Association of Testosterone Treatment With Alleviation of Depressive Symptoms in Men

Abstract

IMPORTANCE Countering depressive disorders is a public health priority. Currently, antidepressants are the first-line treatment, although they show modest effects. In men, testosterone treatment is a controversial alternative or adjunct treatment option. OBJECTIVES To examine the association of testosterone treatment with alleviation of depressive symptoms in men and to clarify moderating effects of testosterone status, depression status, age, treatment duration, and dosage. DATA SOURCES English-language studies published in peer-reviewed journals identified from PubMed/Medline, Embase, Scopus, PsychINFO, and the Cochrane Controlled Trials Register from database inception to March 5, 2018, using the search terms testosterone, mood, administration, dosage, adverse effects, deficiency, standards, therapeutic use, therapy, treatment, and supplementation. STUDY SELECTION Randomized placebo-controlled clinical trials (RCTs) of testosterone treatment that together cover a broad age range and hypogonadal or eugonadal men reporting depressive symptoms on psychometrically validated depression scales. DATA EXTRACTION AND SYNTHESIS Of 7690 identified records, 469 were evaluated against full study inclusion criteria after removing duplicates, reviews, and studies that did not examine male patients or testosterone. Quality assessment and data extraction from the remaining 27 RCTs were performed. MAIN OUTCOMES AND MEASURES Primary outcomes were testosterone treatment effectiveness (standardized score difference after treatment), efficacy (proportion of patients who responded to testosterone treatment with a score reduction of 50% or greater), and acceptability (proportion of patients who withdrew for any reason). RESULTS Random-effects meta-analysis of 27 RCTs including 1890 men suggested that testosterone treatment is associated with a significant reduction in depressive symptoms compared with placebo (Hedges g, 0.21; 95% CI, 0.10-0.32), showing an efficacy of odds ratio (OR), 2.30 (95% CI, 1.30-4.06). There was no significant difference between acceptability of testosterone treatment and placebo (OR, 0.79; 95% CI, 0.61-1.01). Meta-regression models suggested significant interactions for testosterone treatment with dosage and symptom variability at baseline. In the most conservative bias scenario, testosterone treatment remained significant whenever dosages greater than 0.5 g/wk were administered and symptom variability was kept low. CONCLUSIONS AND RELEVANCE Testosterone treatment appears to be effective and efficacious in reducing depressive symptoms in men, particularly when higher-dosage regimens were applied in carefully selected samples. However, given the heterogeneity of the included RCTs, more preregistered trials are needed that explicitly examine depression as the primary end point and consider relevant moderators.

European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males

“…TRT improved mood, and depressive symptoms using several self‐report instruments in the TTrials, although the magnitude of the effects was small . This is in line with data reported in available meta‐analyses . The positive effect of TRT was confirmed only in hypogonadal patients, with apparently higher efficacy in those <60 years and those with minor depressive symptoms…”

Kaleidoscope

“…Well, to return to science, Walther et al meta-analysed data on testosterone treatment in men with major depressive disorders. 8 Testosterone is neuroactive including in influencing affect, and it alters serotonin release, but any role in mental illness has been heavily debated. Low testosterone has been shown to be related with depression in some studies, but data are mixed and it is not a treatment recommended by standard guidelines.…”

Associations between digit ratio (2D4D), mood, and autonomic stress response in healthy men

“…In utero T exposure in men might therefore be further investigated with regard to its effect on stress-related disorders such as depressive disorders. Attempts to formulate a male-specific pathophysiology for affective disorders are emerging, which integrate in utero and postnatal testosterone's organizational effects (Walther, Penz, Ijacic, & Rice, 2017;Walther, Rice, Kufert, & Ehlert, 2017) as well as the effect of testosterone in adulthood (Fiacco, Walther, & Ehlert, 2018;Walther, Breidenstein, & Miller, 2018).…”