Weight-Loss Injections During Menopause: What Role HRT May Play

This is the eighth part of our monthly blog series on the latest findings in metabolic medicine.

Many women who start GLP-1 therapy are also in perimenopause or postmenopause. And many ask themselves: Does this combination make sense? Does hormone replacement therapy affect how the medication works? Or the other way around?

The answer emerging from current studies is more interesting than expected. It is not only about tolerability. Early data suggest that the combination of hormone replacement therapy and GLP-1 or dual incretin therapy may be associated with greater weight loss.

However, it is important to be clear: the data so far are not final. They show interesting associations, but they do not yet prove cause and effect.

In this article, I look at what the data show, what the biology behind it may be, and what this may mean specifically for women during menopause.

If you would like to learn more about weight loss with injections, Wegovy or Mounjaro, one thing always applies: whether treatment is medically appropriate should be assessed individually by a physician.

Medical note: This article does not replace individual medical advice. The decision for or against hormone replacement therapy should always be made with a gynecologist. GLP-1 therapy should also only be used after a medical eligibility assessment and under medical supervision.

Why menopause and weight are connected

With the onset of menopause, many women experience a noticeable change in body composition. This is not simply due to age, but also to the decline in estrogen.

When estrogen levels fall, fat tissue may shift more toward the abdominal area. At the same time, muscle mass often decreases. This can also reduce resting energy expenditure. Many women do not eat more than before, yet they gain weight more easily or lose weight more slowly.

Sleep disturbances, hot flashes, mood changes, stress and lower energy levels may also occur. These factors can indirectly affect eating behavior, movement and body weight.

Against this background, the question of HRT and GLP-1 becomes especially relevant. GLP-1 affects appetite, satiety and blood sugar regulation, among other things. If hormonal signals change during menopause, this may also be relevant for the effect of weight-loss injections.

You can find a general overview of this topic in our article on losing weight during menopause.

What is HRT?

HRT stands for hormone replacement therapy. The term MHT, or menopause hormone therapy, is also often used. It means that hormones the body no longer produces in sufficient amounts during menopause are supplied externally.

During menopause, this mainly involves estrogen and, in women with a uterus, an additional progestogen or progesterone. Estrogen is the main hormone that may relieve typical menopausal symptoms such as hot flashes, sleep disturbances and mood changes. Progesterone is given when the uterus is present in order to protect the uterine lining.

HRT is available in different forms: as a patch, spray or gel absorbed through the skin, or as a tablet. There are also local applications such as vaginal creams, vaginal tablets or suppositories, which mainly act locally.

HRT is not suitable for every woman. Certain hormone-sensitive conditions in the medical history, such as breast cancer, are clear contraindications. Age, time since menopause, uterine status, bleeding pattern, thrombosis risk and individual medical history also play a role.

The decision for or against HRT therefore always belongs in a careful discussion with a gynecologist.

What the studies show

The interesting question is: Is the combination of HRT and GLP-1 merely tolerable, or can it actually influence weight loss during menopause?

The current data suggest that postmenopausal women on GLP-1 or dual incretin therapy may lose more weight if they also use HRT. At the same time, we have to stay very precise: the most important data so far come from retrospective or observational analyses. They show associations, but do not prove causality.

Hurtado et al. 2024: 30% greater weight loss with HRT

In a retrospective Mayo Clinic analysis, postmenopausal women with overweight or obesity treated with semaglutide were studied. Women with and without hormone replacement therapy were compared.

After twelve months, a clear difference was observed: women using HRT lost more body weight in the analysis than women not using HRT. In the original text, the values are 16% weight loss in the HRT group and 12% without HRT. This corresponds to about 30% greater weight loss in the HRT group.

The limitation is important: this was not a randomized trial. The groups may have differed in other characteristics that could partly explain the effect. Still, the result is relevant because it suggests a possible association between HRT and a stronger treatment response to semaglutide.

Castaneda et al. 2026: 35% greater weight loss with HRT

A follow-up study examined the same relationship for tirzepatide. Here, too, postmenopausal women with overweight or obesity were studied, with and without menopause hormone therapy.

The results pointed in a similar direction: women using HRT achieved greater weight loss in the analysis than women not using HRT. In the original text, the values are 19.2% weight loss with HRT and 14% without HRT. This corresponds to a difference of around 35%.

Here as well, the data are observational. They do not prove that HRT caused the greater weight loss. But they confirm that the connection is also a relevant research topic for tirzepatide.

You can learn more about tirzepatide on our page about Mounjaro.

Model et al. 2024: the biological explanation

Why might HRT and GLP-1 influence each other? Preclinical data from Model et al. provide a possible explanation.

Estrogen and GLP-1 use partially overlapping signaling pathways in tissues that are important for appetite, satiety and metabolism. These include the liver, the central nervous system and white adipose tissue.

The hypothalamus is particularly interesting. It plays a central role in appetite regulation and energy balance. Estrogen may support the appetite-suppressing effect of GLP-1 there. When estrogen is low, this enhancing effect may be reduced. HRT could at least partially restore it.

Here, too, the same limitation applies: preclinical data are not direct proof of the same effect in humans. But they provide a biologically plausible explanation for what the retrospective studies show.

Why HRT as a patch, spray or gel may be preferred

One practical question is especially important in this combination: which form of HRT makes sense?

The British Menopause Society points out that incretin-based therapies such as semaglutide and tirzepatide can delay gastric emptying. As a result, the absorption of oral medications may theoretically be affected.

Transdermal forms avoid this route. HRT as a patch, spray or gel is absorbed through the skin and is therefore not dependent on how quickly the stomach empties.

Another advantage: transdermal estrogen is often considered more favorable than oral estrogen with regard to thrombosis risk. This is particularly relevant when overweight or obesity are present as additional risk factors.

This does not mean that every oral HRT is automatically unsuitable. It means that if a woman is using GLP-1 or tirzepatide therapy and is also taking HRT, the form of HRT should be discussed specifically with her gynecologist.

What is currently supported and what remains open

The data are promising, but not final. That is why a clear distinction is important.

Supported or observed: In retrospective analyses, HRT use in postmenopausal women treated with semaglutide or tirzepatide was associated with greater weight loss than treatment without HRT.

Biologically plausible: Estrogen and GLP-1 may use overlapping signaling pathways, especially in tissues relevant to appetite, satiety and metabolism.

Still open: Whether HRT itself is the cause of the greater weight loss has not been conclusively proven. Prospective, randomized studies are still missing.

Practical recommendation: With simultaneous GLP-1 or tirzepatide therapy, transdermal HRT, meaning patch, gel or spray, may be more appropriate than oral HRT. This decision should be made individually with a gynecologist.

What this means for you in practice

If you are in perimenopause or postmenopause and are starting GLP-1 therapy or are already being treated, a few points are practically relevant.

• If you are taking HRT or considering it, actively bring this up during your consultation.
• If you are using GLP-1 or tirzepatide therapy at the same time, the form of HRT should be reviewed by your gynecologist.
• Patches, sprays or gels may have advantages over oral forms because they bypass the gastrointestinal tract.
• If you are losing less weight than expected despite GLP-1 therapy and are not using HRT, the hormonal context may be a topic to discuss with your gynecologist.
• The data are not yet confirmed by randomized studies. HRT should therefore not be started for weight-loss reasons alone.

One thing remains important: HRT is not suitable for every woman. There are clear contraindications, for example certain hormone-sensitive tumor diseases in the medical history. The decision for or against HRT should always be made individually and in consultation with your gynecologist.

Weight-loss injections should also not be viewed in isolation. Especially during menopause, body composition, muscle mass, sleep, nutrition, movement, stress and long-term stabilization all play an important role.

Conclusion: HRT and GLP-1 are an important topic for women during menopause

The combination of HRT and GLP-1 therapy is medically interesting, but not yet fully clarified. Early studies show that women using menopause hormone therapy may lose more weight under semaglutide or tirzepatide than women not using HRT. At the same time, it remains open whether HRT itself is the cause.

Biologically, the connection is plausible: estrogen, GLP-1, appetite regulation, fat distribution and metabolism interact at several points. This connection may be particularly relevant during menopause.

For patients, this means: if you are in perimenopause or postmenopause, use HRT or are considering HRT, and also want to use a weight-loss injection, this should be actively discussed during your consultation.

The key message remains: neither HRT nor GLP-1 should be considered in isolation. What matters is an individual medical assessment with gynecological expertise, physician-led weight-loss support and a long-term plan for weight, health and quality of life.

Studies and sources

• Hurtado MD et al. 2024: Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use. Menopause. DOI: 10.1097/GME.0000000000002310.
• Castaneda R et al. 2026: The role of menopause hormone therapy in modulating tirzepatide-associated weight loss in postmenopausal women with overweight or obesity. The Lancet Obstetrics, Gynaecology & Women’s Health. DOI: 10.1016/S3050-5038(25)00145-1.
• Model JFA et al. 2024: Interactions between glucagon like peptide 1 (GLP-1) and estrogen replacement therapy in metabolic tissues. Biochemical Pharmacology. DOI: 10.1016/j.bcp.2024.116623.
• British Menopause Society: Use of incretin-based therapies in women using hormone replacement therapy. Tool for Clinicians, April 2025.
• ClinicalTrials.gov: NCT06715514. Menopausal Hormone Therapy, GLP-1 Agonists, and Glucose and Energy Homeostasis in Postmenopausal Women with Diabetes.