Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial

Aims/hypothesis. Studies examining the effect of postmenopausal hormone therapy on concentrations of glucose, insulin and diabetes incidence have been inconclusive, in part because many of the studies were too small. We examined the effect of oestrogen plus progestin on diabetes incidence and insulin resistance. Methods. The study was a randomised, double-blind trial comparing the effect of daily 0.625 mg conjugated equine oestrogens plus 2.5 mg medroxyprogesterone acetate with that of placebo during 5.6 years of follow-up. The participants were 15,641 postmenopausal women enrolled in the Women's Health Initiative Hormone Trial. These women were aged 50 to 79 and all had an intact uterus. Diabetes incidence was ascertained by self-report of treatment with insulin or oral hypoglycaemic medication. Fasting glucose, insulin, and lipoproteins were measured in a random sample at baseline and at 1 and 3 years. Results. The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2% in the placebo group (hazard ratio 0.79, 95% CI 0.67-0.93, p=0.004). There was little change in the hazard ratio after adjustment for changes in BMI and waist circumference. During the first year of follow-up, changes in fasting glucose and insulin indicated a significant fall in insulin resistance in actively treated women compared to the control subjects (Year 1 to baseline between-group difference -0.22+/-0.10, p=0.03). Interpretations/conclusion. These data suggest that combined therapy with oestrogen and progestin reduces the incidence of diabetes, possibly mediated by a decrease in insulin resistance unrelated to body size. Future studies of alternative postmenopausal hormone therapy regimens and selective oestrogen agonists and/or antagonists should consider the effects of these regimens on insulin resistance and diabetes.