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Differential effects of oral and transdermal estrogen/progesterone regimens on sensitivity to activated protein C among postmenopausal women: a randomized trial.
Oger E., Alhenc-Gelas M., Lacut K., Blouch M.-T., Roudaut N., Kerlan V., Collet M., Abgrall J.-F., Aiach M., Scarabin P.-Y. et al
Arteriosclerosis, Thrombosis, and Vascular Biology 23, 9 (2003) 1671-6 - http://hal.univ-brest.fr/hal-00722263
Sciences du Vivant/Médecine humaine et pathologie
(12869355)
Differential effects of oral and transdermal estrogen/progesterone regimens on sensitivity to activated protein C among postmenopausal women: a randomized trial.
Emmanuel Oger1, Martine Alhenc-Gelas2, Karine Lacut1, Marie-Thérèse Blouch1, 3, Nathalie Roudaut4, Véronique Kerlan1, 4, Michel Collet1, 5, Jean-François Abgrall3, Martine Aiach2, Pierre-Yves Scarabin6, Dominique Mottier1,
1 :  GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
Université de Bretagne Occidentale [UBO]
CHU de la Cavale Blanche Département de médecine interne et pneumologie 29609 BREST
France
2 :  Risque thrombotique et mécanismes de l'hémostase
INSERM : U428 – IFR71 – Université Paris V - Paris Descartes
4, avenue de l'observatoire 75270 Paris Cedex 06
France
3 :  Service d'hématologie biologique
CHU Brest
29200 Brest
France
4 :  CHRU - Endocrino - Service d'Endocrinologie
CHRU Brest
Hôpital de la Cavale Blanche boulevard Tanguy Prigent 29609 BREST Cédex
France
5 :  BREST - Gynéco-Obs - Service de Gynécologie-Obstétrique
CHRU Brest
Hôpital Morvan avenue Foch BREST
France
6 :  CESP - Centre de recherche en épidémiologie et santé des populations
INSERM : U1018 – Université Paris XI - Paris Sud – Hôpital Paul Brousse – Assistance publique - Hôpitaux de Paris (AP-HP)
16 avenue Paul Vaillant Couturier 94807 Villejuif Cedex, France
France
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.
Anglais

Articles dans des revues avec comité de lecture
10.1161/01.ATV.0000087141.05044.1F
Arteriosclerosis, Thrombosis, and Vascular Biology (Arterioscler Thromb Vasc Biol)
Publisher American Heart Association
ISSN 1079-5642 (eISSN : 1524-4636)
internationale
01/09/2003
17/07/2003
23
9
1671-6

Administration – Cutaneous – Administration – Oral – Estrogens – Female – Humans – Postmenopause – Progesterone – Protein C