5-ARIs use not linked to dementia risk but associated with depression: JAMA

The study showed that men receiving 5-ARIs for androgenic alopecia and benign prostatic hyperplasia (BPH) had a greater dementia risk in the initial period after treatment initiation; however, the magnitude of the association decreased over time. This suggested that the risk may be entirely or partly due to the increased detection of dementia in patients with benign prostate enlargement. Dutasteride and finasteride were shown to be similarly associated with depression with a constant risk over time, while neither drug was linked with suicide.

There has been an increasing interest in the possible adverse neurological effects of 5-ARIs in recent decades, which have been used mainly for androgenic alopecia and benign prostatic hyperplasia. Several studies and reports have suggested associations of 5-ARIs with suicide and depression. However, most of these studies had methodological shortcomings, and little is known about the potential associations of 5-ARIs with dementia.

Against the above background, Miguel Garcia-Argibay from Örebro University in Örebro, Sweden, and the team aimed to investigate the association of 5-ARI use with Alzheimer's disease, all-cause dementia, depression, vascular dementia, and suicide in a Swedish register-based cohort study.

A recorded prescription in the Swedish national prescription register of dutasteride or finasteride and duration of use. The study included 2 236 876 men aged 50 to 90 between 2005 and 2018. The study's primary outcomes were a diagnosis of Alzheimer's disease, all-cause dementia, depression, vascular dementia, or completed suicide.

The authors reported the following findings:

• Of 2 236 876 men (median age at the start of follow-up, 55 years and treatment initiation, 73 years), 3.2% (n=70 645) started finasteride treatment, and 0.4% (n=8774) started dutasteride treatment.
• Men taking finasteride or dutasteride were at increased risk of all-cause dementia (finasteride: hazard ratio [HR], 1.22; dutasteride: HR, 1.10), Alzheimer's disease (finasteride: HR, 1.20; dutasteride: HR, 1.28), vascular dementia (finasteride: HR, 1.44; dutasteride: HR, 1.31), and depression (finasteride: HR, 1.61; dutasteride: HR, 1.68).
• The magnitude of the association decreased over time, and the findings became statistically nonsignificant with continuous exposures over four years, except for depression, which showed a constant risk over time, with no differences between finasteride and dutasteride.
• 5-ARIs was not associated with suicide (finasteride: HR, 1.22; dutasteride: HR, 0.98).

"The results of this cohort study suggest that provided the decreasing magnitude of the association over time, 5-ARI medications—dutasteride and finasteride —do not seem to be associated with all-cause dementia, vascular dementia, Alzheimer's disease, or suicide," the researchers wrote. "However, individuals receiving 5-ARI treatment may be at increased depression risk."

Reference:

Garcia-Argibay M, Hiyoshi A, Fall K, Montgomery S. Association of 5α-Reductase Inhibitors With Dementia, Depression, and Suicide. JAMA Netw Open. 2022;5(12):e2248135. doi:10.1001/jamanetworkopen.2022.48135