Women's Health

GLP-1s in perimenopause and menopause: what the evidence supports, and what it does not

By the US Health Digest editorial team · Published August 26, 2026 · Every claim linked to its primary source

Women aged 50 to 64 report the highest GLP-1 use of any age-and-sex group in the United States — one in five, or 20 percent, have ever taken one, in a nationally representative RAND American Life Panel survey of 8,793 adults — and yet the ClinicalTrials.gov records of five pivotal obesity trials report nothing about menopausal status. The one menopause-specific question with real data behind it is whether menopausal hormone therapy changes the weight response, and that data is retrospective, not randomised: among 106 postmenopausal women at Mayo Clinic, only 16 of them on hormone therapy, the hormone therapy group lost 16 ± 6% of body weight on semaglutide at 12 months versus 12 ± 8% without — what the authors themselves call "approximately 30% more weight loss," from a design they say "does not allow for the establishment of a causal relation." A randomised trial of the combination is running and has not reported.

The demand is documented. The evidence base is not.

The best current US population estimate comes from RAND: 8,793 respondents from a 16,029-person adult roster of the American Life Panel, a 54.9% completion rate, weighted to the English-speaking US adult population. 11.8% of adults reported ever using a GLP-1 agonist and another 14.0% said they were interested. Use was highest between 50 and 64, and within that band highest in women: 20%. Between 30 and 49, "women are more than twice as likely to have used a GLP-1 agonist than their male peers." (The article's methods section dates the fielding to May 19 through June 13, 2025, while its introduction and figure notes say April and May 2025. We cite the methods section.)

Then the point everyone skips: RAND measured age and sex, not menopausal status. Age 50 to 64 is a proxy for the transition, not a measurement of it. Even the statistic used to describe perimenopausal demand does not record who is perimenopausal.

What the pivotal trials can and cannot tell you

These trials ran overwhelmingly in women, which is what makes the missing variable conspicuous rather than excusable. STEP 1 enrolled 1,453 women out of 1,961 participants, mean age 46 — the population most likely to be crossing the transition. Its registry record contains no occurrence of the string "menopaus" anywhere — not in eligibility, not in the baseline characteristics table, not among the reported subgroups. We ran the same check across four more pivotal records on August 26, 2026. In only one, ATTAIN-1, does the string appear at all, and there it is an adverse-event term — "postmenopausal haemorrhage," a serious adverse event recorded in one participant — not a characteristic anyone stratified on.

This cuts both ways, and the direction people usually assume is the one the data does not support. Nothing in these five registry records indicates that GLP-1s work less well in perimenopause, and nothing in them indicates that they work better: the records carry no menopause variable that could answer the question in either direction. We have not read the journal publications or their supplementary appendices, and we do not claim those are equally silent — but anyone citing a menopause-specific weight-loss figure from these trials should be able to name the analysis that produced it. For what the trials do establish across midlife women generally, see GLP-1s for women over 40 and semaglutide results in women.

The hormone-therapy question, which is the live one

A figure circulates — that women on menopausal hormone therapy lose about 30% more weight on semaglutide. It has a real primary source, and the source is more interesting than the headline.

Hurtado et al., Menopause, April 2024 is a retrospective review of Mayo Clinic Health System electronic records — not a randomised trial. Of 1,023 patients prescribed semaglutide for weight between January 2021 and March 2023, 106 postmenopausal women met criteria: 16 on systemic hormone therapy, 90 who had never received it. Total body weight loss was higher in the hormone therapy group at every timepoint: 7 ± 3% versus 5 ± 4% at 3 months, 13 ± 6% versus 9 ± 5% at 6 months, 15 ± 6% versus 10 ± 6% at 9 months, and 16 ± 6% versus 12 ± 8% at 12 months (the primary endpoint, P = 0.04). The association held in two multivariable models — one adjusting for the baseline variables that actually differed between the groups (race, dyslipidemia, depression), the other for variables known to affect semaglutide response (age, baseline weight, type 2 diabetes, and nutritional and behavioural support) — and again in a subgroup restricted to women who reached a high semaglutide dose. Dose was handled by that subgroup analysis, not as a covariate.

Now the parts that do not travel. Sixteen women is the whole exposed group. The authors write that the retrospective design "does not allow for the establishment of a causal relation between HT use and weight loss response to semaglutide or for the minimization of confounding factors," and they name the mechanism that would produce this result without any drug interaction at all: healthy-user bias, since hormone therapy users "generally pursue healthier lifestyle, are more physically active, leaner, and less likely to smoke, and have better access to medical care." Baseline groups differed too — dyslipidemia in 68% of non-users versus 25% of users — and the cohort was 91% White. Read it as a hypothesis with a number attached, not as an effect.

The same Mayo group published a companion retrospective cohort on tirzepatide in The Lancet Obstetrics, Gynaecology, & Women's Health (2026;2(2):e118–e128). We could not reach its full text or abstract from any open source and it is not indexed in PubMed, so we report its existence and design label — retrospective cohort — and none of its numbers. A specific percentage attributed to it circulates in secondary coverage; we are not repeating that number, because we have not read the paper that produced it and have no way to check it.

What would settle this is a randomised trial, and one exists. NCT06715514 randomises 96 early postmenopausal women with prediabetes or type 2 diabetes to hormone therapy alone, a GLP-1 alone, or both. Note the fine print before waiting on it: the primary endpoint is change in HbA1c at 12 weeks, body weight is a secondary objective, the design is open-label, and the population has diabetes. Primary completion is estimated for December 17, 2026.

What menopause changes, and what ageing changes

This is where most coverage is loose. The cleanest separation comes from SWAN, which fitted piece-wise models to repeated DXA scans anchored to each woman's final menstrual period rather than to her age. Greendale et al., JCI Insight, 2019 found that at the start of the transition the rate of fat gain doubled and lean mass began to decline, with both continuing until two years after the final period, then flattening. Their conclusion is specific: "Accelerated gains in fat mass and losses of lean mass are MT-related phenomena."

And then the finding almost nobody repeats, from the same analysis: weight itself "climbed linearly during premenopause without acceleration at the MT," because the extra fat and the lost lean cancel on the scale. So the honest version is not "menopause makes you gain weight faster." It is that body composition shifts at the transition while the scale keeps doing what ageing was already making it do. That distinction changes what is worth measuring.

It also has consequences. In 539 SWAN participants taking no bone-active medication, each standard-deviation increment of lean mass lost across the transition was associated with 63% greater fracture hazard afterwards (P = 0.001), essentially unchanged after adjusting for bone mineral density.

Where the risks land differently

Two concerns that are ordinary at 30 are not ordinary during the transition, and both have their own pages here rather than a summary.

• Lean mass. Weight loss on a GLP-1 includes lean tissue, and it arrives in the same window in which the transition is already removing it. The trial-level evidence, including the STEP 1 DXA substudy, is set out in GLP-1s and muscle loss.
• Bone. Transmenopausal bone loss is well characterised independent of any medication, and the SWAN fracture data above ties it to the same body-composition change. How GLP-1 treatment interacts with that window is covered in GLP-1s for women over 40.

One adjacent signal worth knowing: in a separate Mayo retrospective analysis of 1,039 adults on tirzepatide for at least 12 months, female sex independently predicted greater weight loss while age did not (15.1% versus 10.7% at 15 months). That abstract stratifies by sex and by age band — not by menopausal status. Even the studies asking the closest question keep measuring the proxy.

On hormone therapy itself

We do not characterise hormone therapy's risks or benefits in our own voice. The current US reference is the 2022 hormone therapy position statement of The North American Menopause Society, which states that hormone therapy "remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause and has been shown to prevent bone loss and fracture," that "the risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used," and that treatment "should be individualized using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing therapy." The same statement ties the balance to timing: for women younger than 60 or within 10 years of menopause onset and without contraindications, "the benefit-risk ratio is favorable for treatment of bothersome VMS and prevention of bone loss," while for women initiating more than 10 years from onset or older than 60, "the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia." Weight management is not among the indications enumerated in that statement's published abstract, which is the version we were able to read in full. Nothing on this page is a reason to start, stop, or change hormone therapy or any other medication; that decision belongs to a clinician who knows your history.

Questions for your prescriber

This is evidence reporting, not medical advice.

• Where am I in the transition — perimenopausal, postmenopausal, or unclear — and was that considered at all in this plan?
• The pivotal trials did not report menopausal status. When you tell me what to expect, is that trial data, cohort data, or clinical judgment?
• I am on (or considering) hormone therapy. The evidence linking it to greater weight loss on a GLP-1 is retrospective and small. How much weight do you put on it, and why?
• Given that lean mass falls at the transition and again with weight loss, how will we measure body composition and physical function rather than scale weight alone?
• Given that the transition itself removes lean mass, should my bone density be assessed before we start rather than after?
• If my main complaint is vasomotor symptoms or sleep rather than weight, which problem are we actually treating first?
• Which symptoms during treatment should I report before the next appointment rather than save up for it?

Related reading: side effects in women, GLP-1s and PCOS, and the GLP-1 FAQ for women.

Absence claims and how we tested them

Four statements above claim something does not exist, each scoped to what we searched on August 26, 2026. One: five pivotal obesity trial registry records report no menopausal status — we pulled each full JSON record from the ClinicalTrials.gov v2 API and string-searched for "menopaus"; STEP 1, SURMOUNT-1, SURMOUNT-5 and OASIS 4 returned zero hits, ATTAIN-1 returned one, an adverse-event term. We do not claim the journal publications and supplements are equally silent; we did not read them, and the claim is scoped to the registry records. Two: no completed randomised trial has tested hormone therapy added to a GLP-1 with a weight endpoint — two ClinicalTrials.gov API queries (condition menopause/postmenopausal with intervention semaglutide/tirzepatide; and estrogen/estradiol/hormone therapy with GLP-1 terms in obesity/overweight) returned one relevant randomised study, NCT06715514, which is active, not yet reported, HbA1c-primary and in women with diabetes. Three: the tirzepatide-and-hormone-therapy paper's contents were not verifiable from here — the DOI resolves and Crossref confirms journal, volume, pages and authorship, but thelancet.com and sciencedirect.com both return 403 to this system and a PubMed search returned no record, so we quote no figure from it. Four: weight management is not an indication in the 2022 NAMS position statement — based on the indications enumerated in the statement's own published abstract, which we read in full; we did not have access to the 28-page full text.

Sources

1. Bozick R, Donofry SD, Rancaño KM. New Weight Loss Drugs: GLP-1 Agonist Use and Side Effects in the United States. Rand Health Quarterly. 2025;13(1):3. Open-access full text (PubMed Central); PubMed 41415116. RAND American Life Panel, n = 8,793.
2. Hurtado MD, Tama E, Fansa S, et al. Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use. Menopause. 2024;31(4):266-274. PubMed 38446869; open-access full text (PubMed Central).
3. Castaneda R, Bechenati D, Tama E, et al. The role of menopause hormone therapy in modulating tirzepatide-associated weight loss in postmenopausal women with overweight or obesity: a retrospective cohort study. The Lancet Obstetrics, Gynaecology, & Women's Health. 2026;2(2):e118-e128. doi:10.1016/S3050-5038(25)00145-1. Cited for existence and design only; full text not accessible to us.
4. Castaneda R, Bechenati D, Rivera Gutierrez RJ, et al. Sex, Not Age, Predicts Weight Loss Outcomes With Tirzepatide: A Retrospective Analysis. Obesity (Silver Spring). 2026. PubMed 42290037.
5. Greendale GA, Sternfeld B, Huang M, et al. Changes in body composition and weight during the menopause transition. JCI Insight. 2019;4(5):e124865. PubMed 30843880. Study of Women's Health Across the Nation (SWAN).
6. Shieh A, Karlamangla AS, Karvonen-Gutierrez CA, Greendale GA. Menopause-Related Changes in Body Composition Are Associated With Subsequent Bone Mineral Density and Fractures. Journal of Bone and Mineral Research. 2023;38(3):395-402. PubMed 36542065.
7. "The 2022 Hormone Therapy Position Statement of The North American Menopause Society" Advisory Panel. Menopause. 2022;29(7):767-794. PubMed 35797481.
8. ClinicalTrials.gov registry records and posted results, read August 26, 2026: NCT03548935 (STEP 1), NCT04184622 (SURMOUNT-1), NCT05822830 (SURMOUNT-5), NCT05564117 (OASIS 4), NCT05869903 (ATTAIN-1). National Library of Medicine.
9. ClinicalTrials.gov registry record, NCT06715514 — Effects of Combined Menopausal Hormone Therapy and GLP-1 Receptor Agonist Therapy on Glucose and Energy Homeostasis in Early Postmenopausal Women With or at Risk of Diabetes. Randomised, open-label, estimated enrolment 96; primary endpoint change in HbA1c at 12 weeks.
10. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). New England Journal of Medicine. 2021;384(11):989-1002. PubMed 33567185.