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In Contrast to Oral Estrogen Therapy, Transdermal Estrogen Therapy Does Not Increase the Risk of Venous Thromboembolism in Postmenopausal Women Who Carry a Prothrombotic Mutation

December 2, 2005

By Sahar Bedrood B.S. and Asher Kimchi M.D.

Villejuif, France - There are many factors that can increase the risk of venous thromboembolism (VTE). Oral estrogen therapy is one known factor that can increase the risk of VTE in postmenopausal women. Celine Straczek PhD, et al from the Cardiovascular Epidemiology Unit at INSERM in France investigated the impact of the route of estrogen administration on the association between a prothrombotic mutation and VTE risk. Their findings, published in the November 29, 2005 issue of Circulation, indicate that in contrast to oral estrogen, transdermal estrogen does not confer additional risk on women who carry a prothrombotic mutation.

The study was a multi-center case-control study of VTE among postmenopausal women who enrolled in 7 clinical centers in France. It consisted of 235 patients who had a documented episode of idiopathic VTE and 554 patients were controls who admitted to the hospital with an a priori diagnosis unrelated to VTE or hormone therapy. All patients were genotyped for Factor V Leiden and G20210A mutation, another prothrombotic mutation. The prevalence of the prothrombotic mutation among controls was 4.9% for the factor V leiden and 2.5% for the prothrombin G20210A mutation, as expected in the white population.

Factor V Leiden was associated with a 3.4-fold increased risk of VTE (95% CI, 2.0-5.8) and a prothrombin mutation was associated with a 4.8 fold increased risk of VTE (95% CI, 2.5 to 9.4). Oral but not transdermal estrogen was associated with an increased risk of VTE (OR 4.3; 95% CI, 2.6 to 7.2). After adjustment for confounding factors, the combination of either factor V leiden or prothrombin G20219A mutation and oral estrogen gave a 25-fold increased risk of VTE compared with nonusers with the mutation ( 95% CI, 6.9 to 9.5). The risk for a women with prothrombotic mutation using transdermal estrogen was similar to that of women with a mutation who were not using estrogen (OR, 4.4; 95% CI, 2.0-9.9; and OR 4.1; 95%CI, 2.3 to 7.4, respectively.)

Overall, the thrombotic risk associated with oral estrogen use is substantially increased among women carrying a prothrombotic mutation. Transdermal estrogen administration seems safer than oral estrogen therapy with respect to thrombotic risk.

Co-authors: Céline Straczek, PhD; Emmanuel Oger, MD, PhD; Marianne Beau Yon de Jonage-Canonico, PhD;Geneviève Plu-Bureau, MD, PhD; Jacqueline Conard, PhD; Guy Meyer, MD; Martine Alhenc-Gelas, PhD; Hervé Lévesque, MD; Nathalie Trillot, MD; Marie-Thérèse Barrellier, MD; Denis Wahl, MD, PhD; Joseph Emmerich, MD, PhD; Pierre-Yves Scarabin, MD, MSc; for the Estrogen and Thromboembolism Risk (ESTHER) Study Group


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