Post Marinka S, van der Mooren Marius J, van Baal W Marchien, Blankenstein Marinus A, Merkus Hans M W M, Kroeks Maurice V A M, Franke Henk R, Kenemans Peter, Stehouwer Coen D A
Project Aging Women and the Institute for Cardiovascular Research-Vrije Universiteit, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
Am J Obstet Gynecol. 2003 Nov;189(5):1221-7. doi: 10.1067/s0002-9378(03)00599-4.
This study was undertaken to investigate the effect of transdermal and oral estrogen replacement therapy in healthy postmenopausal women on markers of coagulation and fibrinolysis associated with coronary artery disease.
In a randomized, placebo-controlled, double-blind study, healthy hysterectomized postmenopausal women received daily either placebo (n=49), transdermal 17beta-estradiol (E(2)) 50 microg (tE(2) group, n=33), oral E(2) 1 mg (oE(2) group, n=37), or oral E(2) 1 mg combined with gestodene 25 microg (oE(2)+G group, n=33) for thirteen 28-day treatment cycles. Hemostatic variables were measured in blood samples collected at baseline and in cycles 4 and 13.
No significant changes versus baseline and placebo were found in the tE(2) group, except for plasminogen activator inhibitor type-1 (PAI-1) in cycle 13 (-32.4%, P=.01). In the oE(2) group, significant percentage changes from baseline versus placebo in cycle 13 were found in fibrinogen, -5.4% (P<.05); factor VII, -7.3% (P<.05); thrombin-antithrombin III complexes, -13.3% (P<.05); tissue-type plasminogen activator (t-PA), -17.3% (P<.001); and PAI-1, -54.3% (P<.001). In the oE(2)+G group, respective changes were factor VII, -17.6% (P<.001); t-PA, -14.5% (P=.01); PAI-1, -36.4% (P<.01); and D-dimer, +21.8% (P<.05). No significant changes were observed in prothrombin fragment 1+2 and plasmin-alpha(2)-antiplasmin complexes.
Low-dose oral estradiol therapy was associated with an increase in fibrinolysis and small decreases in procoagulant variables. Transdermal therapy had minor effects.
本研究旨在探讨经皮和口服雌激素替代疗法对健康绝经后女性与冠状动脉疾病相关的凝血和纤维蛋白溶解标志物的影响。
在一项随机、安慰剂对照、双盲研究中，健康的子宫切除术后绝经后女性每天接受安慰剂（n = 49）、经皮17β-雌二醇（E₂）50微克（tE₂组，n = 33）、口服E₂ 1毫克（oE₂组，n = 37）或口服E₂ 1毫克联合孕二烯酮25微克（oE₂ + G组，n = 33），为期13个28天的治疗周期。在基线以及第4和第13周期采集的血样中测量止血变量。
与基线和安慰剂相比，tE₂组未发现显著变化，但在第13周期时纤溶酶原激活物抑制剂-1（PAI-1）有变化（-32.4%，P = 0.01）。在oE₂组中，第13周期与安慰剂相比，纤维蛋白原从基线的显著百分比变化为-5.4%（P < 0.05）；因子VII为-7.3%（P < 0.05）；凝血酶-抗凝血酶III复合物为-13.3%（P < 0.05）；组织型纤溶酶原激活物（t-PA）为-17.3%（P < 0.001）；PAI-1为-54.3%（P < 0.001）。在oE₂ + G组中，相应变化为因子VII -17.6%（P < 0.001）；t-PA -14.5%（P = 0.01）；PAI-1 -36.4%（P < 0.01）；D-二聚体 +21.8%（P < 0.05）。凝血酶原片段1 + 2和纤溶酶-α₂-抗纤溶酶复合物未观察到显著变化。
低剂量口服雌二醇疗法与纤维蛋白溶解增加和促凝血变量小幅降低有关。经皮疗法影响较小。
