Use of 5α-reductase inhibitors for benign prostate hypertrophy and risk of high grade prostate cancer: a French population-based study

Objective: To assess the association between 5α-reductase inhibitor (5-ARI) use and high grade (Gleason score 8-10) prostate cancer.

Patients and methods: We conducted a population-based nested matched case-control study using the French national health insurance database linked to data from all pathology laboratories in Brittany, France. Among 74 596 patients with ≥1 drug reimbursement for symptomatic benign prostate hypertrophy (BPH) between 1 January 2010 and 31 December 2011, 767 incident prostate cancer cases between 1 January 2012 and 31 December 2013 were matched according to age and delay between the first observed delivery of drug for BPH (5-ARIs, α-blockers or phytotherapy) and diagnostic date of the case to five control patients, using an incidence density sampling design.

Results: A total of 963 patients (153 cases, 810 controls) had been exposed to 5-ARIs. A significant heterogeneity (P = 0.005) was detected across cancer grades when estimating the association between prostate cancer and long-term (≥2 years) 5-ARI use vs no 5-ARI exposure: adjusted conditional odds ratio 1.76 (95% confidence interval [CI] 0.97-3.21) for Gleason score ≥8 and 0.64 (95% CI 0.44-0.93) for Gleason score < 8.

Conclusion: Our results indicate an increased risk of high grade and a decreased risk of low grade prostate cancer associated with 5-ARI use. Patients treated for >2 years with 5-ARIs should be informed about the increased risk of development of high grade disease.