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


METHODS
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).


RESULTS
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.


CONCLUSIONS
This study provides evidence that GnRH agonists may inhibit fibrinolytic system by decreasing t-PA levels.
Agirbasli
Mehmet
M
Department of Cardiology, Marmara University School of Medicine, Tophanelioglu Caddesi 13/15, Altunizade, Istanbul 34662, Turkey. agirbasli@gmail.com
Baykan
Oytun A
OA
Tekin
Ali
A
Sengor
Feridun
F
Cincin
Altug A
AA
Demir
Muzaffer
M
Vaughan
Douglas E
DE
D000368:Aged; D015415:Biomarkers / Q000097:blood; D005342:Fibrinolysis / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D017273:Goserelin / Q000494:pharmacology* / Q000627:therapeutic use; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000187:drug effects
D015415:Biomarkers; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D010959:Tissue Plasminogen Activator; D017430:Prostate-Specific Antigen