Could this medication combo solve menopausal weight gain?

Ever since they exploded in popularity a few years ago, GLP-1 medications have been on a winning streak, with more and more news coming out about just how good they can be for your overall health, not just your weight. Now, research suggests their effects could be enhanced with the addition of hormone replacement therapy (HRT) — also known as menopausal hormone therapy (MHT) — a long misunderstood treatment option for women experiencing hot flashes, sleep issues, and other menopause symptoms.

Recent studies have found that for postmenopausal women taking a GLP-1, the addition of hormone therapy can amplify weight loss, leading to a bigger reduction in weight than you'd get from taking a GLP-1 alone. Here’s what the science shows — and what to look forward to down the line.

Why menopausal weight gain happens

While weight gain is really common during the menopause transition — around 1.5 pounds a year — “menopause weight gain” is a bit of a misnomer, since “it’s mostly related to aging,” says Dr. Stephanie S. Faubion, M.D., director for Mayo Clinic's Center for Women's Health, medical director for The Menopause Society, and member of the WeightWatchers Scientific Advisory Board.

Menopause can, however, produce changes in the body that contribute to weight gain. (Take hot flashes and night sweats; they're associated with less exercise and worse sleep, which can add pounds.) And it can also have a significant impact on body composition.

As estrogen levels drop, “we preferentially put fat in our midsections,” says Faubion. This increase in visceral fat — the fat stored around internal organs — is linked to higher risks of heart disease, stroke, and other health problems.

“Declining estrogen [also] shifts how responsive our body is to insulin,” says Dr. Kim Boyd, M.D., chief medical officer at WeightWatchers. “That can mean needing more insulin for the same foods.”

That’s why, even if you’re eating similarly and doing the same workouts, you may notice changes to your body composition. And that has its own domino effect. “Even if your weight stays the same, if body fat rises from 20% to 30%, you’re carrying less muscle and your body’s metabolic balance can tip toward dysregulation,” says Boyd.

What’s more, the visceral fat around your organs releases signals that raise low-grade inflammation and make insulin less effective, setting up a vicious cycle: Less muscle and more visceral fat leads to more inflammation, worse insulin sensitivity, and easier fat gain around the middle.

What HRT can offer

Prescription hormone replacement therapy delivers estrogen, which can be taken as a pill, capsule, or through the skin via patch, gel, or spray. If you still have a uterus and are using systemic estrogen, progesterone is important to protect the uterine lining.

Low-dose vaginal estrogen (creams, tablets, or rings) is used locally and doesn’t produce whole-body effects. “With prescription hormone therapy, you're not necessarily restoring to baseline levels or going back to what you were when you were 20, but you're supporting your hormones,” says Boyd. “And when you're supporting estrogen and progesterone, you put those really important messengers back into the equation.”

Used to treat a host of menopause-related concerns, such as hot flashes, poor sleep, vaginal dryness or discomfort, and for preventing bone loss, studies show that HRT may also reduce the change in body composition that occurs during menopause. “While it doesn’t replace strength training or preserve muscle by itself, hormone therapy may improve insulin sensitivity and temper abdominal fat gain,” says Boyd.

That said, HRT isn’t for everyone. Generally, the best candidates are women under the age of 60 or within 10 years of menopause onset who have bothersome symptoms, and don't have contraindications to systemic hormone therapy (which include a history of blood clots and certain types of cancer, like breast cancer), according to Faubion.

The role of GLP-1 medications

GLP-1s (which stand for “glucagon-like peptide-1”) have been hugely popular for years now — mostly because they’re incredibly effective. Unlike previous anti-obesity medications, many of which worked by suppressing appetite, this class of medications works in a completely different way.

A gut hormone that serves as a messenger with receptors all over the body, GLP-1 stimulates insulin levels and inhibits glucagon, a hormone that raises your blood sugar. Together, these actions can lower your blood sugar after you eat. GLP-1 medications use a drug form of GLP-1 to extend its effects. “One of the things that people notice is a reduction in appetite — but it is a much more profoundly acting molecule,” says Boyd. “GLP-1s have an anti-inflammatory effect and influence cravings and food preference patterns — to the degree that these medications are being studied for alcohol use and substance-use disorders.”

GLP-1s have become a way to drive unprecedented weight loss. Research shows that the weight-loss average with semaglutide 2.4 mg (Wegovy) is about 15% of your starting weight. With tirzepatide (Zepbound), the effect is even more pronounced. Studies show that people achieve an average loss of 21% of their body weight after a year and a half. But these medications offer other benefits, too. For instance, “some of the trials on cardiovascular risk have shown reduction in cardiovascular risk even before weight loss occurs,” says Boyd.

The effects of combining HRT and GLP-1s

Both hormone therapy and GLP-1s are powerful in their own respects — and their individual benefits seem to complement one another.

While hormone therapy is not a weight-loss drug (and should not be used as one), “it can improve glucose control in [people with diabetes], and is associated with fewer cases of diabetes,” says Faubion. That’s due to its effect on visceral fat, she adds: If you accumulate less visceral fat, you tend to have better control over your blood sugar. GLP-1s, of course, have a dramatic effect on lowering blood sugar in their own right.

Now, research is looking into the effects of taking both medications. The newest study, which was yet to be published, found that postmenopausal women using both hormone therapy and tirzepatide (the active drug Zepbound and Mounjaro) experienced more weight loss than those taking tirzepatide alone, losing 17% of their body weight on average versus 14% for those taking only tirzepatide over the course of 18 months. That's on the heels of a paper from 2024, which found that postmenopausal women taking semaglutide (the active drug in Wegovy and Ozempic) and hormone therapy lost more weight than those not on hormone therapy, although both groups had improvements in their cholesterol and blood pressure.

The exact reason for this synergy is not yet known. Some research has found that women experience greater weight loss and possibly enhanced appetite suppression with GLP-1 therapy compared to men. Another study determined that combining GLP-1 and estrogen activated estrogen receptors in GLP-1-targeted tissues with “unprecedented efficacy” in order to improve metabolic syndrome — a cluster of conditions including high blood pressure, high cholesterol, and high blood sugar. And yet another paper found that there's a whole area of the brain that seems to reduce food reward, food intake, and body weight in rats when targeted by a GLP-1-estrogen combo.

It’s also possible that by improving menopause symptoms — hot flashes, night sweats, sleep issues, urinary issues — you’re in a better place to lose weight.

“When you're exhausted and you haven't slept all night, you're going to carb-load to try to stay up, and not feel like exercising because you haven't slept,” says Faubion. “So, helping women feel better by treating their menopause symptoms might help them adhere to lifestyle recommendations.” That’s key, since lifestyle is still the foundation of all healthy weight loss, no matter what medication you take.

What to keep in mind

Both hormone therapy and GLP-1s come with potential side effects and should be prescribed appropriately based on your medical history and current symptoms. Because systemic hormone therapy involves supplying the body with estrogen, it’s often not an option for women who have a history of or are at high risk for certain cancers or blood clots. (Low-dose vaginal estrogen is different and may be considered for local symptoms).

It’s also worth noting that GLP-1s can have challenging side effects that are mostly GI-related, like vomiting, nausea, diarrhea, and constipation. All to say: It’s critical if you’re interested in either to get a personalized evaluation tailored to your concerns and medical history. As far as using them together, the recent findings are promising, but they’re still very early, says Faubion.

If you’re looking for relief for menopause symptoms and your provider thinks you could be a good candidate for hormone therapy, then great. If your doctor also thinks you’re a good candidate for a GLP-1 — independent of any menopause symptoms — based on early data, you may see more weight loss with the combination than with a GLP-1 alone.

Either way, medication shouldn’t be the sole change you make. Even separately, hormone therapy and GLP-1s can be much more impactful when you pair them with lifestyle changes. “These medications can be life-changing, but they work best alongside core habits,” says Boyd.

WeightWatchers for Menopause gives you access to menopause-trained Clinicians who can address your symptoms while guiding you towards a healthy diet, daily movement, sound sleep, and emotional well-being — all of which can have a huge benefit for your overall health.