Hormone Therapy May Enhance Tirzepatide-Associated Weight Loss in Postmenopausal Women: The Lancet
Researchers have found in a retrospective cohort study that postmenopausal women with obesity treated with tirzepatide experienced greater weight loss when they were also using menopause hormone therapy compared with tirzepatide alone. Hormone therapy users additionally showed improvements in diastolic blood pressure, triglyceride levels, and liver enzymes. These findings will be evaluated further in a randomized clinical trial to assess whether the benefits extend beyond weight reduction. The study was published in The Lancet Obstetrics, Gynaecology, & Women’s Health journal by Regina C. and colleagues.
Although menopause is linked to higher adiposity and metabolic disorders, there is a lack of information on the efficacy of contemporary anti-obesity therapies in postmenopausal women. There is also even less information regarding the impact of systemic hormone therapy on weight reduction or cardiometabolic risk changes with these drugs. This retrospective cohort study utilized the electronic health record database from the Mayo Clinic Health System.
Postmenopausal women with overweight or obesity receiving tirzepatide for at least 12 months were selected. Overweight was considered as a body mass index (BMI) of 27 kg/m² or greater with at least one comorbidity related to adiposity, and obesity was considered as a BMI of 30 kg/m² or greater, regardless of comorbidities. Women receiving systemic hormone therapy were matched in a 1:2 ratio to women not receiving hormone therapy based on age, BMI, age and type of menopause, diabetes, and previous treatment with anti-obesity medications.
Key findings
Between June 3, 2022, and May 25, 2024, a total of 15,639 female participants were screened, and 120 postmenopausal women were identified as meeting inclusion criteria.
Of these, 40 women on hormone therapy were compared to 80 women not on hormone therapy.
The mean age of the population was 56.4 years (SD 6.4), and 94% of the population was White.
Clinical information was obtained at baseline and during follow-up visits at approximately 3, 6, 9, 12, and 15 months, as well as at the last available follow-up.
Postmenopausal women on hormone therapy lost significantly more weight than those not on hormone therapy.
At the last follow-up, the hormone therapy group lost a mean of 19.2% of total body weight (SD 9.9), compared with 14.0% (SD 8.0) for the non-hormone therapy group.
The mean difference in weight loss between groups was 5.2 % (95% CI 1.90-8.54; p = 0.0023).
In postmenopausal women with obesity or overweight, the concomitant use of hormone therapy was found to result in significantly greater weight reduction and improved cardiometabolic outcomes with the use of tirzepatide. The results of the study indicate that hormone therapy could potentially be used as an adjunct to tirzepatide therapy in postmenopausal women with obesity.
Reference:
Castaneda, R., Bechenati, D., Tama, E., Rivera Gutierrez, R., Espinosa, M. A., Villamarin, J., Rajjo, T. I., Acosta, A., Faubion, S., Shufelt, C., & Hurtado Andrade, M. D. (2026). The role of menopause hormone therapy in modulating tirzepatide-associated weight loss in postmenopausal women with overweight or obesity: a retrospective cohort study. The Lancet. Obstetrics, Gynaecology, & Women’s Health. https://doi.org/10.1016/s3050-5038(25)00145-1
