Why does ADT increase the risk of cardiovascular disease?

This is an editorial/essay built around O’Farrell et al paper (blogged here on May 6th, 2015). Dr. Basaria extracts three key observations about the specific ways that ADT increases the risk of cardiovascular disease. To quote:

1. "The short interval between initiation of ADT and cardiovascular disease argues against the progression of atherosclerosis as the predominant underlying etiology."

2. “Both orchiectomy and GnRH agonists were associated with an increased risk of cardiovascular disease, in contrast to previous reports showing that men in the GnRH agonist group were at a higher risk than patients who had undergone orchiectomy.

3. “… men undergoing monotherapy with antiandrogens were at a 13% lower risk for incident cardiovascular disease than the comparison population, suggesting that endogenous estradiol levels might have some protective effect.

From these observations, Basaria makes a good case for a study directly on how ADT affects cardiovascular function. Indeed, he correctly points out that what we know about ADT and cardiovascular effects has always been based on an after-the-fact fall out of other studies that didn’t have cardiovascular status as the primary outcome.

One odd statement in this paper is that using LHRH (=GnRH) drugs for ADT allows for "the psychological harm associated with orchiectomy to be avoided…." In fact, we know of no studies that have shown that a voluntary orchiectomy, when used to treat prostate cancer, is any more psychologically burdensome than the LHRH drugs themselves. 


Basaria S. 2015. Cardiovascular disease associated with androgen-deprivation therapy: time to give it due respect. J Clin Oncol 33(11):1232-1234. www.ncbi.nlm.nih.gov/pubmed/25753444