Testosterone for Androgen Deficiency-Like Symptoms in Men Without Pathologic Hypogonadism: A Randomized, Placebo-Controlled Cross-over With Masked Choice Extension Clinical Trial

Abstract

Abstract Background Off-label testosterone prescribing for androgen deficiency (AD)-like sexual and energy symptoms of older men without pathologic hypogonadism has increased dramatically without convincing evidence of efficacy. Methods In a randomized, double-blind, placebo-controlled study with three phases, we entered 45 men aged at least 40 years without pathologic hypogonadism but with AD-like energy and/or sexual symptoms to either daily testosterone or placebo gel treatment for 6 weeks in a cross-over study design with a third, mandatory extension phase in which participants chose which previous treatment they preferred to repeat while remaining masked to their original treatment. Primary endpoints were energy and sexual symptoms as assessed by a visual analog scale (Lead Symptom Score [LSS]). Results Increasing serum testosterone to the healthy young male range produced no significant benefit more than placebo for energy or sexual LSS. Covariate effects of age, body mass index, and pretreatment baseline serum testosterone on quality-of-life scales were detected. Only 1 out of 22 indices from seven quality-of-life scales was significantly improved by testosterone treatment over placebo. Participants did not choose testosterone significantly more than placebo as their preferred treatment in the third phase. Conclusions Six-week testosterone treatment does not improve energy or sexual symptoms more than placebo in symptomatic men without pathologic hypogonadism.