{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:54:52Z","timestamp":1789124092702,"version":"build-2803163510"},"reference-count":48,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The incidence of venous thrombosis associated with estrogen treatment in male-to-female (M\u2192F) transsexuals is considerably higher with administration of oral ethinyl estradiol (EE) than with transdermal (td) 17-\u03b2-estradiol (E2).<\/jats:p><jats:p>To find an explanation for the different thrombotic risks of oral EE and td E2 use, we compared the effects of treatment of M\u2192F 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 and protein C were determined with functional assays after complete activation of the zymogens with specific snake venom proteases.<\/jats:p><jats:p>CPA-only, td-E2+CPA, or oral-E2+CPA treatment produced rather small effects on hemostatic variables, whereas oral EE treatment resulted in a large increase in APC resistance from 1.2 \u00b1 0.8 to 4.1 \u00b1 1 (P &amp;lt; 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 &amp;lt; 0.005). The large differential effect of oral EE and oral E2 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\u2192F transsexuals treated with oral EE are exposed to a higher thrombotic risk than transsexuals treated with td E2. Testosterone administration to female-to-male transsexuals had an antithrombotic effect.<\/jats:p>","DOI":"10.1210\/jc.2003-030520","type":"journal-article","created":{"date-parts":[[2003,12,11]],"date-time":"2003-12-11T22:23:51Z","timestamp":1071181431000},"page":"5723-5729","source":"Crossref","is-referenced-by-count":177,"title":["Venous Thrombosis and Changes of Hemostatic Variables during Cross-Sex Hormone Treatment in Transsexual People"],"prefix":"10.1210","volume":"88","author":[{"given":"A. W. F. T.","family":"Toorians","sequence":"first","affiliation":[{"name":"Departments of Endocrinology\/Andrology (A.W.F.T.T., L.J.G.G.), 1007 MB Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C. L. G. 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P.","family":"Magdeleyns","sequence":"additional","affiliation":[{"name":"Department of Biochemistry (M.C.L.G.D.T., E.J.P.M., G.T., J.R.), Cardiovascular Research Institute Maastricht, Maastricht University, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Tans","sequence":"additional","affiliation":[{"name":"Department of Biochemistry (M.C.L.G.D.T., E.J.P.M., G.T., J.R.), Cardiovascular Research Institute Maastricht, Maastricht University, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. J. 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