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By Daniella Gray
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Menopause can make losing weight significantly harder, even as an increasing number of women turn to GLP-1 medications such as Ozempic and Wegovy for help.
A new study presented by researchers at Mayo Clinic Florida suggests estrogen may play a role in how some women respond to GLP-1-based obesity treatments.
The retrospective cohort study examined electronic health records from overweight and obese women aged 45 and older who were prescribed either semaglutide—sold under brand names such as Ozempic and Wegovy—or tirzepatide, marketed as Mounjaro and Zepbound.
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What the Study Showed
Researchers compared women using menopause hormone therapy with those who were not.
The semaglutide group included 2,379 women, while the tirzepatide group included 1,476 women.
Researchers used propensity score matching to balance the groups for factors such as age, body mass index, prior obesity medication use and Type 2 diabetes status.
Among semaglutide users, women taking hormone therapy experienced significantly greater weight loss beginning at nine months.
By 15 months, hormone therapy users had lost an average of 11.6 percent of their body weight compared with 9.7 percent in nonusers.
At their final follow-up, average weight loss was 11.9 percent versus 10.9 percent.
Women receiving hormone therapy were also more likely to achieve larger weight-loss goals.
Fifty-five percent lost at least 10 percent of their body weight compared with 51 percent of nonusers, while 13 percent achieved at least 25 percent weight loss compared with 10 percent of those not taking hormone therapy.
A similar, but weaker, pattern emerged among women taking tirzepatide.
Hormone therapy users lost slightly more weight during the first three months of treatment, but differences were not statistically significant at later time points.
"The observed association appeared stronger among women using semaglutide than among those using tirzepatide, although our study was not designed to directly compare the two medications, and the tirzepatide sample was smaller," lead author Dr. Regina Castaneda of Mayo Clinic Florida told Newsweek.
She said a possible explanation is that tirzepatide's greater overall weight-loss efficacy may leave less room to detect an additional benefit from hormone therapy.
What Role Could Estrogen Play?
"One biologically plausible explanation is the growing body of preclinical evidence suggesting synergy between estrogen signaling and GLP-1 pathways," Castaneda said. "Preclinical studies have shown that estrogen can amplify the appetite-suppressing effects of GLP-1 signaling."
Estrogen also influences energy balance, insulin sensitivity and body composition, she said, raising the possibility that hormone therapy could enhance responsiveness to incretin-based medications in some menopausal women.
However, the findings should not prompt women to seek hormone therapy solely to lose weight.
"Weight loss is not an indication for menopause hormone therapy," Castaneda said. "For women who are experiencing bothersome menopausal symptoms and are already appropriate candidates for hormone therapy, our findings provide reassurance that hormone therapy may offer additional metabolic benefits when used alongside GLP-1 medications."
Independent expert Dr. Jessica Duncan, the chief medical officer at Ivím Health and a board-certified obesity medicine physician, said the results are encouraging and consistent with what she sees in practice.
"Many midlife women seem to do better on a GLP-1 when their menopause symptoms are also being treated," she told Newsweek.
Still, she said observational studies cannot fully rule out other explanations.
"Women on hormone therapy are often healthier, more engaged with their care and better supported, and the matching may not have captured all of that," Duncan said.
She added that a randomized clinical trial would be needed to determine whether hormone therapy directly improves weight-loss outcomes in women taking GLP-1 medications.
"Whether hormone therapy directly enhances that effect is the question a randomized trial now needs to answer," Duncan said. "As the researchers noted, hormone therapy shouldn't be started for weight loss. But for women who already have a reason to use it, this is encouraging."
Contact Newsweek editors on this story: Kara Dolman and Shakeema Edwards.
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