Effects of Testosterone Supplementation on Separate Cognitive Domains in Cognitively Healthy Older Men: A Meta-analysis of Current Randomized Clinical Trials

Sherilyn Tan; Hamid R Sohrabi; Michael Weinborn; Michelle Tegg; Romola S Bucks; Kevin Taddei; Malcolm Carruthers; Ralph N Martins

doi:10.1016/j.jagp.2019.05.008

Effects of Testosterone Supplementation on Separate Cognitive Domains in Cognitively Healthy Older Men: A Meta-analysis of Current Randomized Clinical Trials

Am J Geriatr Psychiatry. 2019 Nov;27(11):1232-1246. doi: 10.1016/j.jagp.2019.05.008. Epub 2019 May 20.

Authors

Sherilyn Tan¹, Hamid R Sohrabi², Michael Weinborn³, Michelle Tegg⁴, Romola S Bucks⁵, Kevin Taddei⁶, Malcolm Carruthers⁷, Ralph N Martins⁸

Affiliations

¹ Australian Alzheimer's Research Foundation, Nedlands, Western Australia, Australia; School of Psychological Science, University of Western Australia, Perth, Western Australia, Australia.
² Australian Alzheimer's Research Foundation, Nedlands, Western Australia, Australia; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia; School of Psychiatry and Clinical Neurosciences, University of Western Australia, Nedlands, Western Australia, Australia; Department of Biomedical Sciences, Faculty of Medicine and Health Science, Macquarie University, Sydney, New South Wales, Australia. Electronic address: h.sohrabi@ecu.edu.au.
³ Australian Alzheimer's Research Foundation, Nedlands, Western Australia, Australia; School of Psychological Science, University of Western Australia, Perth, Western Australia, Australia; School of Psychiatry and Clinical Neurosciences, University of Western Australia, Nedlands, Western Australia, Australia.
⁴ School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
⁵ School of Psychological Science, University of Western Australia, Perth, Western Australia, Australia.
⁶ Australian Alzheimer's Research Foundation, Nedlands, Western Australia, Australia; School of Psychiatry and Clinical Neurosciences, University of Western Australia, Nedlands, Western Australia, Australia.
⁷ Centre for Men's Health, London, United Kingdom.
⁸ Australian Alzheimer's Research Foundation, Nedlands, Western Australia, Australia; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia; School of Psychiatry and Clinical Neurosciences, University of Western Australia, Nedlands, Western Australia, Australia; Department of Biomedical Sciences, Faculty of Medicine and Health Science, Macquarie University, Sydney, New South Wales, Australia.

PMID: 31296441
DOI: 10.1016/j.jagp.2019.05.008

Abstract

Background: An increasing body of literature suggests a positive, neuroprotective effect for testosterone on cognition in older men. However, randomized clinical trials (RCTs) examining the effects of testosterone supplementation (TS) on cognitive function have been inconclusive.

Objective: To investigate the potential for TS to prevent cognitive decline in otherwise cognitively healthy older men, by examining the differential effects of TS on cognitively healthy older men in RCTs.

Methods: Comprehensive search of electronic databases, conference proceedings, and grey literature from 1990 to 2018 was performed to identify RCTs examining the effects of TS on cognition before and after supplementation, in cognitively healthy individuals.

Results: A final sample of 14 eligible RCTs met inclusion criteria. Using pooled random effects expressed as Hedge's g, comparison of placebo versus treatment groups pre- and postsupplementation showed improvements in the treatment group in executive function (g (11) = 0.14, 95% confidence interval [CI]: 0.03-0.26, z = 0.56, p = 0.011). However, it was noted that two studies in our sample did not report a significant increase in mean serum total testosterone (TT) levels in the treatment group after supplementation. Following exclusion of these studies, analysis indicated improvement in the treatment group for the overall cognitive composite (g (11) = 0.18, 95% CI: 0.02-0.33, z = 2.18), psychomotor speed (g (3) = 0.22, 95% CI: 0.01-0.43, z = 2.07) and executive function (g (9) = 0.15, 95% CI: 0.03-0.28, z = 2.35). No significant differences were noted for the global cognition, attention, verbal memory, visuospatial ability or visuospatial memory domains.

Conclusion: Overall, our findings support the potential for TS as a preventative measure against cognitive decline, although the effect sizes were small. These findings warrant further observational studies and clinical trials of good methodological quality, to elucidate the effect of TS on cognition.

Keywords: Alzheimer's disease; Testosterone supplementation; ageing; cognitive decline; cognitive function; hypogonadism; memory.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review

MeSH terms

Aged
Cognition / drug effects
Cognitive Dysfunction / prevention & control*
Dietary Supplements
Humans
Male
Memory / drug effects
Men's Health
Randomized Controlled Trials as Topic
Testosterone / blood*
Testosterone / pharmacology*

Substances

Testosterone