Differential effects of oral and transdermal estrogen/progesterone regimens on sensitivity to activated protein C among postmenopausal women: a randomized trial.

Emmanuel Oger 1 Martine Alhenc-Gelas 2 Karine Lacut 1 Marie-Thérèse Blouch 3, 1 Nathalie Roudaut 4 Véronique Kerlan 1, 4 Michel Collet 1, 5 Jean-François Abgrall 3 Martine Aiach 2 Pierre-Yves Scarabin 6 Dominique Mottier 1 Non Renseigné
1 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
2 Risque thrombotique et mécanismes de l'hémostase
3 Service d'hématologie biologique
4 CHRU - Endocrino - Service d'Endocrinologie
5 BREST - Gynéco-Obs - Service de Gynécologie-Obstétrique
6 CESP - Centre de recherche en épidémiologie et santé des populations
Abstract : OBJECTIVE: Activated protein C (APC) resistance not related to the factor V Leiden mutation is a risk factor for venous thrombosis. Oral estrogen replacement therapy (ERT) has been reported to induce APC resistance. Little is known about the effect of transdermal estrogen. METHODS AND RESULTS: We enrolled 196 postmenopausal women who were randomly allocated to receive either 1 mg 17beta-estradiol orally (n=63) or 50 microg 17beta-estradiol transdermally per day (n=68), both associated with 100 mg progesterone daily or placebo (n=65) for 6 months. An activated partial thromboplastin time (APTT)-based test and the effect of APC on thrombin potential (ETP) were used. Oral ERT induced an ETP-based APC resistance compared with both placebo (P=0.006) and transdermal ERT (P<0.001), but there was no significant effect of transdermal ERT compared with placebo (P=0.191). There was no significant effect of ERT on the APTT-based APC sensitivity ratio. Prothrombin fragment 1+2 plasma levels were significantly higher after 6 months of treatment in women allocated to oral ERT compared with those on placebo and transdermal ERT and were positively and significantly correlated with changes in ETP-based APC sensitivity ratio. CONCLUSIONS: Our data show that oral, unlike transdermal, estrogen induces APC resistance and activates blood coagulation. These results emphasize the importance of the route of estrogen administration.
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Article dans une revue
Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2003, 23 (9), pp.1671-6. 〈10.1161/01.ATV.0000087141.05044.1F〉
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Contributeur : Ghislaine Calvez <>
Soumis le : mercredi 1 août 2012 - 10:15:16
Dernière modification le : vendredi 15 février 2019 - 13:58:12

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Emmanuel Oger, Martine Alhenc-Gelas, Karine Lacut, Marie-Thérèse Blouch, Nathalie Roudaut, et al.. Differential effects of oral and transdermal estrogen/progesterone regimens on sensitivity to activated protein C among postmenopausal women: a randomized trial.. Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2003, 23 (9), pp.1671-6. 〈10.1161/01.ATV.0000087141.05044.1F〉. 〈hal-00722263〉

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