Lower Diabetes Risk with Hormone Replacement Therapy: An Encore for Estrogen?

In this issue, Kanaya and colleagues (1) report a lower risk for new-onset type 2 diabetes mellitus in postmenopausal women receiving combined estrogen–progestin hormone replacement therapy (HRT). This news from the Heart and Estrogen/progestin Replacement Study (HERS) is encouraging because it comes from a well-conducted substudy within a clinical trial that has focused largely on cardiovascular outcomes. At the start of the study, the postmenopausal participants had fasting glucose levels measured and were categorized as normal, having impaired fasting glucose, or having diabetes. They were followed for the development of new type 2 diabetes mellitus over 4 years. Daily treatment with 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate resulted in a 35% lower risk for type 2 diabetes mellitus during follow-up.

Previous work in smaller samples, such as that reported by Espeland and coworkers (2) from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial, set the stage for Kanaya and colleagues' analysis. The earlier report described lower levels of fasting glucose and insulin after estrogen replacement in a prospective study environment. Favorable effects on fasting glucose and insulin levels, but not necessarily postchallenge levels during a glucose tolerance test, were found for estrogen alone and for combined treatment with estrogen and progestin (2). Over the past few years, investigators have continued to report neutral …