Testosterone-Blocking Drugs Raise Heart Disease Risk When Used in Combination

Cancer treatment often involves difficult tradeoffs, particularly with testosterone-blocking drugs used in prostate cancer therapy. These medications work through two primary mechanisms: Androgen Deprivation Therapies (ADTs) halt the body’s production of testosterone, a hormone that fuels prostate cancer growth, while a newer class of drugs called Androgen-Receptor Signaling Inhibitors (ARSIs) block testosterone by preventing it from binding to its cell receptor. Although ADTs can control prostate cancer and ARSIs have been shown to enhance survival rates in advanced stages of the disease, their combined use, known as intensified ADT, introduces significant cardiovascular risks.

A recent study conducted by British researchers and published in June revealed that combining ADTs with ARSIs exacerbates cardiovascular risks. The research, which analyzed 24 clinical trials involving 22,166 men aged 63 to 77, sought to compare the effects of traditional ADT with intensified ADT on cardiac health. The trials included participants with varying stages of prostate cancer, from nonmetastatic with aggressive features to metastatic cases unresponsive to ADT alone. The systematic review focused on evaluating the frequency of cardiac events such as hypertension, arrhythmias, blood clots, heart attacks, and strokes.

Findings indicate that the addition of ARSIs to ADT roughly doubles the risk of cardiac events, irrespective of the prostate cancer stage. Severe “grade 3” cardiac events, which may necessitate hospitalization, were observed in 7.8% to 15.6% of cases. The study particularly highlighted that using two ARSIs—abiraterone acetate and enzalutamide—resulted in a fourfold increase in cardiac risk. Evidence suggests that combining these two ARSIs not only amplifies side effects but does not confer additional survival benefits, leading expert groups worldwide to recommend against their concurrent use.

The increased risk is notably higher for patients with pre-existing cardiac conditions. Dr. Katelyn Atkins, a radiation oncologist at Cedars-Sinai Medical Center in Los Angeles, emphasized the importance of assessing cardiovascular health in prostate cancer patients. Cardiovascular disease remains the second leading cause of death among these men. She recommended evaluating patients for atherosclerosis and managing cardiovascular risk factors through lifestyle changes and, if necessary, medications like statins.

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Dr. David Crawford, head of urologic oncology at the University of Colorado Anschutz Medical Campus, acknowledged the benefits of intensified therapy in prolonging survival and potentially achieving a cure. However, he stressed the need to address the cardiovascular risks associated with such treatments. Maintaining a healthy weight, engaging in regular exercise, and managing blood pressure and cholesterol levels are crucial for improving outcomes and mitigating risks.

Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School, also underscored the importance of integrating cardiovascular considerations into treatment decisions. While intensified treatment with ARSIs has significantly advanced prostate cancer management, he advised physicians to carefully weigh and discuss pre-existing risk factors to optimize treatment efficacy while minimizing adverse effects.

In summary, while intensified ADT can be effective in treating prostate cancer, the combination of ADTs and ARSIs introduces significant cardiovascular risks. Patients undergoing this treatment should be closely monitored for heart-related side effects, and strategies to manage cardiovascular health should be integrated into their care plan to improve overall outcomes.

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