Mayo Clinic discovers hormone replacement improves tirzepatide obesity treatment

UAE—Postmenopausal women receiving menopausal hormone therapy alongside tirzepatide may achieve substantially greater weight loss than those using the obesity medication alone, according to a new study led by Mayo Clinic.

The findings, published in The Lancet Obstetrics, Gynaecology & Women’s Health, suggest that combining the two treatments could offer a more effective approach to managing obesity and reducing cardiometabolic risk in women after menopause.

Greater weight loss after menopause

Researchers found that postmenopausal women taking hormone therapy while receiving tirzepatide lost approximately 35% more weight than women treated with tirzepatide alone.

Tirzepatide is approved by the US Food and Drug Administration (FDA) to treat overweight and obesity and has become one of the leading medicines in the growing class of GLP-1-based weight-loss therapies.

Menopause often accelerates age-related weight gain because declining estrogen levels alter metabolism, body fat distribution, and appetite regulation.

These hormonal changes also increase the risk of cardiovascular disease, type 2 diabetes, and other obesity-related conditions, making effective weight management particularly important for women during this stage of life.

Regina Castaneda, M.D., the study’s first author and a postdoctoral research fellow at Mayo Clinic, said the findings could help clinicians develop more personalised strategies for reducing cardiometabolic risk in postmenopausal women

Study examined real-world patients

The research team reviewed medical records from 120 adults with overweight or obesity who received tirzepatide for at least 12 months.

Investigators compared women who used menopausal hormone therapy with similar patients who received tirzepatide without hormone therapy.

Hormone therapy remains the most effective first-line treatment for common menopausal symptoms such as hot flashes and night sweats, which affect up to three-quarters of postmenopausal women.

Earlier studies had already suggested that hormone therapy could enhance weight loss in women treated with semaglutide, another GLP-1-based medication.

However, this is the first study to investigate a similar relationship with tirzepatide.

Researchers call for randomized trials

Despite the encouraging results, the researchers emphasised that the study was observational rather than a randomised clinical trial.

Maria Daniela Hurtado Andrade, M.D., Ph.D., senior author and endocrinologist at Mayo Clinic, noted that the findings demonstrate an association rather than proof that hormone therapy directly caused the additional weight loss.

Women receiving hormone therapy may already have adopted healthier lifestyles or experienced improved sleep and quality of life after relief from menopausal symptoms, making it easier to maintain healthy eating habits and regular physical activity.

The researchers also pointed to preclinical evidence suggesting that estrogen may strengthen the appetite-suppressing effects of GLP-1 medicines, providing a possible biological explanation for the observed benefit.

They now plan to launch a randomised clinical trial to determine whether combining hormone therapy with tirzepatide improves not only weight loss but also broader cardiometabolic outcomes, including cardiovascular health and metabolic risk factors.

Mayo Clinic advances GLP-1 research

The latest findings add to Mayo Clinic’s expanding research on GLP-1 therapies.

Recently, Mayo Clinic researchers indicated that the links between GLP-1 medicines and thyroid cancer might mainly result from increased medical monitoring rather than a direct causative effect.

This provides additional reassurance regarding the long-term safety of these medications, which are being prescribed more frequently.