Treatment of the Postmenopausal Woman (eBook)

Front cover 1
Treatment of the Postmenopausal Woman 4
Copyright page 5
Contributors 6
Preface 10
Table of contents 12
Chapter 1. The Menopause: A Signal for the Future 16
I. AGE OF MENOPAUSE 17
II. SYMPTOMS OF MENOPAUSE 18
III. GROWTH OF THE OLDER POPULATION 21
IV. THE RECTANGULARIZATION OF LIFE 22
V. SUCCESSFUL AGING: THE ROLE OF PREVENTIVE HEALTH CARE 23
VI. MENOPAUSE AS AN OPPORTUNITY 24
VII. THE MENOPAUSE AS A SIGNAL FOR THE FUTURE 24
VIII. CONCLUSION 25
Section I Basics to Enhance Our Understanding 30
Chapter 2. Molecular Pharmacology of Estrogen and Progesterone Receptors 32
I. INTRODUCTION 32
II. ESTROGEN AND PROGESTERONE RECEPTORS 32
III. ESTABLISHED MODELS OF ESTROGEN AND PROGESTERONE ACTION 33
IV. NONCLASSICAL MODELS OF ESTROGEN AND PROGESTERONE RECEPTOR ACTION 34
V. ESTROGEN AND PROGESTERONE RECEPTOR ISOFORMS AND SUBTYPES 36
VI. REGULATION OF ESTROGEN AND PROGESTERONE RECEPTOR FUNCTION BY LIGANDS 37
VII. ESTROGEN AND PROGESTERONE RECEPTOR ASSOCIATED PROTEINS 39
VIII. AN UPDATED MODEL OF ESTROGEN AND PROGESTERONE RECEPTOR ACTION 40
Chapter 3. Genetic Programming in Ovarian Development and Oogenesis 44
I. OVARIAN DIFFERENTIATION REQUIRES ONLY ONE X (CONSTITUTIVE) 44
II. POLYGENIC AND STOCHASTIC CONTROL OVER OOCYTE NUMBER 45
III. MONOSOMY X 45
IV. X CHROMOSOMAL MOSAICISM: 45,X/46,XX AND 45,X/47,XXX 47
V. PITFALLS IN LOCALIZING OVARIAN MAINTENANCE GENES TO SPECIFIC REGIONS OF THE X 47
VI. CYTOGENETICS OF X CHROMOSOMAL ABERRATIONS 48
VII. OVARIAN GENES ON THE X 51
VIII. AUTOSOMAL CHROMOSOMAL ABNORMALITIES 52
IX. AUTOSOMAL GENES 52
X. HOW OFTEN IS PREMATURE OVARIAN FAILURE GENETIC? 57
Chapter 4. Basic Biology: Ovarian Anatomy and Physiology 64
I. STATEMENT OF THE PROBLEM 64
II. THE PRIMORDIAL FOLLICLE 65
III. THE ADULT OVARY 66
IV. OVARY RESERVE 72
V. ACCELERATED LOSS IN OR: THE ACTIVIN HYPOTHESIS 76
VI. NEW DATA ON THE EFFECTS OF ACTIVIN 78
VII. CONCLUSION 78
Chapter 5. Endocrine Changes During the Perimenopause 82
I. ENDOCRINE DYNAMICS: THE NORMAL REPRODUCTIVE CYCLE 82
II. ENDOCRINE DYNAMICS: THE PERIMENOPAUSE 83
III. CLINICAL SEQUELAE OF ENDOCRINE CHANGES IN THE PERIMENOPAUSE 88
IV. HORMONE-INDUCED CHANGES IN THE PERIMENOPAUSE 89
V. ENDOCRINE PROFILE ASSESSMENT OF THE PERIMENOPAUSAL WOMAN 89
VI. CONCLUSION 90
Chapter 6. Epidemiology of Menopause: Demographics, Environmental Influences, and Ethnic and International Differences in the Menopausal Experience 92
I. INTRODUCTION 92
II. DEMOGRAPHIC CHARACTERISTICS 94
III. ETHNIC AND INTERNATIONAL DIFFERENCES 96
IV. ENVIRONMENTAL INFLUENCES 97
V. CONCLUSIONS 105
Section II. Ovarian Senescence and Options 112
Chapter 7. Premature Ovarian Failure 114
I. INTRODUCTION 114
II. CLINICAL FEATURES OF PREMATURE OVARIAN FAILURE 114
III. PREVALENCE OF PREMATURE OVARIAN FAILURE 116
IV. ETIOLOGY OF PREMATURE OVARIAN FAILURE 116
V. EVALUATION OF INDIVIDUALS WITH HYPERGONADOTROPIC AMENORRHEA 120
VI. TREATMENT 121
Chapter 8. Reproductive Options for Perimenopausal and Menopausal Women 126
I. NATURAL FERTILITY IN THE PERIMENOPAUSE 129
II. DEVELOPMENT OF OOCYTE AND EMBRYO DONATION AND ITS APPLICATION IN OLDER WOMEN 132
III. CHILDBEARING BY THE PERIMENOPAUSAL AND MENOPAUSAL WOMAN 133
IV. SCREENING AND PREPARATION OF POTENTIAL RECIPIENTS 134
V. OBSTETRIC MANAGEMENT AND DELIVERY CONSIDERATIONS 135
VI. FUTURE APPLICATIONS 136
Section III. The Perimenopause 140
Chapter 9. Neuroendocrine Regulation of the Perimenopause Transition 142
I. DEFINITION OF PERIMENOPAUSE 142
II. OVARIAN DETERMINANTS OF REPRODUCTIVE AGING 143
III. DYNAMIC GONADOTROPIN SECRETION IN YOUNG WOMEN 147
IV. GONADOTROPIN CHANGES DURING THE PERIMENOPAUSE 149
V. THE NEUROREPRODUCTIVE AXIS IN THE POSTMENOPAUSE 153
VI. BRAIN AGING AND REPRODUCTIVE SENESCENCE 157
VII. FUTURE STUDIES 158
Chapter 10. Changes in the Menstrual Pattern During the Menopause Transition 164
I. INTRODUCTION 164
II. CONCLUSION 170
Chapter 11. Decisions Regarding Treatment During the Menopause Transition 172
I. CHANGES ASSOCIATED WITH AGING 174
II. CHANGES IN THE HORMONAL ENVIRONMENT 174
III. COMMON COMPLAINTS AND HEALTH RISKS ASSOCIATED WITH THE MENOPAUSAL TRANSITION 178
IV. HORMONE THERAPY IN THE MENOPAUSAL TRANSITION 179
V. SUMMARY 180
Chapter 12. Use of Contraceptives for Older Women 184
I. ORAL CONTRACEPTIVES 184
II. INTRAUTERINE DEVICES 190
III. INJECTABLE CONTRACEPTION 190
IV. IMPLANTABLECONTRACEPTIVES 191
V. TRANSDERMAL CONTRACEPTION 192
VI. STEROIDAL VAGINAL CONTRACEPTIVE 192
VII. BARRIER CONTRACEPTIVES 192
VIII. SUMMARY 195
Section IV. Changes Occurring After Menopause 200
Chapter 13. Menopausal Hot Flashes 202
I. EPIDEMIOLOGY OF HOT FLASHES 202
II. DESCRIPTIVE PHYSIOLOGY 202
III. OBJECTIVE MEASUREMENT OF HOT FLASHES 204
IV. ENDOCRINOLOGY 205
V. THERMOREGULATION AND HOT FLASHES 207
VI. CIRCADIAN RHYTHMS 209
VII. HOT FLASHES AND SLEEP 209
VIII. TREATMENT OF HOT FLASHES 210
IX. SUMMARY 211
Chapter 14. Clinical Effects of Sex Steroids on the Brain 214
I. CLINICAL EFFECTS OF SEX STEROIDS ON THE BRAIN 214
II. THE BRAIN AND SEX STEROIDS 215
III. HORMONES AND BRAIN FUNCTIONS OF CLINICAL IMPORTANCE TO THE MENOPAUSE 219
Chapter 15. Impact of the Changing Hormonal Milieu on Psychological Functioning 232
I. EPIDEMIOLOGY OF PSYCHOLOGICAL SYMPTOMS 232
II. NEUROBIOLOGIC EFFECTS OF ESTROGEN, ANDROGEN, AND PROGESTIN 233
III. SEX STEROIDS AND MOOD 234
IV. ESTROGEN AND COGNITIVE FUNCTIONING 236
V. SEX STEROIDS AND SEXUALITY 236
VI. SUMMARY AND CLINICAL IMPLICATIONS 238
Chapter 16. Connective Tissue Changes in the Menopause and with Hormone Replacement Therapy 242
I. INTRODUCTION 242
II. BONE 242
III. BONE AND SKIN 243
IV. COLLAGEN MARKERS 244
V. SKIN 245
VI. CAROTID ARTERIES 247
VII. INTERVERTEBRAL DISCS 248
VIII. CONCLUSION 248
Chapter 17. Menopause and the Skin 252
I. INTRODUCTION 252
II. DRY SKIN 252
III. SWEATING 256
IV. ATROPHY 256
V. WOUND HEALING 258
VI. PSYCHOLOGIC EFFECTS OF MENOPAUSAL CHANGES RELATED TO SKIN APPEARANCE — SELF-IMAGE 260
VIII. TOPICAL HORMONE REPLACEMENT THERAPY 260
VII. SUMMARY 261
Chapter 18. Urogenital Symptoms around the Menopause and Beyond 266
I. INTRODUCTION 266
II. INNERVATION 268
III. MECHANISMS OF CONTINENCE 268
IV. TREATMENT MODALITIES FOR FEMALE URINARY INCONTINENCE 269
Chapter 19. Vulvovaginal Complaints 278
I. INTRODUCTION 278
II. VULVOVAGINAL COMPLAINTS 278
III. ESTROGEN LOSS 279
IV. SEXUAL COMPLAINTS 280
V. EVALUATION 280
VI. TREATMENT 282
VII. CONCLUSION 283
Chapter 20. Sexuality: Clinical Implications from Epidemiologic Studies 286
I. INTRODUCTION 286
II. EFFECTS OF AGING 287
III. AGING VERSUS MENOPAUSAL STATUS 287
IV. RELATIVE IMPORTANCE OF HORMONAL TO RELATIONAL AND OTHER PSYCHOSOCIAL FACTORS 288
V. ETHNICITY 288
VI. SURGICAL MENOPAUSE 288
VII. SUMMARY AND CLINICAL IMPLICATIONS 289
Section V. Brain Function 292
Chapter 21. Menopause and Cognition 294
I. MEMORY AND THE MENOPAUSAL TRANSITION 294
II. ESTROGEN AND OBJECTIVE MEASURES OF MEMORY 295
III. BIOLOGIC PLAUSIBILITY FOR ESTROGEN EFFECTS ON THE BRAIN: NEUROIMAGING STUDIES 296
IV. SELECTIVE ESTROGEN RECEPTOR MODULATORS AND COGNITIVE FUNCTION 298
V. INDIRECT EFFECTS OF ESTROGEN ON COGNITIVE FUNCTION 298
VI. SUMMARY 298
Chapter 22. Cognitive Health in the Postmenopausal Woman 302
I. MENOPAUSE, ESTROGEN, AND COGNITION 302
II. DEMENTIA AND COGNITIVE FUNCTIONING IN WOMEN AGED 65 AND OLDER 303
III. COGNITIVE FUNCTIONING IN YOUNGER POSTMENOPAUSAL WOMEN 305
IV. SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMs) AND COGNITION 305
V. UNANSWERED QUESTIONS AND FUTURE DIRECTIONS 306
VI. SUMMARY AND CONCLUSIONS 306
Chapter 23. The Role of Sex Steroids in Alzheimer’s Disease: Prevention and Treatment 310
I. ESTROGEN AND THE BRAIN 311
II. ESTROGEN AND COGNITION 312
III. HORMONE THERAPY AND THE PREVENTION OF ALZHEIMER’S DISEASE: OBSERVATIONAL STUDIES 313
IV. HORMONE THERAPY AND THE PREVENTION OF ALZHEIMER’S DISEASE: WHIMS 313
V. HORMONE THERAPY AND ALZHEIMER’S DISEASE TREATMENT 315
VI. OTHER COMPOUNDS 315
VII. CONCLUSIONS AND RECOMMENDATIONS 317
Chapter 24. Estrogens and Depression in Women 322
I. INTRODUCTION 322
II. BACKGROUND 322
III. METHODOLOGIC PROBLEMS IN INVESTIGATIONS OF THE RELATIONSHIP BETWEEN DEPRESSION, MIDLIFE, AND REPRODUCTIVE AGING 324
IV. EFFECTS ON ESTROGEN ON THE CENTRAL NERVOUS SYSTEM 325
V. WHAT IS THE EVIDENCE OF AN ASSOCIATION BETWEEN THE MENOPAUSAL TRANSITION AND DEPRESSION? 326
VI. WHAT FACTORS INFLUENCE THE RISK FOR DEPRESSION DURING THE MENOPAUSAL TRANSITION? 327
VII. EFFICACY OF ESTROGEN IN MOOD DISORDERS 328
VIII. SUGGESTED EVALUATION AND MANAGEMENT OF PERIMENOPAUSE-RELATED DEPRESSION 329
IX. FUTURE DIRECTIONS 330
Section VI. Bone Changes 336
Chapter 25. Pathogenesis of Osteoporosis 338
I. INTRODUCTION 338
II. PEAK BONE MASS AND ITS DETERMINANTS 338
III. THE PATHOGENESIS OF BONE LOSS 339
IV. ESTROGEN DEFICIENCY 343
Chapter 26. Assessment of Bone Density and Bone Strength 346
I. INTRODUCTION 346
II. BONE MASS AND BONE MINERAL DENSITY 346
III. CONCLUSION 351
Chapter 27. Biochemical Markers of Bone Turnover 352
I. MARKERS OF BONE TURNOVER 352
II. VARIABILITY OF MARKERS 356
III. CHANGES IN MARKERS AT MENOPAUSE, IN OSTEOPOROSIS, AND IN RESPONSE TO THERAPY 357
IV. PREDICTION OF BONE LOSS, FRACTURE, AND RESPONSE TO THERAPY 359
V. MONITORING THERAPY 360
VI. CONCLUSION 360
Chapter 28. Interventions for Osteoporosis 366
I. THE MAGNITUDE OF THE DISEASE 366
II. DEFINITION OF OSTEOPOROSIS 366
III. GENETIC AND ENVIRONMENTAL INFLUENCES ON BONE MASS 368
IV. BONE REMODELING AND OSTEOPOROSIS 368
V. THE TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS 370
VI. EFFECTS OF SERMS ON POSTMENOPAUSAL OSTEOPOROSIS 381
Chapter 29. Treatment of Osteoporosis 392
I. INTRODUCTION 392
II. ESTROGEN AND ESTROGEN-PROGESTOGEN REPLACEMENT THERAPY 393
III. ESTROGEN ANALOGS 397
IV. BISPHOSPHONATES 398
V. CALCITONIN 400
VI. ANABOLIC STEROIDS AND ANDROGENS 402
VII. PARATHYROID HORMONE 403
VIII. STRONTIUM RANELATE 403
IX. GENERAL GUIDELINES 404
Chapter 30. Potentials of Estrogens in the Prevention of Osteoarthritis: What Do We Know and What Questions are Still Pending? 408
I. DEFINITION OF OSTEOARTHRITIS 408
II. PREVALENCE AND INCIDENCE OF OSTEOARTHRITIS 408
III. POTENTIALS OF ESTROGEN IN CHONDROPROTECTION 409
IV. CONCLUSIONS AND PERSPECTIVES 414
Section VII. Cardiovascular 418
Chapter 31. Epidemiology and Risk Factors of Cardiovascular Disease in Postmenopausal Women 420
I. BACKGROUND 420
II. EPIDEMIOLOGY OF CVD IN WOMEN 421
III. PATHOGENESIS OF CARDIAC ISCHEMIA 422
IV. RISK FACTORS FOR CARDIAC ISCHEMIA IN WOMEN 424
V. ESTROGEN AND CHD 438
VI. CHD RISK ASSESSMENT 445
VII. CHD RISK REDUCTION 447
VIII. AN EYE INTO THE FUTURE 454
Chapter 32. Mechanisms of Action of Estrogen on the Cardiovascular System 468
I. INTRODUCTION 468
II. SYSTEMIC AND DIRECT EFFECTS OF ESTROGEN ON THE CARDIOVASCULAR SYSTEM 469
III. SUMMARY 472
Chapter 33. Lipids and Lipoproteins and Effects of Hormone Therapy 476
I. MAJOR LIPOPROTEINS AND METABOLIC PATHWAYS 476
II. EFFECTS OF ESTROGENS ON PLASMA LIPOPROTEIN METABOLISM 478
III. PROGESTIN EFFECTS ON LIPOPROTEIN METABOLISM 479
IV. EFFECTS OF POSTMENOPAUSAL HORMONE TREATMENT ON PLASMA LIPID AND LIPOPROTEIN CHOLESTEROL LEVELS 479
V. EFFECTS OF HORMONE REPLACEMENT THERAPY ON OTHER LIPOPROTEIN PARAMETERS THAT MAY AFFECT CARDIOVASCULAR DISEASE RISK 481
VI. RELATION OF HORMONE TREATMENT EFFECTS ON PLASMA LIPOPROTEINS TO CARDIOVASCULAR DISEASE RISK 482
Chapter 34. The Effects of Hormone Therapy on Inflammatory, Hemostatic, and Fibrinolytic Markers in Postmenopausal Women 486
I. INTRODUCTION 486
II. EFFECTS OF HORMONE THERAPY ON INFLAMMATION MARKERS 487
III. EFFECTS OF HORMONE THERAPY ON HEMOSTASIS AND FIBRINOLYSIS MARKERS 489
IV. TIBOLONE 492
V. CLINICAL IMPLICATIONS AND FUTURE PROSPECTS 492
Chapter 35. Hormone Therapy and Hemostasis 496
I. HEMOSTASIS REVISITED 496
II. VESSEL WALL 496
III. PLATELET FACTOR 497
IV. COAGULATION-ANTICOAGULATION 498
V. FIBRIN FORMATION AND FIBRINOLYSIS 499
VI. CLINICAL MARKERS OF THROMBOSIS 500
VII. COAGULATION AND CLINICAL SYNDROMES 501
VIII. HRT AND ARTERIAL THROMBOSIS: CLINICAL CONSIDERATIONS 502
IX. CONCLUSION 503
Chapter 36. Risk of Pulmonary Embolism/Venous Thrombosis 506
I. CLINICAL ENTITIES 506
II. DIAGNOSIS AND TREATMENT 507
III. PATHOPHYSIOLOGY 507
IV. INCIDENCE AND PROGNOSIS 508
V. CLINICAL RECOMMENDATIONS 513
Chapter 37. Glucose Metabolism After Menopause 516
I. INTRODUCTION 516
II. THE METABOLIC SYNDROME 516
III. HORMONAL THERAPY AND DIABETES 519
IV. CONCLUSION 520
Chapter 38. Stage of Reproductive Life, Atherosclerosis Progression and Estrogen Effects on Coronary Artery Atherosclerosis 524
I. INTRODUCTION 524
II. PROGRESSION OF CORONARY ARTERY ATHEROSCLEROSIS AMONG NORTH AMERICAN WOMEN 525
III. PRIMARY VERSUS SECONDARY PREVENTION — CHD VERSUS CORONARY ARTERY ATHEROSCLEROSIS 526
IV. PREMENOPAUSAL DETERMINANTS OF CORONARY ARTERY ATHEROSCLEROSIS PROGRESSION 526
V. CORONARY ARTERY ATHEROSCLEROSIS AND THE PERIMENOPAUSAL TRANSITION 529
VI. ESTROGEN EFFECTS IN EARLY POSTMENOPAUSE (EARLY INTERVENTION) 532
VII. MECHANISMS FOR ATHEROPROTECTION OF ESTROGENS ADMINISTERED IN EARLY MENOPAUSE 533
VIII. ESTROGEN EFFECTS IN LATE MENOPAUSE (LATE INTERVENTION) 536
IX. CLINICAL TRIALS OF THE TIMING HYPOTHESIS 539
X. CONCLUSIONS 540
Chapter 39. Randomized Controlled Trials and the Effects of Postmenopausal Hormone Therapy on Cardiovascular Disease: Facts, Hypotheses, and Clinical Perspective 544
I. INTRODUCTION 544
II. MORBIDITY/MORTALITY TRIALS OF POSTMENOPAUSAL HORMONE THERAPY 545
III. ARTERIAL IMAGING TRIALS OF POSTMENOPAUSAL HORMONE THERAPY 552
IV. DISCORDANCE BETWEEN RANDOMIZED CONTROLLED TRIALS AND OBSERVATIONAL STUDIES OF POSTMENOPAUSAL HORMONE THERAPY 556
V. EVIDENCE FOR A CARDIOPROTECTIVE EFFECT ACCORDING TO DURATION OF POSTMENOPAUSAL HORMONE THERAPY 557
VI. EVIDENCE FOR A CARDIOPROTECTIVE EFFECT ACCORDING TO TIMING OF INITIATION OF POSTMENOPAUSAL HORMONE THERAPY 560
VII. EVIDENCE THAT THE CARDIOPROTECTIVE EFFECT OF POSTMENOPAUSAL HORMONE THERAPY REQUIRES HEALTHY ENDOTHELIUM 562
VIII. EVIDENCE FOR A DUALITY OF CEE+MPA THERAPY ON CORONARY HEART DISEASE 563
IX. EVIDENCE FOR A CARDIOPROTECTIVE EFFECT OF POSTMENOPAUSAL HORMONE THERAPY ACCORDING TO BODY MASS INDEX 565
X. STROKE AND POSTMENOPAUSAL HORMONE THERAPY 566
XI. VENOUS THROMBOEMBOLIC EVENTS AND POSTMENOPAUSAL HORMONE THERAPY 567
XII. MORTALITY AND POSTMENOPAUSAL HORMONE THERAPY 569
XIII. CLINICAL PERSPECTIVE OF POSTMENOPAUSAL HORMONE THERAPY 570
XIV. CONCLUSION 574
Section VIII. Neoplasia 580
Chapter 40. Body Weight, Menopausal Hormone Therapy, and Risk of Breast Cancer 584
I. KEY RISK FACTORS 585
II. MODELING BREAST CANCER RISK 585
III. WEIGHT EFFECTS IN MODEL TERMS 587
IV. MENOPAUSAL HORMONE THERAPY EFFECTS IN MODEL TERMS 588
V. EPIDEMIOLOGIC STUDIES OF ET AND EPT 590
VI. CONCLUSIONS 591
Chapter 41. Postmenopausal Breast Surveillance 594
Chapter 42. Endometrial Cancer and Hormonal Replacement Therapy 600
I. INCIDENCE 600
II. RISK FACTORS 601
III. PATHOPHYSIOLOGY 602
IV. EFFECT OF HORMONAL THERAPY 602
V. HORMONAL REPLACEMENT, OBESITY, AND ENDOMETRIAL CANCER 604
VI. PROGNOSIS WITH AN ESTROGEN-ASSOCIATED ENDOMETRIAL CANCER 604
VII. ESTROGEN REPLACEMENT THERAPY AFTER TREATMENT FOR ENDOMETRIAL CANCER 604
VIII. CONCLUSIONS 605
Chapter 43. Ovarian Cancer and Its Detection 608
I. RISK ASSESSMENT 608
II. SCREENING FOR EOC 610
III. NEW SCREENING MODALITIES 611
Chapter 44. Hormone Replacement Therapy in Menopause and Breast, Colorectal, and Lung Cancer: An Update 614
I. BREAST CANCER 614
II. COLORECTAL CANCER 617
III. LUNG CANCER 621
Section IX. Clinical Trials and Observational Data 624
Chapter 45. The Women’s Health Initiative — Data and Discussion 626
I. BACKGROUND 626
II. WHI HORMONE THERAPY TRIAL 626
III. WHI DIETARY MODIFICATION TRIAL 630
IV. WHI CALCIUM VITAMIN D TRIAL 630
V. WHI OBSERVATION TRIAL 631
VI. CHALLENGES 631
VII. FUTURE WHI REPORTS 632
Chapter 46. Postmenopausal Hormone Therapy in the 21st Century: Reconciling Findings from Observational Studies and Randomized Clinical Trials 634
I. INTRODUCTION 634
II. EFFECTS OF HT 634
III. THE EFFECT OF HT ON CARDIOVASCULAR DISEASE INCIDENCE 635
IV. OTHER DISEASE END POINTS 637
V. POSSIBLE EXPLANATIONS FOR DISCORDANT FINDINGS BETWEEN OBSERVATIONAL STUDIES AND RCTS 638
VI. CONCLUSIONS 640
Chapter 47. Morbidity and Mortality Changes with Hormone Therapy 642
I. THE STUDIES 642
II. THE OUTCOMES 645
III. WHY RESULTS DIFFER 647
IV. THE RISKS AND BENEFITS OF HORMONE THERAPY 649
Section X. Life Cycle and QOL 652
Chapter 48. Issues Relating to Quality of Life in Postmenopausal Women and Their Measurement 654
I. INTRODUCTION 654
II. HOW TO ASSESS MENOPAUSAL SYMPTOMS AND QUALITY OF LIFE 655
III. CONCLUSION 667
Chapter 49. Role of Exercise and Nutrition 670
I. ROLE OF EXERCISE AND NUTRITION 670
II. CARDIOVASCULAR DISEASE AND THE ROLE OF NUTRITION 670
III. CARDIOVASCULAR DISEASE: THE ROLE OF EXERCISE 674
IV. OBESITY 678
V. DIABETES 680
VI. OSTEOPOROSIS 682
VII. TRACE ELEMENTS 688
VIII. DEPRESSION 689
IX. PHYTOESTROGENS 690
X. SUMMARY AND CONCLUSIONS 690
Chapter 50. Herbs, Phytoestrogens, and Other CAM Therapies 698
I. PHYTOESTROGENS 698
II. HERBS 700
III. SUMMARY 703
Section XI. Urinary Symptoms and Pelvic Support 706
Chapter 51. Lower Urinary Tract Disorders in Postmenopausal Women 708
I. INTRODUCTION 708
II. ANATOMY OF THE LOWER URINARY TRACT 708
III. URINARY INCONTINENCE 711
IV. INTERSTITIAL CYSTITIS 732
V. LOWER URINARY TRACT INFECTION 740
Chapter 52. Pelvic Organ Prolapse in Postmenopausal Women 754
I. INTRODUCTION 754
II. ANATOMY OF THE PELVIC SUPPORT 754
III. CLASSIFICATION AND QUANTIFICATION OF PROLAPSE 758
IV. EPIDEMIOLOGY 762
V. PATHOPHYSIOLOGY 762
VI. EVALUATION AND DIAGNOSIS 765
VII. TREATMENT 768
Section XII. Hormonal Therapy 780
Chapter 53. Pharmacology of Estrogens 782
I. ESTROGEN PRODUCTION AND ACTION 782
II. ESTROGEN METABOLISM 784
III. PHARMACOLOGY OF ESTROGEN PREPARATIONS 784
IV. CLINICAL ASPECTS OF ESTROGEN THERAPY 789
Chapter 54. Structure-Function Relationships, Pharmacokinetics, and Potency of Orally and Parenterally Administered Progestogens 794
I. INTRODUCTION 794
II. CLASSIFICATION OF PROGESTOGENS 795
III. STRUCTURE-FUNCTION RELATIONSHIPS OF PROGESTOGENS 796
IV. PHARMACOKINETICS OF ORALLY ADMINISTERED PROGESTOGENS 799
V. PHARMACOKINETICS OF PROGESTOGENS ADMINISTERED PARENTERALLY 806
VI. POTENCY OF PROGESTOGENS 807
VII. CONCLUSIONS 811
Chapter 55. Intervention: Androgens 814
I. INTRODUCTION 814
II. ANDROGEN PHYSIOLOGY IN THE REPRODUCTIVE YEARS 814
III. PHYSIOLOGIC AND NONPHYSIOLOGIC CAUSES OF TESTOSTERONE DEFICIENCY IN WOMEN 815
IV. CLINICAL CONSEQUENCES OF ANDROGEN INSUFFICIENCY AND EVIDENCE FOR BENEFITS OF TESTOSTERONE REPLACEMENT IN WOMEN 816
V. POTENTIAL RISKS OF TESTOSTERONE REPLACEMENT IN WOMEN 819
VI. WHICH WOMEN ARE MOST LIKELY TO BENEFIT FROM TESTOSTERONE? 822
VII. ASSESSMENT OF POTENTIAL CANDIDATES FOR ANDROGEN THERAPY 822
VIII. HOW SHOULD TESTOSTERONE REPLACEMENT BE PRESCRIBED? 823
IX. CONCLUSIONS 824
Chapter 56. Future Strategies in Climacteric Medicine 828
I. INTRODUCTION 828
II. DEVELOPMENT OF ESTROGEN COMPONENTS 829
III. DEVELOPMENT OF PROGESTOGENS AND PROGESTERONE 830
IV. FUTURE AVENUES FOR MIDLIFE WOMEN’S HEALTH 830
Section XIII. Some Alternative Medical Therapies 834
Chapter 57. Alternative Therapy: Dehydroepiandrosterone for Menopausal Hormone Replacement 836
I. DHEA IN MENOPAUSE AND AGING 837
II. STRATEGIES FOR DHEA REPLACEMENT 839
III. CLINICAL APPLICATIONS 839
IV. SAFETY 841
V. CONCLUSIONS 842
Chapter 58. Melatonin 844
I. CHEMISTRY, SYNTHESIS, AND METABOLISM 844
II. REGULATION OF MAMMALIAN PINEAL MELATONIN RHYTHM AND DETECTION IN BLOOD 845
III. MELATONIN RECEPTORS AND EFFECTS OF MELATONIN ON THE SUPRACHIASMATIC NUCLEUS 846
IV. PHYSIOLOGIC AND PATHOPHYSIOLOGIC ASPECTS OF MELATONIN SECRETION 846
V. COMPOUNDS THAT ALTER MELATONIN SECRETION 847
VI. THERAPEUTIC INTERVENTIONS USING MELATONIN 848
VII. SUMMARY 849
Chapter 59. Selective Estrogen Receptor Modulators 852
I. INTRODUCTION 852
II. TAMOXIFEN 852
III. RALOXIFENE 854
IV. SERMS IN DEVELOPMENT 857
V. SUMMARY 857
Chapter 60. Tibolone: Selective Tissue Estrogen Activity Regulator Utilization in Postmenopausal Women 862
I. PHARMACOKINETICS OF TIBOLONE 863
II. CLINICAL PROFILE OF TIBOLONE 863
III. CONCLUSIONS 865
Section XIV. Women’s Centers, Information Needed for Clinical Trials, and the Future 868
Chapter 61. Integrated Adult Women’s Medicine: A Model for Women’s Health Care Centers 870
I. THE PRINCIPLES 870
II. THE PRACTICE 871
III. CLINIC DESIGN 874
IV. TECHNOLOGY: CLINICAL RESEARCH AND CONSUMER EDUCATION 874
V. CONCLUSION 875
Chapter 62. Clinical Trials in Postmenopausal Hormone Therapy 878
I. INTRODUCTION 878
II. HISTORICAL ASPECTS 879
III. CLINICAL RESEARCH 879
IV. GENERAL REGULATORY REQUIREMENTS 880
V. SPECIFIC REQUIREMENTS FOR HORMONE THERAPY STUDIES 882
VI. CHANGING VIEWS: THE CASE OF CARDIOPROTECTION 887
VII. FUTURE DIRECTIONS 887
Chapter 63. The Future of Therapy and the Role of Hormone Therapy 890
I. THE DECISION TO TREAT OR NOT TREAT WITH HT 892
II. LOOKING TO THE FUTURE 894
Index 896