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The prospects of wider application of testosterone (T) in novel indications such as male contraception have prompted renewed interest in the investigation of nonreproductive actions and safety of androgens. This study investigated potential changes in mood and behavior in response to elevations in circulating T concentrations produced by the new long-acting preparation, T undecanoate (TU). Twenty-eight eugonadal men were randomized into one of two treatment groups: A1) active, receiving 1000 mg TU i.m. followed by A2) washout, followed by A3) placebo, receiving 4 ml castor oil i.m.; B1) placebo, 4 ml castor oil i.m.; B2) washout followed by B3) active, receiving 1000 mg TU i.m.. Mood, self- and partner-reported physical and verbal aggression, anger, hostility, irritability, assertiveness, self-esteem, and sexual function were assessed. A single injection of 1000 mg TU i.m. increased plasma T concentrations from 20.7 +/- 1.5 to 37.5 +/- 2.2 nmol/liter at wk 1 and 31.6 +/- 1.5 nmol/liter at wk 2, and estradiol from 74.0 +/- 4.9 to 120.4 +/- 10.7 pmol/liter at wk 1, and 100.0 +/- 6.3 pmol/liter at wk 2. The T increment was associated with detectable but minor mood changes. Increased circulating T was associated with significant increases in anger-hostility from baseline (mean score = 7.48) to wk 2 (mean score = 10.71) accompanied by an overall reduction in fatigue-inertia (treatment = 6.21 vs. placebo = 7.84). TU treatment did not increase aggressive behavior or induce any changes in nonaggressive or sexual behavior. Changes in estradiol were not associated with any behavioral alterations. Our results suggest that exogenous TU-induced elevation of circulating T, to the range likely to be used in hormonal male contraception, has limited psychological effects. Future research should investigate the implications of these minor mood changes.

Effects of Testosterone on Mood, Aggression, and Sexual Behavior in Young Men: A Double-Blind, Placebo-Controlled, Cross-Over Study