Men with an enlarged prostate (otherwise known as benign prostatic hyperplasia or BPH) commonly use a class of drugs called 5-alpha reductase inhibitors (5?RIs). 5?RIs reduce the size of enlarged prostates, alleviate the symptoms of BPH, and decrease the need for surgery. However, the hormonal changes associated with their use may alter their risk of anaemia (low levels of red blood cells or haemoglobin in the blood). To our knowledge, this potential drug side effect has not been thoroughly investigated in a real-world setting. We will, therefore, study this research question using the Clinical Practice Research Datalink (CPRD). Our study population will include all patients with a diagnosis for BPH. These patients will be classified as those treated with 5?RIs and those treated with ?-blockers (an alternative therapy for BPH). We will then compare the number of men with anaemia between each treatment group. We will thus be able to determine if 5?RI use increases the chances of having anaemia compared with the ?-blocker use among men with BPH.
5?RIs reduce prostate size among men with BPH by lowering levels of dihydrotestosterone, an androgen that promotes prostate growth. Previous studies have reported that decreased androgen levels are associated with an increased risk of anaemia; however, the anaemia effects of 5?RIs have not been previously assessed in a real-world setting. We will thus conduct a population-based retrospective cohort study using the CPRD to compare the risk of anaemia of 5?RIs versus that of ?-blockers. We will identify all patients with incident BPH in the CPRD from April 1998 to March 2019. Using an active comparator, new-user approach, patients will enter the cohort on their first eligible prescription for a 5?RI or an ?-blocker. In our primary analysis, we will use an as-treated exposure definition and will follow patients until the development of anaemia, discontinuation of the study drug, initiation of the other study drug or combination therapy, or administrative censoring. Secondary outcomes will include different World Health Organization (WHO)-defined categories of anaemia severity: mild (129-110g/l), moderate (109-80g/l), and severe (<80g/l) anaemia. We will match 5?RI users to ?-blocker users and use Cox-proportional hazards models estimate the hazard ratio and 95% CIs for anaemia with 5?RIs versus ?-blockers. In secondary analyses, we will examine the risk by molecule, by the duration of use, and whether any observed increased risk is reversible.
Anaemia (overall and by severity)
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Kristian Filion - Corresponding Applicant - McGill University
Antonios Douros - Collaborator - McGill University
Henok Tadesse Ayele - Collaborator - Merck Sharp & Dohme LLC
Kristian Filion - Collaborator - McGill University
pauline reynier - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Reem Masarwa - Collaborator - McGill University
Henok Tadesse Ayele - Collaborator - McGill University