Menopausal hormone therapy.
BACKGROUND: Although estrogen has been clinically available for more than 6 decades, women have been confused by different opinions regarding the risks and benefits of menopausal hormone therapy (HT), estrogen therapy (ET), and estrogen-progestin therapy (EPT). The publication of recent randomized controlled trials (RCTs), notably, the Heart and Estrogen Replacement Study (HERS), Women's Health Initiative (WHI), and Women's Health Initiative Memory Study (WHIMS), has intensified the risk versus benefit controversy and prompted this review. OBJECTIVE: We provide a systematic, comprehensive, and critical review of selected literature that addresses the basic and clinical aspects of menopausal HT. RESULTS: Solid, consistent evidence based on observational, epidemiologic, and randomized controlled trials underpins the efficacy of menopausal HT for its regulatory agency-approved indications: vasomotor symptoms, vulvovaginal atrophy symptoms, and osteoporosis-related fracture prevention. ET and EPT increase the risk for venous thromboembolism, although the absolute number of events and the risk are both small. Though there is a small increase in the number of breast cancers in women who have used menopausal HT for more than 10 years, the biological meaning of this observation (cause versus unmasking versus chance) is unresolved. Most evidence shows that menopausal HT does not affect breast cancer recurrence and that overall longevity is higher in breast cancer survivors who select menopausal HT. Strong basic science and clinical observational evidence show a benefit of menopausal HT in the cardiovascular and central nervous systems. Data from recent RCTs that included predominantly overweight women aged between 63 and 71 years have been reported to show more harm than benefit; the rush to generalize these studies to all women and all menopausal HT regimens is unjustified. CONCLUSION: Menopausal HT improves vasomotor symptoms and vulvovaginal atrophy symptoms and prevents osteoporosis-related fracture. Menopausal HT increases the likelihood of venous thromboembolism, but other harms such as breast cancer require further controlled studies. A clinical benefit of menopausal HT for cardiovascular or central nervous system disease prevention is unproven. RCTs of menopausal HT in newly menopausal women, or in women less than 3 years from menopause, are urgently needed to investigate the prevention of cardiovascular and central nervous system aging diseases.