Castration reduces human platelet TXA 2 receptor density and aggregability

Background Exogenous testosterone T upregulates platelet TXA 2 receptors and enhances aggregation response to TXA 2 mimetics in healthy men. Aim Investigate the impact of reduction in plasma testosterone on platelet TXA 2 receptors . Methods Design A cross sectional study. Subjects: surgically castrated men with prostate cancer n= 8, aged 71±8yrs and age‐matched urologic cases n=7, 67±9yrs, Setting: tertiary referal hospital Radioligand binding studies for platelet TXA 2 receptors using 125 I‐BOP, and platelet aggregation studies using I‐BOP and thrombin were undertaken. Results Castrated patients had reduced plasma T,16± 5, compared to controls 308 ng/dl (p< 0.001). Platelet TXA 2 receptor B max but not K d was reduced in castrated (0.50±0.12 pmol/mg protein) compared to controls(1.01±0.17pmol/mg protein) p= 0.03. The E max of platelet aggregation but not EC 50 to 1‐BOP was reduced in the castrated (53±2%) compared to control patients (63±2%)[p=0.003ANOVA. In vitro , hydroxyflutamide at high concentration 100uM, did not affect I‐BOP binding, but competitively inhibited U46619 aggregation (p< 0.05 ANOVA). Conclusion Endogenous testosterone genomically regulates human platelet TXA 2 B max and aggregation response to TXA 2 mimetic I‐BOP, and thrombin. Inhibition of androgen production or receptor blockade may reduce platelet aggregation. There is indirect evidence that there are functional androgen receptors on human platelets, which regulate TXA 2 receptor expression. Clinical Pharmacology & Therapeutics (2005) 77 , P53–P53; doi: 10.1016/j.clpt.2004.12.093