BETHESDA, MD USA (UroToday.com) - Dr. Jehonathan Pinthus presented a meta-analysis of population-based studies by Zhao and colleagues who compared 129 802 androgen deprivation patients vs 165 605 controls. Compared to non-ADT patients, they found that ADT had a 10% higher risk of cardiovascular disease and was associated with a higher risk of cardiovascular mortality (HR =1.17, CI =1.04-1.32, p=0.01; PLOS One, Sept 2014).
It is known that testosterone replacement in hypogonadal men results in a decrease in serum triglycerides, LDL, and atherosclerosis (mouse models), along with improved insulin sensitivity. It’s unclear, though, whether this is due to increased testosterone or decreased FSH via feedback inhibition. Dr. Pinthus’s group used a mouse model to explore this: mice underwent orchiectomy, sham surgery, sham surgery + degarelix, or sham surgery + leuprolide, and were followed for 4 months. Visceral fat, glucose tolerance, FSH/LH/T, and atherosclerotic plaques were all measured. The investigators found that mice treated with surgery and leuprolide had significantly higher levels of visceral fat and fasting glucose levels compared to the degarelix group. Blood pressure on average was 143/112 for controls compared to 161/129 for castrated mice at week 10. Plaque size in the orchiectomy and leuprolide groups was significantly larger than that of controls. Perhaps, most importantly, the necrotic portion of the plaques—the driver of cardiovascular events—was larger in the orchiectomy and leuprolide groups compared to the degarelix group. Albertsen and colleagues confirmed this result as they found that among men with prior cardiovascular disease, the 1-year event risk with a GnRH antagonist was reduced compared to that of a GnRH agonist (HR 0.44, CI 0.26-0.74, p=0.002; Eur Urol 2014).
Dr. Pinthus concluded that ADT induces metabolic syndrome and atherosclerosis to a mode-specific extent, and that FSH plays a major role in the pathogenesis of cardiovascular disease. These findings provide us with the opportunity to select a more “cardio-friendly” ADT strategy.
Jehonathan H. Pinthus, MD, PhD
Juravinski Cancer Center, Hamilton, Ontario Canada
Nikhil Waingankar, MD* from the 2014 Winter Meeting of the Society of Urologic Oncology (SUO) "Defining Excellence in Urologic Oncology" - December 3 - 5, 2014 - Bethesda, MD USA
*Fox Chase Cancer Center, Philadelphia, PA USA