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

Abstract

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 = 0.09; CI 95%: -0.02 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: -0.04 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.

Keywords: androgens; cognitive functions; meta-analysis; systematic review; testosterone supplementation.

Figure 1.

Flowchart of study selection.

Figure 2.

Individual effect sizes and forest plots. Individual studies’ overall effect sizes (Hedges g) are shown in the second column and are the unit of analysis. The summary pooled effect size (Hedges g) computed with a random effect model is shown in the bottom row of the second column. Notation: Forest plot. Each square represents the effect size of one individual study. Size of the square indicates the relative weight assigned to the study, with more weight assigned to more precise studies, as indicated by larger squares. Lines: Each line represents a 95% CI of the effect size of the study. The diamond represents the summary pooled g of all of the individual gs. Precision of the summary effect is indicated by the width of the diamond.

Figure 3.

Funnel plot of the overall pooled effect with missing studies imputed. Funnel plot of precision [1/SE (Std Err)] by effect sizes (Hedges g) with imputed studies. Each open circle represents precision as a measure of the sample size on the y-axis as a function of the effect size of each independent study on the x-axis. Closed circles represent imputed studies. The open diamond in the bottom of the plot indicates the summary effect size of the analysis. The closed diamond indicates the summary effect size with imputed studies included. A 95% CI is indicated by the lines. Within these lines, 95% of the circles are expected to be located. The overall pooled effect size is indicated by a vertical line in the middle of the plot.