AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Cardiometabolic Effects of Menopause Hormone Therapy in Women with or at Risk for Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
By Setrice Patricia C, Kiyimba DM, Ramteke HD et al.
Introduction: Reanalysis of the Women's Health Initiative has renewed debate on menopause hormone therapy (MHT) and cardiovascular risk. Whether MHT's cardiometabolic effects differ by formulation, route, or timing of initiation in women with or at risk for cardiovascular disease (CVD) remains unclear. This meta-analysis synthesizes the latest RCT evidence. Methods: We systematically searched databases for RCTs reporting cardiometabolic endpoints in women with or at high risk for CVD, including long-term follow-up from KEEPS and ELITE. Random-effects meta-analyses stratified by estrogen-alone vs. estrogen-progestin, oral vs. transdermal route, and early vs. late initiation relative to menopause onset. Results: Twelve RCTs (N=28,431) were included. In women initiating MHT within 10 years of menopause (early timing), estrogen alone reduced coronary heart disease (CHD) risk (RR 0.78; 95% CI 0.66-0.92), all-cause mortality (RR 0.81; 95% CI 0.70-0.94), and myocardial infarction (RR 0.82; 95% CI 0.69-0.97) versus placebo. Estrogen plus progestin showed neutral CHD effects (RR 1.00; 95% CI 0.87-1.15) but increased stroke risk (RR 1.28; 95% CI 1.02-1.58) and venous thromboembolism (VTE) (RR 1.52; 95% CI 1.12-2.06). Late initiation (>10 years) conferred no cardioprotection for any formulation. Transdermal estradiol (vs. oral) was associated with lower triglycerides (mean difference -12.4 mg/dL; 95% CI -18.2 to -6.6), reduced VTE (RR 0.59; 95% CI 0.38-0.91), and lower systolic blood pressure (MD -3.1 mmHg; 95% CI -5.4 to -0.8). No significant differences in heart failure hospitalization were observed by route (RR 0.92; 95% CI 0.73-1.16). Early estrogen alone reduced diabetes incidence (RR 0.73; 95% CI 0.59-0.90). Conclusion: Early initiation of estrogen-alone MHT may reduce CHD, mortality, MI, and diabetes in women at risk for CVD, but adding progestin negates cardiac benefits and elevates stroke and VTE risk. Transdermal administration offers a safer metabolic and thrombotic profile. These findings support formulation-, route-, and timing-guided MHT recommendations.