King's Thrombosis Centre, King's College Hospital NHS Foundation Trust, London, UK.
J Thromb Haemost. 2010 Aug;8(8):1736-44. doi: 10.1111/j.1538-7836.2010.03953.x. Epub 2010 Jun 14.
The metabolism of estrogen contained within hormone replacement therapy (HRT) is influenced by the route of administration, and this may affect the risk of venous thromboembolism. Thrombin generation, a global coagulation assay, is a marker of hypercoagulability and is of potential use in determining the thrombotic risk associated with particular HRT administration routes.
To determine whether any effect of oral and transdermal HRT on thrombin generation is related to the plasma estrogen profile.
We investigated the effects of oral, transdermal and no HRT (controls) in 52, 39 and 52 postmenopausal women, respectively, on thrombin generation, standard markers of thrombophilia, estradiol level and estrone level.
All parameters of thrombin generation were altered in women using oral HRT as compared with controls (P<0.001 for all comparisons). No such differences were found in women using transdermal HRT. Estrone levels correlated with peak thrombin generation (R=0.451, P<0.001) in women using oral HRT, but there was no correlation in women using the transdermal route.
Thrombin generation is significantly increased in women who use HRT administered by the oral route. This is probably mediated by the hepatic first-pass metabolism of estrone, the main metabolite of oral estradiol, which is avoided by the transdermal route. The effect of estrone on thrombin generation may provide the explanation for the higher thrombotic risk seen in women using oral rather than transdermal HRT.
激素替代疗法（HRT）中所含雌激素的代谢受给药途径的影响，这可能会影响静脉血栓栓塞的风险。凝血酶生成是一种全面的凝血检测，是高凝状态的标志物，对于确定特定 HRT 给药途径相关的血栓形成风险具有潜在的应用价值。
确定口服和经皮 HRT 对凝血酶生成的任何影响是否与血浆雌激素谱有关。
我们分别在 52、39 和 52 名绝经后妇女中研究了口服、经皮和无 HRT（对照组）的影响，检测了凝血酶生成、血栓形成倾向的标准标志物、雌二醇水平和雌酮水平。
与对照组相比，使用口服 HRT 的女性所有凝血酶生成参数均发生改变（所有比较 P<0.001）。使用经皮 HRT 的女性则没有发现这种差异。口服 HRT 的女性中，雌酮水平与峰值凝血酶生成呈正相关（R=0.451，P<0.001），而经皮途径则没有相关性。
使用口服途径给予 HRT 的女性凝血酶生成显著增加。这可能是由口服雌二醇的主要代谢物雌酮的肝首过代谢介导的，而经皮途径则避免了这种代谢。雌酮对凝血酶生成的影响可能解释了使用口服而非经皮 HRT 的女性血栓形成风险更高的原因。
