In postmenopausal women receiving treatment with tirzepatide for overweight or obesity, concurrent use of hormone therapy confers greater reduction in weight as well as improvement in cardiometabolic outcomes, according to a retrospective cohort study.
Analysis of data on 120 postmenopausal women who were on tirzepatide for at least 12 months showed that at the last follow-up visit, the percentage of body weight lost was greater for those who did vs did not use hormone therapy concomitantly (–19.2 percent vs –14 percent; mean difference, –5.2 percent, 95 percent CI, 1.90–8.54; p=0.0023), reported first author Dr Regina Castaneda from Mayo Clinic, Rochester, Minnesota, US, and colleagues. [Lancet Obstet Gynaecol Womens Health 2026;2:e118-e128]
Significantly more women in the hormone vs no-hormone therapy group achieved a weight loss of ≥20 percent (45 percent vs 24 percent; p=0.022), ≥25 percent (28 percent vs 8 percent; p=0.0050), and ≥30 percent (18 percent vs 4 percent; p=0.015), Castaneda and colleagues added.
Cardiometabolic risk parameters improved in both groups, with significant reductions observed in concentrations of fasting glucose, HbA1c, high-density lipoprotein cholesterol, alanine aminotransferase, and systolic blood pressure. Women in the hormone therapy group showed additional significant reductions in diastolic blood pressure, triglycerides, and aspartate aminotransferase concentration.
Side-effects were reported in 32 percent of women in the hormone therapy group and in 43 percent in the no-hormone therapy group. The most common side-effects were gastrointestinal symptoms, occurring in 30 percent and 43 percent of women in the respective groups.
“This study suggests that hormone therapy enhances the therapeutic effect of tirzepatide, supporting its potential role as an adjunct to obesity pharmacotherapy in women with excess adiposity who also have a clinical indication for hormone therapy, such as vasomotor symptoms,” said Castaneda and colleagues.
“However, the use of hormone therapy, including the type, dose, and route of administration, should be evaluated in the context of its potential risks, including thromboembolic events, breast cancer, and stroke… The potential benefits of combined therapy should therefore be weighed against the potential risks in a personalized, shared, decision-making process,” the authors pointed out.
Castaneda and colleagues advocated for personalized treatment strategies that “thoughtfully integrate hormone therapy with emerging antiobesity pharmacotherapies.”
For the study, the authors used data from the Mayo Clinic Health System and identified 120 postmenopausal women (mean age 56.4 years, 94 percent White) with overweight or obesity (mean BMI 33.6 kg/m2) treated with tirzepatide for ≥12 months.
Of the women, 40 used hormone therapy (mean duration 4.5 years) and 80 did not. Adiposity-related comorbidities did not differ significantly between the groups, with the most prevalent being dyslipidaemia, hypertension, and type 2 diabetes. The mean follow-up time was 17 months in the hormone therapy group and 18 months in the no-hormone therapy group.