In a Mayo Clinic-led study, postmenopausal women receiving menopausal hormone therapy reported significant weight loss when taking tirzepatide, a Food and Drug Administration-approved drug to treat overweight and obesity. These women lost about 35% more weight on average than women who used tirzepatide alone. The result is Lancet Obstetrics, Gynecology, Women’s Healthpoints to new possibilities for treating obesity and related health conditions in postmenopausal women.
Menopause is often associated with increased weight gain and an increased risk of developing overweight and obesity. These changes increase the likelihood of developing serious health problems such as cardiovascular disease and type 2 diabetes. In addition to weight gain, decreased estrogen levels during menopause can cause other changes in the body that can further increase cardiovascular risk. “This study provides important insights for developing more effective, personalized strategies to manage cardiometabolic risk in postmenopausal women,” said Regina Castaneda, MD, PhD, a postdoctoral fellow at the Mayo Clinic and lead author of the study.
Exploring the role of hormone therapy in weight loss
Hormone therapy is the most effective first-line option for reducing 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 effectiveness of weight loss drugs is not well understood. Previous research suggested that women on hormone therapy may lose more weight when treated with GLP-1-based drugs such as semaglutide, but data on tirzepatide were lacking.
To address this gap, researchers analyzed data from 120 overweight or obese adults who were treated with tirzepatide for at least 12 months. They compared the results of groups that also used hormone therapy with those that did not, and found that both groups had similar baseline characteristics.
Study results and major limitations
Analysis showed that women who received both treatments lost significantly more weight. “In this observational study, women who received menopausal hormone therapy lost about 35 percent more weight than women who received tirzepatide alone. Because this was not a randomized trial, we cannot say that hormone therapy caused additional weight loss,” says María Daniela Hurtado Andrade, MD, an endocrinologist at the Mayo Clinic and the study’s senior author.
“Women using hormone therapy may have already engaged in healthier behaviors, or the relief of menopausal symptoms may have improved their sleep and quality of life, making them more likely to stick with dietary and physical activity changes.”
Potential synergy between estrogen and GLP-1 drugs
Although more controlled studies are needed, the researchers say their findings have clinical implications. Dr. Castaneda notes that the magnitude of the differences observed warrants further research into how hormone therapy and GLP-1-based drugs work together. “Given the magnitude of this difference, future studies that may help clarify how GLP-1-based obesity drugs and menopausal hormone therapy interact are warranted. Interestingly, preclinical data suggest a potential synergistic effect, and estrogen appears to potentiate the anorexigenic effects of GLP-1,” says Dr. Castaneda.
What comes next after research?
Future research will focus on confirming these results in randomized clinical trials and investigating whether there are effects beyond weight loss. “Next, we plan to test these observations in randomized clinical trials to determine whether the effects extend beyond weight loss and, specifically, whether hormonal therapy enhances the effects of these drugs on cardiometabolic measures,” added Dr. Hurtado-Andrade. “If confirmed, this study could accelerate the development and implementation of new evidence-based strategies to reduce risk for the millions of postmenopausal women who experience this life stage.”
This study was funded by the Mayo Clinic Women’s Health Research Center.
