Traditional hormone therapy usually consists of two types of drugs; GnRH agonists (like Lupron and Zoladex) and antiandrogens (Casodex). Although they both are drugs that manipulate the hormone system their modes of action are different.

GnRH agonists block the production of the male hormone testosterone while the antiandrogen drug blocks the ability of the prostate cancer to absorb any testosterone generated by the body. Antiandrogens do not inhibit the actual production of testosterone!

We are aware that ADT does increase a man’s risk for cardiovascular events and mortality. The question is which of these drugs might be responsible for the increased risk?

A recent retrospective study published in the Journal of Clinical Oncology.1 has found that the treatment using GnRH agonists, but not antiandrogens, increases risk of having cardiovascular events and mortality.

The study also found that men with prostate cancer treated with gonadotropin-releasing hormone (GnRH) agonists are at increased risk for cardiovascular events and mortality if they have a recent history of cardiovascular events.

The study also showed that the risk of cardiovascular events is reduced in men with prostate cancer treated with antiandrogens but increased in men who have undergone surgical orchiectomy.

Data for the study results came from an analysis of data included in the National Prostate Cancer Register of Sweden between 2006 and 2012.

This study was very robust and included 41,362 men with prostate cancer, 10,656 who were taking antiandrogens, 25,955 were taking GnRH agonists with or without antiandrogens as flare protection, and 3,747 underwent orchiectomy.

When the researchers evaluated the data against the control group they found that the risk of having a cardiovascular event or mortality was higher in the men on GnRH agonists and in the men who had an orchiectomy.

By contrast, the risk of cardiovascular events or mortality was lower in the men on just antiandrogens than in the comparison.

They also concluded that in men treated with GnRH agonists, the risk of cardiovascular disease was markedly higher in the 2 years after initiation of therapy than in the 2 years before therapy began. Likewise, the risk did not increase in men treated with antiandrogens either before or after initiation of therapy.

They also found that men with a history of 2 or more cardiovascular events, with the latest having occurred within 1 year before the initiation of androgen deprivation therapy, were at the highest risk of additional events during the 6 months after initiation of any of the three therapies.

Men with no history of cardiovascular disease were still at increased risk while on GnRH agonist therapy.

Men are designed to have testosterone. When the production of testosterone is inhibited they become susceptible to complications, including the serious increase risk for developing cardiovascular events. Men on GnRH agonists or treated with orchiectomy lose the protective effect of testosterone. Men with a history of cardiovascular events are even more vulnerable.

Since antiandrogens block the absorption of testosterone, but do not reduce circulating testosterone men seem to maintain the protective effect of testosterone.

1. O’Farrell S, Garmo H, Holmberg L, et al. Risk and timing of cardiovascular disease after androgen-deprivation therapy in men with prostate cancer. J Clin Oncol. March 2, 2015. [Epub ahead of print] pii: JCO.2014.59.1792.

Joel T. Nowak, M.A., M.S.W.