A Mayo Clinic retrospective cohort study published in The Lancet Obstetrics, Gynaecology, & Women’s Health in January 2026 found that postmenopausal women using concurrent hormone therapy lost 35% more weight on tirzepatide than those on tirzepatide alone (–19.2% vs. –14.0% total bodyweight loss; p=0.0023), with 45% of hormone therapy users achieving ≥20% total bodyweight loss compared to just 18% of controls. The propensity score-matched analysis of 120 women also showed additional cardiometabolic benefits in the hormone therapy group, including further reductions in diastolic pressure, triglycerides, and liver enzymes. These findings build on an earlier Mayo Clinic study (Menopause,2024) which similarly showed that hormone therapy use was associated with significantly greater weight loss in postmenopausal women on semaglutide — suggesting a consistent synergistic pattern across GLP-1-based therapies. Researchers propose that estrogen’s roles in improving insulin sensitivity, adaptive thermogenesis, and fat distribution may synergize with tirzepatide’s mechanisms — positioning hormone optimization as a potential metabolic amplifier for postmenopausal women pursuing GLP-1-based obesity treatment. Prospective randomized trials are needed to confirm
causality.

Citation: Castaneda R, Bechenati D, Tama E, et al. The role of menopause hormone therapy in modulating tirzepatide-associated weight loss in postmenopausal women with overweight or obesity: a retrospective cohort study. Lancet Obstet Gynaecol Womens Health. 2026;2(2):e118. doi:10.1016/S3050-5038(25)00145-1