Postmenopausal women using hormone therapy experienced the greatest weight loss with tirzepatide, according to a Mayo Clinic retrospective study presented at the 2025 Annual Meeting of The Menopause Society.
Tirzepatide treatment resulted in substantial weight loss across all reproductive stages, with postmenopausal women receiving menopausal hormone therapy (MHT+) achieving. The greatest total body weight loss (TBWL), averaging 19.9% (standard error [SE] 1.4), was greater than the 15.6% (SE 1.6) observed among postmenopausal women not using MHT. Premenopausal and perimenopausal women achieved TBWL of 18.7% (SE 1.9) and 18.6% (SE 1.3), respectively, with similar outcomes observed in the MHT+ group.
The study evaluated the influence of reproductive stage and MHT on real-world tirzepatide weight-loss outcomes. Researchers conducted a retrospective study of women prescribed tirzepatide for weight management, categorizing participants into four groups: premenopausal, perimenopausal, postmenopausal without MHT (MHT–), and postmenopausal with MHT (MHT+). Premenopausal women were defined as younger than 45 years with no menopausal signs, while perimenopausal women were 45 to 54 years. Postmenopausal status was determined by amenorrhea lasting at least 12 months, bilateral oophorectomy, or follicle-stimulating hormone levels exceeding 50 IU/L after hysterectomy or ablation.
To minimize confounding, researchers applied 1:1 nearest-neighbor propensity-score matching across the groups, controlling for diabetes, prior weight-loss medication use, and baseline body mass index. The final cohort included 160 women (mean age 50 ± 10 years; body mass index 34 ± 5 kg/m²), evenly divided among the four reproductive-stage categories. Longitudinal TBWL was assessed using linear mixed-effects models with restricted maximum-likelihood estimation and Kenward-Roger adjustment for degrees of freedom. The average follow-up period was 18 months.
The researchers reported no conflicts of interest.