Confirming a belief of many of us, new research has found that hormone therapy (endocrine therapy or ADT) is associated with a very large increased risk of developing various major heart problems. This research also tells us that some therapy options have a higher risk profile than others.
At Europe’s biggest cancer congress, ECCO 15 – ESMO 34, in Berlin on Sept. 22, researchers shared their study findings (the largest and most comprehensive study to date) on the effect that ADT has on heart problems. The study found that ADT has a very significant effect on heart health; to the degree, they are urging doctors to consider heart-related side effects when they prescribe endocrine therapy (ADT) for prostate cancer. The effects can be so significant they urge men be referred to a cardiologist before starting treatment!
In the past, some small studies have found that some types of hormone therapy increase the risk of coronary heart disease and heart attacks while others have found no increased risk. This study is by far the largest to investigate how different regimes of ADT affect a wide range of heart problems. The study provides 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, Ms Mieke Van Hemelrijck, a cancer epidemiologist at King’s College in London. “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 (anti-androgens like casodex) were associated with the least heart risk, while those that reduce the production of testosterone (gonadotropin releasing hormone agonist like lupron) were associated with a higher risk. This may have implications for treatment choice.”
In the 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 their disease between 1997 and 2006. The men were followed for an average of three years with most men getting of the three hormone treatment choices, but 38% got a combination of the two types of drugs.
The researchers calculated the risk of developing heart problems requiring hospitalization as well as the risk of dying from these heart diseases by comparing the rates among the cancer patients with the normal Swedish population. They evaluated: ischemic heart disease (a restriction in blood supply); heart attacks (the death of heart muscle from the sudden blockage of a coronary artery by a blood clot); arrhythmia (abnormal electrical activity in the heart) and heart failure (a problem with the structure or function of the heart impairs its ability to supply sufficient blood flow to meet the body’s needs).
“We found that 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,” Ms Van Hemelrijck said, adding that the problems started happening within a few months of initiating treatment.
The increase in risk factors for men on ADT was very large. Twenty-four percent (24%) of the men had an increased risk of having a non-fatal heart attack, a nineteen percent (19%) increased risk of arrhythmia, a thirty one percent (31%) increased risk of ischemic heart disease and a twenty six percent (26%) increased risk of heart failure. The risk of a fatal heart attack increased by twenty eight percent (28%), the risk of dying from heart disease by twenty one percent (21%), the risk of heart failure death increased by twenty six percent (26%) and the risk of fatal arrhythmia increased by five percent (5%).
The researchers also looked at the difference in risk factors depending upon the type of ADT used. “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 only anti-androgen therapy (i.e. casodex), and we saw no increase in risk of death from heart disease in this group,” Ms Van Hemelrijck said. “Patients on gonadotropin releasing hormone agonist therapy ((GnRH agonist, i.e. Lupron) had the highest risk of these problems.”
For instance, the increased heart failure risk for anti-androgens was five percent (5%), compared with thirty four percent (34%) for gonadotropin releasing hormone agonists and the increased ischemic heart disease risk was thirteen percent (13%) in the anti-androgen group, compared with thirty percent (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,” said Van Hemelrijck.
The heart health risks posed by the surgical removal of the testicles as opposed to chemical castration were similar according to Ms Van Hemelrijck.
The increased risk of heart events requiring hospitalization was less evident in patients who already had heart disease before starting hormone treatment. Ms Van Hemelrijck said there was a seventeen percent (17%) risk increase for a new ischemic heart disease event among those with a history of heart disease, compared with a forty one percent (41%) increase among men who didn’t have any heart trouble before hormone treatment. She felt that could be because the men who already had heart disease were likely to be taking heart medications that protected them from further heart risk imposed by the endocrine treatment.
“We now need studies verifying the association and exploring plausible biological mechanisms. Then we would know how to best use these treatments according to a patient’s history of various types of heart disease and whether it would be a good idea to give patients heart medicines to counteract these side effects,” Ms Van Hemelrijck concluded.
The study was funded by the Swedish Research Council, the Stockholm Cancer Society and Cancer Research UK.
This research only complicates an already difficult situation for us. ADT is often needed prior to primary prostate cancer treatment to shrink the size of the gland. The first level and most common treatment when there is a PSA recurrence is hormone therapy. Now we find out that ADT exposes us to a significant hart health risk when taking hormone therapy. Does hormone therapy extend life? How do you balance the increased risk for heart problems against the possibility of some life extension from ADT?
Joel T Nowak MA, MSW