Straczek Céline, Oger Emmanuel, Yon de Jonage-Canonico Marianne Beau, Plu-Bureau Geneviève, Conard Jacqueline, Meyer Guy, Alhenc-Gelas Martine, Lévesque Hervé, Trillot Nathalie, Barrellier Marie-Thérèse, Wahl Denis, Emmerich Joseph, Scarabin Pierre-Yves
INSERM, Cardiovascular Epidemiology Unit, Villejuif, France.
Circulation. 2005 Nov 29;112(22):3495-500. doi: 10.1161/CIRCULATIONAHA.105.565556. Epub 2005 Nov 21.
Oral estrogen increases the risk of venous thromboembolism (VTE) in postmenopausal women, particularly in those with a prothrombotic mutation. Transdermal estrogen may be safe with respect to VTE. We investigated the impact of the route of estrogen administration on the association between a prothrombotic mutation (factor V Leiden or prothrombin G20210A mutation) and VTE risk.
We performed a multicenter case-control study of VTE among postmenopausal women who were enrolled in 1999 through 2004 at 7 clinical centers in France. We recruited 235 consecutive patients with a first documented episode of idiopathic VTE and 554 controls. Factor V Leiden was associated with a 3.4-fold-increased risk of VTE (95% confidence interval [CI], 2.0 to 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 (odds ratio [OR], 4.3; 95% CI, 2.6 to 7.2; and OR, 1.2; 95% CI, 0.8 to 1.7, respectively). After adjustment for potential confounding factors, the combination of either factor V Leiden or prothrombin G20210A mutation and oral estrogen gave a 25-fold-increased risk of VTE compared with nonusers without mutation (95% CI, 6.9 to 95.0). However, the risk for 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 to 9.9; and OR, 4.1; 95% CI, 2.3 to 7.4, respectively).
In contrast to oral estrogen, transdermal estrogen does not confer additional risk on women who carry a prothrombotic mutation. The safety of transdermal estrogen has to be confirmed in randomized trials.
口服雌激素会增加绝经后女性发生静脉血栓栓塞（VTE）的风险，尤其是那些存在血栓形成前突变的女性。经皮雌激素在VTE方面可能是安全的。我们研究了雌激素给药途径对血栓形成前突变（因子V莱顿突变或凝血酶原G20210A突变）与VTE风险之间关联的影响。
我们对1999年至2004年期间在法国7个临床中心招募的绝经后女性进行了一项VTE的多中心病例对照研究。我们连续招募了235例首次有特发性VTE记录的患者和554例对照。因子V莱顿突变与VTE风险增加3.4倍相关（95%置信区间[CI]，2.0至5.8），凝血酶原突变与VTE风险增加4.8倍相关（95%CI，2.5至9.4）。口服而非经皮雌激素与VTE风险增加相关（优势比[OR]分别为4.3；95%CI，2.6至7.2；以及OR为1.2；95%CI，0.8至1.7）。在对潜在混杂因素进行调整后，与无突变的非使用者相比，因子V莱顿突变或凝血酶原G20210A突变与口服雌激素联合使用使VTE风险增加25倍（95%CI，6.9至95.0）。然而，使用经皮雌激素的血栓形成前突变女性的风险与未使用雌激素的突变女性相似（OR分别为4.4；95%CI，2.0至9.9；以及OR为4.1；95%CI，2.3至7.4）。
与口服雌激素不同，经皮雌激素不会给携带血栓形成前突变的女性带来额外风险。经皮雌激素的安全性必须在随机试验中得到证实。
