Dose-dependent effects of testosterone on sexual function, mood, and visuospatial cognition in older men

Context: The relationships between testosterone dose and its effects on sexual function, mood, and visuospatial cognition are poorly understood. Objective: To elucidate testosterone dose-response relationships in older men, we examined the effects of graded testosterone doses on sexual function, mood, and visuospatial cognition in healthy, older men (age, 60-75 yr). Setting: This study was performed at the General Clinical Research Center. Intervention/Methods: Subjects each received a long-acting GnRH agonist to suppress endogenous testosterone production and were randomized to receive one of five doses (25, 50, 125, 300, and 600 mg) of testosterone enanthate weekly for 20 wk. Questionnaires were used to evaluate sexual function. Scores for overall sexual function as well as subcomponents of sexual function (libido, sexual activity, and erectile function) were calculated. Results: Changes in overall sexual function (P = 0.003) and waking erections (P = 0.024) differed by dose. An interaction between libido and being sexually active was observed, such that libido changed by testosterone dose only among men who reported being sexually active at the beginning of the study (P = 0.009). Men's log-transformed free testosterone levels during treatment were positively correlated with overall sexual function (P = 0.001), waking erections (P = 0.040), spontaneous erections (P = 0.047), and libido (P = 0.027), but not with intercourse frequency ( P = 0.428) or masturbation frequency (P = 0.814). No effects of testosterone dose were observed on two measures of mood: Hamilton's Depression Inventory (P = 0.359) and Young's Mania Scale (P = 0.851). The number of trials completed on a computer-based test of visuospatial cognition differed by dose (P = 0.042), but the number of squares correctly completed on this task did not differ by dose (P = 0.159). Conclusions: Different aspects of male behavior respond differently to testosterone. When considered together with previous data from young men, these data indicate that testosterone dose-response relationships for sexual function and visuospatial cognition differ in older and young men.