Abstract

Testosterone is an androgen hormone that plays a role in reproductive function and mood, cognition, and stress-associated neural circuits. Low levels of testosterone due to sickness or age have been linked to fatigue, low mood, loss of motivation, cognitive decline, and some of these symptoms are identical to those of depressive disorders in men. Based on this, testosterone replacement therapy (TRT) for hypogonadism has been developed and prescribed as a clinical intervention to restore physiologic levels and enhance the physical and psychological health of the patient. It has become of increasing interest in recent years due to its neurobiological activity, especially its modulatory effect on hippocampal plasticity, monoaminergic systems, and hypothalamic-pituitary-adrenal (HPA) axis regulation. The present review was conducted to summarize the recent evidence critically to assess the effect of TRT on mental health outcomes in adult male patients. Some evidence suggested that TRT might have a small to moderate effect on depressive symptoms, particularly in men with low levels of testosterone or in men with treatment-resistant depression (but this varies by studies and populations). Cognitive outcomes have been mixed, and few conclusions have been drawn about overall improvement, though some suggested that certain areas, such as memory and visuospatial functioning, have improved. However, there were several key safety concerns to consider with TRT, including erythrocytosis, cardiovascular risk markers, prostate monitoring requirements, and side effects from the TRT formulation. Pharmacokinetics and risks for intramuscular, transdermal, oral, and implantable routes vary and should be tailored to the patient.

Key words: Testosterone replacement therapy, hypogonadism, depression, testosterone, mental health, narrative review