Research Summary

Menopause Hormone Therapy Linked to Greater Tirzepatide-Associated Weight Loss in US Postmenopausal Women with Obesity

Edited by:
Ashton L. Stahl

Key Highlights:

  • Postmenopausal women using hormone therapy experienced a greater percentage of bodyweight loss with tirzepatide than non-users.
  • A higher proportion of hormone therapy users achieved clinically significant weight loss thresholds of at least 20%, 25%, and 30%.
  • Both groups showed cardiometabolic improvements, with additional benefits observed among hormone therapy users.

Obesity risk increases during the menopause transition, contributing to heightened cardiometabolic risk in midlife women. Tirzepatide is currently the most effective pharmacologic therapy for obesity, yet data in postmenopausal populations and the potential influence of menopause hormone therapy are limited. A retrospective cohort study published in The Lancet Obstetrics, Gynaecology, & Women’s Health evaluated whether hormone therapy use enhances weight loss and cardiometabolic response to tirzepatide in postmenopausal women with overweight or obesity treated in the United States.

Researchers analyzed electronic health record data from the Mayo Clinic Health System, focusing on postmenopausal women who were prescribed tirzepatide for weight management and followed for at least 12 months. Eligible participants were overweight, defined as having a BMI of at least 27 kg/m² with an adiposity-related comorbidity, or obesity, defined as a BMI of at least 30 kg/m² regardless of comorbidities.

Women using systemic hormone therapy were propensity score matched in a 1:2 ratio to non-users based on age, body mass index, age at and type of menopause, prior obesity medication use, and diabetes status. Data were collected at baseline and at follow-up visits at 3, 6, 9, 12, and 15 months and at the most recent available follow-up. The primary endpoint was the percentage change in total body weight at the last follow-up; secondary outcomes included weight loss at predefined intervals, categorical weight-loss thresholds, and changes in cardiometabolic parameters.

Study Findings

Between June 3, 2022, and May 25, 2024, 15,639 women were screened, and 120 postmenopausal women met the inclusion criteria. Of these, 40 hormone therapy users were matched to 80 non-users. The mean age was 56.4 years, and 94% of participants were White.

At the last follow-up, women using hormone therapy experienced greater mean percentage bodyweight loss than non-users (–19.2% vs –14.0%), corresponding to a mean difference of –5.2% (95% CI, 1.90–8.54; P = .0023). A higher proportion of hormone therapy users achieved weight loss thresholds of at least 20%, 25%, and 30%.

Both groups demonstrated improvements in glycaemia, blood pressure, and liver enzyme concentrations. Additional reductions in diastolic blood pressure, triglycerides, and aspartate aminotransferase were observed among women using hormone therapy.

Clinical Implications

According to the study authors, the findings suggest that concurrent menopause hormone therapy may enhance weight loss and cardiometabolic outcomes during tirzepatide treatment in postmenopausal women who are overweight or obese. The authors emphasized that prospective, randomized controlled trials are needed to confirm these observations, establish causality, and inform clinical decision-making.

Expert Commentary

“In postmenopausal women with overweight or obesity, concurrent use of hormone therapy was associated with greater weight loss and improved cardiometabolic outcomes during tirzepatide treatment,” the researchers concluded.

Reference

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; DOI:10.1016/S3050-5038(25)00145-1