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Gonadotropin‐releasing hormone antagonist associated with lower cardiovascular risk compared with gonadotropin‐releasing hormone agonist in prostate cancer: A nationwide cohort and in vitro study
Author(s) -
Chen DongYi,
Su PoJung,
See LaiChu,
Liu JiaRou,
Chuang ChengKeng,
Pang SeeTong,
Tseng ChiNan,
Chen ShaoWei,
Hsieh IChang,
Chu PaoHsien,
Lin YungChang,
Hsu ChengLung,
Chang John WenCheng,
Lin MiaoSui,
Pang JongHwei S.,
Hsieh MingJer,
Huang WenKuan
Publication year - 2021
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.24187
Subject(s) - medicine , gonadotropin releasing hormone antagonist , prostate cancer , hazard ratio , gonadotropin releasing hormone , agonist , endocrinology , hormone antagonist , antagonist , proportional hazards model , hormone , confidence interval , cancer , luteinizing hormone , receptor
Background We aimed to determine whether cardiovascular (CV) risk in patients with prostate cancer (PCa) differs between those who receive gonadotropin‐releasing hormone (GnRH) agonist (GnRHa) therapy and those who receive GnRH antagonist therapy. Methods Using the Taiwan National Health Insurance Research Database, we analyzed data by comparing 666 participants receiving GnRH antagonists and 1332 propensity score‐matched participants treated with GnRHa in a 1:2 fashion during the period from May 1, 2015, to September 30, 2018. Cox proportional‐hazards models were used to estimate the treatment effect on CV outcomes. Furthermore, we conducted an in vitro study to investigate the effect of a GnRHa (leuprolide) or a GnRH antagonist (degarelix) on matrix metalloproteinase‐9 (MMP‐9) expression and invasion ability in THP‐1 differentiated macrophages. Results GnRH antagonist therapy was associated with a lower risk of composite CV events of myocardial infarction, ischemic stroke, or CV death (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.25–0.90) than GnRHa therapy, with a mean follow‐up period of 1.21 years. Significantly lower risks of CV death (HR, 0.21; 95% CI, 0.06–0.70) and all‐cause mortality (HR, 0.77; 95% CI, 0.61–0.97) were observed in the GnRH antagonist group. In the in vitro study, leuprolide, but not degarelix, significantly increased the expression of MMP‐9 activity and the invasive ability of THP‐1 differentiated macrophages through gelatin zymography and the matrix invasion assay, respectively. Conclusion GnRH antagonists were associated with reduced risk CV events compared with the GnRHa among patients with PCa, which may be through effects on macrophages.