Short term effects of GnRH agonists on plasma fibrinolytic balance in patients with advanced prostate cancer

Abstract

Gonadotropin releasing hormone (GnRH) agonists are the cornerstone of metastatic prostate cancer treatment. Cardiovascular effects of GnRH agonists are unclear. In this study, we investigated the short term effects of GnRH agonists on plasma fibrinolytic parameters in patients with metastatic prostate cancer. Eleven patients (mean age 69.3 +/- 6.5) with metastatic prostate cancer and a clinical indication for GnRH agonist therapy were selected. Plasma plasminogen activator inhibitor (PAI-1) antigen (Ag), tissue plasminogen activator (t-PA) Ag and thrombin-activatable fibrinolysis inhibitor (TAFI) activity levels were measured at baseline and at 4 weeks after the first dose of GnRH agonist, Goserelin Acetate (Zoladex, subcutaneous administration, 10.8 mg). Serum prostate specific antigen (PSA) levels significantly decreased from 36.6 +/- 19.3 to 1.1 +/- 0.3 ng/ml after Goserelin acetate treatment (P = 0.005). Significant changes occurred in the fibrinolytic parameters. GnRH agonists decreased plasma t-PA Ag levels (16.3 +/- 4.9 vs. 12.2 +/- 2.8 ng/ml, P = 0.047) and increased PAI-1/t-PA molar ratio (4.8 +/- 3.6 vs. 6.6 +/- 3.4, P = 0.16), on the other hand, plasma PAI-1 Ag (59.0 +/- 48.5 vs. 56.4 +/- 30.5 ng/ml, P = 0.8), and TAFI levels (130.6 +/- 9.5 vs. 124.2 +/- 26.5% activity, P = 0.3) did not change significantly. This study provides evidence that GnRH agonists may inhibit fibrinolytic system by decreasing t-PA levels.