Effects of testosterone on cognitive and brain aging in elderly men.

Older age is associated with functional declines throughout the body, including some aspects of cognitive performance. While dementia develops in only some elderly individuals, declines in cognitive functioning have an impact on daily living for many others. There are individual differences in age-related cognitive changes, however, and the factors that contribute to this variability have not been well-characterized. Recent evidence suggesting that age-related alterations in the endocrine environment may modulate cognitive changes has generated considerable interest. Currently, there is a discordance between the rapidly expanding number of studies of the possible neuroprotective effects of estrogens in postmenopausal women, and the relative dearth of analogous research on the putative effects of testosterone on cognitive and brain function in older men. This paper reviews the extant literature and reports new findings on the effects of testosterone loss and supplementation on cognitive and brain function in elderly men. Preliminary evidence suggests that testosterone loss may be a risk factor for cognitive decline and possibly for dementia. Conversely, the maintenance of higher testosterone levels either endogenously or through exogenous supplementation may prove beneficial for cognitive and brain function in elderly men. However, most studies are associational in nature and the intervention studies are of short-duration testosterone exposure in small samples of subjects. Large-scale placebo-controlled intervention studies are required to resolve ambiguities in the literature. Testosterone intervention to ameliorate cognitive decline may be warranted only when the efficacy and safety of longer-term use is firmly established.