Hemelaar Majoie, Rosing Jan, Kenemans Peter, Thomassen M Christella L G D, Braat Didi D M, van der Mooren Marius J
Project Aging Women and Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU), Department of Obstetrics and Gynecology, VU University Medical Center, De Boelelaan 1117, 1081 HV, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1660-6. doi: 10.1161/01.ATV.0000224325.96659.53. Epub 2006 Apr 27.
To compare the effects of intranasal and oral administration of 17beta-estradiol (E2) and norethisterone(acetate) [NET(A)] in healthy postmenopausal women on activated protein C (APC) resistance and other hemostatic parameters associated with venous thrombosis.
In this 2-center, randomized, double-blind, 1-year trial, 90 postmenopausal women (56.6+/-4.7 years of age) received daily either an intranasal spray with 175 microg/275 microg E2/NET (n=47) or 1 mg/0.5 mg oral E2/NETA (n = 43). Normalized APC sensitivity ratios (nAPCsr) were determined with a thrombin generation-based APC resistance test. After 1 year, the increase in nAPCsr was smaller in the intranasal than in the oral group: 11% (95% CI, 1% to 22%) versus 53% (95% CI, 37% to 72%). Overall, the decrease in antithrombin and increase in prothrombin fragment 1+2 (F1+2) were smaller and the decrease in free protein S larger in the intranasal compared with the oral group after 1 year. In both groups, the decreases in protein C and prothrombin, and the increase in d-dimer were similar.
Compared with oral E2/NETA therapy, intranasal administration of E2/NET had less effect on APC resistance and on a number of other parameters associated with venous thrombosis. This observation suggests the possibility of a lower venous thrombosis risk for intranasal E2/NET compared with oral therapy.
比较健康绝经后女性经鼻和口服17β-雌二醇（E2）与炔诺酮（醋酸酯）[NET(A)]对活化蛋白C（APC）抵抗及其他与静脉血栓形成相关的止血参数的影响。
在这项为期1年的2中心、随机、双盲试验中，90名绝经后女性（年龄56.6±4.7岁）每日接受经鼻喷雾175微克/275微克E2/NET（n = 47）或口服1毫克/0.5毫克E2/NETA（n = 43）。通过基于凝血酶生成的APC抵抗试验测定标准化APC敏感性比值（nAPCsr）。1年后，经鼻组nAPCsr的升高幅度小于口服组：分别为11%（95%CI，1%至22%）和53%（95%CI，37%至72%）。总体而言，1年后与口服组相比，经鼻组抗凝血酶的降低幅度和凝血酶原片段1+2（F1+2）的升高幅度较小，游离蛋白S的降低幅度较大。两组中，蛋白C和凝血酶原的降低以及D-二聚体的升高相似。
与口服E2/NETA治疗相比，经鼻给予E2/NET对APC抵抗及其他一些与静脉血栓形成相关的参数影响较小。这一观察结果提示，与口服治疗相比，经鼻给予E2/NET发生静脉血栓形成的风险可能较低。
