Abstract
Disclosure: D. Bechenati: None. R. Castaneda: None. R.D. Rivera Gutierrez: None. M.A. Espinosa: None. J.L. Villamarin: None. E. Tama: None. J.L. Meek: None. S. Faubion: Era Women’s Health Platform, PriMed, AiCME, MedAll, Medscape, Weight Watchers. C. Shufelt: Bayer Pharmaceutics. T. Rajjo: None. Given the metabolic changes associated with menopause (increased abdominal fat, decreased muscle mass, altered energy expenditure), menopause hormone therapy (MHT) may influence weight loss outcomes. Although semaglutide studies suggest a potential benefit of MHT on weight loss in postmenopausal women, the impact of tirzepatide (TZP) remains unclear. This real-world study investigates whether TZP efficacy differs between postmenopausal women using MHT (+MHT) and those not using MHT (-MHT) in the treatment of overweight or obesity. This retrospective cohort study included postmenopausal women prescribed TZP for the treatment of overweight or obesity, with or with MHT. Exclusion criteria were <12 months of TZP use, prior bariatric surgery, active malignancy, and concomitant anti-obesity medication. MHT consisted of transdermal or oral estrogen, with or without progesterone. Data, collected through November 1, 2024, were obtained from electronic medical records. To minimize confounding, 1:2 propensity score matching was used, matching each +MHT participant to two -MHT controls based on age, BMI, age at menopause, menopause type, and diabetes status. Primary endpoints were total body weight loss percentage (TBWL%) at 3, 6, 9, 12, and 15 months, and at last follow-up. Secondary endpoints included the percentage of participants achieving ≥5%, ≥10%, ≥15%, and ≥20% TBWL. Data was non-normal distributed, as such results are presented as median [interquartile range (IQR)], and group comparisons used the Wilcoxon rank-sum test. After propensity score matching of 400 postmenopausal women, 120 were included in this analysis: 40 in the +MHT group (56 [53-58] years, BMI 34 [31-37] kg/m²) and 80 in the -MHT group (57 [53-61] years, BMI 33 [29-36] kg/m²). Baseline characteristics and adiposity-related comorbidities were similar between groups. The median follow-up duration was 18 [15-22] months for the +MHT group and 18 [16-22] months for the -MHT group, with no significant difference between the groups (p=0.4). At the last follow-up, the +MHT group achieved significantly greater TBWL compared to the -MHT group: 17% [11-25] vs 14% [8-18] (p=0.01). Additionally, by the last follow-up, a higher proportion of women in the +MHT group achieved ≥20% TBWL (45% vs. 18%, p=0.001) compared to the -MHT group. In postmenopausal women with overweight or obesity treated with TZP, the use of MHT is associated with superior weight loss outcomes. Further studies with larger sample sizes are needed to confirm these findings and to explore the mechanisms driving this differential weight loss response. Presentation: Saturday, July 12, 2025