Association of Gonadotropin-Releasing Hormone Agonists for Prostate Cancer With Cardiovascular Disease Risk and Hypertension in Men With Diabetes

JAMA Netw Open. 2022 Aug 1;5(8):e2225600. doi: 10.1001/jamanetworkopen.2022.25600.


Importance: Men with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Meanwhile, gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer (PCa) are associated with increased risk of CVD.

Objective: To evaluate the association between GnRH agonist use, PCa diagnosis per se, and CVD risk in men with type 2 diabetes.

Design, setting, and participants: This nationwide population-based cohort study identified men with type 2 diabetes by use of data in the Prostate Cancer Data Base Sweden version 4.1 and the Swedish National Diabetes Register, with longitudinal data from 2006 to 2016. These data were used to create 2 cohorts, 1 including men with and without PCa and the other including men with PCa who received and did not receive GnRH agonists. Data analysis was conducted from January 2006 to December 2016.

Exposures: Treatment with GnRH agonists and PCa diagnosis were the primary exposures.

Main outcomes and measures: Primary outcome was a 10% increase in predicted 5-year CVD risk score. Secondary outcome was worsening hypertension as defined by the European Society of Hypertension Guidelines. Cox proportional hazards regression models were used to analyze the association.

Results: The PCa exposure cohort included 5714 men (median [IQR] age, 72.0 [11.0]), and the non-PCa cohort included 28 445 men without PCa (median [IQR] age, 72.0 [11.0]). The GnRH agonist-exposure cohort included 692 men with PCa who received a GnRH agonist, compared with 3460 men with PCa who did not receive a GnRH agonist. 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).

Conclusions and relevance: In this population-based cohort study, there was an increased risk of CVD in men with type 2 diabetes who received a GnRH agonist for PCa. These findings highlight the need to closely control CVD risk factors in men with type 2 diabetes treated with GnRH agonists. The association between GnRH agonist use and decreased blood pressure levels warrants further study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiovascular Diseases* / epidemiology
  • Cohort Studies
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Gonadotropin-Releasing Hormone
  • Humans
  • Hypertension* / complications
  • Hypertension* / drug therapy
  • Hypertension* / epidemiology
  • Male
  • Prostatic Neoplasms* / therapy


  • Gonadotropin-Releasing Hormone