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, K. Taddei, Malcolm Carruthers, Ralph N. Martins

Research output: Contribution to journalReview article

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.

Original languageEnglish
JournalAmerican Journal of Geriatric Psychiatry
DOIs
Publication statusE-pub ahead of print - 2019

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Testosterone
Meta-Analysis
Randomized Controlled Trials
Cognition
Confidence Intervals
Executive Function
Literature
Aptitude
Neuroprotective Agents
Therapeutics
Observational Studies
Placebos
Clinical Trials
Databases
Serum

Cite this

@article{3a8c6f6243674a7da1f00d0475c7c068,
title = "Effects of testosterone supplementation on separate cognitive domains in cognitively healthy older men: a meta-analysis of current randomized clinical trials",
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 = "ageing, Alzheimer's disease, cognitive decline, cognitive function, hypogonadism, memory, Testosterone supplementation",
author = "Sherilyn Tan and Sohrabi, {Hamid R.} and Michael Weinborn and Michelle Tegg and Bucks, {Romola S.} and K. Taddei and Malcolm Carruthers and Martins, {Ralph N.}",
year = "2019",
doi = "10.1016/j.jagp.2019.05.008",
language = "English",
journal = "Americal journal of geriatric psychiatry",
issn = "1064-7481",
publisher = "Academic Press",

}

TY - JOUR

T1 - Effects of testosterone supplementation on separate cognitive domains in cognitively healthy older men

T2 - a meta-analysis of current randomized clinical trials

AU - Tan, Sherilyn

AU - Sohrabi, Hamid R.

AU - Weinborn, Michael

AU - Tegg, Michelle

AU - Bucks, Romola S.

AU - Taddei, K.

AU - Carruthers, Malcolm

AU - Martins, Ralph N.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - ageing

KW - Alzheimer's disease

KW - cognitive decline

KW - cognitive function

KW - hypogonadism

KW - memory

KW - Testosterone supplementation

UR - http://www.scopus.com/inward/record.url?scp=85068468185&partnerID=8YFLogxK

U2 - 10.1016/j.jagp.2019.05.008

DO - 10.1016/j.jagp.2019.05.008

M3 - Review article

JO - Americal journal of geriatric psychiatry

JF - Americal journal of geriatric psychiatry

SN - 1064-7481

ER -