Venous thrombosis and changes of hemostatic variables during cross-sex hormone treatment in transsexual people.
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-beta-estradiol (E(2)). To find an explanation for the different thrombotic risks of oral EE and td E(2) use, we compared the effects of treatment of M-->F transsexuals with cyproterone acetate (CPA) only, and with CPA in combination with td E(2), oral EE, or oral E(2) 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 and protein C were determined with functional assays after complete activation of the zymogens with specific snake venom proteases. CPA-only, td-E(2)+CPA, or oral-E(2)+CPA treatment produced rather small effects on hemostatic variables, whereas oral EE treatment resulted in a large increase in APC resistance from 1.2 +/- 0.8 to 4.1 +/- 1 (P < 0.001), a moderate increase in plasma protein C (9%; P = 0.012), and a large decrease in both total and free plasma protein S (30%; P < 0.005). The large differential effect of oral EE and oral E(2) indicates that the prothrombotic effect of EE is due to its molecular structure rather than to a first-pass liver effect (which they share). Moreover, these differences may explain why M-->F transsexuals treated with oral EE are exposed to a higher thrombotic risk than transsexuals treated with td E(2). Testosterone administration to female-to-male transsexuals had an antithrombotic effect.
Toorians
A W F T
AW
Departments of Endocrinology/Andrology, Vrije Universiteit University Medical Center, 1007 MB Amsterdam, The Netherlands.
Thomassen
M C L G D
MC
Zweegman
S
S
Magdeleyns
E J P
EJ
Tans
G
G
Gooren
L J G
LJ
Rosing
J
J
D020016:Activated Protein C Resistance; D000328:Adult; D000726:Androgen Antagonists / Q000627:therapeutic use; D000728:Androgens / Q000627:therapeutic use; D017373:Cyproterone Acetate / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000009:adverse effects; D004967:Estrogens / Q000009:adverse effects; D004997:Ethinyl Estradiol / Q000009:adverse effects; D005260:Female; D012739:Gonadal Steroid Hormones / Q000009:adverse effects* / Q000627:therapeutic use*; D006487:Hemostasis / Q000187:drug effects*; D006728:Hormones / Q000097:blood; D006801:Humans; D008297:Male; D012727:Sex Characteristics; D013739:Testosterone / Q000627:therapeutic use; D014189:Transsexualism / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D020246:Venous Thrombosis / Q000139:chemically induced* / Q000517:prevention & control*
D000726:Androgen Antagonists; D000728:Androgens; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D006728:Hormones; D013739:Testosterone; D004997:Ethinyl Estradiol; D017373:Cyproterone Acetate; D004958:Estradiol