The Effects of Testosterone Supplementation on Cognitive Functioning in Older Men.

Abstract

Reduction in testosterone levels in men during aging is associated with cognitive decline and risk of dementia. Animal studies have shown benefits for testosterone supplementation in improving cognition and reducing Alzheimer’s disease pathology. In a randomized, placebo-controlled, crossover study of men with subjective memory complaint and low testosterone levels, we investigated whether testosterone treatment significantly improved performance on various measures of cognitive functioning. Forty-four men were administered a battery of neuropsychological tests to establish the baseline prior to being randomly divided into two groups. The first group (Group A) received 24 weeks of testosterone treatment (T treatment) followed by 4 weeks washout, and then 24 weeks of placebo (P); the second group (Group B) received the same treatments, in reverse order (Placebo, washout, and then T treatment). In group A (TèP), compared to baseline, there was a modest (1 point) but significant improvement in general cognitive functioning as measured by the Mini Mental State Examination (MMSE) following testosterone treatment. This improvement from baseline was sustained following the washout period and crossover to placebo treatment. Similar Mini Mental State Examination (MMSE) scores were observed when comparing testosterone treatment with placebo. In group B (PèT) a significant increase was observed from baseline following testosterone treatment and a trend towards an increase when compared to placebo treatment. Improvements in baseline depression scores (assessed by Geriatric Depression Scale) were observed following testosterone/placebo treatment in both groups, and no difference was observed when comparing testosterone with placebo treatment. Our findings indicate a modest improvement on global cognition with testosterone treatment. Larger clinical trials with a longer follow- up and with the inclusion of blood and brain imaging markers are now needed to conclusively determine the significance of testosterone treatment.

Testosterone therapy in men with testosterone deficiency: Are we beyond the point of no return?

“…The adverse impact of TD on mood and depressive symptoms has been reported in several studies [355565758596061]. Although the magnitude of improvements differed among the various studies, a link between TD, mood and depressive symptoms exists.…”

“…Observational studies of 799 men on T therapy showed 22% reduction in fatigue scores over 6 months [57]. A modest improvement on global cognition with T therapy was also reported (Table 1) [61]. …”

2D:4D digit ratio is associated with cognitive decline but not frailty in community‐dwelling older adults

“…There is also evidence that cognitive function could be influenced by testosterone levels (Barrett‐Connor, Goodman‐Gruen, & Patay, ; Moffat et al, ). Low testosterone levels in older men appear to be associated with cognitive decline and risk of dementia (Wahjoepramono et al, ). However, there is conflicting evidence showing that cognitive function does not suffer any interference from testosterone intake (Huang et al, ).…”

Sex differences in Alzheimer’s-related Tau biomarkers and a mediating effect of testosterone

“…In women, circulating estradiol levels experience a substantial decline during menopause, whereas post-menopausal women continue to demonstrate a range of circulating testosterone levels that continue to be lower than levels in men [17]. Despite this sex difference in hormone levels, most studies examining links between testosterone and AD-related outcomes have been solely in men [18][19][20][21][22][23], and the link between testosterone and Tau has been minimally examined in humans.…”

“…Suggestive of a more causative than consequential role for testosterone on AD-related outcomes, longitudinal studies have shown that low free and/or total testosterone levels precede development of AD dementia [23] and cognitive dysfunction on measures of global cognition [26,29] and episodic memory [29] . Furthermore, exogenous testosterone supplementation led to improved performance over time in a range of cognitive domains including global cognition [19,33], psychomotor speed [33], executive function [33], osterone on AD-related outcomey ni cant contributor tonitive impairmentthey suggest that the f AD pathology and that this cogand spatial and verbal memory [34,35], although not always [36].…”