TL;DR
Get health and wellness essentials 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, the difference appeared only at three months; the observational findings do not show that hormone therapy caused additional weight loss.
A retrospective study presented at the Menopause Society annual meeting found that women taking menopausal hormone therapy alongside semaglutide had greater average weight loss from nine months onward than women taking the drug alone. For women taking tirzepatide, hormone therapy was linked to a small difference at three months but not at later measured points; the study cannot establish that hormone therapy caused the differences.
The analysis used multisite electronic health record data from 2017 through December 2025. It included women aged 45 or older with a body mass index of at least 27 kg/m² who had used semaglutide or tirzepatide for at least 12 months. Researchers excluded women with a history of bariatric surgery, active cancer, pregnancy, or concurrent use of other obesity medications.
In the semaglutide group, average total body weight loss among hormone-therapy users was 9.8% at nine months, compared with 8.2% among those not using hormone therapy. At 12 months, the figures were 11.0% and 9.5%; at 15 months, 11.6% and 9.7%. The reported differences were statistically significant at each of those time points.
The semaglutide cohort comprised 2,379 women: 793 taking semaglutide alone and 1,586 taking it with hormone therapy. In the tirzepatide cohort of 1,476 women, 492 used hormone therapy and 984 did not. Average weight loss at three months was 6.6% with hormone therapy and 5.9% without it, a statistically significant difference in the analysis. No significant differences remained at later time points.
Among semaglutide users, a greater share of hormone-therapy users reached weight-loss thresholds of 10%, 20%, 25% and 30%. For tirzepatide, hormone therapy was associated with a higher share reaching at least 5% weight loss—88% versus 84%—but not with significant differences at higher thresholds. The results were reported by Regina Castaneda, MD, a Mayo Clinic postdoctoral research fellow, in a presentation at the meeting.
Different Patterns With Two Drugs
The findings may be relevant to clinicians and patients weighing how obesity medicines perform among women in midlife, a group whose reproductive stage and hormone status may affect treatment response. The reported pattern differed by medication: the association with hormone therapy persisted at several later measurements for semaglutide, while the measured difference with tirzepatide did not persist beyond three months.
Castaneda told MedPage Today that one possible explanation is a ceiling effect: tirzepatide may produce greater weight loss on its own, leaving less room for an additional measurable difference associated with hormone therapy. She also said the drugs’ different mechanisms could matter. These are possible explanations, not findings established by the study.
The result does not support prescribing hormone therapy to promote weight loss. Castaneda stressed that weight management is not an indication for menopausal hormone therapy, which should be prescribed for established indications. Any treatment decision should be made with a qualified health professional based on an individual’s circumstances.
Products Worth Considering
Withings Body Smart Wi-Fi and Bluetooth Body Composition Scale
TheraGun Relief Massage Gun – 3 Speed, Black
Garmin Forerunner 570 GPS Running Smartwatch, 47mm, Aluminum, Black
As an affiliate, we earn on qualifying purchases.
How the Study Was Built
Earlier, smaller retrospective studies had also suggested that women using menopausal hormone therapy alongside GLP-1 medicines might lose more weight. The new analysis adds a larger real-world cohort and reports results separately for semaglutide and tirzepatide, rather than treating GLP-1-based drugs as a single group.
The researchers reported that baseline characteristics and adiposity-related conditions were balanced between the comparison groups. They also used propensity-score matching to account for measured differences. However, as an observational analysis of health records, it could not control for every difference between hormone-therapy users and nonusers, nor show that hormone therapy itself produced the weight-loss pattern.
“These findings could inform more personalized and effective treatment strategies for GLP-1s in postmenopausal women.”
— JoAnn E. Manson, MD, MPH, DrPH, of Harvard Medical School, speaking to MedPage Today
Causation and Patient Differences
The study cannot establish whether menopausal hormone therapy caused the observed differences. Women who use hormone therapy may differ from nonusers in health behaviors, healthcare access or engagement, socioeconomic circumstances, and medication adherence. Castaneda said residual confounding may remain even after propensity-score matching.
The analysis also does not establish whether results vary by hormone-therapy formulation, delivery route, timing relative to menopause, or individual biological factors. The source report does not provide enough detail to determine how those factors affected outcomes. Nor does the reported weight measure show what happened to body composition, visceral fat, lean mass, bone health, or broader cardiometabolic outcomes.
Because the research was observational and included people who had remained on medication for at least 12 months, it also cannot by itself explain how the results might apply to people who stop treatment earlier or to groups outside the study’s eligibility criteria. The findings should be treated as an association requiring further study, not a treatment recommendation.
Prospective Trials Needed
Castaneda said prospective studies are needed to confirm the association and help shape treatment strategies. Future research could examine hormone-therapy formulation and route, timing in relation to menopause, and biological differences, while tracking outcomes beyond BMI or total weight loss.
Manson likewise said larger prospective trials are needed before the results can guide care. No specific trial or publication timeline was provided in the report. Until stronger evidence is available, the study adds a research signal for follow-up rather than a basis for changing prescribing practice.
Key Questions
Did hormone therapy cause greater weight loss with semaglutide?
That has not been established. The retrospective study found an association between concurrent hormone therapy and greater average weight loss at several time points, but it cannot prove that hormone therapy caused the difference.
Did the same pattern appear with tirzepatide?
Not at later measurements. Hormone-therapy users had a small, statistically significant difference in average weight loss at three months, but no significant differences were reported at later time points.
Does this mean hormone therapy should be prescribed for weight loss?
No. The study’s presenter said weight management is not an indication for menopausal hormone therapy and that it should be prescribed only for established indications. Patients should discuss medical decisions with a qualified health professional.
What research is needed next?
Researchers called for prospective studies to test whether the association holds and to examine differences by hormone-therapy type, route and timing. They also identified outcomes such as body composition, lean mass, bone health and cardiometabolic measures for further investigation.
Source: medpagetoday.com
