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Arterioscler Thromb Vasc Biol. 2003 Sep 1;23(9):1671-6. Epub 2003 Jul 17.

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

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1
Département de Médecine Interne, Hôpital de la Cavale Blanche, Brest, France. emmanual.oger@southernhealth.org.au

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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