Women Over 50 Lost 35 Percent More Weight With this Surprising Combination

A study led by the Mayo Clinic reports that postmenopausal women who received hormone therapy during menopause experienced significantly greater weight loss while taking tirzepatide—a drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of overweight and obesity. On average, these women lost about 35% more weight than those who took tirzepatide alone. The results, published in The Lancet Obstetrics, Gynaecology, & Women’s Health, point to new possibilities for treating obesity and related health problems in postmenopausal women.

Menopause is often associated with increased weight gain and a higher risk of overweight and obesity. These changes can increase 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 further changes in the body that may further increase cardiovascular risk. “This study provides important insights for developing more effective and personalized strategies to manage cardiometabolic risk in postmenopausal women,” says Dr. Regina Castaneda, a postdoctoral fellow at the Mayo Clinic and the study’s first author.

Investigating the Role of Hormone Therapy in Weight Loss

Hormone therapy remains the most effective first-line treatment 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 the effects of weight-loss medications has not yet been fully clarified. Previous studies suggested that women receiving hormone therapy might lose more weight when treated with GLP-1-based medications such as semaglutide, but data on tirzepatide were previously lacking. To fill this gap, the researchers analyzed data from 120 adults with overweight or obesity who were treated with tirzepatide for at least 12 months. They compared the results between those who also received hormone therapy and those who did not, ensuring that both groups had similar baseline characteristics.

The analysis showed that women who received both treatments lost significantly more weight. “In this observational study, women who received hormone therapy during menopause lost about 35% more weight than women who took only tirzepatide. Since this was not a randomized study, we cannot say that hormone therapy caused the additional weight loss,” says Dr. Maria Daniela Hurtado Andrade, Ph.D., an endocrinologist at the Mayo Clinic and lead author of the study. “It’s possible that women who used hormone therapy already had healthier habits, or that the relief from menopausal symptoms improved sleep and quality of life, making it easier to maintain changes in diet and physical activity.”

Possible Synergy Between Estrogen and GLP-1 Medications

Although further controlled studies are needed, the researchers consider the results clinically significant. Dr. Castaneda notes that the magnitude of the observed difference warrants further investigation into how hormone therapy and GLP-1-based medications might interact. “The magnitude of this difference warrants future studies that could help clarify how GLP-1-based medications for obesity and hormone therapy during menopause might interact. Interestingly, preclinical data suggest a potential synergy, with estrogen apparently enhancing the appetite-suppressing effects of GLP-1,” says Dr. Castaneda.

Future research will focus on confirming these findings in randomized clinical trials and investigating whether the benefits extend beyond weight loss. “Next, we plan to test these observations in a randomized clinical trial and determine whether the benefits extend beyond weight loss—specifically, whether hormone therapy also enhances the effect of these medications on cardiometabolic parameters,” adds Dr. Hurtado Andrade. “If this is confirmed, this work could accelerate the development and implementation of new, evidence-based strategies to reduce this risk for millions of postmenopausal women who are in this stage of life.”