ADT May Be Associated With Cardiovascular Risk Factors in nmCRPC

Alicia K. Morgans, MD, PhD, an associate professor of Medicine at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University Feinberg School of Medicine, discusses the cardiovascular risks associated with androgen deprivation therapy (ADT) in men with non-metastatic castration-resistant prostate cancer (nmCRPC).

According to Morgans, ADT alone can increase cardiovascular risk. Previous studies such as the HERO trial (NCT03085095) have found that there is an increased risk of cardiovascular events while receiving ADT. Adding androgen receptors to ADT increases the risk further.

Alone, ADT can cause elevations in total cholesterol and triglycerides. It can also increase high-density lipoprotein (HDL), but not enough to offset other complications. It can also create complications around glucose intolerance. For at-risk men, this could cause pre-diabetes or diabetes. For men with a history of cardiovascular events, ADT could cause complications, according to Morgans. 

0:08 | So, treatment with androgen deprivation therapy on its own does increase some cardiovascular risk. Multiple studies have shown that even in a relatively short period of time, say over the first 12 months on therapy, there can be an increased risk in adverse events related to cardiovascular disease, particularly when we look at population-based studies. But even when we look at clinical trial data, like the recently reported HERO data that compared leuprolide (Eligard) to relugolix (Orgovyx). So, in that context, we know that men already have some risk of having these cardiovascular events on androgen deprivation. And when we add medications like androgen receptor inhibitors, we're actually increasing that. So, what does Androgen deprivation therapy cause on its own, the GnRH agonist and antagonist? Well, it definitely disrupts cardiovascular risk factors. So, it causes elevations in total cholesterol triglycerides, and actually, HDL too, though, that's not enough of a positive risk factor to offset the other complications, it causes an increase in inter abdominal adiposity or basically belly fat that absolutely increases cardiovascular risk. And it also causes some issues in terms of glucose intolerance, and for some men, particularly those at risks, that can seem to push them into pre-diabetes or even diabetes. So, the constellation of these plus some effects that it can have actually on the electrophysiologic system in terms of QT prolongation, really can come together for men, particularly men who have a cardiovascular history and can push them over the edge in these events.