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Suicide Risk with 5 Alpha-Reductase Inhibitors in Older Men

JAMA Intern Med; ePub 2017 Mar 20; Welk, et al

The use of 5α-reductase inhibitors were not found to be associated with an increase in suicide in older men, a recent study found; however, the risk of self-harm and depression were significantly increased, primarily during the first 18 months after initiation of the medication. This population-based matched cohort study included 93,197 men aged ≥66 years who initiated a new prescription for a 5α-reductase inhibitor during the study period of 2003 through 2013. Main outcome was suicide; secondary outcomes were self-harm and depression. Among the findings:

  • Men who used 5α-reductase inhibitors were not at a significantly increased risk of suicide (HR, 0.88).
  • Risk of self-harm was significantly increased during the initial 18 months after 5α-reductase inhibitor initiation (HR, 1.88), but not thereafter.
  • Depression risk was elevated during the initial 18 months after 5α-reductase inhibitor initiation (HR, 1.94), and continued to be elevated, but to a lesser degree, for the remainder of the follow-up period (HR, 1.22).

Citation:

Welk B, McArthur E, Ordon M, Anderson KK, Hayward J, Dixon S. Association of suicidality and depression with 5α-reductase inhibitors. [Published online ahead of print March 20, 2017]. JAMA Intern Med. doi:10.1001/jamainternmed.2017.0089.

Commentary:

5α-reductase inhibitors (5ARI) are recommended for treatment of benign prostatic hypertrophy (BPH) and lower urinary tract symptoms (LUTS) caused by BPH.1 5ARI work by inhibiting 5AR, which is responsible for the conversion of testosterone to dihydrotestosterone. The 2 5ARI’s, finasteride and dutasteride, decrease prostate volume, LUTS, future BPH-related complications, and the need for future prostate surgery.2 However, in 2011, the FDA received a postmarketing submissions raising a concern of self-harm and suicide potentially associated with finasteride. This occurrence is biologically feasible as 5ARI affects the production of a number of neuroactive peptides. Additionally, testosterone and dihydrotestosterone are involved in the body’s stress response, so an alteration in the conversion may affect response to stress. The current observational study supports that such a relationship may exist. Therefore, it may be wise to keep this study in mind when it comes to decision-making regarding 5ARI, especially in men who have a history of depression or who are currently experiencing an unusually high amount of stress. —Neil Skolnik, MD

  1. McVary KT, Roehrborn CG, Avins AL, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011;185(5):1793-1803. doi:10.1016/j.juro.2011.01.074.
  2. McConnell JD, Roehrborn CG, Bautista OM, et al. Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349(25):2387-2398. doi:10.1056/NEJMoa030656.

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