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

by The North American Menopause Society

edited by Swati Mestri, reviewed by Andrew Zinin

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The success stories of GLP-1 weight-loss medications are dominating the airwaves. Midlife women, who commonly experience weight gain resulting from menopause, have been especially drawn to the drugs.

A new study suggests that hormone therapy is associated with greater and sustained weight loss with some GLP-1s. Results of the study will be presented at the 2026 Annual Meeting of The Menopause Society in San Diego, Oct. 20–24, 2026.

Around 20% (one in five) of women ages 50 to 64 report current or past use of a GLP-1 (glucagon-like peptide-1 receptor agonist)-based obesity medication, making this age group the most represented demographic among GLP-1 users in the U.S. Weight gain during midlife is a common concern among women. Although these gains are largely driven by aging, menopause-related factors can contribute to fat accumulation and redistribution.

GLP-1 medications have been proven effective for weight loss, although treatment response may vary by sex and reproductive stage. Female sex and younger age have generally been associated with a greater weight-loss response.

Small retrospective observational cohort studies in postmenopausal women have suggested that the use of hormone therapy is associated with a greater weight-loss response to semaglutide (SEM; GLP-1 RA) and tirzepatide (TZP; a dual GLP-1/glucose-dependent insulinotropic polypeptide agonist).

A new study, however, involves the first known large real-world cohort of midlife women treated for overweight or obesity. It aimed to determine whether weight loss with SEM or TZP differs between midlife women using hormone therapy and those not using hormones. This retrospective observational cohort study included nearly 2,400 women taking SEM and nearly 1,500 women taking TZP who were >45 years old and had a BMI >27 kg/m².

Based on the results, the researchers concluded that hormone therapy is associated with significantly greater and sustained weight loss with SEM. Although the women taking TZP initially showed greater weight loss if they were also using hormone therapy, the final results did not reach statistical significance.

"We are seeing a consistent signal. 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.

"It is also biologically plausible, given preclinical data suggesting a potential synergistic effect between estrogen and GLP-1 signaling. Interestingly, the effect was stronger with semaglutide than with tirzepatide, which deserves further study and may point to an interaction specific to GLP-1 signaling. That said, it is too early to draw firm conclusions.

"These findings need to be confirmed in adequately designed prospective trials, and it's important to remember that weight loss is not an indication for menopause hormone therapy," says Dr. Regina Castaneda, lead study author from Mayo Clinic Florida.

Additional details of the study will be discussed as part of the presentation titled "Menopause Hormone Therapy and Weight Loss Response to GLP-1-Based Therapies in Midlife Women: A Retrospective Cohort Study."

"Weight gain and changes in body composition are among the most common and frustrating concerns women experience during the menopause transition," says Dr. Stephanie Faubion, medical director for The Menopause Society.

"These findings suggest that hormone therapy may influence how some women respond to GLP-1-based weight-loss medications. Although more research is needed, this study highlights the importance of considering menopause-specific factors when developing personalized approaches to weight management for midlife women."

Key medical concepts

Hormone TherapyWeight LossSemaglutideTirzepatide

Clinical categories

Obstetrics & gynecologyEndocrinologyWomen's healthWeight managementClinical pharmacologyHealthy aging Provided by The North American Menopause Society Who's behind this story?

Swati Mestri

Swati Mestri holds a bachelor's degree in Electronics Engineering and has worked as a content editor since 2019. She has experience editing research documents across technology, health care, and materials science, and has a particular interest in technology and space. Full profile →

Andrew Zinin

Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →

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