Cardiovascular Risk in Prostate Cancer: Choosing ADT According to Cardiac Risk
In this article
The Heart Health Paradox in ADT: Agonists or Antagonists?
The Critical Choice Determining Survival in Prostate Cancer
Introduction: Why Is Focusing Only on Cancer Not Enough?
Suppressing testosterone (androgen deprivation therapy—ADT) is essential in treating advanced prostate cancer. However, clinical trials show that a substantial proportion of these patients die from cardiovascular events rather than prostate cancer. This has brought “the cardiovascular toxicity of ADT” into focus, making collaboration between oncology and cardiology specialists—cardio-oncology—essential.
Although testosterone suppression is vital in fighting prostate cancer, the other side of the coin conceals a risk that can threaten patients faster than cancer: Cardiovascular death. In modern oncology practice, choosing androgen deprivation therapy (ADT) is now seen as equivalent not only to controlling the tumor, but also to protecting the patient’s heart rhythm. The large HERO trial and current clinical data demonstrate that, unlike conventional GnRH agonists, receptor-blocking GnRH antagonists reduce the risk of major heart attack and stroke by more than 54% , establishing a new “heart-focused” standard in prostate cancer management.
Study Details: HERO and Other Evidence
Recent studies have investigated the superiority of **GnRH antagonists** (for example, Relugolix and Degarelix) over conventional **GnRH agonists** (for example, Leuprolide and Goserelin).
The HERO Trial (Phase 3)
This large trial comparing relugolix (an oral antagonist) with leuprolide included more than 900 patients. Its results were striking:
- MACE (Major Adverse Cardiovascular Event) Rate: The rate was 2.9% in the Relugolix group and 6.2% in the Leuprolide group.
- High-Risk Groups: Among patients with a previous heart attack or stroke, the risk reduction rose from 54% to as much as 80% .
54% Reduction
The clear reduction in major cardiac events achieved in the antagonist arm.
90 Days
Time for testosterone to return to normal after stopping treatment (with agonists, this may take 6-9 months).
Biological Differences: Why Is the Antagonist Safer?
Experts attribute this safety difference to three main biological mechanisms:
1. Plaque Stability: GnRH receptors are found on macrophages and T cells in vessel walls. Agonist drugs may stimulate these receptors, causing vascular plaques to become inflamed and rupture, triggering a heart attack. Antagonists block these receptors directly.
2. The Role of FSH: GnRH antagonists suppress FSH (follicle-stimulating hormone) levels much more deeply and rapidly than agonists. FSH receptors are present in cardiovascular walls, and high FSH has been associated with atherosclerosis.
3. The “Testosterone Flare” Effect: Agonists temporarily increase testosterone at the beginning of treatment. This fluctuation can impose sudden stress on the metabolic system and the heart.
Clinical Recommendations: Which Patient Should Receive Which Drug?
Expert discussions on Medscape recommend treating patients according to risk scores:
- High-Risk Patients: For patients with known coronary artery disease, a previous stroke, or uncontrolled diabetes, GnRH antagonists should be the preferred option.
- Low-Risk Patients: Although agonists remain an option for younger patients without cardiovascular risk factors, quality of life and a desire for rapid testosterone recovery during intermittent treatment should be considered.
Our oncology practice is now guided not simply by “defeating cancer,” but by “protecting the patient as a whole.” In prostate cancer management, we must choose ADT not only for oncological efficacy, but also after considering the patient’s ECG and cardiac risk profile. HERO’s data show that choosing the right drug can provide a survival advantage as vital as the cancer treatment itself.
1. Shore ND, et al. HERO Study Group. Relugolix for Advanced Prostate Cancer. N Engl J Med. 2020.
2. Lopes RD, et al. PRONOUNCE Trial: Randomized Trial of Degarelix vs Leuprolide. Circulation 2021.
3. Medscape Cardiology - Oncology Interface Analysis (2026).
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