BERLIN—All the endocrine therapies used in the treatment of prostate cancer increase the risk of cardiovascular disease, but some appear to be safer for the heart than others, researchers report.
Their study, the largest and most comprehensive to look at the issue to date, showed that the risk is increased for all types of cardiovascular disease, including ischemic heart disease, myocardial infarction, heart failure, and cardiac arrhythmias.
But in a more detailed analysis by type of endocrine therapy, gonadotropin-releasing hormone agonists appeared to be associated with a higher risk of cardiac problems than anti-androgen drugs are, said Mieke Van Hemelrijck, a PhD candidate in cancer epidemiology at King's College London.
The findings were presented here at a presidential session at the joint Congress of the European CanCer Organisation and European Society for Medical Oncology.
While the study—funded by the Swedish Research Council, the Stockholm Cancer Society, and Cancer Research UK—does not prove cause and effect, it “shows the importance of taking heart disease into account when considering anti-hormone therapy, especially since it is now being given to men with earlier-stage disease,” Ms. Van Hemelrijck said.
“Many of the side effects of endocrine therapy are well known—hot flashes and metabolic changes, for example. But there has been little study into the association between endocrine therapy and different types of heart disease.”
The researchers analyzed data from the Swedish National Prostate Cancer Registry of more than 80,000 men, accounting for more than 96% of prostate cancer cases in Sweden. Overall, 30,642 of the men received endocrine therapy as their primary treatment for prostate cancer between 1997 and 2006.
Eleven percent of the men received anti-androgen drugs, 30% received gonadotropin-releasing-hormone (GnRH) agonists, and 38% received GnRH agonists and short-term anti-androgen drugs. The rest of the men underwent orchidectomy. The men were followed for an average of three years.
The researchers compared the patients' heart disease hospitalization and mortality rates with those of men in the general population, taking into account age and history of heart disease.
The analysis showed that “prostate cancer patients treated with endocrine therapy had an elevated risk of developing all of the individual types of heart problems, and that they were more likely than normal to die from those causes,” Ms. Van Hemelrijck reported.
The risk began to climb within a few months of starting anti-hormone therapy, she added.
Compared with the general population, men taking anti-hormonal therapy for prostate cancer were at 24% increased risk of having a non-fatal myocardial infarction, 19% increased risk of cardiac arrhythmias, 31% increased risk of ischemic heart disease, and 26% increased risk of heart failure.
They were also at 28% increased risk of having a fatal myocardial infarction, 5% increased risk of dying of cardiac arrhythmias, 21% increased risk of dying of ischemic heart disease, and 26% increased risk of fatal heart failure.
“For all hormone therapies put together, we estimate that compared with what is normal in the general population, about 10 extra ischemic heart-disease events a year will appear for every 1,000 prostate cancer patients treated with such drugs,” she said.
Anti-Androgens have Lowest Risk
But further analysis showed that while all three forms of anti-hormone therapy were associated with an increased risk for heart disease, anti-androgens were associated with the lowest risk. Patients on GnRH hormone agonist therapy had the highest risk of these problems, the researchers found.
For example, men given anti-androgen therapy had a 13% increased chance of developing ischemic heart disease vs a 30% increased risk in the men who received GnRH agonists.
Also, the risk of heart failure was increased by 5% with anti-androgens, compared with 34% for the GnRH agonists.
Since men given anti-androgens still have circulating testosterone in the body, while injections of GnRH agonists actually block testosterone production by the testicles, the findings support the hypothesis that testosterone is protective for the heart, she said.
The risks associated with orchidectomy were similar to those posed by GnRH agonists, she added.
Ms. Van Hemelrijck also noted that the increase in cardiovascular disease risk associated with endocrine therapy was less pronounced in men who had a previous history of cardiovascular disease. For example, men who had a history of ischemic heart disease had a 17% increased risk of developing a new event, compared with a 41% increased risk in men with no prior history.
The medications that men with cardiac problems take to protect themselves from further events may have also protected them from risks posed by anti-hormone treatment, Ms. Van Hemelrijck said.
Risks Low in Absolute Terms
While increased, the risks are still low in absolute terms, explained ESMO President José Baselga, MD, Chairman of the Medical Oncology Service at Vall d'Hebron University Hospital in Barcelona.
For example, the researchers estimated that anti-hormone therapies cause an extra one heart problem per year for every 100 prostate cancer patients treated. “It's a balance. Untreated, advanced prostate cancer is a lethal condition. For most men, the benefits of anti-hormone therapy ultimately outweigh the increased risk of heart problems,” Dr. Baselga said.
That said, “if you think a patient is at risk for heart disease, the patient should be referred to a cardiologist for a thorough check-up before starting anti-hormone treatment,” he said.
Ms. Van Hemelrijck also called for further study to verify the association and explore plausible biological mechanisms.