Effects of androgens on glucose metabolism

Type 2 diabetes (T2D) and obesity are common and associated with increased morbidity and mortality. Cross-sectional and longitudinal studies have demonstrated a clear association between T2D, obesity and reduced total testosterone concentration. This relationship becomes less significant or absent with correction for changes in body composition, supporting the notion that changes in body composition are mediating these effects. Moreover, this mediating effect of body composition changes is bi-directional, as evidenced by interventional studies of weight loss and testosterone treatment. On the one hand, in obese men, serum testosterone increases markedly with weight loss. On the other hand, testosterone improves body composition. This relationship is driven by multiple complex interaction between obesity and insulin resistance and the hypothalamic-pituitary-testicular axis, at all levels. Data from randomised control trials have demonstrated that intervention with testosterone therapy increases muscle mass and reduces adiposity. Most recently it has been shown that treatment with testosterone prevents progression of impaired glucose tolerance to T2D, or reverses newly diagnosed T2D beyond lifestyle intervention alone. At present there are insufficient safety data to support the use of testosterone for prevention of type 2 diabetes.