HRT and exercise combined improve insulin sensitivity in postmenopausal women

Combining hormone replacement therapy with structured exercise produces the largest observed improvement in insulin sensitivity among postmenopausal women compared to either intervention alone, according to interim results from a 12-week randomized study presented at the European Association for the Study of Diabetes 2026 Annual Meeting in Milan.

Insulin Sensitivity Findings From the Milan Trial

The trial evaluated 84 menopausal women aged 45 to 65 years with a body mass index between 18.5 and 30. Participants were naive to hormone therapy and were randomized into three distinct groups: 30 women receiving hormone replacement therapy alone, 25 participating in exercise alone, and 29 undergoing combined hormone replacement therapy and exercise. The intervention period lasted 12 weeks. Hormone replacement therapy consisted of transdermal estrogen administered at 1.53 mg per dose, applied twice in the morning, combined with 100 mg of oral progesterone.

Patrick Calders, PhD, a professor in the Department of Rehabilitation Sciences at Ghent University in Belgium, reported that the reduction in the Homeostatic Model Assessment for Insulin Resistance score—which signifies improved insulin sensitivity—was greatest in the group receiving both hormone replacement therapy and exercise. Exercise alone also produced clear positive effects on insulin sensitivity compared to hormone replacement therapy alone, which showed relatively little change in Homeostatic Model Assessment for Insulin Resistance scores.

You can see that exercise has a clear positive effect, but the combination of HRT and exercise showed the largest effect, Patrick Calders said at the annual meeting.

Changes in Physical Capacity and Body Composition

Beyond glucose metabolism, the trial tracked physical strength, peak aerobic capacity, and body composition. Both the combined-treatment group and the exercise-alone group achieved substantial improvements in physical strength. Relative peak oxygen consumption increased by approximately 3 to 3.5 mL/kg/min in both exercise groups, an increase equivalent to roughly one metabolic equivalent of task that Calders characterized as clinically relevant.

Body composition assessments via bioimpedance showed that exercise contributed to favorable reductions in fat mass. The largest reduction in fat mass occurred in the group receiving both hormone replacement therapy and exercise, while both exercise groups achieved significantly greater reductions in fat mass than the group receiving hormone replacement therapy alone. However, the combined intervention did not yield a statistically significant advantage over exercise alone regarding fat-free mass.

Cardiovascular Risk Factor Stability

Despite the notable gains in insulin sensitivity and aerobic capacity, the 12-week trial did not uncover broad, statistically significant changes in conventional cardiovascular risk markers. Calders noted that no significant overall effects on blood pressure or lipid profiles were observed across the study population, though the combined-treatment group did exhibit an approximate 6-mm Hg reduction in blood pressure.

The study protocol required participants to engage in exercise three times per week. Two sessions were supervised directly by a physiotherapist, while a third session was performed independently at home using a Polar monitor. Each session integrated 20 minutes of aerobic exercise—such as walking, stepping, and cycling at intensities determined by ventilatory thresholds—along with 30 minutes of strength training targeting the upper limbs, lower limbs, and core. Statin use was permitted among participants, but baseline characteristics remained well matched across all three study arms, with mean ages hovering around 55 years and mean body mass indexes ranging from 27 in the hormone replacement therapy group to 29 in the combined group.