Testosterone Treatment & Alleviation of Depressive Symptoms

Discussion in 'Men's Health Forum' started by Michael Scally MD, Nov 15, 2018.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Association of testosterone Treatment with Alleviation of Depressive Symptoms

    Key Points

    Question - Is testosterone treatment associated with an alleviation of depressive symptoms in men compared with placebo?

    Findings - This systematic review and meta-analysis of 27 randomized placebo-controlled clinical trials involving a total of 1890 men found that testosterone treatment was associated with a significant reduction of depressive symptoms, particularly in participants who received higher-dosage regimens.

    Meaning - The available evidence supports the clinical utility of adjunct testosterone treatment for depressive symptoms in men, but more methodologically rigorous trials are needed to unequivocally determine efficacy, ideal dosage regimens, and other moderators.

    Walther A, Breidenstein J, Miller R. Association of testosterone treatment with alleviation of depressive symptoms in men: A systematic review and meta-analysis. JAMA Psychiatry 2018. Testosterone Treatment and Alleviation of Depression in Men

    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.
    Last edited: Nov 15, 2018
  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    testosterone Treatment of Depressive Disorders in Men: Too Much Smoke, Not Enough High-Quality Evidence

    The role of testosterone in the pathophysiology and treatment of depressive disorders in men has remained shrouded in controversy. We do not know whether depressive symptoms are a part of the syndrome of testosterone deficiency in men, and if so, whether testosterone replacement relieves such symptoms, whether low testosterone levels contribute to the pathophysiology of depressive disorders in men, and whether testosterone treatment is efficacious in treating men with depressive disorders.

    A well-performed meta-analysis by Walther et al in this issue of JAMA Psychiatry attempts to synthesize data from randomized, placebo-controlled clinical trials to assess the association of testosterone treatment with depressive symptoms in men. Although this meta-analysis adds to the body of data that testosterone administration may be associated with small improvements in depressive symptoms, we do not know whether these improvements are clinically meaningful.

    These data should not be extrapolated to imply that testosterone treatment induces remission of major depressive disorder (MDD) or that it augments response to antidepressant therapy in such patients. Furthermore, neither the long-term safety nor the efficacy of testosterone therapy has been established in any depressive disorder.

    Because some of the adverse effects of testosterone are associated with its dose and on-treatment concentrations, the use of supraphysiologic doses of testosterone could be associated with increased risk of adverse effects and is currently not recommended.

    Bhasin S, Seidman S. Testosterone treatment of depressive disorders in men: Too much smoke, not enough high-quality evidence. JAMA Psychiatry 2018. Testosterone Treatment of Depressive Disorders in Men

    Attached Files:

    Last edited: Nov 15, 2018
  3. Old

    Old Member

    Do you have a copy of the full article?

    Found elsewhere: "Generally, researchers found a dose-response association in patients administered testosterone, which demonstrated that higher testosterone doses (>500 mg per week) improved depressive symptoms at higher rates, they reported in JAMA Psychiatry."

    That is considered high dosing as rarely does a doctor go above 200mg/wk. And then there is the 1995(?) study with 25, 50, 125, 300, and 600mg/wk TE. Didn't know of any other 'high' dose studies.

    It is natural that there is an immediate repudiation and concern about treating MDD this way. But the vilification of T has been excessive, and blamed on BB though IMO it is a relic of the cold war.

    EDIT: see now the mention of 0.5g in your original post.
  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    I attached the full-text to the posts.
    Old likes this.