Endogenous Sex Hormones and Risk of Type 2 Diabetes Mellitus in Men and Women

Obesity and diabetes are growing health problems in the United States that pose a significant public health burden. It is well established that polycystic ovary syndrome (PCOS), an endocrinopathy of reproductive age women characterized by hyperandrogenism, is associated with an increased risk of subsequent type 2 diabetes. Recent literature in men with clinical hypogonadism of various etiologies shows that they are at increased risk of developing insulin resistance and type 2 diabetes. This suggests that sex hormones in men and women may play a role in regulating glucose metabolism, either through their effects on adiposity or through independent mechanisms. This chapter aims (1) to review the associations of endogenous sex hormones (testosterone, estradiol, and sex hormone-binding globulin) with adiposity, insulin resistance, and type 2 diabetes in men and women; (2) to highlight gender differences and similarities in these associations; and (3) to discuss the pathophysiological mechanisms by which sex hormones may influence insulin sensitivity. To provide a conceptual framework for understanding the gender dimorphism of the association between testosterone and diabetes, it reviews the literature examining the association between diabetes and PCOS in women and hypogonadism in men. However, the majority of the studies reviewed are population-based studies of individuals without clinical gonadal disorders who were not receiving hormone therapy to reduce potential confounding in interpreting the associations.