A new Mayo Clinic study suggests that menopausal hormone therapy may enhance weight loss in postmenopausal women treated with tirzepatide, an FDA-approved medication for overweight and obesity. According to the research, published in The Lancet Obstetrics, Gynaecology, & Women’s Health, women receiving hormone therapy lost approximately 35% more weight than those taking tirzepatide alone.
Menopause often accelerates age-related weight gain and increases the risk of obesity, a major contributor to cardiovascular disease, type 2 diabetes, and other health complications. Declining estrogen levels during menopause can also independently raise 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., postdoctoral research fellow at Mayo Clinic and first author of the study.
Menopausal hormone therapy is a well-established first-line treatment for symptoms such as hot flashes and night sweats, which affect up to 75% of postmenopausal women. Previous research has suggested that hormone therapy may amplify weight loss for women taking GLP-1-based obesity medications like semaglutide. However, until now, no studies had explored whether hormone therapy could similarly influence outcomes with tirzepatide.
To investigate, Dr. Castaneda and colleagues analyzed data from 120 participants with overweight or obesity who had taken tirzepatide for 12 months or longer. The study compared women using hormone therapy alongside tirzepatide to those on tirzepatide alone with similar demographic and clinical characteristics.
The results indicated that women on hormone therapy lost about 35% more weight than their counterparts. “Because this was not a randomized trial, we cannot conclude that hormone therapy directly caused the additional weight loss,” noted Maria Daniela Hurtado Andrade, M.D., Ph.D., endocrinologist at Mayo Clinic and senior author of the study. She added that hormone therapy could indirectly support weight loss by improving menopause symptoms, sleep, quality of life, and engagement in healthy behaviors.
Dr. Castaneda emphasized that while further studies controlling for these factors are needed, the findings are clinically significant. “The magnitude of this difference warrants future research to clarify how GLP-1-based obesity medications and menopausal hormone therapy may interact. Preclinical data even suggest that estrogen may enhance the appetite-suppressing effects of GLP-1,” she said.
The researchers plan to test these observations in a randomized clinical trial to determine whether hormone therapy can enhance not only weight loss but also cardiometabolic benefits. “If confirmed, this work could accelerate the development of new evidence-based strategies to reduce health risks for millions of postmenopausal women,” Dr. Hurtado Andrade said.
This study was funded by the Mayo Clinic Center for Women’s Health Research.
