Cancer treatments often come with difficult tradeoffs, and this is true for testosterone-blocking drugs used to treat prostate cancer. These medications operate in two primary ways. Androgen deprivation therapies (ADT) reduce the body’s production of testosterone, a hormone that promotes prostate cancer growth. A newer class of drugs, called androgen-receptor signaling inhibitors (ARSIs), block testosterone by preventing it from binding to its cellular receptor.
ADT is effective in slowing or controlling prostate cancer, and growing evidence suggests that adding ARSIs can enhance survival in advanced stages of the disease. This combined treatment approach is known as intensified ADT. Researchers are now exploring the use of intensified ADT for some men with early-stage prostate cancer as well.
However, all testosterone-blocking drugs come with significant side effects, including metabolic changes that can negatively impact cardiovascular health. In June, British researchers reported that the cardiovascular risks associated with these drugs worsen when ADT and ARSIs are used together. They concluded that men undergoing intensified ADT should be informed about these risks and monitored for heart disease before and during treatment.
Study Goals and Findings
The findings come from a systematic review of 24 clinical trials that examined ADT and ARSI treatments for prostate cancer. Conducted between 2012 and 2024, these trials included a total of 22,166 men aged 63 to 77, with various stages of prostate cancer, from aggressive nonmetastatic cases to metastatic cancer unresponsive to ADT alone.
The goal of the review was to compare the incidence of cardiac events, including hypertension, arrhythmias, blood clots, and severe events like heart attack or stroke, between ADT and intensified ADT.
The results indicated that adding an ARSI to ADT roughly doubles the risk of a cardiac event across all stages of prostate cancer. The risk for severe “grade 3” events, which may require hospitalization, ranged from 7.8% to 15.6%. Notably, combining two ARSIs—abiraterone acetate and enzalutamide—led to a nearly fourfold increase in cardiac risk. Evidence shows that this combination worsens side effects without improving prostate cancer survival, and its use is now widely discouraged by experts.
The study also highlighted that intensified therapy poses greater risks for men with pre-existing cardiac conditions compared to healthier men. In an accompanying editorial, Dr. Katelyn Atkins, a radiation oncologist at Cedars-Sinai Medical Center, noted that cardiovascular disease is the second leading cause of death among men with prostate cancer.
Managing Cardiovascular Risks
Candidates for traditional or intensified ADT should be evaluated for atherosclerosis, which involves fatty plaques in coronary arteries that can accumulate without symptoms. Fortunately, cardiac risk factors are manageable through lifestyle changes like lowering blood pressure, following a heart-healthy diet, exercising, and sometimes using cholesterol-lowering drugs like statins.
Expert Opinions
“More research shows that intensive therapy can prolong survival and potentially even cure some men,” said Dr. David Crawford, head of urologic oncology at the University of Colorado Anschutz Medical Campus. “Effective cancer treatment often involves combining drugs. However, we must also focus on preventing cardiovascular events and other side effects of ADT. Men who maintain their weight, exercise, and manage cardiovascular risk factors generally fare better.”
“This study underscores the importance of considering a patient’s cardiovascular history when choosing treatments,” said Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School. “While intensifying treatment by adding drugs earlier in prostate cancer management is beneficial, it’s crucial to discuss and address pre-existing risk factors to maximize positive outcomes and minimize side effects.”