Menopausal hormone therapy linked to greater weight loss with tirzepatide

A new study led by Mayo Clinic found that postmenopausal women receiving menopausal hormone therapy lost 35% more weight while taking tirzepatide, a Food and Drug Administration-approved drug for the treatment of overweight and obesity. The findings, published in The Lancet Obstetrics, Gynaecology, & Women's Health, could expand treatment possibilities for millions of women struggling with obesity and obesity-related diseases after menopause.

Menopause can accelerate age-related weight gain and increase the likelihood of developing overweight and obesity, which are major risk factors for cardiovascular disease, type 2 diabetes and other conditions. The decline in estrogen levels characteristic of menopause is also linked to changes independent of weight that can potentially raise 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.

Hormone therapy is the most effective first-line treatment for menopausal symptoms, including hot flashes and night sweats, which affect up to 75% of postmenopausal women. While evidence on how this therapy may interact with weight-loss medications is limited, some research has shown that postmenopausal women using hormone therapy experience greater weight loss when treated with the GLP-1-based obesity medication semaglutide.

No previous studies have examined whether hormone therapy might influence outcomes with tirzepatide. Dr. Castaneda and a team of researchers set out to investigate 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 along with hormone therapy were compared to participants with similar characteristics who were not using hormone therapy.

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."

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."

Dr. Castaneda says, while more studies that control for these factors are needed, the findings are clinically meaningful. "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.

"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.