5α- Reductase Inhibitors Linked to Depression, but Not Dementia or Suicide

A new study found that 5α- reductase inhibitors (5-ARIs), used in the treatment of benign prostatic hyperplasia and androgenic alopecia, may be associated with depression.

“Pharmacologically, 5-ARIs selectively inhibit the enzyme 5α-reductase (5-AR), which is involved in the conversion of testosterone into the androgen metabolite 5α-dihydrotestosterone (DHT) and expressed in many tissues, such as the prostate, testes, and hair follicles,” study researchers wrote in JAMA Network Open.

According to the researchers, “in recent decades, clinical and public health concerns have arisen on the possible adverse neurological effects of 5-ARIs because low androgen levels have been potentially associated with elevated risk of cognitive decline and dementia.”

This Swedish register-based study included data from more than 2.2 million men age 50- 90 years old from July, 2005-December, 2018. Of the study’s subjects, 3.2% started treatment with finasteride, and 0.4% started dutasteride during the study’s period.

Men taking either drug had an increased risk of all-cause dementia (finasteride hazard ratio HR=1.22 and dutasteride HR=1.28). There was also an increased risk for Alzheimer’s, vascular dementia, and depression.

The researchers noted that the magnitude of the association decreased over time. The association became nonsignificant with continuous exposures over 4 years, except in the case of depression, which showed constant risk over time. The researchers suggested that initial increase in the diagnosis of dementia “may be, entirely or in part, due to increased dementia detection among patients with benign prostate enlargement.”

No association with suicide was identified.