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The Cardiovascular Effects of Gonadotropin-Releasing Hormone Antagonists in Men with Prostate Cancer

Aims: The aim of this study was to determine whether gonadotropin-releasing hormone (GnRH) antagonists (an emerging class of drugs to suppress testosterone synthesis in the treatment of prostate cancer) cause less adverse cardiovascular events than the more commonly use GnRH agonists.

Methods and Results: We conducted a systematic review to identify all randomized, controlled trials in which a GnRH antagonist was compared with a GnRH agonist in men with prostate cancer. We identified 10 eligible studies including two different GnRH antagonists, degarelix (n = 1681) and relugolix (n = 734), which were compared with the GnRH agonists, leuprolide (n = 714) and goserelin (n = 600). The pooled risk ratios (95% confidence intervals) among GnRH antagonist recipients for adverse cardiovascular events, cardiovascular death, and all-cause mortality were 0.57 (0.39-0.81); 0.49 (0.25-0.96); and 0.48 (0.28-0.83), respectively. Important limitations of the included trials were their short duration of follow-up, unblinded study design and (in most of the studies) the identification of adverse cardiovascular events through safety reporting mechanisms rather than as a pre-specified outcome. There was no evidence of heterogeneity of findings among the studies.

Conclusions: There is consistent but methodologically limited data to suggest that GnRH antagonists-a relatively new class of androgen deprivation therapy for prostate cancer-cause significantly less cardiovascular adverse effects than the more frequently used GnRH agonists.
Filipe Cirne,1 Nazanin Aghel,1 Jo-Anne Petropoulos,2 Laurence Klotz,3 Daniel J Lenihan,4 Fred Saad,5 Jehonathan Pinthus,6 Darryl P Leong1,7,8

  1. Department of Medicine, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada.
  2. Health Sciences Library, McMaster University, Hamilton, ON, Canada.
  3. Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON, Canada.
  4. Cardio-Oncology Center of Excellence, Washington University in St. Louis, 660 South Euclid, St. Louis, MO, USA.
  5. University of Montreal Hospital Center, 900 Rue St. Denis, Montreal, Quebec, Canada.
  6. Department of Surgery, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada.
  7. Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
  8. The Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada.
Source: Cirne, F., Aghel, N., Petropoulos, J., Klotz, L., Lenihan, D. J., Saad, F., Pinthus, J. H., & Leong, D. P. (May 5, 2022). The cardiovascular effects of gonadotropin-releasing hormone antagonists in men with prostate cancer. European Heart Journal - Cardiovascular Pharmacotherapy, 8(3), 253–262.