Hormone therapy may boost weight loss for postmenopausal women on semaglutide

Key takeaways:

• Postmenopausal women on hormone therapy had higher total body weight loss with semaglutide for up to 12 months vs. no hormone therapy.
• Cardiometabolic risk markers improved with and without hormone therapy use.

Hormone therapy was associated with an improved weight-loss response for postmenopausal women with overweight or obesity treated with semaglutide, according to cohort study results published in Menopause.

Currently, semaglutide (Novo Nordisk) is approved for the treatment of overweight and obesity leading to a mean weight loss of 15% after 68 weeks, the researchers wrote.

“During menopause, hormone therapy use, compared to no hormone therapy use, has been shown to attenuate the increase in total and visceral abdominal adiposity by around 60% and to decrease waist circumference and BMI by 0.8%,” Maria D. Hurtado, MD, PhD, a physician-scientist with the Precision Medicine for Obesity Laboratory at Mayo Clinic, and colleagues wrote. “Hormone therapy use has not only been associated with the attenuation of lean mass loss, but with an increase in lean mass by 1%.”

Hurtado and colleagues conducted a retrospective cohort study utilizing electronic medical record data from 106 postmenopausal women (mean age, 58.4 years; mean BMI, 38.5 kg/m²) with overweight or obesity treated with semaglutide for 3 months or longer from January 2021 to March 2023. At 2, 6, 9 and 12 months, researchers recorded total body weight loss percentage with semaglutide treatment and compared weight-loss outcomes and changes in cardiometabolic risk markers with semaglutide treatment for postmenopausal women with and without hormone therapy use.

Primary outcomes were total body weight loss percentage after 12 months of semaglutide treatment based on hormone therapy use status, the percentage of women who achieved 5% or greater and 10% or greater total body weight loss, and changes in glucose, blood pressure and lipids at 12 months.

Overall, 16 postmenopausal women were on hormone therapy, of whom 50% received transdermal estradiol 0.025 mg per day to 0.1 mg per day and 50% received daily oral estradiol 0.5 mg to 1 mg.

Postmenopausal women on hormone therapy had a higher percentage of total body weight loss at 3 (7% vs. 5%; P = .01), 6 (13% vs. 9%; P = .01), 9 (15% vs. 10%; P = .02) and 12 (16% vs. 12%; P = .04) months of semaglutide treatment compared with no hormone therapy. At 12 months, more postmenopausal women using hormone therapy achieved 5% or greater (100% vs. 77.4%; P = .01) and 10% or greater (85.7% vs. 58.1%; P = .04) total body weight loss compared with no hormone therapy.

Both postmenopausal women on hormone therapy and those not on hormone therapy had improvements in cardiometabolic risk markers. From baseline to 12 months of semaglutide treatment, postmenopausal women on hormone therapy had improvements in HbA1c (P = .04), triglycerides (P = .004) and total cholesterol (P = .01). In addition, postmenopausal women not on hormone therapy had improvements in fasting glucose (P = .001), HbA1c (P = .0002) and systolic BP (P = .008) from baseline to 12 months.

“Larger studies are needed to confirm these results. Further, future studies are needed to identify the mechanisms behind this differential weight loss response,” the researchers wrote. “While the effect of hormone therapy use on body composition could partly explain this difference, additional mechanisms are probably involved, such as the effect of hormone therapy on sleep quality, vasomotor symptoms and quality of life.”