madman
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Association of Testosterone Treatment With Alleviation of Depressive Symptoms in Men
A Systematic Review and Meta-analysis (2018)
Andreas Walther, PhD; Jonas Breidenstein, BSc; Robert Miller, PhD
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.
Dosages of greater than 500 mg/week using transdermal application
*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.
- use of transdermal testosterone >500 mg/week
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.
Conclusions
Previous research provided evidence that testosterone treatment is effective in reducing depressive symptoms in hypogonadal,or middle-aged men up to age 60 years.This meta-analysis provides important new evidence that testosterone treatment may also be effective and efficacious for eugonadal and older men when higher testosterone dosages are administered. For acceptability, testosterone treatment was not significantly associated with fewer dropouts than placebo. Safety monitoring in testosterone treatment trials continues to be important owing to a lack of sufficiently powered long-term studies to determine increased risk for adverse events. Because our results as well as previous investigations have indicated that risk of bias is considerable in most studies, we call for large, preregistered RCTs of good quality investigating testosterone treatment’s effect in men on depression as the primary outcome.
A Systematic Review and Meta-analysis (2018)
Andreas Walther, PhD; Jonas Breidenstein, BSc; Robert Miller, PhD
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.
Dosages of greater than 500 mg/week using transdermal application
*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.
- use of transdermal testosterone >500 mg/week
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.
Conclusions
Previous research provided evidence that testosterone treatment is effective in reducing depressive symptoms in hypogonadal,or middle-aged men up to age 60 years.This meta-analysis provides important new evidence that testosterone treatment may also be effective and efficacious for eugonadal and older men when higher testosterone dosages are administered. For acceptability, testosterone treatment was not significantly associated with fewer dropouts than placebo. Safety monitoring in testosterone treatment trials continues to be important owing to a lack of sufficiently powered long-term studies to determine increased risk for adverse events. Because our results as well as previous investigations have indicated that risk of bias is considerable in most studies, we call for large, preregistered RCTs of good quality investigating testosterone treatment’s effect in men on depression as the primary outcome.
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