What the Women's Health Initiative has taught us about menopausal hormone therapy

Our understanding of the complex relationship between menopausal hormone therapy (MHT) and cardiovascular disease (CVD) risk has been informed by detailed analyses in the Women's Health Initiative (WHI), the largest randomized, placebo-controlled trial evaluating MHT in postmenopausal women. Although the WHI demonstrated increased risk of CVD events with MHT in the overall cohort, subsequent secondary analyses demonstrated that these risks were influenced by the woman's age and time since menopause, with lower absolute risks and hazard ratios for younger than older women. As MHT is the most effective treatment for the vasomotor symptoms of menopause, it is important to understand its risks and how to conduct risk stratification for symptomatic women. In addition to reviewing the WHI findings, studies pre- and post-WHI are reviewed to describe the relationship between MHT and CVD risk in menopausal women. The absolute risks of adverse cardiovascular events for MHT initiated in women close to menopause are low, and all-cause mortality effects are neutral or even favorable for younger menopausal women. The WHI has advanced and refined our understanding of the relationship between MHT and CVD risk. Although MHT should not be used for CVD prevention, absolute risks of CVD are low when MHT is started close to menopause in healthy women and hazard ratios tend to be lower for younger than older women. For women in early menopause and without contraindications to treatment, the benefits of MHT are likely to outweigh the risks when used for menopausal symptom management.