As men age, a substance in the blood called testosterone, the male sex hormone, decreases, resulting in a medical condition termed hypogonadism. The symptoms of hypogonadism may include tiredness and depression, lack of interest or enjoyment in sexual activities, increased fat mass, as well as decreased bone and muscle mass, among others. Treatment of hypogonadism with testosterone has been shown to be effective in reversing these symptoms. Previously, there had been concerns that testosterone may increase the risk of heart attacks and strokes in men receiving this treatment. However, recent studies have found no such increased risk, and it remains unclear as to whether testosterone is indeed safe for the treatment of hypogonadism. Therefore, the objective of our study is to formally evaluate the safety of testosterone, by determining how frequently men treated with testosterone experience heart attacks and strokes as compared to men who are not treated. We will also determine whether these patients have a higher risk of death. Finally, we will also conduct additional analyses to determine whether the safety of these medications differs among different patient groups, such as the elderly, those with a history of heart attack or stroke, diabetes or chronic kidney disease.
It is unclear whether testosterone replacement therapy (TRT) increases the risk of cardiovascular and cerebrovascular events. Therefore, the objective of our study is to evaluate the safety of TRT, specifically with respect to myocardial infarction and ischemic stroke, as well as all-cause mortality. We will create a cohort of men aged 45 or older, diagnosed with hypogonadism, and with no history of TRT use prior to diagnosis. In primary analyses, exposure to TRT will be defined as a time-dependent variable, and Cox regression will be used to evaluate the rates of myocardial infarction, ischemic stroke, and all-cause mortality, comparing current TRT exposure to no exposure. These outcomes will be evaluated both as a composite outcome, and separately. In secondary analyses, we will assess whether this risk varies with cumulative duration of TRT use (< 6 months, 6 months - 2 years, > 2 years). The primary analyses will be repeated, with stratification on TRT formulation, as well as patient age (45-59, 60-74, and 75 years and older), history of myocardial infarction, history of ischemic stroke, diabetes, and chronic kidney disease status. Finally, we will use marginal structural Cox models to evaluate the safety of TRT while accounting for time-dependent covariates.
Ischemic stroke; Myocardial infarction; All-cause mortality.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Christel Renoux - Corresponding Applicant - McGill University
Laurent Azoulay - Collaborator - McGill University
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Rui Nie - Collaborator - McGill University
Simone Loo - Collaborator - McGill University
HES Admitted Patient Care;ONS Death Registration Data