The effects of menopausal hormone therapy on cardiovascular disease, cancer, cognition and depression in younger women: A systematic review.

Objective: The Women's Health Initiative (WHI), a randomized controlled trial, found no overall health benefit of menopausal hormone therapy. Our objective was to evaluate the hypothesis that initiating hormonal therapy prior to age 60 or within a few years after the last menstrual period provides health benefits in menopausal women. Design: A search was conducted in MEDLINE, Scopus, and ClinicalTrials.gov from inception until August 26, 2025. Randomized controlled trials in which at least one arm was a pharmaceutical oestrogen and one arm was a placebo were included. We required studies to present clinical health outcomes. Setting: Systematic review. Participants: Menopausal women age 60 or younger or within a short time of the last menstrual period, as defined by individual study authors. Main outcome measures: Studies were categorized based on primary endpoints, namely cardiovascular disease, cancer, depression, and cognition. Risk of bias was assessed using a standard tool. The reliability of conclusions was assessed using the core GRADE method. Results: Thirty-one papers, reporting on seventeen randomized controlled trials, met eligibility criteria. Menopausal hormone therapy in young menopausal women was not shown to have beneficial effects on cardiovascular disease, cancer, depression, or cognition with the exception of some cardiovascular endpoints in women on oestrogen alone in the WHI, a finding not confirmed in other randomized controlled trials and not confirmed in women with vasomotor symptoms. Conclusions: Menopausal hormone therapy in young menopausal women has not been shown in randomized controlled trials to have beneficial effects on cardiovascular disease, cancer, depression, or cognition.