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We found that allopurinol use is associated with lowered risk of BPH medication, diagnosis and surgery. A possible explanation could be antioxidative effects of urate-lowering allopurinol.

Background Allopurinol is gout medication that inhibits uric acid formation. Its possible anti-carcinogenic properties have been under research in past years. Studies based on Taiwanese registries showed that long term allopurinol use might reduce prostate cancer (PCa) incidence. However, our studies based on Finnish registries did not support those findings. In this study, we evaluate whether allopurinol use is associated with prostate cancer-specific survival (CSS) or overall survival (OS) in a Finnish population-based cohort. Methods The study cohort was originally enrolled for the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). We included all newly diagnosed PCa cases during 1996–2015, 9252 men in total. Information on allopurinol purchases was from the national prescription registry of the Social Insurance Institution of Finland. Information about deaths, treatments, and use of other medications was obtained from registries, and tumor stage and PSA at diagnosis from medical records. Follow-up started at diagnosis, and we analysed separately two endpoints: PCa-specific death and overall death. We used an extended Cox regression with adjustment for age at diagnosis, Charlson comorbidity index, FinRSPC trial arm, use of other drugs and EAU PCa risk group. Results During a median follow-up of 9.86 years, 2942 deaths occurred, including 883 from PCa. There was no difference in CSS between allopurinol user and non-users, but allopurinol users had lower OS (multivariable-adjusted hazard ratio 1.77; 95% CI: 1.57–2.00). However, this decrease in OS was mitigated along with increasing intensity of allopurinol use. Conclusions We found no marked difference in CSS by allopurinol use. Allopurinol users had lower OS but there were no significant differences by duration or intensity of allopurinol use. Allopurinol use may not have anticancer effects against prostate cancer; instead, it may be a surrogate for metabolic problems causing shorter OS among men with PCa.

1.1 Background Metabolic syndrome and obesity are linked with hyperuricemia, and it has also been proposed that oxidative stress associated with hyperuricemia may promote benign prostatic hyperplasia (BPH). However, it is currently unknown whether use of antihyperuricemic medication is associated with risk of developing BPH. We studied the association between BPH and use of antihyperuricemic allopurinol in a Finnish population-based cohort. 1.2 Methods The study cohort consisted of 74,754 men originally identified for the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). Information on gout and BPH medication usage (5αreductase inhibitors, 5ARIs) during 1996-2014 was obtained from the national medication reimbursement database. Information on BPH diagnoses from in-and outpatient hospital visits and BPH-related surgery was obtained from the National Health Care Registry. Men with a record of BPH at baseline were excluded. We used Cox regression to analyze risk of starting BPH medication, having a recorded diagnosis or undergoing BPH surgery by allopurinol use with adjustment for age and simultaneous use of statins, antidiabetic or antihypertensive drugs and aspirin or other NSAIDs. Medication use was analyzed as a time-dependent variable to minimize immortal time bias. 1.3 Results Men using allopurinol had a decreased risk for all three BPH endpoints: BPH medication (HR 0.81; 95% CI 0.75-0.88), BPH diagnosis (HR 0.78; 95% CI 0.71-0.86) and BPH-related surgery (HR 0.67; 95% CI 0.58-0.76) after multivariable adjustment. The risk association did not change by cumulative use. The risk decrease disappeared after one to two years lag time. Only BMI modified the risk association; the risk decrease was observed only among men with BMI above the median (27.3 kg/m 2); p for interaction < 0.05 for each endpoint. 1.4 Conclusions We found that allopurinol use is associated with lowered risk of BPH medication, diagnosis and surgery. A possible explanation could be antioxidative effects of urate-lowering allopurinol.