TL;DR
Get workout gear delivered free with Prime
- Fast, free delivery on millions of items
- Prime Video, Amazon Music and more included
- Member-only deals all year
A retrospective study of midlife women found that those taking menopausal hormone therapy alongside semaglutide had greater average weight loss from nine months onward than women taking semaglutide alone. With tirzepatide, a modest difference appeared at three months but not later; the observational findings do not prove hormone therapy caused the difference.
A retrospective study of women aged 45 and older found that those taking menopausal hormone therapy with semaglutide lost a greater share of their body weight from nine months onward than women taking semaglutide alone. The pattern was different for tirzepatide: hormone therapy was associated with a small advantage at three months, but no significant difference at later measured points. The findings, presented at the Menopause Society annual meeting, do not show that hormone therapy caused the additional weight loss.
Researchers analyzed multisite electronic health record data from 2017 through December 2025. The study included women aged at least 45 with a body mass index of 27 or higher who had used semaglutide or tirzepatide for at least 12 months. The semaglutide group included 2,379 women: 793 taking the drug alone and 1,586 also using menopausal hormone therapy. The tirzepatide group included 1,476 women, split between 984 taking the medication alone and 492 using hormone therapy as well.
In the semaglutide cohort, average total body weight loss was 9.8% versus 8.2% at nine months for hormone-therapy users and nonusers, respectively. At 12 months, the figures were 11.0% and 9.5%; at 15 months, they were 11.6% and 9.7%. The reported differences were statistically significant at each of those timepoints. Hormone-therapy users were also more likely to reach several weight-loss thresholds, including at least 10% of body weight (55% versus 51%) and at least 20% (22% versus 18%).
For tirzepatide, the corresponding average weight loss at three months was 6.6% with hormone therapy and 5.9% without it, a modest difference. The researchers found no significant differences at later timepoints. Hormone-therapy users were more likely to reach at least 5% weight loss (88% versus 84%), but there were no significant differences at higher thresholds. Regina Castaneda, MD, a Mayo Clinic postdoctoral research fellow and study presenter, said the contrast between drugs could reflect tirzepatide’s greater weight-loss effect on its own, or differences in how the medications work. Those explanations remain possibilities, not findings established by the study.
A Possible Difference Between the Drugs
The results suggest that menopausal status and hormone use may be relevant when researchers study how people respond to obesity medications. The sustained association seen with semaglutide could point to a difference worth testing in future studies. It does not establish that prescribing hormone therapy would improve weight loss, or that the observed difference would apply to every patient.
JoAnn E. Manson of Harvard Medical School, who was not involved in the research, told MedPage Today that the findings may inform more personalized approaches if confirmed. She also said larger prospective studies are needed. For patients and clinicians, the distinction matters: hormone therapy should not be used as a weight-loss treatment on the basis of this research. Castaneda emphasized that weight management is not an indication for menopausal hormone therapy, which should be prescribed for established indications.
Products Worth Considering
Withings Body Smart Wi-Fi and Bluetooth Body Composition Scale
Blueair Blue Pure 511i Max Air Purifier for Home and Bedroom
Oral-B iO Series 3 Rechargeable Electric Toothbrush for Adults, Black
As an affiliate, we earn on qualifying purchases.
How the Study Compared Treatments
Earlier small retrospective studies had also suggested that women using menopausal hormone therapy alongside GLP-1 medications might lose more weight. But prior research did not always examine hormone therapy’s role or report results separately for each medication. This analysis adds a larger real-world comparison, with results reported separately for semaglutide and tirzepatide.
The study excluded women with a history of bariatric surgery, active cancer, pregnancy, or concurrent use of other obesity medications. Researchers reported that baseline characteristics and adiposity-related health conditions were balanced between the comparison groups. They also used propensity-score matching, a statistical method intended to make groups more comparable. Because the research was retrospective and based on health records, it can identify associations but cannot establish cause and effect.
“These findings could inform more personalized and effective treatment strategies for GLP-1s in postmenopausal women.”
— JoAnn E. Manson, MD, MPH, DrPH, Harvard Medical School
What the Records Cannot Establish
The study does not establish that hormone therapy caused the additional weight loss. Women who use hormone therapy may differ from nonusers in health behaviors, healthcare access or engagement, socioeconomic circumstances, and medication adherence. Castaneda said that residual confounding remains possible even after the authors used propensity-score matching.
The report also leaves open whether outcomes vary by hormone-therapy formulation, route of administration, or timing relative to menopause. The analysis focused on body-weight measures; it does not settle how hormone therapy might relate to body composition, visceral fat, lean mass, bone health, or wider cardiometabolic outcomes. The researchers said prospective studies are needed, and the reported findings should not be taken as individualized treatment advice.
Prospective Trials and Broader Outcomes
The next step is to test the association in larger prospective studies, which can follow participants under a defined research plan and better evaluate whether hormone therapy affects weight-loss response. Future work could compare hormone-therapy types and routes, examine when treatment begins relative to menopause, and account for individual biological factors.
Researchers have also called for outcomes beyond BMI and total weight, including changes in body composition, visceral adiposity, preservation of lean mass, bone health, and cardiometabolic measures. Until those results are available, the study provides a signal for further investigation—not evidence to add menopausal hormone therapy to semaglutide or tirzepatide for weight loss.
Key Questions
Did hormone therapy cause more weight loss with semaglutide?
The study cannot show causation. It found an association in retrospective health-record data, which may be affected by differences between hormone-therapy users and nonusers.
Was the same pattern found with tirzepatide?
No sustained difference was reported. Hormone-therapy users had modestly greater average weight loss at three months, but the groups did not differ significantly at later measured timepoints.
Should menopausal hormone therapy be taken for weight loss?
No conclusion from this study supports that use. Castaneda said weight management is not an indication for menopause hormone therapy, which should be prescribed for established indications.
What research is still needed?
Researchers called for larger prospective studies and further analysis of hormone-therapy formulation, route, and timing, as well as measures such as body composition, lean mass, bone health, and cardiometabolic outcomes.
Source: medpagetoday.com
