💉 Where the Science Is Going on Menopausal Hormone Therapy Plus GLP‑1 Drugs

When I started the Hit Play Not Pause podcast six years ago, there was still a lot of hesitancy around hormone therapy and very little talk of GLP-1-based medications. Now? When I scroll through our private Hit Play Not Pause Facebook group, every other post is a community member asking advice regarding hormones, and curiosity around and use of GLP-1s is rising like a river in a storm.

It’s understandable. Hands down the number one concern women in our community have is body composition changes—specifically weight gain—despite still training and fueling the same way. That’s because the hormonal shifts of the menopause transition impact metabolism, insulin sensitivity, lean mass, and fat distribution. By some estimates, women may experience an annual weight gain of up to 2 kg (~4 ½ lbs), with the menopause transition marked by accelerated fat gain and lean mass loss, and a shift toward more abdominal/visceral fat. In premenopausal women, visceral fat usually makes up only a small portion of total body fat—on the order of 5–10% in some studies. After menopause, that share can roughly triple to around 15–20% of total fat.

It can feel maddening. And as millions of women can attest, though lifestyle, diet, and exercise are helpful here, sometimes it feels like nothing makes a meaningful difference, which is where hormone therapy and GLP-1s are entering the picture. Before I go any further, this is an objective look at all this. I’m not making recommendations or endorsements. I just know and see many women who struggle and are looking to understand the landscape of therapies available to them. 

One strategy that is quickly emerging to the point of becoming mainstream is the use of menopausal hormone therapy (MHT) and GLP‑1–based obesity medications together in women navigating perimenopause and postmenopause. Early data suggest these therapies may be more potent in combination than either alone, but the science is still in its early phases and deserves a clear, evidence‑based look.

Why Combine Hormones and GLP‑1s?

As outlined above, menopause is a metabolic inflection point. MHT is associated with lower visceral and central fat and prevention of age‑related VAT gain, particularly in current users in the early postmenopausal window. Systemic estrogen‑based therapy also improves insulin resistance/insulin sensitivity in otherwise healthy postmenopausal women. 

As we know, GLP‑1 receptor agonists and dual GLP‑1/GIP agonists (such as semaglutide and tirzepatide) drive substantial weight loss and reduce visceral fat. They also may work synergistically. Several early clinical studies now suggest that concurrent MHT enhances the weight‑loss and metabolic response to GLP‑1–based medications in postmenopausal women.

A 2024 retrospective cohort study in Menopause found that women on semaglutide (e.g., Ozempic) plus hormone therapy lost more weight and were more likely to reach clinically meaningful thresholds for weight loss than those not using the combined therapy.

More recently, a 2026 retrospective study evaluated postmenopausal women treated with tirzepatide, again comparing those using MHT with those not on hormones. They found that women on tirzepatide with hormone therapy experienced greater weight loss and also had some additional cardiovascular health benefits such as reductions in diastolic blood pressure and triglycerides. 

Research is ongoing, and more GLP-1-based drugs are coming down the pipeline, but it’s become pretty common to hear providers talking about MHT and GLP-1s, particularly tirzepatide (e.g., Zepbound) in the same breath. 

Scientific Questions Still in Play

Given how new all this is, unsurprisingly, there are plenty of questions that remain unanswered, not the least of which is the mechanisms at work. Scientists are still digging into exactly how GLP-1s themselves work, let alone the mechanisms of synergy with hormone therapy. Trials have also not yet established whether starting MHT first, GLP‑1 first, or initiating both together yields the best balance of efficacy, side effects, and cost, nor whether MHT allows lower effective GLP‑1 doses with fewer GI side effects.

We also need more information about the impacts on long-term bone and muscle health. MHT can protect against bone loss and, to a much lesser extent, may have modest or short‑term benefits for lean mass; GLP‑1–associated weight loss can include bone and muscle loss if not paired with resistance training and adequate protein. We don’t yet know how concurrent therapy modifies fracture risk or lean mass/bone loss trajectories. 

For active women in this audience, there are also many questions about how GLP-1s can influence or interfere with proper fueling, since they slow gastric emptying and blunt appetite. Side effects like nausea or other GI issues can impair performance. And some women find they experience lack of motivation because of anhedonia from changes the drugs can have in the dopamine or reward center of the brain. 

There’s also the issue with long-term adherence: Real‑world studies suggest that roughly half to two‑thirds of people discontinue GLP‑1 medications within one year, with some research showing nearly three quarters stopping by two years. The most common reason given is side effects, but cost and other issues like folks missing the enjoyment of eating also come into play.

Where does this leave us? 🤷🏻‍♀️I wish I had a crystal ball. My suspicion is that there will be new drugs with fewer side effects and experts will figure out how to cycle or titrate them in ways that have fewer negative impacts. In the meantime, I think it’s always good to go into any treatment clear-eyed and armed with all the knowledge you need to make an informed decision. While a lot of this can be challenging, I’ll do my best to make that part a little bit easier.