A closer look at a large cohort of patients show 5α-reductase inhibitors (5-ARI) use was associated with an increased risk of depression and a number of neurological disorders, including dementia and Alzheimer disease.

A team, led by Miguel Garcia-Argibay, PhD, Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, identified the association of 5-ARI use with all-cause dementia, Alzheimer disease, vascular dementia, depression, and suicide.

5α-Reductase Inhibitors

Research has focused on the possible adverse neurological effects of 5-ARIs) in recent decades. However, the treatments have been mostly used for benign prostatic hyperplasia and androgenic alopecia.

There have been studies indicating the medications are associated with increased risks for depression and suicide, but these studies have methodological shortcomings, with little known about any potential association with dementia.

In the Swedish register-based cohort, the investigators examined data from 2.2 million males aged 50-90 between July 1, 2005 and December 31, 2018. The median age at the start of follow-up was 55 years and at treatment initiation was 73 years. In addition, 3.2% (n = 70,645) of patients started finasteride treatment and 0.4% (n = 8774) started dutasteride treatment.

The investigators sought main outcomes of all-cause dementia, Alzheimer disease, vascular dementia, depression, or completed suicide.

The Risk

The results show finasteride or dutasteride were associated with an increased risk of all-cause dementia (finasteride: hazard ratio, 1.22; 95% CI, 1.17-1.28; dutasteride: HR, 1.10; 95% CI, 1.01-1.20), as well as Alzheimer disease (finasteride: HR, 1.20; 95% CI, 1.10-1.31; dutasteride: HR, 1.28; 95% CI, 1.09-1.50) and vascular dementia (finasteride: HR, 1.44; 95% CI, 1.30-1.58; dutasteride: HR, 1.31; 95% CI, 1.08-1.59).

The same was also true for depression (finasteride: HR, 1.61; 95% CI, 1.48-1.75; dutasteride: HR, 1.68; 95% CI, 1.43-1.96).

Moreover, the magnitude of these associations decreased over time to the point where the findings become statistically nonsignificant with continuous exposures over 4 years, with the exception of depression, which showed a constant risk over time with no differences between the 2 treatments.

On the other hand, 5-ARI treatment was not linked to suicide (finasteride: HR, 1.22; 95% CI, 0.99-1.49; dutasteride: HR, 0.98; 95% CI, 0.62-1.54).

“This cohort study found that, while men receiving 5-ARI treatment showed a higher risk for dementia in the initial periods after starting treatment, the decreasing magnitude of the association over time suggested that the risk may be, entirely or in part, due to increased dementia detection among patients with benign prostate enlargement,” the authors wrote. “Both finasteride and dutasteride were similarly associated with depression with a constant risk over time, while neither drug was associated with suicide. Prescribing clinicians and potential users should be aware of the possible risks for depression associated with 5-ARI use.”

The study, “Association of 5α-Reductase Inhibitors With Dementia, Depression, and Suicide,” was published online by JAMA Network Open.