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(Circulation. 2007;115:840-845.)
© 2007 American Heart Association, Inc.

Cardiovascular Disease in Women

Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women

Impact of the Route of Estrogen Administration and Progestogens: The ESTHER Study

Marianne Canonico, PhD; Emmanuel Oger, MD, PhD; Geneviève Plu-Bureau, MD, PhD; Jacqueline Conard, PhD; Guy Meyer, MD; 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

From Inserm Unit 780, Cardiovascular Epidemiology Section, Villejuif (M.C., E.O., G.P.-B., P.-Y.S.); Université Paris-Sud 11, Villejuif (M.C., E.O., P.-Y.S.); Département de Médecine Interne, GETBO, Hôpital de la Cavale Blanche, Brest (E.O.); Université Paris 5 Réné Descartes, Service d’Hématologie Biologique, Hôpital Hôtel-Dieu, Paris (G.P.-B., J.C.); Université Paris-Descartes, Faculté de Médecine; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris (G.M.); Département de Médecine Interne, CHU Rouen, Rouen (H.L.); Institut d’Hématologie-Transfusion, CHUR, Lille (N.T.); Service d’Explorations Fonctionnelles, CHU Côte de Nacre, Caen (M.-T.B.); Unité de Médecine Interne Thrombose Maladies Vasculaires, CHU Nancy, Hôpital de Brabois, and INSERM U734, Faculté de Médecine de Nancy-Université Henri Poincaré, Vandoeuvre-Les-Nancy (D.W.); and Université Paris Descartes, Inserm U428 and Service de Médecine Vasculaire-HTA, Hôpital Européen Georges Pompidou, Paris (J.E.), France.

Correspondence to P.Y. Scarabin, Inserm Unit 780, Cardiovascular Epidemiology Section, 16 Avenue Paul Vaillant Couturier, 94807 Villejuif Cedex, France. E-mail scarabin{at}vjf.inserm.fr

Received May 26, 2006; accepted November 8, 2006.

Background— Oral estrogen therapy increases the risk of venous thromboembolism (VTE) in postmenopausal women. Transdermal estrogen may be safer. However, currently available data have limited the ability to investigate the wide variety of types of progestogen.

Methods and Results— We performed a multicenter case–control study of VTE among postmenopausal women 45 to 70 years of age between 1999 and 2005 in France. We recruited 271 consecutive cases with a first documented episode of idiopathic VTE (208 hospital cases, 63 outpatient cases) and 610 controls (426 hospital controls, 184 community controls) matched for center, age, and admission date. After adjustment for potential confounding factors, odds ratios (ORs) for VTE in current users of oral and transdermal estrogen compared with nonusers were 4.2 (95% CI, 1.5 to 11.6) and 0.9 (95% CI, 0.4 to 2.1), respectively. There was no significant association of VTE with micronized progesterone and pregnane derivatives (OR, 0.7; 95% CI, 0.3 to 1.9 and OR, 0.9; 95% CI, 0.4 to 2.3, respectively). In contrast, norpregnane derivatives were associated with a 4-fold-increased VTE risk (OR, 3.9; 95% CI, 1.5 to 10.0).

Conclusions— Oral but not transdermal estrogen is associated with an increased VTE risk. In addition, our data suggest that norpregnane derivatives may be thrombogenic, whereas micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk. If confirmed, these findings could benefit women in the management of their menopausal symptoms with respect to the VTE risk associated with oral estrogen and use of progestogens.

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