Benign prostate enlargement, is the medical term for an enlarged prostate gland in men. Finasteride and dutasteride are 5alpha-reductase inhibitors, medications that are commonly used to treat the symptoms of an enlarged prostate. While these medications are known to be effective at treating an enlarged prostate, recently there have been concerns that they may have negative effects, possible increases in risk of certain cancers, including cancer of the kidney, bladder and prostate, as well as other non-cancer effects such as dementia and diabetes. Few studies have investigated these potential harmful effects, and these studies have found mixed results, with some studies finding increases in risk while others found no difference. Given these discrepancies, new well-conducted studies are needed to assess these important safety questions. This study will aim to investigate whether the use of these medications increase the risk of these cancers and non-cancer events in men diagnosed with an enlarged prostate, providing important information for patients, physicians and regulatory agencies.
Evidence from preclinical and observational studies suggest that 5alpha-reductase inhibitors (5ARIs) may increase the risk of urological cancers. Similarly, emerging evidence suggests 5ARIs may be associated with a number of non-cancer adverse events, such as dementia and diabetes. However few observational studies have been conducted and these have had a number of limitations. Thus, the objective of this study will be to assess these adverse events by assembling a cohort of patients who received a diagnosis of benign prostatic hyperplasia from January 1 1998, from the CPRD, linked to the National Cancer Data Repository and ONS mortality data. Time-dependent Cox proportional hazard models will be used to estimate hazard ratios and 95% confidence intervals of adverse events associated with the use 5ARIs, compared with non-use of 5ARIs Secondary analyses will investigate whether the risk varies according to cumulative duration of use and time since medication initiation. This study will provide further evidence regarding these potential adverse associations, providing concerned stakeholders with important information, enabling the assessment of the risks and benefit of these medications.
Primary analyses will investigate the use of 5alpha-reductase inhibitors and risk of urological cancer (based on ICD codes from NCDR, by site, histology and stage/Gleason score), diabetes (determined by Read codes from CPRD Gold) and dementia/Alzheimer's disease (determined by Read codes from CPRD Gold). Secondary hypothesis will investigate osteoporosis, cancer at other sites and cardiovascular outcomes (including heart failure, myocardial infarction, stroke and all-cause and cardiovascular specific-mortality from GP & ONS records).
Blánaid Hicks - Chief Investigator - Queen's University Belfast
Blánaid Hicks - Corresponding Applicant - Queen's University Belfast
Anton Pottegård - Collaborator - University Of Southern Denmark
Chris Cardwell - Collaborator - Queen's University Belfast
Chris Hill - Collaborator - Belfast Health and Social Care Trust
NCRAS Cancer Registration Data;ONS Death Registration Data;Patient Level Index of Multiple Deprivation