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Gonadotropin releasing hormone agonists (GnRH agonists) and cardiovascular (CV) risk in prostate cancer

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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In a cohort study of 5714 men with prostate cancer (PCa) and 28 445 men without PCa, men with type 2 diabetes and PCa who received a gonadotropin releasing hormone agonists (GnRH) agonist had 53% higher risk of an increase in CVD risk compared with men with type 2 diabetes and PCa who did not receive a GnRH agonist (1):

  • primary outcomes of the study were 10% or 5% increase in predicted 5-year CVD risk score, which was estimated by use of a CVD risk model
  • Men with PCa receiving GnRH agonists had an increased estimated 5-year CVD risk score compared with men without PCa (hazard ratio [HR], 1.25; 95% CI, 1.16-1.36) and compared with men with PCa not receiving GnRH agonists (HR, 1.53; 95% CI, 1.35-1.74)
  • men receiving GnRH agonists had decreased blood pressure compared with men without PCa (HR, 0.70; 95% CI, 0.61-0.80) and compared with men with PCa not receiving GnRH agonists (HR, 0.68; 95% CI, 0.56-0.82)
  • study authors stated that population-based cohort study, there was an increased risk of CVD in men with type 2 diabetes who received a GnRH agonist for PCa

Androgen deprivation therapy (ADT) and specifically GnRH agonists, have been associated with increased cardiovascular (CV) morbidity and mortality in observational studies, and men with pre-existing CVD are most at risk (2)

An analysis of real-world data from the UK primary care setting showed that relative risk of experiencing cardiac events was significantly lower with degarelix, a GnRH antagonist, compared with GnRH agonists (risk ratio: 0.39 [95% confidence interval 0.191, 0.799]; p = 0.01) (3):

  • study authors concluded:
    • "..available data suggests that GnRH agonists increase CV events, and this effect appears to be greatest in patients with pre-existing CVD, and GnRH antagonists may be associated with lower rates of certain CV events vs GnRH agonists, particularly in patients with pre-existing CVD. The results in the present study support the hypothesis that the risk of cardiac events may be lower in patients receiving a GnRH antagonist such as degarelix, compared with GnRH agonists..."

 

Reference:

  1. Lin E, Garmo H, Van Hemelrijck M, et al. Association of Gonadotropin-Releasing Hormone Agonists for Prostate Cancer With Cardiovascular Disease Risk and Hypertension in Men With Diabetes. JAMA Netw Open. 2022;5(8):e2225600. doi:10.1001/jamanetworkopen.2022.25600
  2. O'Farrell S, Garmo H, Holmberg L, Adolfsson J, Stattin P, Van Hemelrijck M. Risk and timing of cardiovascular disease after androgen-deprivation therapy in men with prostate cancer. J Clin Oncol. 2015 Apr 10;33(11):1243-51
  3. Davey P, Kirby MG. Cardiovascular risk profiles of GnRH agonists and antagonists: real-world analysis from UK general practice. World J Urol. 2021 Feb;39(2):307-315. doi: 10.1007/s00345-020-03433-3. Epub 2020 Sep 26. Erratum in: World J Urol. 2022 Jun;40(6):1603.

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