The Effect of Androgen Deprivation Therapy on the Cardiovascular System in Advanced Prostate Cancer

Abstract

Androgen deprivation therapy (ADT) is a mainstay treatment for metastatic prostate cancer, improving progression-free survival. ADT suppresses the production of testosterone and reduces circulating levels of the hormone. Luteinizing hormone-releasing hormone (LH-RH) agonists are the most commonly used ADT modality. They can be given alone or in combination with androgen synthesis inhibitors or androgen receptor antagonists. An estimated 40% of prostate cancer patients will receive ADT as part of their therapy during their lifetime. However, ADT has numerous adverse effects, including an increased cardiovascular risk that impacts quality of life. Relugolix is an alternative form of ADT. It is the only oral gonadotropin-releasing hormone antagonist, circumventing injection site reactions, making it easier for patients to take, and thus increasing compliance. Testosterone suppression with relugolix is excellent and testosterone recovery after discontinuation is rapid. This paper reviews the ADT and anti-androgen treatment options for men with prostate cancer and the cardiovascular effects of these therapies. There is accumulating evidence that cardiovascular risk with relugolix is lower than with other ADT medications and also lower than with androgen synthesis inhibitors and androgen receptor antagonists. This paper provides insight into the use of different ADT regimens based on the cardiovascular status and circumstances. It explores strategies to mitigate negative cardiovascular consequences and highlights the need for further study.

Keywords: advanced prostate cancer; androgen deprivation therapy; cardiovascular; hormonal therapies; management strategies; testosterone.

Figure 1

ADT initiates a number of interrelated molecular and physiologic changes associated with increased cardiovascular risk. Increased expression of adhesion molecules and thromboxane promote clotting while metabolic disruptions and loss of testosterone interact to raise blood pressure and increase adiposity. QT prolongation elevates the risk of arrhythmia. Ultimately, these changes may contribute to multiple forms of cardiovascular disease, including myocardial infarction, stroke, heart failure, and arrhythmias. ↓ = decrease Abbreviations: ADT—androgen deprivation therapy; ICAM—intercellular adhesion molecule; VCAM—vascular cell adhesion molecule.