SOURCE: Snyder PJ, Bhasin S, Cunningham GR, et al. Effects of testosterone treatment in older men. N Engl J Med 2016;374:7:611-624.

Male hypogonadism is best defined as a clinical syndrome (changes in libido, sexual function, mood, and strength) confirmed by subnormal testosterone. This definition dissuades clinicians from measuring testosterone in asymptomatic men and instituting treatment solely on the basis of low testosterone levels. On one hand, clinical trials of testosterone in asymptomatic men have not demonstrated salutary outcomes. On the other hand, numerous trials confirm improvements in symptoms of hypogonadism through testosterone replacement, albeit with some uncertainty about potential toxicity of testosterone replacement.

Snyder et al performed a double-blind, randomized, placebo-controlled 12-month trial of testosterone replacement (using testosterone gel) in symptomatic hypogonadal men (n = 790) ≥ 65 years of age. Testosterone replacement restored testosterone levels to the mid-normal range for young adult men. Testosterone replacement resulted in statistically significant improvements in sexual function, desire, mood, and depression. Testosterone replacement did not improve walking distance. Testosterone generally was well tolerated, although seven men in the testosterone treatment group developed a hemoglobin > 17.5 mg/dL (none in the placebo group). There was no signal for increased cardiovascular risk, although a much larger trial would be necessary to provide definitive evidence of cardiovascular safety. The authors did not observe any worsening of symptoms relevant to benign prostatic hyperplasia. Testosterone replacement provides several areas of potential symptomatic improvement for hypogonadal men, but ongoing monitoring for adverse events (such as polycythemia) is necessary.