A new study suggests that a common menopause treatment may influence how effectively certain weight-loss medications work.
A new study led by Mayo Clinic reports that postmenopausal women who used menopausal hormone therapy lost significantly more weight while taking tirzepatide, a drug approved by the U.S. Food and Drug Administration to treat overweight and obesity. According to the research, these women experienced about 35% greater weight loss than those who used tirzepatide alone.
The findings were published in The Lancet Obstetrics, Gynaecology, & Women’s Health and suggest that combining hormone therapy with certain obesity medications could open new treatment options for millions of women who face weight gain and related health risks after menopause.
Menopause is often associated with faster weight gain as people age. It also raises the chances of developing overweight and obesity, both of which increase the risk of cardiovascular disease, type 2 diabetes, and other health problems. In addition, the drop in estrogen levels that occurs during menopause is linked to biological changes that may raise cardiovascular risk even when body weight remains the same.
“This study provides important insights for developing more effective and personalized strategies for managing cardiometabolic risk in postmenopausal women,” says Regina Castaneda, M.D., postdoctoral research fellow at Mayo Clinic and first author of the study.
Hormone Therapy and Weight-Loss Medications
Hormone therapy is widely considered the most effective first line treatment for common menopausal symptoms such as hot flashes and night sweats. These symptoms affect up to 75% of postmenopausal women.
Scientists still have limited information about how hormone therapy may interact with medications used for weight loss. However, some earlier studies have suggested that postmenopausal women receiving hormone therapy may lose more weight when treated with the GLP-1 based obesity medication semaglutide.
Until now, researchers had not examined whether hormone therapy could influence results in people taking tirzepatide. To explore this possibility, Dr. Castaneda and her colleagues analyzed medical data from 120 participants with overweight or obesity who used tirzepatide for weight management for at least 12 months.
The researchers compared patients who used tirzepatide together with hormone therapy with individuals who had similar characteristics but were not receiving hormone therapy.
“In this observational study, women who used menopausal hormone therapy lost about 35% more weight than women taking tirzepatide alone. Because this was not a randomized trial, we cannot say hormone therapy caused additional weight loss,” says Maria Daniela Hurtado Andrade, M.D., Ph.D., endocrinologist at Mayo Clinic and senior author of the study.
“It is possible that women using hormone therapy were already engaged in healthier behaviors, or that menopause symptom relief improved sleep and quality of life, making it easier to stay engaged with dietary and physical activity changes.”
Possible Biological Synergy
Dr. Castaneda notes that additional research is needed to control for these possible influences. Even so, she says the size of the difference observed in the study makes the results noteworthy.
“The magnitude of this difference warrants future studies that could help clarify how GLP-1-based obesity medications and menopausal hormone therapy may interact. Interestingly, preclinical data suggest a potential synergy, with estrogen appearing to enhance the appetite-suppressing effects of GLP-1,” says Dr. Castaneda.
“Next, we plan to test these observations in a randomized clinical trial and determine if benefits extend beyond weight loss — specifically, whether hormone therapy also enhances the effects of these medications on cardiometabolic measures,” adds Dr. Hurtado Andrade. “If confirmed, this work could speed the development and adoption of new, evidence-based strategies to reduce this risk for millions of postmenopausal women navigating this life stage.”
Reference: “The role of menopause hormone therapy in modulating tirzepatide-associated weight loss in postmenopausal women with overweight or obesity: a retrospective cohort study” by Regina Castaneda, Dima Bechenati, Elif Tama, Rene Rivera Gutierrez, Maria A Espinosa, Jose Villamarin, Tamim I Rajjo, Andres Acosta, Stephanie Faubion, Chrisandra Shufelt and Maria D Hurtado Andrade, 22 January 2026, The Lancet Obstetrics, Gynaecology, & Women’s Health.
DOI: 10.1016/S3050-5038(25)00145-1
This research was funded by the Mayo Clinic Center for Women’s Health Research.
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