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Should Prostate Cancer Patients With History of Cardiovascular Events Be Preferentially Treated With LHRH Antagonists?

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Below is the abstract of the article. or on the link below.

Androgen-deprivation therapy (ADT) is a cornerstone in the management of prostate cancer. For many years now, luteinizing hormone-releasing hormone (LHRH) agonists have remained the mainstay of ADT. However, an aggregation of observational reports suggested that LHRH agonists may induce cardiovascular (CV) toxicity. The American Heart Association and the FDA subsequently expressed concerns over this potential risk, but its clinical significance has been debated.

Until recently, additional studies were conducted, but a definitive conclusion has remained elusive because of mixed results, a lack of high-quality data, and a possible overestimation of induced CV events.

LHRH antagonists were hailed as a potential solution to ADT-related CV toxicity. Differential levels of follicle-stimulating hormone (FSH) between agonists and antagonists, as well as agonist-induced testosterone flare were suspected as possible culprits.

In vivo models of atherosclerosis found that mice on antagonists had lower FSH levels and smaller, less necrotic plaques in their vessel lumen than their counterparts on agonists. The binding of FSH receptor in monocytes was also speculated to promote osteoclast differentiation and resorption of atherosclerotic calcifications in plaque.

The activation of LHRH/gonadotropin-releasing hormone receptors on circulating T cells, with differentiation into TH1 cells, represented yet another pathway believed to induce a proinflammatory cascade leading to the release of collagenases in plaque.

Furthermore, FSH was thought to indirectly contribute to CV mortality through weight gain, insulin resistance, and dysfunctional fats. Alternatively, the transient increase of testosterone from agonist-related flare phenomena was thought to promote angiogenesis and neutrophil accumulation in atherosclerotic plaque, thus increasing the likelihood of plaque instability and rupture.

We conclude that higher CV risk should be managed optimally in the CV sense, but this finding should not be an indication for the preferential use of LHRH antagonists in patients with prostate cancer.

Read an interview about the article here and expert commentary about it here.

Read the full article

Should Prostate Cancer Patients With History of Cardiovascular Events Be Preferentially Treated With LHRH Antagonists?

Primary Source

Journal of Clinical Oncology

Source Reference:

ASCO Publications Corner

ASCO Publications Corner