Is there a neuroendocrinological rationale for testosterone as a therapeutic option in depression?

Abstract

Depression is a disease of growing incidence and economic burden worldwide. In view of increasing treatment resistance, new therapeutic approaches are urgently needed. In addition to its gonadal functions, testosterone has many effects on the central nervous system. An association between testosterone levels and depressive symptoms has been proposed. Many hormones and neurotransmitters are involved in the aetiology and the course of depression including serotonin, dopamine, noradrenaline, vasopressin and cortisol. Testosterone is known to interact with them. Preclinical data suggest that testosterone has antidepressant potential. However, the data from clinical studies have been inconsistent. This review provides a critical overview on the currently available preclinical and clinical literature and concludes with clinical recommendations.

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“…Nevertheless, most studies do not show any association between T plasma levels and depression [85,89]. It has been suggested that low T is related to mild dysthymic symptoms rather than major depression [85].…”

“…T easily crosses the blood-brain barrier. It is also a neurosteroid synthesized in the central nervous system (CNS) [85]. Androgen and GnRH receptors are present in several CNS structures related to depression [57,58,82,85,86].…”

“…It is also a neurosteroid synthesized in the central nervous system (CNS) [85]. Androgen and GnRH receptors are present in several CNS structures related to depression [57,58,82,85,86]. Animal studies have suggested an effect of T on the serotoninergic, dopaminergic, noradrenergic and vasopressin/oxytocin systems, as well as the hypothalamic-pituitary-adrenal axis [85].…”

“…Androgen and GnRH receptors are present in several CNS structures related to depression [57,58,82,85,86]. Animal studies have suggested an effect of T on the serotoninergic, dopaminergic, noradrenergic and vasopressin/oxytocin systems, as well as the hypothalamic-pituitary-adrenal axis [85]. Finally, TRT has been associated with an increased perfusion in brain areas related to emotion, as well as mood improvement in hypogonadal depressed patients [85,87].…”

“…Animal studies have suggested an effect of T on the serotoninergic, dopaminergic, noradrenergic and vasopressin/oxytocin systems, as well as the hypothalamic-pituitary-adrenal axis [85]. Finally, TRT has been associated with an increased perfusion in brain areas related to emotion, as well as mood improvement in hypogonadal depressed patients [85,87]. In a meta-analysis, greater age and T gel formulations predicted better responses of depressive symptoms to TRT [88].…”