testosterone, Obesity and The Metabolic Syndrome in Males - Do We Need to Replace Steroids? Testosterone, obesity and the metabolic syndrome in males-do we need to replace steroids? | ECE2018 Background: In men with obesity and the metabolic syndrome there is an increased prevalence of low serum testosterone. Overweight and moderate obesity is associated mainly with low total testosterone (T) secondary to decreased concentrations of SHBG, which are strongly inversely associated with indices of adiposity and insulin resistance, and preserved free T levels. In more severe obesity and metabolic abnormalities (often with type 2 diabetes) low total T can be accompanied by low free T, usually without appropriate increase of gonadotropins indicating contribution of altered central regulation of gonadal function, of which the underlying mechanisms remain to be fully elucidated. These observations have raised the question whether treatment with T may be needed or beneficial. The main issues involved will be reviewed. Main points: Are these men hypogonadal? A large proportion of the men with low total T and preserved free T should not be considered as hypogonadal. Those with low free T might be considered hypogonadal if they also present with symptoms of hypogonadism (e.g. sexual dysfunction). Is low T causal in the risk for – or aggravation of obesity and metabolic syndrome? Although the relation between low T and obesity/metabolic syndrome appear to some extent bidirectional, a critical appraisal of the literature indicates that a causal role of T is likely to be only limited with low T rather the consequence than the cause. Is the low T reversible? Weight loss and improved metabolic control can normalize or improve serum T. What are the effects of T therapy on the evolution of obesity and metabolic syndrome? Pharmacologic treatment with T can reduce fat mass and increase lean mass, which may have indirect favorable effects on metabolic control. A critical appraisal of controlled studies learn that these effects remain rather limited and can have at best a marginal effect besides more specific approaches such as based on lifestyle, more specific pharmacologic treatment or bariatric surgery. Is T therapy effective to treat hypogonadism in obese men or men with metabolic syndrome/type 2 diabetes? Yes treatment is effective although possibly less effective than in lean hypogonadal men. How safe is T therapy in these men? Some safety aspects may require special attention (e.g. risk for venous thromboembolism, sleep apnea). Conclusion: In the present state-of-the-art obesity and metabolic syndrome as such should not be considered as indications for T therapy. Conversely weight loss and improved metabolic control can normalize low T in men with obesity and metabolic syndrome in the absence of other (organic) causes of hypogonadism. In men with obesity and metabolic syndrome and with established hypogonadism (unequivocally low free T and symptoms) T therapy should be considered if measures intended at reducing weight and improving metabolic control fail to normalize or substantially improve serum FreeT.