GLP-1s and Menopause: What the Research Actually Shows

If you have hit your mid-forties and watched the same eating habits produce a different body, you are not imagining it. The menopause transition changes fat distribution, muscle mass and daily energy burn in ways that are well documented. What is newer is the question a lot of women are now bringing to their doctors: do Ozempic, Wegovy, Mounjaro and Zepbound work during menopause, and does hormone therapy change the answer?

This article walks through what the published evidence shows, where it is strong, and where it is thin enough that you should treat headlines with suspicion.

This is general health information, not medical advice. Where it describes how these drugs are used, it is summarizing the FDA-approved prescribing information and Instructions for Use, not giving instructions; follow your own prescription and your own provider. Whether any of these medicines are right for you is a conversation with a healthcare provider who knows your history.

What actually happens to your weight during menopause?

The clinical literature describes a bundle of changes that arrive together [1][2].

Weight goes up in a large share of women during the transition, with published estimates putting the average gain at roughly 2.1 kg, or about 4.6 pounds [1]. That number sounds small, and on its own it is. The bigger change is in composition and distribution.

Across the menopause transition, total 24-hour energy expenditure falls by about 9 percent, and the energy spent on spontaneous physical activity, the fidgeting and moving you do without thinking about it, falls by about 30 percent [1]. Fat mass rises, lean mass falls, and fat shifts toward the abdomen [1][3].

A 2026 clinical review in Obesity Pillars, the Obesity Medicine Association’s journal, states that these body composition changes are driven primarily by estrogen deficiency and occur independent of chronological age [3]. That is the key point: this is not simply “getting older.” Something specific is happening.

The consequence is cardiometabolic. Type 2 diabetes, dyslipidemia, MASLD (fatty liver disease) and cardiovascular disease all become more common after menopause [1]. That is the medical reason GLP-1 drugs entered this conversation at all, rather than the cosmetic one.

Do GLP-1 drugs still work after menopause?

Yes, and the evidence on this is reasonably good.

Eli Lilly researchers went back through the SURMOUNT-1, SURMOUNT-3 and SURMOUNT-4 trials and retrospectively sorted the female participants into premenopause, perimenopause and postmenopause groups [4]. In SURMOUNT-1, tirzepatide produced significantly greater weight reduction than placebo in all three groups: 26 percent versus 2 percent in premenopausal women, 23 percent versus 3 percent in perimenopausal women, and 23 percent versus 3 percent in postmenopausal women. Waist circumference fell substantially in every group too, by 20 to 22 cm on tirzepatide versus 4 to 5 cm on placebo [4].

Novo Nordisk ran a parallel exercise on its own trials. A post hoc analysis of the STEP program and OASIS 4, presented at ObesityWeek 2025, classified participants by menopausal status and reported that semaglutide reduced body weight regardless of menopausal status [5]. That analysis covered both subcutaneous semaglutide 2.4 mg and oral semaglutide 25 mg.

Both of these are post hoc analyses, meaning the menopause question was asked after the trials were finished, and menopausal status was assigned from age and self-report rather than from hormone testing [4][5]. That is a real limitation. But the direction is consistent and the effect sizes are large enough that it would be strange for menopausal status to erase them.

Is there a difference in how much weight women lose by age?

Here it gets more interesting.

An analysis presented at the 2026 American Diabetes Association Scientific Sessions looked at STEP 1 (1,482 participants) and SELECT (17,604 participants) to work out why women lose roughly 40 percent more weight than men on semaglutide [6]. Drug exposure alone did not explain it.

The researchers reported that in SELECT, men showed consistent weight loss across ages 45 to 90, while weight loss in women decreased with age [6]. Circulating FSH and LH, the pituitary hormones that rise as ovarian function declines, distinguished menopausal status and predicted the size of the weight loss, most strongly during perimenopause [6].

Read carefully, that is not “the drug stops working after menopause.” Postmenopausal women in SURMOUNT-1 still lost 23 percent of their body weight [4]. It is closer to “the size of the advantage women have over men appears to narrow with age, and hormonal status seems to be part of the mechanism.”

This was a conference abstract, not a peer-reviewed paper [6]. Treat it as a lead, not a conclusion.

Does hormone therapy make GLP-1 drugs work better?

This is the claim generating the most headlines, and it deserves careful handling.

The first study came out of Mayo Clinic in 2024 and was published in Menopause, the journal of The Menopause Society [7]. Researchers looked back at postmenopausal women treated with semaglutide for overweight or obesity for at least three months, and compared those who were also on menopause hormone therapy with those who were not.

The women on hormone therapy lost more weight at every time point [7]:

• 3 months: 7 percent versus 5 percent of total body weight
• 6 months: 13 percent versus 9 percent
• 9 months: 15 percent versus 10 percent
• 12 months: 16 percent versus 12 percent

The association held after adjusting for confounders, and more women on hormone therapy hit both the 5 percent and the 10 percent weight loss thresholds at 12 months [7].

Now the catch. There were 16 women on hormone therapy and 90 not on it [7]. Sixteen. That is a pilot-sized group, and the women on hormone therapy differed from those not on it in ways beyond the drug: dyslipidemia and depression were more common in the no-hormone-therapy group [7].

In early 2026, a Mayo-led team published the tirzepatide version: Castaneda and colleagues, in The Lancet Obstetrics, Gynaecology and Women’s Health, 2026;2(2):e118-e128 [8]. They reviewed 120 postmenopausal women with overweight or obesity treated with tirzepatide, using 1:2 propensity score matching on age, BMI, age at menopause, menopause type and diabetes status. Mayo Clinic’s summary of the paper reports that women on menopause hormone therapy lost about 35 percent more weight over 12 months than women who were not [9].

That is a better-designed study than the 2024 one, and it is the first to test this with tirzepatide. It is still retrospective, still modest in size, and still from a single health system [8].

So should you start hormone therapy to lose more weight?

No, and the professional bodies are unusually direct about this.

The Spanish Menopause Society published a 20-point expert position statement in Maturitas in August 2026 that states the association between hormone therapy and greater semaglutide-related weight loss “remains hypothesis-generating and should not justify initiating hormone therapy solely to augment weight loss” [2].

The Obesity Pillars clinical review says the same thing from the other direction: hormone therapy may blunt central fat accumulation and preserve favorable body composition, but it is not indicated as a primary weight management intervention, and it should be prescribed for established clinical reasons: moderate to severe vasomotor symptoms, osteoporosis prevention, treatment of hypoestrogenism and treatment of genitourinary symptoms [3].

The honest summary is that hormone therapy is a decision with its own risks and benefits that has nothing to do with weight. If you would benefit from it anyway, the weight data are an interesting bonus. If you would not, this evidence is nowhere near strong enough to change that.

A randomized trial is underway that should improve on this. DECLARED-CT (NCT06715514), run out of University Hospital Bern, is testing combined menopause hormone therapy plus GLP-1 therapy against GLP-1 therapy alone in early postmenopausal women with or at risk of type 2 diabetes, with primary completion scheduled for December 2026 [10]. Its primary objective is glucose control, with body weight among the secondary objectives [10].

What about hot flashes and night sweats?

A 2026 scoping review in Cureus searched PubMed and Embase for studies on GLP-1 drugs in menopausal and postmenopausal women [11]. It found the drugs were associated with weight loss and reduced central adiposity in this group. On vasomotor symptoms, the review found “limited studies” reporting improvement, and concluded that further research is needed [11].

No GLP-1 drug is approved anywhere for hot flashes, night sweats or any other menopausal symptom [2][11]. If vasomotor symptoms are your main problem, that is a different conversation with a different set of treatments.

Is muscle loss a bigger deal after menopause?

This is the concern menopause specialists keep raising, and it is a reasonable one.

Menopause already reduces lean mass [1][3]. GLP-1 drugs cause weight loss, and some of any weight loss is lean tissue. Stacking those two is at least worth thinking about.

The best current evidence comes from a systematic review and meta-analysis published in Drugs in September 2026, conducted with a WHO Collaborating Centre and the World Health Organization’s Ageing and Life Course team [12]. It pulled in 60 articles covering 1,250,717 individuals: 46 randomized trials, 13 real-world studies and one pharmacovigilance study.

Its findings split three ways [12]:

• Bone: no effect on bone mineral density at any site, and no effect on fractures at any site, when the most adjusted effect estimates were used.
• Joints: no significant change in WOMAC pain, physical function or stiffness.
• Muscle: a consistent decrease in lean body mass and fat-free mass, standardized mean difference -0.52 (95 percent confidence interval -0.8 to -0.23), driven mainly by liraglutide and semaglutide against placebo, and robust across all sensitivity analyses.

The authors rated the certainty of the lean mass finding as low, noted that the changes appeared largely related to the weight loss itself rather than to the drug specifically, and said plainly that “whether these changes translate into clinically meaningful impairments in muscle function or physical performance remains uncertain” [12]. Almost none of the studies measured strength or physical performance at all.

The Spanish Menopause Society’s practical response is to frame incretin therapy in menopause within a functional framework that includes skeletal muscle health, fracture risk, resistance exercise, adequate protein intake and structured monitoring of functional as well as metabolic outcomes [2]. That is guidance for clinicians, not a self-directed program, but it tells you what a good conversation with your provider should cover.

Does the pill still work if you are perimenopausal and on one of these drugs?

Perimenopause is not infertility, and this question matters.

The answer depends entirely on which drug. Mounjaro and Zepbound, both tirzepatide, carry an explicit instruction: advise patients using oral hormonal contraceptives to switch to a non-oral contraceptive method, or add a barrier method of contraception, for 4 weeks after starting the drug and for 4 weeks after each dose escalation [13].

The reason is in section 12.3 of the label itself. In a drug interaction study, a combined oral contraceptive (0.035 mg ethinyl estradiol and 0.25 mg norgestimate) given with a single 5 mg dose of tirzepatide had its mean peak concentrations reduced by 59 percent for ethinyl estradiol, 66 percent for norgestimate and 55 percent for the active metabolite norelgestromin, with total exposure down 20, 21 and 23 percent respectively and time to peak delayed by 2.5 to 4.5 hours [13]. The label also notes that the gastric-emptying effect is greatest after the first 5 mg dose and diminishes with subsequent doses, which is why the instruction attaches to initiation and to each escalation [13].

Semaglutide products carry no equivalent instruction. The Ozempic label says semaglutide did not affect the absorption of orally administered medicines to any clinically relevant degree in clinical pharmacology trials, while still advising caution [14]. The Wegovy label asks for increased monitoring for oral drugs with a narrow therapeutic index, but does not tell anyone to change contraceptive method [15].

One more gap worth knowing about: a September 2026 review in Maturitas points out that the only pharmacokinetic data for tirzepatide involve one combined oral contraceptive formulation, and that no equivalent data exist for the oral progestogens used for endometrial protection during hormone therapy or for gynecologic conditions [16]. The authors call a clinically meaningful interaction biologically plausible but unproven. If you are on both, that is worth raising with your prescriber.

What should a good conversation with your doctor cover?

Based on what the guidance documents actually say, these are reasonable things to bring up:

• Whether your weight change is best explained by menopause, by something else, or by both [1][3].
• Whether you have a reason to consider hormone therapy on its own merits, separate from weight [2][3].
• What the plan is for protecting muscle: resistance training, protein intake and how function will be tracked, not just the number on the scale [2][12].
• Which drug, and what that means for contraception if you could still become pregnant [13][15].
• Bone density, if you have other osteoporosis risk factors. The meta-analysis found no bone mineral density signal, but menopause itself is the main driver of bone loss [12].

Sources

1. Hurtado MD, Tama E, Fansa S, et al. Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use. Menopause. 2024. https://doi.org/10.1097/gme.0000000000002310
2. Sánchez-Prieto M, Romero-Domínguez M, Orozco R, et al. Incretin-based therapies in peri- and postmenopausal women with obesity: an expert position statement from the Spanish Menopause Society. Maturitas. 2026 Aug 25. https://doi.org/10.1016/j.maturitas.2026.109101
3. Clinical review: Menopause hormone therapy in weight management. Obesity Pillars. 2026 Mar 14. https://doi.org/10.1016/j.obpill.2026.100258
4. Body weight reduction in women treated with tirzepatide by reproductive stage: a post hoc analysis from the SURMOUNT program. Obesity. 2025. https://pubmed.ncbi.nlm.nih.gov/40074721/
5. Semaglutide reduces body weight regardless of menopause status: STEP and OASIS 4 post hoc analysis. Novo Nordisk ScienceHub, ObesityWeek 2025. https://sciencehub.novonordisk.com/content/dam/sciencehub/global/en/congresses-and-scientific-publications/congresses/ow2025/andrade/sliders/STEP_OASIS_WH_CM_OW25_slides_final.pdf
6. 1711-P: Menopausal Hormonal Status and Estradiol Use Modulate Semaglutide-Associated Weight Loss in Women: Analyses from STEP1 and SELECT. Diabetes. 2026 Jun 5. https://doi.org/10.2337/db26-1711-p
7. Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use. Menopause journal full text. https://www.ovid.com/jnls/menopausejournal/pdf/10.1097/gme.0000000000002310~weight-loss-response-to-semaglutide-in-postmenopausal-women
8. Castaneda A, 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. https://doi.org/10.1016/S3050-5038(25)00145-1
9. Mayo Clinic. New study links combination of hormone therapy and tirzepatide to greater weight loss after menopause. 2026 Jan 22. https://newsnetwork.mayoclinic.org/discussion/new-study-links-combination-of-hormone-therapy-and-tirzepatide-to-greater-weight-loss-after-menopause/
10. DECLARED-CT: Menopausal Hormone Therapy, GLP-1 Agonists, and Glucose and Energy Homeostasis in Postmenopausal Women With Diabetes. NCT06715514. https://clinicaltrials.gov/study/NCT06715514
11. Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) for Obesity and Symptoms in Menopause: A Review. Cureus. 2026 Jan 16. https://doi.org/10.7759/cureus.101693
12. Beaudart C, Malréchauffé Y, van Heden S, et al. GLP-1 Receptor Agonists and Musculoskeletal Outcomes: A Systematic Literature Review and Meta-Analysis. Drugs. 2026 Sep 12. https://doi.org/10.1007/s40265-026-02365-3
13. ZEPBOUND (tirzepatide) US Prescribing Information. Eli Lilly. https://uspl.lilly.com/zepbound/zepbound.html
14. OZEMPIC (semaglutide) US Prescribing Information. Novo Nordisk. https://www.novo-pi.com/ozempic.pdf
15. WEGOVY (semaglutide) US Prescribing Information. Novo Nordisk. https://www.novo-pi.com/wegovy.pdf
16. Viana DPDC, Invitti AL, Jacobsen L, Schor E. Tirzepatide and oral progestogens: A hypothesis-generating review. Maturitas. 2026 Sep 10. https://doi.org/10.1016/j.maturitas.2026.109116