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.

Androgen Therapy in Neurodegenerative Diseases

“…To illustrate, T administration improved cognition [ 142 ], and visual-spatial skills [ 143 ] in some cases, whereas other studies showed no positive effects on memory or mental impairment [ 144-147 ]. In a recent meta-analysis, Buskbjerg et al [ 147 ] showed that T therapy in men with normal plasma T levels had no significant clinical effect on cognitive function; T effects on men with hypogonadism remain to be evaluated.…”

Age‐related cognitive impairment is associated with low serum concentrations of testosterone and CSF levels of amyloid beta 42 in male cynomolgus monkeys (Macaca fascicularis)

“…It is speculated that testosterone correlates with cognitive performance because hormone receptors are located near areas related to cognitive function, including the hippocampus, [18][19][20] and this hormone supports mechanisms related to cognitive function, such as increasing cerebral blood perfusion, influencing neuronal activity, and other neural-protective effects. [21][22][23][24] Similar positive associations between testosterone and cognitive ability have been described in chimpanzees, which may suggest that neuro-hormones, such as testosterone, play an important role in cognitive function 25,26 in apes and humans, as well as in other non-human primates. 27 Our findings support that old individuals with lower than normal testosterone serum level, have poorer cognitive performance.…”

Age-Related Male Hypogonadism and Cognitive Impairment in the Elderly: Focus on the Effects of Testosterone Replacement Therapy on Cognition

“…Considering these heterogenous study designs and protocols, these positive results on cognition could be the consequences of several biases. In a recently published metanalysis, Buskbjerg et al extensively evaluated the effect of T supplementation on cognition, finding a great variability in the results [ 89 ]. Particularly, different sources of bias have been verified.…”