Semaglutide and menopause: what the research says about GLP-1s in midlife

Many women notice their body changing in their 40s and 50s, even when their habits have not. The waistband gets tighter. The weight that used to come off with a few weeks of effort stays put. If you are wondering whether semaglutide or tirzepatide works differently at this stage of life, you are asking a question researchers have only recently started to study.

Here is what has been measured so far. Most of it is encouraging, some of it is early, and a few parts need careful reading.

What changes around menopause

Researchers at Mayo Clinic note that up to 70% of women gain weight during the menopause transition ^[1]. Body composition shifts too: fat mass tends to go up, lean mass tends to go down, and more fat is stored around the abdomen ^[1]. A team analyzing the tirzepatide trials made the same point: more body fat and a less healthy fat distribution are common in midlife and with the onset of menopause ^[2].

That matters for two reasons. Belly fat is linked to heart and metabolic risk. And losing lean mass while gaining fat is the opposite of what you want for strength and bones as you age.

Do GLP-1s work as well during and after menopause?

The best data so far come from tirzepatide. A 2025 analysis looked back at women in three large trials (SURMOUNT-1, -3 and -4) and sorted them by reproductive stage: premenopause, perimenopause or postmenopause ^[2]. None of them had type 2 diabetes ^[2].

In every stage, 97% to 98% of women on tirzepatide lost at least 5% of their weight, compared with 29% to 33% on placebo ^[2]. The results in SURMOUNT-3 and -4 were similar ^[2]. The authors concluded that tirzepatide was linked to meaningful weight and waist reductions regardless of reproductive stage ^[2].

Two cautions. This was a post hoc analysis, meaning the question was asked after the trials were done, and several of its authors work for the drug's maker ^[2]. It is useful, but it is not the same as a trial designed to answer this question.

For semaglutide, the menopause-specific evidence is mostly observational. A 2026 position statement from the Spanish Menopause Society says semaglutide currently has the most direct menopause-specific evidence of the incretin medicines, but that this evidence is still limited and largely observational ^[3]. It calls tirzepatide promising but says it needs menopause-specific study ^[3].

Does hormone therapy change how semaglutide works?

This is the question many women ask, and the answer is: maybe, but we do not know yet.

A Mayo Clinic team reviewed the records of postmenopausal women who took semaglutide for overweight or obesity for at least 3 months, between 2021 and 2023 ^[1]. Hormone therapy in this study meant oral or transdermal estradiol, with or without a progestogen, started before semaglutide ^[1]. Only 16 women were on hormone therapy, compared with 90 who were not ^[1].

Women on hormone therapy lost more weight at every checkpoint. At 12 months, they had lost 16% of their body weight on average, compared with 12% for women not on hormone therapy ^[1]. The difference held after the researchers adjusted for other factors ^[1]. Both groups saw improvements in heart and metabolic markers ^[1].

Here is why that result is a starting point, not an answer:

• It looked back at records. The authors say a study like this cannot establish cause and effect ^[1].
• It was small. With 16 women on hormone therapy, the authors note that the small size may have affected some results ^[1].
• It was not very diverse. The group was largely White and college-educated, which may limit how far the results apply ^[1].
• The authors call for larger studies to confirm the finding ^[1].

The Spanish Menopause Society describes the link as hypothesis-generating, and says it should not justify starting hormone therapy solely to boost weight loss ^[3]. Hormone therapy is a decision about your menopause symptoms, bones and overall risks. Our articles on HRT safety and HRT and weight cover that side.

Bones and muscle: the part to plan for

Menopause already puts bones and muscle under pressure. Losing a lot of weight adds to that. This is the area where the evidence calls for the most care, and where your clinician should look beyond the scale.

Bones. In a large heart outcomes trial of semaglutide, more women on the drug than on placebo had hip and pelvis fractures: 1% compared with 0.2% ^[5]. The same trial found more of these fractures in people aged 75 and older on semaglutide ^[5]. That does not mean semaglutide is wrong for you, but it is a reason for your clinician to consider your bone health and fracture risk. The Spanish Menopause Society lists fracture risk among the things to include when using these medicines in menopause ^[3].

Muscle. Both drug labels say the weight lost is more fat than lean mass ^{[5, 6]}. Still, some lean mass is lost. A 2026 review of semaglutide in postmenopausal women notes that a drop in lean mass does not necessarily mean a meaningful loss of muscle or function, and that the real-world effects are not fully understood ^[4]. It suggests that resistance exercise and enough protein and micronutrients may help protect muscle, while noting that the evidence in postmenopausal women on semaglutide is still indirect ^[4].

For the numbers on muscle and lean mass, read semaglutide and tirzepatide muscle loss.

Other practical points for midlife women

• Birth control pills in perimenopause. Tirzepatide may make oral contraceptives less effective. Its label advises a non-oral method, or adding a barrier method, for 4 weeks after starting and after each dose increase ^[6].
• Pregnancy is still possible in perimenopause. Both labels say to stop the medicine when pregnancy is recognized, and the semaglutide label says to stop at least 2 months before a planned pregnancy ^{[5, 6]}.
• Thyroid medicine. Many midlife women take levothyroxine. In a study with the semaglutide tablet, exposure to levothyroxine rose by 33% ^[5]. The label advises monitoring oral medicines like this ^[5].
• Side effects are mostly digestive. See semaglutide side effects and tirzepatide side effects.

The takeaway

The research so far suggests GLP-1 medicines can work for women in midlife, including after menopause ^[2]. What is less settled is how hormone therapy and these medicines interact ^{[1, 3]}, and how best to protect bone and muscle along the way ^{[3, 4]}. The Spanish Menopause Society recommends looking at these medicines through a wider lens that includes belly fat, muscle health, fracture risk, heart health, individual hormone therapy decisions, resistance exercise, protein and regular monitoring ^[3].

WarriorBabe Health clinicians focus on women in perimenopause and menopause. We offer semaglutide injections, a semaglutide tablet and tirzepatide injections. Ours are compounded by a licensed pharmacy and are not FDA-approved; the FDA does not review compounded drugs for safety, effectiveness or quality before they are sold ^[7]. The studies in this article used the FDA-approved products.

This article is for general information. It is not medical advice and does not replace a visit with a licensed clinician who knows your history. Do not start, stop or change a medication without talking to your clinician. If you think you are having a medical emergency, call 911.