The antidepressant effect of testosterone: An effect of neuroplasticity?

Background Rodent and human studies indicate that testosterone has an antidepressant effect. The mechanisms via which testosterone exerts its antidepressant effect, however, remain to be elucidated. Some studies assume downstream effects of testosterone on sexual function and vitality followed by improvement of mood. Emerging evidence suggests that testosterone may be acting in the brain within depression-relevant areas, whereby eliciting direct antidepressant effects, potentially via neuroplasticity. Methods Literature was searched focusing on testosterone treatment and depression and depression-like behavior. Due to the unilateral clinical use of testosterone in men and the different modes of action of sex hormones in the central nervous system in men and women, predominantly studies on male populations were identified. Results The two proposed mechanisms via which testosterone might act as antidepressant in the central nervous system are the support of neuroplasticity as well as the activation of the serotonin system. Additionally, testosterone downregulates glucocorticoid output and reduces levels of pro-inflammatory markers, thereby acting as important counter regulatory agent reducing levels of neurotoxic factors in the central nervous system. Conclusion Although it is possible that testosterone acts via the serotonin system or the downregulation of the immune or hyperactive stress physiological systems, recent evidence supports the hypothesis that testosterone also elicits anti-depressant effects via directly promoting neuroplasticity. Potential implementations of testosterone treatment in mood disorders are discussed