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The incidence of venous thrombosis associated with estrogen treatment in male-to-female (M→F) transsexuals is considerably higher with administration of oral ethinyl estradiol (EE) than with transdermal (td) 17-β-estradiol (E₂).

To find an explanation for the different thrombotic risks of oral EE and td E₂ use, we compared the effects of treatment of M→F transsexuals with cyproterone acetate (CPA) only, and with CPA in combination with td E₂, oral EE, or oral E₂ on a number of hemostatic variables [activated protein C (APC) resistance and plasma levels of protein S, protein C, and prothombin], all of which are documented risk factors for venous thrombosis. APC resistance was determined by quantification of the effect of APC on the amount of thrombin generated during tissue factor-initiated coagulation; plasma levels of total and free protein S were determined by standard ELISA; and levels of prothrombin …