Hormone therapy linked to sustained semaglutide weight loss in observational cohort

A large retrospective observational cohort study found that midlife women using menopause hormone therapy experienced significantly greater and sustained weight loss while taking semaglutide than women who were not using hormone therapy. For tirzepatide, women using hormone therapy initially showed greater weight loss, but the difference at the end of treatment did not reach statistical significance. The findings indicate an association, not proof that hormone therapy caused stronger weight-loss responses.

The study included nearly 2,400 women taking semaglutide and nearly 1,500 taking tirzepatide. Participants were over 45 years old and had a body mass index above 27 kg/m², and they were receiving treatment for overweight or obesity. Investigators compared weight-loss responses between hormone-therapy users and nonusers. The release described the research as the first known large real-world cohort of midlife women treated with these GLP-1-based obesity medications.

The result was consistent with earlier, smaller retrospective studies in postmenopausal women, which had suggested an association between hormone therapy and greater weight-loss responses to semaglutide and tirzepatide. The new analysis was presented as a larger, independent cohort. Its stronger finding for semaglutide may point to an interaction specific to GLP-1 signaling, the researchers said, while emphasizing that the difference between the two drugs deserves further investigation.

Dr. Regina Castaneda of Mayo Clinic Florida, the lead study author, said the consistent signal should not be overlooked. She also said it was too early to draw firm conclusions and that the findings need confirmation in adequately designed prospective trials. Castaneda noted that the association was biologically plausible in light of preclinical data suggesting a potential synergistic effect between estrogen and GLP-1 signaling. Because the study was observational, its findings should not be interpreted as establishing a causal treatment effect or as grounds for prescribing hormone therapy to improve weight loss. Weight loss is not an indication for menopause hormone therapy, the release emphasized.

The results were scheduled for discussion at The Menopause Society’s 2026 Annual Meeting in San Diego in a presentation titled “Menopause Hormone Therapy and Weight Loss Response to GLP-1-Based Therapies in Midlife Women: A Retrospective Cohort Study.” Around 20% of women aged 50 to 64 report current or past use of a GLP-1-based obesity medication, according to the release. The practical scope of the findings therefore remains limited to the population and medicines studied: an association was observed between hormone-therapy use and greater, sustained weight loss with semaglutide, whereas the final difference for tirzepatide was not statistically significant.

Subject of Research: Menopause hormone therapy and weight-loss response to GLP-1-based obesity medications in midlife women

Article Title: Hormone therapy may increase weight loss effectiveness of GLP-1s

Article References: Hormone therapy may increase weight loss effectiveness of GLP-1s. Original publication (Bibliographic details unavailable.)

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Keywords: semaglutide, tirzepatide, menopause, hormone therapy, weight loss, midlife women, GLP-1 medications, observational cohort, treatment response, Hormone, therapy, increase