For millions of women navigating perimenopause, the formulation and timing of hormone therapy may matter as much as the decision to use it at all. A reanalysis of one of medicine's most influential — and most misunderstood — trials is reshaping how clinicians weigh the cardiovascular calculus of menopausal hormone therapy (MHT), with meaningful implications for women in their 50s who delayed treatment out of fear.

This review, published in Current Opinion in Obstetrics & Gynecology, synthesizes recent evidence on MHT's risk-benefit profile across several domains. The reanalysis of the Women's Health Initiative (WHI) — long the source of widespread hormone therapy avoidance — reveals that estrogen carries a protective cardiovascular signal when initiated before age 60 or within a decade of menopause onset, a framework now called the "timing hypothesis." The same temporal window appears relevant to cognitive protection. Crucially, the elevated venous thromboembolism (VTE) risk previously attributed to hormone therapy is route-dependent: oral estrogen formulations carry measurable VTE risk, while transdermal estradiol combined with micronized progesterone does not appear to increase it. Mood disorders during the menopausal transition also emerged as a domain where MHT shows clinical utility.

The WHI's original 2002 publication triggered a dramatic and arguably overcorrected retreat from hormone therapy. Subsequent stratified analyses have consistently shown that the trial's average-age-63 cohort skewed the risk picture significantly. This review reinforces an evidence base that has been quietly accumulating for over a decade — that route, formulation, timing, and individual risk profile collectively determine safety, not hormone therapy as a monolithic category. The key limitation of this synthesis is that most reassuring data remain observational or reanalytic rather than from purpose-built randomized trials in younger menopausal women. Major societies still do not endorse MHT for primary prevention of cardiovascular disease or dementia. For symptomatic women under 60 without contraindications, however, the evidence increasingly supports individualized use as both safe and effective.