Combining Hormone Therapy With GLP-1s May Boost Weight Loss for Menopausal Women

As estrogen inevitably ticks down in menopause, it’s common for weight to tick up, and many women turn to GLP-1 medications for help losing extra pounds. Now, new research suggests that replacing declining estrogen with hormone therapy (HT) makes at least one GLP-1 more effective.

“It is also biologically plausible, given preclinical data suggesting a potential synergistic effect between estrogen and GLP-1 signaling,” she adds.

Semaglutide Appears to Get a Boost From Estrogen Hormone Therapy

Researchers compiled health records from about 2,400 women taking semaglutide and another 1,500 taking the GLP-1/GIP medication tirzepatide (Mounjaro, Zepbound).

On average, the women were 57 years old and weighed about 210 pounds (with a body mass index, or BMI, of 36). The study was retrospective and observational, meaning researchers examined how outcomes differed among participants over time.

After roughly two years, women taking semaglutide plus HT had lost about 25 pounds. Those only taking semaglutide had lost about 23.

The study didn’t investigate why hormone therapy may aid weight loss on a GLP-1, but Castaneda suggests it may have to do with estrogen affecting hunger. “When you give estrogen, it suppresses the food reward system and improves the appetite-suppressing effects of the GLP-1,” she says.

Because this was an observational study, it can’t prove that HT increased weight loss, only that there is a link.

Tirzepatide Yielded Similar Amounts of Weight Loss, With or Without Hormone Therapy

Women taking tirzepatide plus hormone therapy also experienced faster weight loss at the beginning than those just on tirzepatide, but by the end of the study period, there was no meaningful difference.

Nevertheless, women who took tirzepatide lost more weight (about 35 pounds, on average, after 15 months) than peers taking semaglutide. This result is consistent with previous clinical trials, which have found that tirzepatide typically leads to greater weight loss than its competitor.

Weight Gain and Rising Cholesterol Levels Are Common Concerns During the Menopausal Transition

“On any given day, more than 70 percent of patients in my practice express concern about weight and/or body composition changes,” says Makeba Williams, MD, an ob-gyn specializing in perimenopause and menopause who practices at the University of Illinois Hospital and Clinics in Chicago. Dr. Williams was not involved with the study.

What Women Can Do to Improve Health During These Years

Williams says she tries to educate her patients about what underlies the changes they are seeing in their bodies and weight, and normalize what they are experiencing.

“I share with them a call to action to identify the levers and assets in their lives that they can use to address their individual situation. Healthy eating, daily exercise, and strength training two to three times per week are foundational,” she says. She tells her patients to start with changes that are accessible, so they can build habits that stick.

Should You Use HT to Lose Weight?

Castaneda says women should not start hormone therapy solely for weight loss. It’s still too early to draw firm conclusions from the study’s findings, but clinical trials are underway to better understand any potential benefits.

Women face specific benefits and risks when taking GLP-1s during menopause and perimenopause. Castaneda points out that the desired effect of weight loss usually means losing some lean muscle along with fat.

Decreasing estrogen and aging also contribute to muscle loss, which, she says, “is particularly concerning in postmenopausal women. That’s why we always emphasize the importance of protein intake and resistance training.” It’s also worth knowing that GLP-1s are meant to be taken long-term, and weight loss tends to depend on staying on the medication.

Hormone therapy can also carry some risks depending on personal health history — though in late 2025 and 2026, the U.S. Food and Drug Administration removed the strongest warning label from several hormone therapy products, so ask your doctor what the updated guidance means for you, especially if you are older than 60.

Overall, though, experts say the risks of hormone therapy need to be evaluated for each individual and weighed against the benefits, which include:

• Heart disease prevention
• Relief of vasomotor symptoms, including hot flashes and night sweats
• Bone health protection, including a reduced risk of osteoporosis and fractures
• Better sleep, such as relief of sleep disturbances, which are common during menopause

Castaneda says that treating insomnia and fatigue tied to menopause can help women find the energy to exercise and make the lifestyle changes they need to maintain a healthy weight.

The bottom line, she says, is that women need to have a conversation with their clinician if they are experiencing menopause symptoms and weight gain.

“Menopause, yes, is a natural life transition. But it’s also important to know that with the right support … and with the evidence-based strategy that we now have, women can not only navigate this stage successfully, but they can also emerge stronger, healthier, and better equipped for their decades ahead,” she says.