Androgen-deprivation therapy, which is a common treatment for prostate cancer, has been tentatively linked with an increased risk of cardiovascular disease. A new study solidifies these concerns.
Prostate cancer needs testosterone to grow and thrive, so androgen-deprivation therapy (ADT) is designed to reduce the amount of testosterone in the body to close to zero, thereby helping to slow cancer's growth.
Currently, ADT is recommended for advanced prostate cancer. But it is increasingly being used to treat localized prostate cancer, despite minimal evidence for its efficacy.
At the same time, the number of localized prostate cancer cases has increased dramatically over recent years, due in part to the more widespread use of prostate-specific antigen (PSA) testing.
Side effects of ADT — including erectile dysfunction, diabetes, bone loss, and swollen breast tissue, or gynecomastia — can be fairly substantial. Added to this, there is growing evidence to suggest that low testosterone levels might increase the risk of cardiovascular disease (CVD).
A challenging hunt for ADT-CVD links
Studies looking for links between CVD and ADT have reached conflicting conclusions. For instance, one meta-analysis found a 40 percent increased risk of non-fatal CVD in men with prostate cancer who had received ADT. On the other hand, an earlier study found no link at all between ADT and cardiovascular mortality.
It has therefore been difficult for researchers, so far, to draw accurate lines between heart health and ADT.
Studies have run into a range of problems: some primarily looked at older men, wherein heart conditions would already be more common, and some did not take information about the other medications that participants were taking.
And, even when links have been found, it is difficult to know whether ADT caused the CVD or simply worsened a pre-existing heart condition.
A new study set out to rectify the issues experienced in previous studies. Led by Reina Haque, Ph.D., of Kaiser Permanente Southern California in Pasadena, their findings are published this month in the British Journal of Cancer.
The authors write, "[O]ur goal was to assess the association of ADT and important incident CVD outcomes in a cohort that also included younger men."
"We accounted," they add, "for important confounders, including prior CVD history, PSA levels, CVD medications, and CVD risk factors. Additionally, we assessed whether ADT only has effect on new-onset CVD or also on the progression of pre-existing cardiovascular conditions."
ADT and heart failure risk
In total, the study included 7,637 men who had recently been diagnosed with localized prostate cancer. Of these men, almost a third (30 percent) received ADT. They were followed-up for a maximum of 13 years.
After controlling for the variables described above — as well as others including body mass index (BMI) and smoking — individuals who had ADT and no pre-existing CVD had an 81 percent increased risk of heart failure.
Men who did have pre-existing CVD saw a 44 percent increase in their risk of arrhythmia. Similarly, the risk of conduction disorder — which is a problem with the way that electrical impulses move through the heart — tripled.
When discussing why the link between CVD and ADT might occur, the researchers cover a range of potential factors.
Firstly, testosterone deficiency increases fat mass, which is a risk factor for CVD. Also, men with low testosterone levels are more likely to have abnormal lipid profiles, increased levels of pro-inflammatory factors, and hypertension.
The authors hope that these results might help to identify prostate cancer patients who are more at risk of CVD. They can then give them regular cardiac check-ups, encourage them to exercise, and monitor their blood pressure and diabetes more closely.