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.

After years of successfully intensifying hormonal therapy, the focus in prostate cancer is shifting toward de-intensification. Researchers are exploring intermittent therapy for top responders and developing non-hormonal approaches like radioligands to spare patients the chronic, life-altering side effects of permanent castration.

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.

With multiple FDA-approved oral SERDs available, clinical decision-making is heavily influenced by their distinct side effect profiles. Elacestrant predominantly causes nausea, while iminoralestrant causes diarrhea. This distinction is a primary factor in tailoring treatment to individual patients.

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.

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.

When using intermittent androgen deprivation, GnRH antagonists like relugolix are preferred over LHRH agonists like leuprolide. Antagonists allow for a much faster recovery of testosterone during off-treatment periods, which is a significant quality-of-life benefit for patients. With agonists, testosterone recovery can sometimes take years.