Hormonal changes and their impact on cognition and mental health of ageing men

Demographic changes resulting in ageing of the world's population have major implications for health. As men grow older, circulating levels of the principal androgen or male sex hormone testosterone (T) decline, while the prevalence of ill-health increases. Observational studies in middle-aged and older men have shown associations between lower levels of T and poorer mental health in older men, including worse cognitive performance, dementia and presence of depressive symptoms. The role of T metabolites, the more potent androgen dihydrotestosterone (DHT) and the oestrogen receptor ligand estradiol (E2) in the pathophysiology of cognitive decline are unclear. Studies of men undergoing androgen deprivation therapy in the setting of prostate cancer have shown subtle detrimental effects of reduced T levels on cognitive performance. Randomised trials of T supplementation in older men have been limited in size and produced variable results, with some studies showing improvement in specific tests of cognitive function. Interventional data from trials of T therapy in men with dementia are limited. Lower levels of T have also been associated with depressive symptoms in older men. Some studies have reported an effect of T therapy to improve mood and depressive symptoms in men with low or low-normal T levels. T supplementation should be considered in men with a diagnosis of androgen deficiency. Beyond this clinical indication, further research is needed to establish the benefits of T supplementation in older men at risk of deteriorating cognition and mental health.