ABSTRACT
Pre-clinical evidence suggests that 5-alpha reductase inhibitors (5ARi's), prescribed in the treatment of benign prostatic hyperplasia, reduce colorectal and gastro-oesophageal cancer incidence via action on the male hormonal pathway. However, few studies to date have investigated this association at the population level. Our study aimed to investigate the risk of colorectal and gastro-oesophageal cancers with the use of 5ARi's. We conducted a retrospective cohort study of new users of 5ARi's and alpha-blockers among patients with benign prostatic hyperplasia in the UK Clinical Practice Research Datalink. Patients were followed until a first ever diagnosis of colorectal or gastro-oesophageal cancer, death from any cause or end of registration with the general practice or 31st of December 2017. Cox proportional hazards models with inverse probability of treatment weights were used to calculate weighted hazard ratios (HR) and 95% confidence intervals (CIs) of incident colorectal cancer or gastro-oesophageal cancer associated with the use of 5ARi's compared to alpha-blockers. During a mean follow-up of 6.6 years, we found no association between the use of 5ARi's and colorectal (HR: 1.13, 95% CI 0.91-1.41) or gastro-oesophageal (HR 1.14, 95% CI 0.76-1.63) cancer risk compared to alpha-blockers. Sensitivity analysis showed largely consistent results when varying lag periods, using multiple imputations, and accounting for competing risk of death. Our study found no association between the use of 5ARi's and risk of colorectal or gastro-oesophageal cancer in men with benign prostatic hyperplasia.
Subject(s)
5-alpha Reductase Inhibitors , Prostatic Hyperplasia , Humans , Male , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/epidemiology , 5-alpha Reductase Inhibitors/therapeutic use , 5-alpha Reductase Inhibitors/adverse effects , Aged , Retrospective Studies , Middle Aged , Incidence , Gastrointestinal Neoplasms/epidemiology , United Kingdom/epidemiology , Adrenergic alpha-Antagonists/therapeutic use , Adrenergic alpha-Antagonists/adverse effects , Aged, 80 and over , Colorectal Neoplasms/epidemiology , Proportional Hazards Models , Risk Factors , Esophageal Neoplasms/epidemiologyABSTRACT
BACKGROUND: Preclinical evidence suggests that 5α-reductase inhibitors (5ARi), commonly used to treat benign prostatic hyperplasia (BPH), are associated with reduced incidence of certain urologic cancers, yet epidemiologic studies are conflicting. This study aimed to determine whether 5ARi's are associated with a reduced risk of kidney and bladder cancers. METHODS: We conducted a new-user active-comparator cohort study in the United Kingdom Clinical Practice Research Datalink. From a base cohort of patients with incident BPH, new users of 5ARi's and α-blockers were identified. Patients were followed up until a first ever diagnosis of kidney or bladder cancer, death from any cause, end of registration, or December 31, 2017. Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI) for incident kidney and bladder cancer. RESULTS: There were 5,414 and 37,681 new users of 5ARi's and α-blockers, respectively. During a mean follow-up of 6.3 years, we found no association between the use of 5ARi's and kidney (adjusted HR, 1.26; 95% CI, 0.74-2.12; n = 23) or bladder (adjusted HR, 0.89; 95% CI, 0.64-1.23; n = 57) cancer risk compared with α-blockers. Similar results were observed across sensitivity analyses. CONCLUSIONS: In this study, we found no association between the use of 5ARi's and kidney or bladder cancer incidence in men with BPH when compared with α-blocker use. IMPACT: The findings of this study indicate that 5ARi's are unlikely to reduce kidney or bladder cancer risk.