Testosterone and Cognitive Impairment or Dementia in Middle-Aged or Aging Males: Causation and Intervention, a Systematic Review and Meta-Analysis

To investigate the association between testosterone levels and the risk of dementia and to assess the effectiveness of testosterone supplement treatment in patients with cognitive impairment or dementia.

We searched Pubmed, Cochrane Library, and EMBASE on September 30, 2019.

The risk factor portion of the review included 27 studies with 18 599 participants. Studies revealed inconsistent findings on the association between testosterone levels and the risk of all-cause dementia or Alzheimer disease (AD). The result from our meta-analysis showed an increased risk of all-cause dementia with decreasing total testosterone (total-T, 4572 participants, hazard ratio: 1.14, 95% CI: 1.04-1.26). Some studies also found an increased risk of AD with a lower level of total-T, free testosterone, and bioavailable testosterone. Testosterone supplement treatment may improve general cognitive function and motor response in the short term as measured by the Developmental Test of Visual-Motor Integration (mean difference [MD]: 4.4, 95% CI: 1.20-7.59) and the Mini-Mental State Examination (MD: 3.4, 95% CI: 0.83-5.97) and verbal memory as measured by story recall delay at 3 months (MD: 8.4, 95% CI: 0.49-16.3).

Lower levels of testosterone may be associated with an increased risk of all-cause dementia or AD. Testosterone supplement treatment may or may not improve general cognitive function in patients with cognitive impairment/AD.