Venous Thrombosis and Changes of Hemostatic Variables during Cross-Sex Hormone Treatment in Transsexual People

A. W.F.T. Toorians, M. C.L.G.D. Thomassen, S. Zweegman, E. J.P. Magdeleyns, G. Tans, L. J.G. Gooren, J. Rosing

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)5723-5729
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number12
DOIs
Publication statusPublished - Dec 2003

Cite this

Toorians, A. W.F.T. ; Thomassen, M. C.L.G.D. ; Zweegman, S. ; Magdeleyns, E. J.P. ; Tans, G. ; Gooren, L. J.G. ; Rosing, J. / Venous Thrombosis and Changes of Hemostatic Variables during Cross-Sex Hormone Treatment in Transsexual People. In: Journal of Clinical Endocrinology and Metabolism. 2003 ; Vol. 88, No. 12. pp. 5723-5729.
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title = "Venous Thrombosis and Changes of Hemostatic Variables during Cross-Sex Hormone Treatment in Transsexual People",
abstract = "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.",
author = "Toorians, {A. W.F.T.} and Thomassen, {M. C.L.G.D.} and S. Zweegman and Magdeleyns, {E. J.P.} and G. Tans and Gooren, {L. J.G.} and J. Rosing",
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Venous Thrombosis and Changes of Hemostatic Variables during Cross-Sex Hormone Treatment in Transsexual People. / Toorians, A. W.F.T.; Thomassen, M. C.L.G.D.; Zweegman, S.; Magdeleyns, E. J.P.; Tans, G.; Gooren, L. J.G.; Rosing, J.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 88, No. 12, 12.2003, p. 5723-5729.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Venous Thrombosis and Changes of Hemostatic Variables during Cross-Sex Hormone Treatment in Transsexual People

AU - Toorians, A. W.F.T.

AU - Thomassen, M. C.L.G.D.

AU - Zweegman, S.

AU - Magdeleyns, E. J.P.

AU - Tans, G.

AU - Gooren, L. J.G.

AU - Rosing, J.

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N2 - 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.

AB - 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.

U2 - 10.1210/jc.2003-030520

DO - 10.1210/jc.2003-030520

M3 - Article

VL - 88

SP - 5723

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JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

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ER -