Is Estradiol a Biomarker of Type 2 Diabetes Risk in Postmenopausal Women?

Abstract

Cross-sectional studies have suggested an association between the main female hormone, 17β-estradiol (E2), and the risk of type 2 diabetes (T2D) in postmenopausal women (1,2). Even prospective studies have found that among postmenopausal women not using hormone therapy, higher circulating levels of total and free E2 were strongly and prospectively associated with increased long-term risk of T2D, independently of adiposity or insulin resistance (3,4). In this issue of Diabetes , Muka et al. (5) examine the association among sex hormone–binding globulin (SHBG)—a protein that binds and carries E2 in the blood and limits its bioavailability—sex hormones, and T2D risk in a large population-based sample of healthy postmenopausal women who were free of T2D at baseline, with a median follow-up of 11 years. They report that lower levels of SHBG (which translate into higher bioavailable E2) and higher concentrations of total E2 are associated with increased risk of T2D, independently of established risk factors, including BMI and insulin resistance. In contrast, they observed no association between testosterone and T2D risk. Their findings are reinforced by a systematic meta-analysis of 13 studies with 14,902 participants who included 1,912 case subjects with T2D, confirming that lower SHBG and increased total E2 are robust risk markers of T2D in postmenopausal women. Of …