Elsevier

Neurology, Psychiatry and Brain Research

The antidepressant effect of testosterone: An effect of neuroplasticity?

Highlights

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Testosterone has antidepressant effects whereby the underlying mechanisms are still unknown.

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Promoted neuroplasticity and the activation of the serotonin system may underlie the antidepressant effect of testosterone.

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Studies suggest that a combination of testosterone and current antidepressants enhance antidepressant-induced neurogenesis.

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Testosterone actions within the HPA axis and during inflammation may additionally contribute to the mood enhancing effects.

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Not only testosterone alone, but also its conversion to estradiol may contribute to the observed antidepressant effects.

Abstract

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.

Keywords

Testosterone

Depression

Men

Neurogenesis

Neuroplasticity

Antidepressant

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