Hormones and Cardiovascular Disease, CESP Centre for researchin Epidemiology and Population Health, U1018, Inserm, Villejuif, France.
Menopause. 2010 Nov-Dec;17(6):1122-7. doi: 10.1097/gme.0b013e3181e102eb.
Although the route of estrogen administration is known to be an important determinant of the thrombotic risk among postmenopausal women using hormone therapy, recent data have shown that norpregnane derivatives but not micronized progesterone increase venous thromboembolism risk among transdermal estrogens users. However, the differential effects of progesterone and norpregnanes on hemostasis have not yet been investigated.
We set up a cross-sectional study among healthy postmenopausal women aged 45 to 70 years. The impact of activated protein C (APC) on endogenous thrombin potential was investigated in the plasma samples of 108 women who did not use any hormone therapy (n = 40) or who were treated with transdermal estrogens combined with micronized progesterone (n = 30) or norpregnane derivatives (n = 38).
After exclusion of women with factor V Leiden and/or G20210A prothrombin gene mutations, there was no significant change in APC sensitivity among women who used transdermal estrogens combined with micronized progesterone compared with nonusers. Women using transdermal estrogens combined with norpregnanes were less sensitive to APC than were nonusers (P = 0.003) or users of transdermal estrogens combined with micronized progesterone (P = 0.004). In addition, prothrombin fragment 1 + 2 concentration was higher in users of transdermal estrogens plus norpregnanes than in nonusers (P = 0.004). Other hemostatic parameters did not vary significantly across the different subgroups.
Transdermal estrogens combined with norpregnanes may induce APC resistance and activate blood coagulation. These results provide a biological support to epidemiological data regarding the potential thrombogenic effects of norpregnanes. However, these findings need to be confirmed in a randomized trial.
尽管雌激素给药途径已知是绝经后激素治疗女性血栓形成风险的重要决定因素，但最近的数据表明，诺孕烷衍生物而非微粒化孕酮会增加经皮雌激素使用者的静脉血栓栓塞风险。然而，孕激素和诺孕烷对止血的不同影响尚未得到研究。
我们在年龄在 45 至 70 岁的健康绝经后妇女中进行了一项横断面研究。在未使用任何激素治疗（n=40）或接受经皮雌激素联合微粒化孕酮（n=30）或诺孕烷衍生物（n=38）治疗的 108 名女性的血浆样本中，研究了活化蛋白 C (APC) 对内源性凝血酶潜能的影响。
排除携带因子 V 莱顿和/或凝血酶原基因 G20210A 突变的女性后，与非使用者相比，使用经皮雌激素联合微粒化孕酮的女性 APC 敏感性无显著变化。与非使用者（P=0.003）或使用经皮雌激素联合微粒化孕酮的女性（P=0.004）相比，使用经皮雌激素联合诺孕烷的女性对 APC 的敏感性较低。此外，经皮雌激素联合诺孕烷使用者的凝血酶原片段 1+2 浓度高于非使用者（P=0.004）。不同亚组之间其他止血参数无显著差异。
经皮雌激素联合诺孕烷可能诱导 APC 抵抗并激活血液凝固。这些结果为诺孕烷具有潜在促血栓形成作用的流行病学数据提供了生物学支持。然而，这些发现需要在随机试验中得到证实。
