A new Mayo Clinic–led study suggests that menopausal hormone therapy could significantly enhance the weight-loss effects of tirzepatide, a U.S. Food and Drug Administration–approved medication for overweight and obesity. Researchers found that postmenopausal women who used hormone therapy while taking tirzepatide lost about 35% more weight than those who took the drug alone.
The findings, published in The Lancet Obstetrics, Gynaecology, & Women’s Health, point to new treatment possibilities for millions of women who struggle with obesity and related health conditions after menopause.
Menopause is known to accelerate age-related weight gain and raise the risk of overweight and obesity—major contributors to cardiovascular disease, type 2 diabetes and other chronic illnesses. Declining estrogen levels during menopause are also associated with metabolic changes that may independently increase cardiovascular risk.
“This study provides important insights for developing more effective and personalized strategies for managing cardiometabolic risk in postmenopausal women,” said Regina Castaneda, M.D., a postdoctoral research fellow at Mayo Clinic and the study’s first author.
Hormone therapy is the most effective first-line treatment for menopausal symptoms such as hot flashes and night sweats, which affect up to 75% of postmenopausal women. While limited research has explored how hormone therapy interacts with weight-loss medications, prior studies have shown that women using hormone therapy may lose more weight when treated with semaglutide, another GLP-1–based obesity drug.
Until now, no studies had examined whether hormone therapy influences outcomes with tirzepatide. To address this gap, the Mayo Clinic team reviewed data from 120 participants with overweight or obesity who had received tirzepatide for at least 12 months. Researchers compared women who used tirzepatide alongside hormone therapy with those who took tirzepatide alone but had similar clinical characteristics.
“In this observational study, women who used menopausal hormone therapy lost about 35% more weight than women taking tirzepatide alone,” said Maria Daniela Hurtado Andrade, M.D., Ph.D., an endocrinologist at Mayo Clinic and senior author of the study. “Because this was not a randomized trial, we cannot say hormone therapy caused additional weight loss.”
Dr. Hurtado Andrade noted that other factors could have influenced the results. “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,” she said.
Despite these limitations, the researchers say the findings are clinically meaningful. “The magnitude of this difference warrants future studies that could help clarify how GLP-1–based obesity medications and menopausal hormone therapy may interact,” Dr. Castaneda said. “Interestingly, preclinical data suggest a potential synergy, with estrogen appearing to enhance the appetite-suppressing effects of GLP-1.”
The team plans to test the observations in a randomized clinical trial to determine whether the benefits extend beyond weight loss. “Specifically, we want to see whether hormone therapy also enhances the effects of these medications on cardiometabolic measures,” Dr. Hurtado Andrade said. “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.”
The research was funded by the Mayo Clinic Center for Women’s Health Research. A full list of authors, disclosures and funding details is available in the published study.
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