OBJECTIVETo determine whether testosterone therapy improves glucose metabolism in men with type 2 diabetes (T2D) and lowered testosterone. RESEARCH DESIGN AND METHODSWe conducted a randomized, double-blind, parallel, placebo-controlled trial in 88 men with T2D, aged 35-70 years with an HbA 1c £8.5% (69 mmol/mol), and a total testosterone level, measured by immunoassay, of £12.0 nmol/L (346 ng/dL). Participants were randomly assigned to 40 weeks of intramuscular testosterone undecanoate (n = 45) or matching placebo (n = 43). All study subjects were included in the primary analysis. Seven men assigned to testosterone and six men receiving placebo did not complete the study. Main outcome measures were insulin resistance by homeostatic model assessment (HOMA-IR, primary outcome) and glycemic control by HbA 1c (secondary outcome). CONCLUSIONSTestosterone therapy does not improve glucose metabolism or visceral adiposity in obese men with moderately controlled T2D and modest reductions in circulating testosterone levels typical for men with T2D.Observational studies consistently show that 30-50% of men with type 2 diabetes (T2D) have lowered circulating testosterone levels, relative to references based on healthy young men (1-3). This association is independent of age and obesity (4,5), and low testosterone levels in men with T2D are independently associated with insulin resistance (3). However, it is not known whether low testosterone levels are a cause or a consequence of T2D or its associated clinical features. Several lines of evidence lend support to the hypothesis that testosterone treatment decreases insulin resistance. Experimental evidence, reviewed in Grossmann

ADT for prostate cancer results in accumulation of both visceral and subcutaneous abdominal fat. Increased visceral fat area appears more closely linked to testosterone than oestradiol deficiency. Increased insulin resistance may arise secondary to visceral fat accumulation, rather than as a direct result of sex steroid deficiency.

Low testosterone levels are very commonly found in men with T2D and are associated with aging and obesity. Whether testosterone treatment in men with T2D decreases insulin resistance above that attributable to its fat-reducing effect is currently unknown. Future studies should compare testosterone treatment with lifestyle changes (exercise and weight loss measures), and other insulin-sensitizing agents. Until further evidence is available, testosterone therapy outside clinical trials should be reserved for diabetic men with unequivocal hypogonadism.