Efstathiou JA et al. (2008) Cardiovascular mortality after androgen deprivation therapy for locally advanced prostate cancer: RTOG 85-31. J Clin Oncol 27: 92–99

Risk factors for cardiovascular disease, including impaired insulin sensitivity, increased fat mass and high levels of cholesterol and triglycerides, are exacerbated by gonadotropin-releasing hormone (GnRH) agonists. Analysis of data from the phase III Radiation Therapy Oncology Group trial 85-31 has shown that this elevation of risk does not translate into a greater likelihood of death due to cardiovascular disease in men with locally advance prostate cancer.

Men (n=945, median age 70 years) were randomized to either radiotherapy alone or to radiotherapy plus adjuvant androgen deprivation therapy with the GnRH agonist goserelin (Zoladex®, AstraZeneca, Wilmington, DE). During a median follow-up period of 8.1 years, 574 patients died; 117 of these deaths were related to cardiovascular disease.

There was no significant association between treatment with goserelin and cardiovascular mortality, defined as sudden death or death from myocardial infarction, cardiac arrest, cardiovascular arrhythmia, cardiomyopathy, coronary artery disease, cardiovascular disease or congestive heart failure. Re-analysis using different definitions of cardiovascular mortality (i.e. on the basis of age, prevalent cardiovascular disease or diabetes) and adjustment for missing data and censoring of data from patients treated with salvage goserelin, also failed to detect an association.

Long-term adjuvant treatment with GnRH agonists does not increase cardiovascular mortality. The authors warn, however, that these drugs might still contribute to noncancer deaths via a noncardiovascular mechanism.