194, 233, 287, 291, 295 Therapeutics, 25, 41, 93, 103, 152, 161, 202, 295 Thigh, 6, 50, 256, 295 Thorax, 229, 268, 295 Threshold, 255, 261, 295 Thrombin, 256, 281, 284, 295 Thrombocytes, 281, 295 Thromboembolism, 7, 21, 22, 47, 295 Thrombolytic, 280, 295 Thrombomodulin, 284, 295 Thrombophilia, 47, 295 Thrombosis, 82, 91, 101, 284, 293, 295 Thrombus, 51, 247, 263, 265, 273, 281, 295, 299 Thymus, 162, 263, 269, 295 Thymus Gland, 295 Thymus Hormones, 162, 295 Thyroid, 91, 161, 162, 262, 265, 295, 296 Thyroid Gland, 161, 262, 295, 296 Thyroid Hormones, 296 Thyrostatic, 161, 296 Thyrotropin, 262, 296 Thyroxine, 161, 296 Tin, 241, 281, 296 Tinnitus, 216, 296, 299 Tolerance, 28, 50, 229, 258, 296 Tomography, 119, 296 Tooth Preparation, 230, 296 Topical, 154, 155, 160, 255, 277, 296 Torsion, 263, 296 Total hysterectomy, 120, 296 Toxaemia, 282, 296 Toxic, iv, 237, 259, 274, 296 Toxicity, 251, 296

Toxicology, 15, 208, 296 Toxins, 234, 253, 263, 296 Trachea, 240, 295, 296 Traction, 243, 297 Transcription Factors, 181, 275, 297 Transdermal, 77, 85, 97, 126, 148, 149, 155, 156, 159, 162, 163, 172, 181, 182, 194, 297 Transfection, 238, 297 Transgenes, 62, 297 Transient Ischemic Attacks, 25, 135, 297 Translation, 32, 297 Translational, 9, 297 Transmitter, 229, 251, 270, 274, 294, 297 Transplantation, 4, 243, 263, 297 Trauma, 188, 273, 297 Triglyceride, 5, 28, 261, 262, 297 Trophic, 33, 297 Tryptophan, 244, 290, 297 Tuberculosis, 246, 268, 297 Tumor marker, 238, 297 Tumour, 77, 297 Tunica Intima, 253, 297 Type 2 diabetes, 5, 85, 95, 111, 185, 297 U Ulcer, 297, 298 Ulceration, 29, 298 Ultrasonography, 39, 298 Unconscious, 262, 298 Ureters, 298 Urethra, 284, 298 Urinary, 7, 14, 19, 107, 132, 135, 160, 163, 175, 188, 243, 248, 258, 263, 293, 298 Urinary Fistula, 188, 298 Urinary tract, 7, 160, 163, 298 Urine, 45, 185, 238, 248, 251, 254, 255, 263, 266, 284, 293, 298 Urodynamic, 188, 298 Urogenital, 129, 152, 190, 258, 298 Uterine Contraction, 154, 298 V Vaccine, 284, 298 Vagina, 12, 157, 160, 178, 270, 287, 292, 298 Vaginal, 7, 12, 71, 72, 73, 81, 110, 149, 152, 157, 160, 163, 178, 188, 298 Vaginitis, 7, 298 Vascular, 5, 7, 25, 31, 39, 41, 44, 47, 51, 56, 62, 77, 82, 87, 101, 111, 150, 153, 165, 184, 237, 247, 253, 261, 263, 264, 271, 274, 275, 276, 280, 282, 295, 298 Vascular Resistance, 31, 237, 298 Vasoactive, 24, 25, 62, 184, 298 Vasoconstriction, 10, 254, 298

Index 315

Vasodilation, 10, 31, 62, 298 Vasodilator, 9, 25, 63, 239, 251, 298 Vasomotor, 12, 58, 59, 81, 111, 149, 152, 172, 178, 255, 298 VE, 72, 126, 298 Vein, 50, 233, 236, 265, 274, 289, 298, 299 Venous, 7, 21, 22, 23, 47, 82, 119, 192, 193, 236, 239, 275, 284, 299 Venous blood, 48, 239, 299 Venous Thrombosis, 22, 192, 299 Ventricle, 260, 262, 285, 294, 299 Ventricular, 25, 39, 41, 108, 299 Ventricular Dysfunction, 41, 299 Ventricular Function, 25, 39, 299 Ventricular Remodeling, 41, 299 Venules, 238, 241, 253, 271, 299 Vertebral, 65, 111, 159, 163, 299 Vestibulocochlear Nerve, 296, 299 Vestibulocochlear Nerve Diseases, 296, 299 Veterinary Medicine, 207, 299 Viral, 32, 275, 284, 299, 300 Viral Load, 32, 299 Virulence, 236, 296, 299 Virus, 32, 237, 253, 261, 280, 299 Visceral, 6, 35, 236, 299

Visceral fat, 6, 35, 299 Visual Acuity, 28, 299 Vitamin A, 175, 200, 288, 300 Vitro, 19, 62, 300 Vivo, 32, 62, 300 W Waist circumference, 5, 300 Warts, 261, 300 Weight Gain, 175, 199, 300 Weight-Bearing, 276, 300 White blood cell, 154, 229, 234, 267, 269, 274, 280, 300 Windpipe, 295, 300 Withdrawal, 100, 178, 300 Womb, 298, 300 X Xenograft, 233, 300 X-ray, 12, 43, 50, 239, 246, 257, 269, 274, 285, 286, 289, 300 Y Yeasts, 279, 300 Z Zygote, 174, 246, 300 Zygote Intrafallopian Transfer, 174, 300 Zymogen, 284, 300

316 Hormone Replacement Therapy