The impact of hormone replacement therapy on cardiovascular health in postmenopausal women: a narrative review

Menopause represents a pivotal transition in women's health, characterized by loss of ovarian hormone production and substantially increased cardiovascular disease (CVD) risk. Hormone replacement therapy (HRT), once widely prescribed for both symptom management and cardiovascular protection, faced significant scrutiny following the Women's Health Initiative (WHI) trial, which associated conventional regimens with elevated risks of stroke, thromboembolism, and breast cancer. Contemporary evidence demonstrates that cardiovascular outcomes vary considerably based on formulation, route of administration, timing of initiation, and patient-specific factors. Modern strategies emphasize individualized patient selection, lower-dose regimens, and transdermal delivery methods. The "timing hypothesis" proposes that HRT initiated within 10 years of menopause onset or before age 60 may confer cardiovascular benefit, whereas later initiation may increase cardiovascular risk. This narrative review synthesizes historical and contemporary evidence on HRT and CVD, examines mechanistic pathways including vascular, metabolic, and immunomodulatory effects, and evaluates evolving clinical guidelines. Despite substantial progress, significant uncertainties persist due to trial heterogeneity, underrepresentation of diverse populations, and inconsistent long-term outcomes. Future research priorities include personalized therapeutic approaches, mechanistic investigations, and rigorous evaluation of cardiovascular endpoints to definitively establish HRT's role in preventive cardiology. This review provides updated evidence for clinicians navigating complex decisions regarding HRT use in postmenopausal women, with emphasis on cardiovascular risk stratification and individualized treatment planning.