Real-world data from the VA suggests abiraterone is associated with increased hospitalizations for cardiovascular events, infections, and acute kidney injury compared to other ARPIs. This finding prompts clinicians to favor AR antagonists like enzalutamide in older, comorbid patients at higher risk for these complications.

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.

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 body has different estrogens: E1 (pro-inflammatory) and E2 (protective). Current breast cancer therapies are blunt instruments, blocking both types. This indiscriminate blocking contributes to negative side effects like cardiometabolic dysfunction, highlighting a need for more targeted future treatments.

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.

Uniquely, the EMPRIS window study in premenopausal patients showed geridestran monotherapy was more effective at suppressing proliferation than tamoxifen without adding an LHRH agonist. This challenges the standard practice of mandatory ovarian function suppression and could simplify treatment for younger women.

A drug-drug interaction study found that apalutamide induces an enzyme (CYP3A4) that lowers relagolix concentrations, leading to suboptimal hormonal suppression. To maintain efficacy when used in combination, the standard dose of the oral GnRH antagonist relagolix must be doubled.

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.

Unlike some endocrine therapies, oral SERDs used in premenopausal women require concurrent ovarian suppression (e.g., with a GnRH agonist). This is a critical safety measure to mitigate the risk of developing ovarian cysts, a potential side effect of using these agents without adequately suppressing ovarian function.