Prostate Cancer Hormone Therapy Associated With Heart Problems

New research has found that hormone therapy used to treat men with advanced prostate cancer is associated with an increased chance of developing various heart problems.

The findings of the study, the largest and most comprehensive to date on the issue, indicate that doctors need to start considering heart-related side effects when they prescribe endocrine therapy for prostate cancer.

A few smaller studies have indicated that some types of hormone therapy increase the risk of coronary heart disease and heart attacks in prostate cancer patients, but others have found no increased risk. This is the first large study to investigate how the broader range of hormone therapies for prostate cancer affect a wider range of heart problems and provides for the first time a detailed picture of the impact of each sort of hormone therapy on individual types of heart trouble.

"If we have observed a causative effect, then for all hormone therapies put together, we estimate that compared with what's 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," said the study's leader, Mieke Van Hemelrijck. "However, not all types of therapy were associated with the risk of heart problems to the same degree. We found that drugs which block testosterone from binding to the prostate cells were associated with the least heart risk, while those that reduce the production of testosterone were associated with a higher risk. This may have implications for treatment choice."

Prostate cancer is diagnosed in more than 670,000 men each year worldwide, making it the second most common cancer among men worldwide, after lung cancer. Hormone therapy is a mainstay treatment for prostate cancer when the cancer is locally advanced and when it has spread to more distant parts of the body, but is increasingly being used in earlier stages of the disease. It involves either removing the testicles to eliminate the main source of testosterone production, injections of gonadotropin releasing hormone agonists to dramatically reduce the production of testosterone from the testicles or anti-androgen pills, which do not reduce the amount of testosterone produced but block it from attaching the prostate cells. Doctors sometimes use a combination of those approaches.

In this study, researchers analyzed the link in 30,642 Swedish men with locally advanced or metastatic prostate cancer who had received hormone therapy as primary treatment for prostate cancer between 1997 and 2006. The men were followed for an average of three years. The researchers calculated the risk of developing ischemic heart disease, heart attacks, arrhythmia and heart failure requiring hospitalization as well as the risk of dying from these heart diseases by comparing the rates among the cancer patients with what's normal in the general Swedish population. Most patients got one of the three hormone treatment choices, but 38% got a combination of the two types of drugs.

Prostate cancer patients treated with hormone 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.

Overall, prostate cancer patients treated with hormone therapy had a 24% increased risk of a non-fatal heart attack, a 19% increased risk of arrhythmia, a 31% increased risk of ischemic heart disease and a 26% increased risk of heart failure. The risk of a fatal heart attack was increased by 28%, the risk of dying from heart disease by 21%, the risk of heart failure death was increased by 26% and the risk of fatal arrhythmia was increased by 5%.

"In a more detailed analysis by type of hormone therapy, the lowest increase in risk for ischemic heart disease, heart attack and heart failure was seen in the group taking anti-androgen therapy, and we saw no increase in risk of death from heart disease in this group," Van Hemelrijck said. "Patients on gonadotropin releasing hormone agonist therapy had the highest risk of these problems."

The increased heart failure risk for anti-androgens was 5%, compared with 34% for gonadotropin releasing hormone agonists and the increased ischemic heart disease risk was 13% in the anti-androgen group, compared with 30% in the gonadotropin releasing hormone agonist therapy group. The finding that anti-androgens carry the least heart risk supports the view that circulating testosterone may protect the heart.

The association with heart risk when the testicles were removed was close to that seen with the gonadotropin releasing hormone agonist therapy.

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References:
1. Mieke Van Hemelrijck, et al. ECCO-the European CanCer Organisation.