Association between duration of gonadotrophin-releasing hormone agonist use and cardiovascular risks: A population-based competing-risk analysis

Background: Although androgen deprivation therapy has known cardiovascular risks, it is unclear if its duration is related to cardiovascular risks. This study thus aimed to investigate the associations between gonadotrophin-releasing hormone (GnRH) agonist use duration and cardiovascular risks.

Methods: This retrospective cohort study included adult patients with prostate cancer receiving GnRH agonists in Hong Kong during 1999-2021. Patients who switched to GnRH antagonists, underwent bilateral orchidectomy, had <6 months of GnRH agonist, prior myocardial infarction (MI), or prior stroke was excluded. All patients were followed up until September 2021 for a composite endpoint of MI and stroke. Multivariable competing-risk regression using the Fine-Gray subdistribution model was used, with mortality from any cause as the competing event.

Results: In total, 4038 patients were analyzed (median age 74.9 years old, interquartile range (IQR) 68.7-80.8 years old). Over a median follow-up of 4.1 years (IQR 2.1-7.5 years), longer GnRH agonists use was associated with higher risk of the endpoint (sub-hazard ratio per year 1.04 [1.01-1.06], p = 0.001), with those using GnRH agonists for ≥2 years having an estimated 23% increase in the sub-hazard of the endpoint (sub-hazard ratio 1.23 [1.04-1.46], p = 0.017).

Conclusion: Longer GnRH agonist use may be associated with greater cardiovascular risks.