Real-world data support tirzepatide + hormone therapy for weight loss in postmenopausal women

In postmenopausal women with overweight or obesity, the use of tirzepatide alongside menopause hormone therapy appears to yield better weight loss outcomes than treating with tirzepatide alone, findings from a real-world analysis have shown.

During the last follow-up, tirzepatide-treated women on menopause hormone therapy achieved significantly greater total body weight loss percentage (TBWL%) as opposed to those who were not on menopause hormone therapy (17 percent vs 14 percent; p=0.01).

Moreover, the proportion of women achieving ≥20-percent TBWL was nearly threefold higher when menopause hormone therapy was added to tirzepatide than with tirzepatide alone (45 percent vs 18 percent; p=0.001). [ENDO 2025, abstract RF09-03]

“These data are the first to show that the combined use of tirzepatide and menopause hormone therapy significantly increases treatment effectiveness in postmenopausal women,” said study investigator Dr Regina Castaneda from the Mayo Clinic, Jacksonville, Florida, US, in the ENDO 2025 press release.

“Previous studies of … semaglutide found similar results. Achieving these outcomes with a second obesity medication may indicate a broader efficacy trend for pairing these two classes of medications,” Castaneda added.

Informs future clinical decisions

Considering the metabolic changes associated with menopause, such as increased abdominal fat, decreased muscle mass, and altered energy expenditure, menopause hormone therapy may have an impact on weight loss outcomes, noted Castaneda and colleagues.

In this real-world study, the investigators sought to evaluate whether the efficacy of tirzepatide against overweight or obesity in postmenopausal women differs between those who do and do not receive concomitant menopause hormone therapy.

Data were obtained from electronic medical records. To minimize confounding, 1:2 propensity score matching was used, matching each participant on menopause hormone therapy with two participants who were not on such therapy (control arm) based on BMI, age, age at menopause, menopause type, and diabetes status.

After propensity score matching of 400 participants, 120 were included in the analysis. Of these, 40 were included in the menopause hormone therapy plus tirzepatide arm (mean age 56 years, BMI 34 kg/m²), while the control arm had 80 participants (mean age 57 years, BMI 33 kg/m²). Menopause hormone therapy could either be transdermal or oral oestrogen, with or without progesterone. The median follow-up duration was 18 months for both treatment arms.

“[The data from] this new study provides important insights to develop more effective and personalized weight management interventions to reduce a postmenopausal woman’s risk of overweight and obesity-related health complications,” noted study co-investigator Dr Maria Daniela Hurtado Andrade, also from the Mayo Clinic, in the ENDO 2025 press release.

“This study underscores the urgent need for further research to better understand how obesity medications and menopause hormone therapy work together … [T]his knowledge could greatly improve the health and well-being of millions of postmenopausal women,” Hurtado Andrade continued. “It also points to the need for better strategies to make these treatments more accessible and available to those who need them.”

The investigators called for future studies with larger populations to validate the results and to explore the mechanisms driving the differential weight loss response between the two regimens evaluated.