Androgen deprivation therapy induces metabolic syndrome-like effects, increasing cardiovascular risk. It is the medical oncologist's responsibility to perform a baseline CV risk assessment using tools like the STAMP questions and to engage cardiology partners when needed for risk mitigation.

While GnRH antagonists like relugolix show a potential cardiovascular advantage, this benefit may disappear when patients receive intensive, proactive cardiovascular management. A trial comparing degarelix to Lupron showed no difference in CV toxicity when all patients underwent rigorous CV assessment and optimization, suggesting proactive care is the most critical factor.

A large meta-analysis (StopCap) revealed that while abiraterone improves prostate cancer-specific survival, it does not improve overall survival in men older than 75. This is likely due to increased cardiovascular toxicity, suggesting other ARPIs with cleaner safety profiles are a better choice for this elderly population.

Contrary to concerns about compliance with daily oral medication, real-world retrospective studies show patients demonstrate higher persistence and adherence to oral relugolix compared to traditional injectable GnRH agonists and antagonists for prostate cancer, challenging clinical biases.

The EMBARK trial showed that enzalutamide monotherapy was superior to standard ADT monotherapy for metastasis-free survival. This suggests potent AR antagonism may be a more effective strategy than simply depleting the testosterone ligand, challenging the long-held dogma of ADT being the fundamental building block for systemic prostate cancer therapy.

The HERO trial found the GnRH antagonist relugolix reduced major adverse cardiovascular events (MACE) by 54% compared to the agonist leuprolide. While absolute rates were low (2.8% vs 5.6%), this suggests a significant safety advantage for antagonists in patients with cardiovascular risk.

Contrary to the common assumption that provider-administered injections ensure superior adherence, real-world data suggests patients on oral ADT (relugolix) are just as, if not more, adherent. This challenges the notion that oral therapies are inherently less reliable for long-term treatment in prostate cancer.

The oral GnRH antagonist Relagolix allows for much quicker testosterone recovery (1-2 months vs. 3-6 for leuprolide). While beneficial in curative-intent settings, this rapid recovery is a double-edged sword that could shorten the "off-therapy" period during intermittent treatment for metastatic disease.

The oral antagonist relugolix allows for rapid testosterone recovery after discontinuation. While useful for planned intermittent therapy, a case study shows this can be a clinical pitfall. In non-adherent patients who self-discontinue, it can lead to an equally rapid rise in PSA and disease progression.