5α-reductase inhibitor treatment implicated in dementia

Men who are receiving treatment with 5α-reductase inhibitors (5-ARIs) are at increased risk of dementia in the immediate period after initiating treatment, a study has shown. Of note, both finasteride and dutasteride are associated with depression, but neither of them is linked to suicide.

The Swedish register-based cohort study involved 2,236,876 men (median age at the start of follow-up 55 years, median age at treatment initiation 73 years). Researchers examined the participants’ recorded prescription of finasteride or dutasteride and duration of use in relation to a diagnosis of all-cause dementia, Alzheimer’s disease, vascular dementia, depression, or completed suicide.

Of the participants, 70,645 (3.2 percent) and 8,774 (0.4 percent) initiated finasteride and dutasteride treatment, respectively. Exposure to either treatment was associated with increased risks of all-cause dementia (finasteride: hazard ratio [HR], 1.22, 95 percent confidence interval [CI], 1.17–1.28; dutasteride: HR, 1.10, 95 percent CI, 1.01–1.20), Alzheimer’s disease (finasteride: HR, 1.20, 95 percent CI, 1.10–1.31; dutasteride: HR, 1.28, 95 percent CI, 1.09–1.50), vascular dementia (finasteride: HR, 1.44, 95 percent CI, 1.30–1.58; dutasteride: HR, 1.31, 95 percent CI, 1.08–1.59), and depression (finasteride: HR, 1.61, 95 percent CI, 1.48–1.75; dutasteride: HR, 1.68, 95 percent CI, 1.43–1.96).

However, the magnitude of the associations shrank over time, with the estimates becoming statistically nonsignificant with continuous exposures over 4 years. The exception was depression risk, which was consistently increased over time, with no differences between finasteride and dutasteride.

Meanwhile, 5-ARI treatment showed no association with suicide (finasteride: HR, 1.22, 95 percent CI, 0.99–1.49; dutasteride: HR, 0.98, 95 percent CI, 0.62–1.54).

According to the researchers, the decreasing magnitude of the association over time may be related, entirely or in part, to increased dementia detection among patients with benign prostate enlargement. In light of the findings, prescribing clinicians and potential users should be aware of the possible risks for depression associated with 5-ARI treatment.