Postmenopausal women using hormone therapy experienced greater weight loss with semaglutide compared to those not on hormone therapy, according to a recent retrospective cohort study.

Researchers analyzed 106 postmenopausal women receiving semaglutide for at least 12 months and found that hormone therapy (HT) users lost more weight at every measured interval. At 3 months, HT users lost 7% of their total body weight versus 5% in non-users. By 6 months, the difference widened to 13% versus 9%, persisting at 9 months (15% vs. 10%) and 12 months (16% vs. 12%). These differences remained significant after adjusting for factors such as age, baseline weight, and type 2 diabetes, according to the research published in Menopause: The Journal of The Menopause Society.

Additionally, more women on HT reached clinically significant weight loss thresholds. At 12 months, 100% of HT users lost at least 5% of their body weight, compared to 78% of non-users. Similarly, 81% of HT users lost at least 10%, compared to 59% of non-users.

Both groups showed improvements in cardiometabolic markers over the 12-month period. HT users had greater reductions in total cholesterol and triglycerides, while non-users saw larger decreases in fasting glucose and systolic blood pressure. However, the between-group differences were not statistically significant.

"As cardiovascular disease (CVD) is the leading cause of mortality in women and menopause is an independent risk factor for CVD, interventions to prevent weight gain and manage overweight and obesity are of particular importance in postmenopausal women," noted Maria D. Hurtado, MD, of the Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Mayo Clinic, Jacksonville, Florida, and colleagues.

The study investigators retrospectively examined electronic medical records from women treated with semaglutide at the Mayo Clinic between January 2021 and March 2023. Participants were classified as HT users (n = 16) or non-users (n = 90). Inclusion criteria required at least 12 months of documented menopause, while exclusions included semaglutide use for under 3 months, prior bariatric surgery, or active malignancy. There were no significant differences in baseline BMI or age between the groups.

Meanwhile, study limitations included a small sample size—only 15% of participants were on HT—its retrospective nature, and a lack of data on lifestyle factors such as diet and physical activity. Researchers emphasized the need for larger prospective studies incorporating data on sleep quality, vasomotor symptoms, and HT timing relative to semaglutide use.

While the findings suggest that HT may enhance weight loss response to semaglutide, causality remains undetermined, noted Dr. Hurtado, and colleagues.

They reported no conflicts of interest.