A Mayo Clinic-led study reports that postmenopausal women using menopausal hormone therapy experienced significantly greater weight loss when taking tirzepatide, a Food and Drug Administration-approved medication for overweight and obesity. On average, these women lost about 35% more weight compared to those using tirzepatide alone. The results, published in The Lancet Obstetrics, Gynaecology, & Women’s Health, point to new possibilities for treating obesity and related health conditions in women after menopause.
Menopause is often associated with increased weight gain and a higher risk of developing overweight and obesity. These changes can raise the likelihood of serious health problems, including cardiovascular disease and type 2 diabetes. In addition to weight gain, declining estrogen levels during menopause can trigger other changes in the body that may further increase cardiovascular risk. “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.
Exploring the Role of Hormone Therapy in Weight Loss
Hormone therapy remains the most effective first-line option for relieving common menopausal symptoms such as hot flashes and night sweats, which affect up to 75% of postmenopausal women. However, its potential role in enhancing weight-loss medications has not been well understood. Earlier studies have suggested that women using hormone therapy may lose more weight when treated with GLP-1-based drugs like semaglutide, but data on tirzepatide had been lacking.
To address this gap, researchers analyzed data from 120 adults with overweight or obesity who were treated with tirzepatide for at least 12 months. They compared outcomes between those who also used hormone therapy and those who did not, ensuring both groups had similar baseline characteristics.
Study Findings and Key Limitations
The analysis showed that women receiving both treatments lost significantly more weight. “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.”
Potential Synergy Between Estrogen and GLP-1 Medications
Although more controlled studies are needed, researchers say the findings are clinically meaningful. Dr. Castaneda notes that the size of the observed difference justifies further investigation into how hormone therapy and GLP-1-based medications may work together. “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.
What Comes Next for Research
Future research will focus on confirming these results in randomized clinical trials and exploring whether the benefits go beyond weight loss. “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.”
This research was funded by the Mayo Clinic Center for Women’s Health Research.