The risk of dementia with the use of 5 alpha reductase inhibitors

Introduction — There has been considerable interest in the interplay between testosterone and cognition. Dihydrotestosterone (DHT), which has been correlated with cognitive function, is significantly reduced with the use of 5 alpha reductase inhibitors (5ARI) for prostatic enlargement. Our objective was to assess whether the use of 5ARIs was associated with an increased risk of incident dementia.

Methods — We used a matched cohort design and linked administrative data from the province of Ontario, Canada. A total of 99 covariates were measured, and a propensity score was used for matching; 81,162 men who used a 5ARIs were matched to an equal number of men who did not.

Results — New initiation of 5ARI medication was associated with an increased risk of dementia during the first (HR 2.18, 95% CI 2.01–2.35) and second (HR 1.52, 95% CI 1.39–1.67) year, however this risk was nonsignificant among the men with the longest exposure to 5ARIs (HR 1.06, 95% CI 0.98–1.14). There was no difference in the results between types of 5ARIs.

Conclusion — As the strength of the association decreased with increased exposure, the higher risk seen in the initial two years likely represents the presentation and treatment of urinary symptoms which coexist with mild cognitive impairment and eventually progresses to a diagnosis of dementia.