Testosterone Supplementation and Cognitive Functioning in Men-A Systematic Review and Meta-Analysis

Testosterone supplementation (TS) is assumed important for cognitive functioning in men, but conflicting results have prevented firm conclusions. The current study systematically reviewed available randomized controlled trials (RCTs) on effects of TS on cognitive functioning in men, subjected the findings to meta-analysis, and explored between-study differences as possible moderators of the effects. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, two authors independently searched for eligible records in the electronic databases of PubMed, PsycINFO, Web of Science, the Cochrane Library, Cumulative Index of Nursing and Allied Health, and Embase and determined eligibility using the following (population, intervention, comparison, outcome) criteria: population, male adults (> 18 years); intervention, TS; comparison, placebo; and outcome, results of standardized neuropsychological tests. Following duplicate removal, 3873 records were screened with 92 remaining for full-text screening. Twenty-one papers reporting results of 23 independent RCTs were included, of which none treated samples of clinically hypogonadal men. The small improvement found in overall cognitive functioning (Hedges g 5 = 0.09; CI 95%: -20.02 to 0.19) failed to reach statistical significance (P = 0.108) and approached zero when adjusting for possible publication bias (g = 0.04). The effects for the 11 individual cognitive domains did not reach statistical significance (g: -20.04 to 0.19, P: 0.061 to 0.989). Small statistically significant (P < 0.05) effects were found for five study subsets but failed to meet the fail-safe criterion. The available evidence indicates that effects of TS on cognitive functioning in men with testosterone levels within normal ranges are less robust and of insufficient magnitude to be of clinical relevance. The effects in clinically hypogonadal men remain to be investigated. Copyright (C) 2019 Endocrine Society