Cardiovascular Toxicities of Androgen Deprivation Therapy

Abstract

Prostate cancer is the second leading cause of cancer death in men, and cardiovascular disease is the number one cause of death in patients with prostate cancer. Androgen deprivation therapy, the cornerstone of prostate cancer treatment, has been associated with adverse cardiovascular events. Emerging data supports decreased cardiovascular risk of gonadotropin releasing hormone (GnRH) antagonists compared to agonists. Ongoing clinical trials are assessing the relative safety of different modalities of androgen deprivation therapy. Racial disparities in cardiovascular outcomes in prostate cancer patients are starting to be explored. An intriguing inquiry connects androgen deprivation therapy with reduced risk of COVID-19 infection susceptibility and severity. Recognition of the cardiotoxicity of androgen deprivation therapy and aggressive risk factor modification are crucial for optimal patient care.

Keywords: Cardiotoxicity; Cardiovascular disease; Hormones; Mortality; Prevention; Prostate cancer; Side effects.

Fig. 1

Potential mechanisms of gonadotropin releasing hormone (GnRH) agonist and antagonist cardiotoxicity. GnRH agonist can lead to testosterone microsurges, promote endothelial dysfunction through follicle stimulating hormone (FSH), and directly activate monocytes and T lymphocytes. Together, these actions may promote atherosclerotic plaque formation, disruption, and thrombosis. In contrast, GnRH antagonists do not lead to testosterone microsurges and more rapidly decrease FSH secretion. Both GnRH agonists and antagonists decrease testosterone levels resulting in wide-ranging effects including insulin resistance, adiposity, dyslipidemia, and increased pro-inflammatory mediators.