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.
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. "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.
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