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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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