Could hormone therapy boost semaglutide weight loss?

Clinical takeaway: For midlife women using GLP-1–based medications for obesity, concomitant menopausal hormone therapy may be associated with greater weight loss, particularly with semaglutide. However, the findings are observational and should not be interpreted as a reason to prescribe hormone therapy solely for weight management.

Weight gain and changes in body composition are common concerns during the menopause transition, and women aged 50-64 represent the largest demographic group of GLP-1 users in the US. Identifying factors that may influence response to anti-obesity medications could help guide more personalized treatment strategies for midlife women.

Hormone therapy use was associated with significantly greater and more sustained weight loss among midlife women treated with semaglutide in a large retrospective real-world cohort study presented at the 2026 Annual Meeting of The Menopause Society. The findings have not yet undergone peer review.

Researchers evaluated nearly 2,400 women aged older than 45 years with overweight or obesity who were treated with semaglutide, along with nearly 1,500 similar women treated with tirzepatide. All participants had a body mass index greater than 27 kg/m². The analysis compared outcomes in women using menopausal hormone therapy with those not using hormones.

Women receiving semaglutide and hormone therapy experienced significantly greater and more durable weight loss than those taking semaglutide alone. A similar early pattern was observed among women receiving tirzepatide, with hormone therapy users initially losing more weight, but differences between groups were not statistically significant by the end of follow-up.

The study builds on earlier, smaller observational analyses suggesting that estrogen exposure may enhance the response to GLP-1–based therapies. Investigators noted that the stronger association observed with semaglutide compared with tirzepatide may point to a mechanism related specifically to GLP-1 signaling, although prospective studies are needed to confirm the finding.

“We are seeing a consistent signal,” said lead author Regina Castaneda of Mayo Clinic Florida. “Our earlier, smaller studies showed an association between hormone therapy use and greater weight loss in postmenopausal women, and the fact that we see the same signal in a larger, independent cohort should not be overlooked.”

Source: The Menopause Society press release (2026 Oct 20). Hormone Therapy May Increase Weight Loss Effectiveness of GLP-1s