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Monogram: Hormone Replacement Therapy in Menopause and Andropause
VN Mishra
SECTION I: POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY
1 CHAPTER:
Physiology of Female Hormones in Menopause and Perimenopausal Transition
DEMOGRAPHIC CHANGES IN THE POPULATION OF WORLD AND INDIA
NOMENCLATURE OF THE STAGES OF REPRODUCTIVE AGING
Late Reproductive Stage (Stage–3)
Early Menopausal Transition (Stage–2)
Late Menopausal Transition (Stage–1)
Early Postmenopause can be Subdivided into Three Sub-stages (+1a, +1b, and +1c)8
Late Postmenopause (Stage +2)
CHANGES IN THE HORMONE LEVEL DURING THE MENOPAUSE TRANSITION
Estradiol
Inhibins
Anti-Müllerian Hormones,Mullerian Inhibiting Substances AMH; MIS
FSH Level
Progesterone
Androgens
ENDOCRINOLOGICAL CHANGES OF MENOPAUSE
Changes in Gonadotropins (Table 1.4)
Estrogens
Androgen
Androstenediones
Testosterone
CONCLUSION
2 CHAPTER:
Nuances of Postmenopausal Hormone Replacement Therapy
INTRODUCTION
REVIEW OF EVIDENCE
POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY: CLINICAL IMPLICATIONS
Benefits of HRT
Risks of HRT
Uncertainties
PRACTICAL GUIDANCE ON hormone replacement therapy PRESCRIPTION
Balancing Risks
Starting HRT
Adjusting Regimens
Duration of Treatment
Stopping HRT
MANAGEMENT OF ADVERSE EFFECTS
FOLLOW-UP
SUMMARY
3 CHAPTER:
Hormone Replacement Therapy Formulations and Route of Administration
INTRODUCTION
HORMONAL REPLACEMENT THERAPY
ADMINISTRATION OF HORMONE REPLACEMENT THERAPY BY ORAL ROUTE
ADMINISTRATION OF HORMONE REPLACEMENT THERAPY BY NON-ORAL ROUTE
HORMONE REPLACEMENT THERAPY IN SURGICAL MENOPAUSE
ADVERSE EFFECTS AND CONTRAINDICATIONS OF HORMONE REPLACEMENT THERAPY18
ALTERNATIVES TO HORMONE REPLACEMENT THERAPY19–21
4 CHAPTER:
Journey of Hormone Replacement Therapy
INTRODUCTION
IMPORTANT MILESTONES
History
The Era of the Prophylactic Hormone Replacement Therapy
The Nurses’ Health Study
The Heart and Estrogen/Progestin Replacement Study Trial
The Heart and Estrogen/Progestin Replacement Study II Trial
The Women's Health Initiative Study
The Estrogen only Arm of Women's Health Initiative
The Million Women Study
The New Women's Health Initiative Investigators Report
The “Timing Hypothesis”
Kronos Early Estrogen Prevention Study (KEEPS, 2013)
Early versus Late Intervention Trial with Estradiol (ELITE, 2015)
Recommendations of Various Menopause Societies
5 CHAPTER:
Managing Vasomotor Symptoms in Menopause
INTRODUCTION
THE VASOMOTOR SYMPTOMS
RISK FACTORS FOR VASOMOTOR SYMPTOMS
HOW DO VASOMOTOR SYMPTOMS AFFECT THE QUALITY OF LIFE?
Short-term Outcome
Long-term Outcome
MANAGEMENT OF VASOMOTOR SYMPTOMS
Lifestyle Modifications
Avoidance of Triggers
Add on Activities
Hormonal Treatment
Nonhormonal Treatment
Isoflavones
Selective Serotonin Reuptake Inhibitors
Serotonin Norepinephrine Reuptake Inhibitors
Management in Males
CONCLUSION
6 CHAPTER:
Role of Hormone Replacement Therapy in Prevention and Treatment of Osteoporosis in Menopause
INTRODUCTION
EFFECTS OF MENOPAUSE ON BONE
OSTEOPOROSIS
CHANGES IN BONE MASS WITH AGE
PATHOPHYSIOLOGY OF OSTEOPOROSIS
SIGNS AND SYMPTOMS OF OSTEOPOROSIS
DIAGNOSIS
Other Diagnostic Tests17,18
Should Osteopenia be Treated?
FRAX, the World Health Organization Fracture Risk Assessment Tool
BIOCHEMICAL MARKERS OF BONE TURNOVER
MANAGEMENT
HORMONE REPLACEMENT THERAPY
ROLE OF RALOXIFENE
ROLE OF TIBOLONE
NEW DRUGS IN DEVELOPMENTAL PHASE
Tissue-specific Estrogens: Bazedoxifene and Conjugated Estrogen
Cathepsin K Inhibitor: Odanacatib
OTHER MODALITIES OF TREATMENT
Calcium Supplementation
25-hydroxy vitamin D
TREATMENT WITH BISPHOSPHONATES
TREATMENT WITH DENOSUMAB
Calcitonin
Fluoride
Strontium
Teriparatide
Alternative Therapies to Prevent Bone Loss
Lifestyle Modifications
Bone Losing Medications
CONCLUSION
7 CHAPTER:
Changing Concepts of Hormone Replacement Therapy in Coronary Artery Disease
INTRODUCTION
EVIDENCE FROM OBSERVATIONAL STUDIES
WOMEN's HEALTH INITIATIVE STUDY
THE HEART AND ESTROGEN PROGESTIN REPLACEMENT STUDY
OTHER SECONDARY PREVENTION TRIALS
THE “TIMING HYPOTHESIS”
EFFECTS OF TREATMENT DURATION
RECENT ONGOING TRIALS
Kronos Early Estrogen Prevention Study (KEEPS)
Early versus Late Intervention Trial with Estradiol (ELITE) Study
CONCLUSION
8 CHAPTER:
Role of Hormone Replacement Therapy in Genitourinary Syndromes of Menopause
INTRODUCTION
UROGENITAL CHANGES SECONDARY TO ESTROGEN LOSS
GENITOURINARY SYMPTOMS
DIAGNOSIS
TREATMENT
Nonhormonal Therapies
Lubricants and Moisturizers
Hormonal Therapies
FOLLOW-UP
Summary of NAMS Recommendations4
9 CHAPTER:
Cognition, Dementia and Estrogen: Present Understanding
INTRODUCTION
OBSERVATIONAL STUDIES
Randomized Clinical Trials
CONCLUSION
10 CHAPTER:
Postmenopausal Hormone Replacement Therapy and Risk of Cancers
INTRODUCTION
FORMS OF HORMONE REPLACEMENT THERAPY
CANCER RISKS WITH POSTMENOPAUSAL hormone replacement therapy
Endometrial Cancer
Breast Cancer
Ovarian Cancer
Lung Cancer
Colon Cancer
CONCLUSION
ABSTRACT
11 CHAPTER:
Phytoestrogens and Menopause
PHYTOESTROGENS AND MENOPAUSE
What are Phytoestrogens?
Dietary Sources of Phytoestrogens
Metabolism and Mechanism of Action
Role of Isoflavones in Managing Menopause
CONCLUSION
12 CHAPTER:
Hormone Replacement Therapy and Cerebrovascular Accidents
INTRODUCTION
EARLY STUDIES: RISE OF HORMONE REPLACEMENT THERAPY
RECENT RANDOMIZED CONTROLLED TRIALS: FALL OF HRT (TABLE 12.2)
Heart and Estrogen/Progestin Replacement Study (HERS)
Women's Estrogen for Stroke Trial (WEST)
Women's Health Initiative-I (WHI-I)
Women's Health Initiative-II (WHI–II)
Women's International Study of Long Duration oestrogen after Menopause (WISDOM)
Danish Osteoporosis Prevention Study (DOPS)
Combined Meta-analysis
Timing Hypothesis
Issue of Route of Administration
Selective Estrogen Receptor Modulators (SERMs) as HRT
Carotid Doppler and other Biomarkers
RECOMMENDATIONS
FUTURE DIRECTIONS AND UNANSWERED QUESTIONS
13 CHAPTER:
Selective Tissue Therapy: Options in Menopause
INTRODUCTION
TIBOLONE
Pharmacology
Clinical Effects
Effect of Tibolone on Mood and Well-being
Tibolone and Cognition
Tibolone and Uterus
Tibolone and Breast
Tibolone and Lipid Metabolism
Tibolone and Bones
Starting Tibolone Therapy
Side Effects
Effect on Long-term Health
Clinical Recommendations for the Use of Tibolone in Asian Women
Conclusion
ESTROGEN RECEPTOR MODULATORS
BENEFITS OF RALOXIFENE
RISKS OF RALOXIFENE
Side Effects and Other Downsides of Raloxifene
Other SERMs
Conclusion
Phytoestrogens:The Natural SERM
SECTION II: ANDROPAUSE AND TESTOSTERONE REPLACEMENT THERAPY
14 CHAPTER:
Andropause: A Myth or Reality
INTRODUCTION
PHYSIOLOGY OF TESTOSTERONE
Dihydrotestosterone (DHT)
Estradiol
AGE-RELATED CHANGES IN TESTOSTERONE
CLINICAL MANIFESTATIONS
Physical
Psychological
Sexual
DIAGNOSIS
CONCLUSION
15 CHAPTER:
Testosterone Replacement Therapy in Andropause: Current Scenario
INTRODUCTION
Screening Before Starting Testosterone Replacement Therapy
Treatment Options for Testosterone Replacement Therapy
Intramuscular Injections
Transdermal Gel (T-gel)
Transdermal Testosterone Patch (T-patch)
Transbuccal Testosterone (Buccal-T) Delivery Systems
Testosterone Subcutaneous Implants (T-pellets)
Oral Testosterone (T-pills)
Monitoring Testosterone Replacement Therapy
16 CHAPTER:
Changing Clinical Profile with Testosterone Replacement Therapy
INTRODUCTION
SYNTHESIS AND MECHANISM OF ACTION
DIAGNOSIS OF TESTOSTERONE DEFICIENCY
MEASURING TESTOSTERONE LEVELS
BENEFITS OF TESTOSTERONE REPLACEMENT THERAPY
Improved Body Composition and Muscle Mass and Strength
Improve Sexual Desire Function and Performance
Mood Energy and Quality of Life
Cognitive Function
Improving Metabolic Syndrome, Type II Diabetes and Cardiovascular Disease
Improving Anemia
Improve Bone Mineral Density
CONTRAINDICATIONS TO TESTOSTERONE REPLACEMENT THERAPY
SAFETY ISSUES WITH TESTOSTERONE REPLACEMENT THERAPY
Lipid Abnormalities
Polycythemia and Sleep Apnea
Benign Prostatic Hyperplasia
Prostate Cancer
Liver Problems
Other Adverse Effects of Testosterone Replacement Therapy
SUMMARY
17 CHAPTER:
Cardiovascular Diseases and Testosterone Replacement Therapy
INTRODUCTION
BIOLOGICAL EFFECTS OF TESTOSTERONE ON THE CARDIOVASCULAR SYSTEM
Testosterone and Atherosclerosis
Testosterone and Vasodilatation
Testosterone and Arterial Stiffness
EPIDEMIOLOGICAL ASSOCIATION BETWEEN TESTOSTERONE AND CARDIOVASCULAR DISEASES
Testosterone and Heart Failure
Testosterone and Coronary Artery Diseases
Testosterone and Stroke
Testosterone and Other Cardiovascular Disease
Testosterone and QT Interval
Adverse Cardiovascular Events with Testosterone Replacement Therapy
CONCLUSION
18 CHAPTER:
Testosterone: Aging and Longevity
INTRODUCTION
TESTOSTERONE AGING AND LONGIVITY
INDEX
TOC
Index
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