MANAGEMENT OF ENDOCRINE DISEASE: Rationale and current evidence for testosterone therapy in the management of obesity and its complications.

Overt hypogonadism in men adversely affects body composition and metabolic health, which generally improve upon testosterone (TS) therapy. As obese men often display lower serum TS levels, in particular when they present with the metabolic syndrome (MetS) or type 2 diabetes (T2DM), there have been claims that androgen therapy prevents or reverses obesity and improves metabolic health. This has contributed to the increase in TS prescriptions during the past two decades. In this narrative review, based on findings from larger observational studies and randomized controlled intervention trials, we evaluate whether low TS predicts or predisposes to obesity and its metabolic consequences, and whether obese men with low TS are truly hypogonadal. We further describe the mechanisms underlying the bi-directional relationships of TS levels with obesity and metabolic health, and finally assess the evidence for TS therapy in men with obesity, MetS and/or T2DM, considering efficacy, safety concerns and possible alternative approaches. It is concluded that low serum sex hormone-binding globulin and total TS levels are highly prevalent in obese men, but that only those with low free TS levels and signs or symptoms of hypogonadism should be considered androgen deficient. These alterations are reversible upon weight loss. Whether low TS is a biomarker rather than a true risk factor for metabolic disturbances remains unclear. Considering the limited number of sound TS therapy trials have shown beneficial effects, the modest amplitude of these effects, and unresolved safety issues, one cannot in the present state-of-the-art advocate TS therapy to prevent or reverse obesity-associated metabolic disturbances. Instead, the focus should remain on lifestyle measures and management of obesity-related consequences.