A new study led by Mayo Clinic researchers found that postmenopausal women receiving menopausal hormone therapy experienced 35% more weight loss while taking tirzepatide, an FDA-approved drug for treating overweight and obesity. The findings, published in The Lancet Obstetrics, Gynaecology, & Women's Health, could expand treatment possibilities for women experiencing obesity and related conditions after menopause.
Menopause is associated with an acceleration of age-related weight gain and an increased likelihood of developing overweight and obesity. These conditions are major risk factors for cardiovascular disease and type 2 diabetes. Declining estrogen levels characteristic of menopause are also linked to changes that can potentially raise cardiovascular risk, independent of weight. Dr. Regina Castaneda, a postdoctoral research fellow at Mayo Clinic and the study's first author, noted that this study offers important insights for developing more effective and personalized strategies to manage cardiometabolic risk in postmenopausal women.
Hormone therapy is considered the most effective first-line treatment for menopausal symptoms like hot flashes and night sweats. While research on the interaction between hormone therapy and weight-loss medications is limited, some studies have shown that postmenopausal women using hormone therapy experience greater weight loss when treated with the GLP-1-based obesity medication semaglutide.
No previous studies had examined whether hormone therapy might influence outcomes with tirzepatide. Dr. Castaneda and her research team investigated this relationship by reviewing data from 120 participants with overweight or obesity who received tirzepatide for weight management for 12 or more months. Patients receiving tirzepatide alongside hormone therapy were compared to participants with similar characteristics who were not using hormone therapy.
Dr. Maria Daniela Hurtado Andrade, an endocrinologist at Mayo Clinic and senior author of the study, stated that in this observational study, women using menopausal hormone therapy lost approximately 35% more weight than women taking tirzepatide alone. She clarified that because this was not a randomized trial, it cannot be definitively concluded that hormone therapy caused the additional weight loss.
Possible explanations for the observed difference include healthier behaviors among women using hormone therapy, or improvements in sleep and quality of life from menopause symptom relief, which could facilitate adherence to dietary and physical activity changes. Dr. Castaneda indicated that while more studies controlling for these factors are needed, the magnitude of this difference is clinically meaningful. She added that preclinical data suggest a potential synergy, with estrogen potentially enhancing the appetite-suppressing effects of GLP-1.
Dr. Hurtado Andrade stated that the next step is to test these observations in a randomized clinical trial to determine if benefits extend beyond weight loss, specifically whether hormone therapy also enhances the effects of these medications on cardiometabolic measures. If confirmed, this research could accelerate the development and adoption of new, evidence-based strategies to reduce health risks for postmenopausal women.