Suicide and Intentional Self-harm Among Older Men Treated With 5-Alpha Reductase Inhibitor or Alpha-blockers for Benign Prostatic Hyperplasia

Abstract

ObjectiveTo compare the risk of intentional self-harm (ISH) and suicide in older men using 5-α reductase inhibitors (5-ARIs) and alpha-blockers for benign prostatic hyperplasia (BPH). Observational research of older men with BPH suggested an increase in ISH with 5-ARI use compared with nonuse; we aimed to address potential confounding by indication with an active comparator reference group. MethodsUsing Medicare data linked to the National Death Index (NDI) from 2007-2016, we implemented a retrospective cohort design in males aged ≥65 years who initiated 5-ARI or alpha-blocker use for BPH. ISH was identified using ICD-9-CM and ICD-10-CM diagnosis codes. Suicides were identified through cause-of-death information from the NDI. We used inverse probability of treatment weighted Cox proportional hazards regression to compare time-to-event between treatment groups, with robust variance estimation. ResultsThe event rates for ISH and suicide, respectively, were 0.314 and 0.308 per 1000 person-years (PY) among 5-ARI users (n=181,675), and 0.364 and 0.382 per 1000PY among alpha-blocker users (n=850,476). For 5-ARI use relative to alpha-blocker use, hazard ratios (HRs) for ISH and suicide, respectively, were 0.88 (95% CI:0.62–1.25) and 0.82 (95% CI:0.54–1.24); for the composite outcome (non-fatal ISH or suicide), the HR was 0.88 (95% CI:0.66–1.16). Subgroup and sensitivity analyses supported these results. Conclusion5-ARI use was not associated with an increased risk for ISH or suicide compared to alpha-blocker use in older men with BPH. Study limitations included low event rates and potentially low sensitivity for ISH events.