Menopause hormone therapy linked to greater weight loss with semaglutide

Women who use menopause hormone therapy may lose more weight while taking semaglutide than women taking the weight-loss drug alone, according to a large observational study. The results suggest that hormonal changes could affect how some women respond to obesity treatment.

The pattern was more pronounced with semaglutide than with tirzepatide, another commonly used injectable medication. Researchers stressed that the study does not prove hormone therapy itself leads to greater weight loss.

The findings were presented at the annual meeting of The Menopause Society in San Diego. The analysis reviewed medical records from nearly 2,400 women using semaglutide and almost 1,500 using tirzepatide.

All of the women were older than 45 and had a body mass index above 27, a threshold often used to define overweight or obesity. Researchers compared weight changes between women receiving menopause hormone therapy and those who were not.

Women on hormone therapy together with semaglutide had significantly larger and more lasting weight loss. In the tirzepatide group, an early advantage appeared for hormone therapy, but the final result was not statistically significant.

That difference is important because the two medications do not act in exactly the same way. Semaglutide works through the GLP-1 pathway, while tirzepatide targets GLP-1 as well as another pathway involved in blood sugar control.

GLP-1 medications help reduce appetite and have produced substantial weight loss in clinical trials. Still, responses vary from person to person, leading researchers to look for clues that might explain why the same treatment works better for some patients than for others.

Weight gain in midlife is affected by aging, and menopause can alter how body fat is distributed. Hormone therapy is prescribed for certain menopause symptoms, but it is not approved as a weight-loss treatment.

Earlier, smaller studies also found a link between hormone therapy and stronger responses to semaglutide. The newer analysis expands that observation in a larger group, though its retrospective design limits how much can be concluded.

Women receiving hormone therapy may differ from other patients in ways that medical records do not fully capture. Their overall health, access to care, treatment history or other factors could partly explain the gap.

Researchers also noted laboratory evidence suggesting a possible interaction between estrogen and GLP-1 signaling. Even so, a biological explanation is not proof that adding hormones improves weight-loss results.

Prospective trials would be needed to follow patients under carefully controlled conditions and determine whether the combination truly offers an advantage. For now, the study raises an important research question rather than supporting hormone therapy solely for weight management.

For more information, please see articles about common weight-loss drugs causing too much muscle loss in older adults and women, and about switching weight-loss drugs may help people stay on treatment longer.

Source: The Menopause Society.