In real‑world reports, the GnRH agonist triptorelin (and similar drugs) shows about a 5% chance of heart‑related side effects, while the antagonist degarelix shows a slightly lower risk. Younger men (<65) have very low heart risk, but serious or even fatal events can still happen, especially with the agonists. This suggests that if you’re using hormone blockers, the type of drug matters for heart health.

GnRH agonists and GnRH antagonists are two of the mainstays of hormonal therapy (HT) for prostate cancer (PCa). These drugs are at increased risk of cardiovascular (CV) adverse events (AEs). Aim of our study was to compare real-life data on AEs associated with GnRH agonists and GnRH antagonists based on Eudra-Vigilance (EV) and Food and Drug Administration (FDA) reported AEs. EV and FDA databases were queried and the number of CV adverse events (AEs) for degarelix, buserelin, goserelin, leuprorelin, triptorelin until September 2021 were recorded. Specific CV AEs were recorded and data were analyzed per age and severity. pooled relative risk (PRR) was used to compare data between drugs. CV events were reported in 315/5128 (6%) for Degarelix, in 55/628 for Buserelin (9%), in 843/12,145 (7%) for Goserelin, in 3395/71,160 (5%) for Leuprorelin and in 214/4969 (5%) for Triptorelin. In terms of specific CV disorders, Degarelix presented lower risk of hypertension (PRR 0.60 (95% CI 0.37-0.98), p&#x2009;=&#x2009;0.04), of myocardial infarction (PRR 0.05 (95% CI 0.01-0.39), p&#x2009;&lt;&#x2009;0.01) and thrombosis (PRR 0.14 (0.02-1.07), p&#x2009;=&#x2009;0.06) when compared to GnRH agonists. Overall, younger patients (&lt;65 years) presented a very low risk of CV AEs. Side effects were classified as serious in 90-96% of the cases. Fatal AEs were 5-20% over the CV AEs and 0.2-1% over the total AEs. Real-life data are consistent with registry studies regarding side effects related to HT. Real-life data suggest GnRH agonists are associated with higher CV AEs when compared to GnRH antagonists. Clinicians should consider these data when prescribing HT especially in patients with CV comorbidities.