J Cancer 2020; 11(14):4015-4022. doi:10.7150/jca.38237

Research Paper

Gonadotropin-releasing hormone agonists, anti-androgens and the risk of cardio-cerebrovascular disease in prostate cancer patients: an asian population-based observational study

Jong-Mi Seong1, Dongho Shin2, Jae Woo Sung2, Shinjay Cho2, Jonghyup Yang2, Sungmin Kang3, Hyong Woo Moon2, Kyu Won Lee2, U-Syn Ha2✉

1. Ewha womans university, Department of pharmacy, Seoul, Republic of Korea
2. Department of Urology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
3. Department of Urology, Catholic Kwandong University College of Medicine, International St. Mary's Hospital, Incheon, Republic of Korea.

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Citation:
Seong JM, Shin D, Sung JW, Cho S, Yang J, Kang S, Moon HW, Lee KW, Ha US. Gonadotropin-releasing hormone agonists, anti-androgens and the risk of cardio-cerebrovascular disease in prostate cancer patients: an asian population-based observational study. J Cancer 2020; 11(14):4015-4022. doi:10.7150/jca.38237. Available from http://www.jcancer.org/v11p4015.htm

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Abstract

Purpose: To conduct a population-based study to determine whether the use of GnRH agonist and antiandrogens are associated with an increased risk of cardio-cerebrovascular disease (CCVD) in Asian patients with prostate cancer using the National Health Insurance Service-Elderly Cohort Database (NHIS-ECD).

Materials and Methods: We included a total of 2,413 men aged 60 years or older with prostate cancer between January 2003 and December 2008. Outcomes of interest included the first occurrence of cardiovascular events [acute myocardial infarction (AMI), ischemic heart disease (IHD)] and cerebrovascular events [ischemic stroke (IS), and cerebrovascular disease (CVD)].

Results: The 5-year AMI-free rates of patients diagnosed with prostate cancer and treated with GnRH agonists, antiandrogens alone, or androgen deprivation therapy (ADT)-naïve interventions were 97.0%, 96.5%, and 98.3%, respectively, while the 5-year IHD-free rates were 93.2%, 92.3%, and 94.5%, respectively. Exposure to GnRH agonists or antiandrogen regimens did not significantly increase the risk of AMI or IHD compared to ADT-naïve treatment in multivariate Cox proportional-hazards models after adjusting for other covariates. Five-year IS-free rates of patients exposed to GnRH agonists, antiandrogens alone, and those with ADT-naïve prostate cancer were 94.8%, 94.7%, and 95.5%, respectively, while the five-year CVD-free rates were 92.9%, 93.3%, and 94.6%, respectively. Cox proportional-hazards models also failed to show that men who received GnRH agonist or antiandrogen treatment alone carried a significantly increased risk for IS or CVD compared to ADT-naïve patients.

Conclusions: The current study based on Asian population suggests that treatment with neither GnRH agonist nor antiandrogens increases the risk of cardio-cerebrovascular disease compared to patients with ADT-naïve prostate cancer.

Keywords: Prostatic Neoplasms, Gonadotropin-Releasing Hormone, Antiandrogens, Cerebrovascular Disease, Cardiovascular Diseases