Nancy L. Keating is the principal investigator of this project.

Androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) agonist is the mainstay of treatment for metastatic prostate cancer and a routine part of the management for many men with nonmetastatic prostate cancer. However, the role of GnRH agonists in treating men with local or regional prostate cancer has not been completely defined, and most randomized controlled trials of androgen deprivation therapy are underpowered to identify infrequent but potentially serous adverse effects. Nevertheless, GnRH agonists are now routinely prescribed for many men with local or regional disease, with use in this group having increased greatly during the last decade.

GnRH agonists have adverse physiologic effects that may be associated with an increased risk of diabetes and cardiovascular disease, including increased fat mass and decreased insulin sensitivity. In addition, preliminary data suggest that GnRH agonists may prolong the QT interval. These adverse effects may contribute to noncancer morbidity and mortality.

In an observational study of men diagnosed with local or regional prostate cancer and followed for up to 10 years, we found that GnRH agonists are associated with greater risk of diabetes, coronary heart disease, myocardial infarction, and sudden cardiac death in men with local/regional prostate cancer. Decisions about GnRH agonist treatment for local-regional prostate cancer should weigh improvements in cancer-specific outcomes against potential increased risks of diabetes and cardiovascular disease. Future research is needed to confirm our findings in other populations, to further define situations for which benefits of GnRH agonists outweigh risks, to identify populations of men at highest risk of adverse complications due to GnRH agonists, and to develop strategies to prevent treatment-related morbidity.