Duvernoy Claire S, Rose Patricia A, Kim H Myra, Kehrer Christine, Brook Robert D
Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48105, USA.
J Womens Health (Larchmt). 2007 Sep;16(7):963-70. doi: 10.1089/jwh.2006.0321.
This study sought to determine whether combined continuous ethinyl estradiol and norethindrone acetate, a postmenopausal hormone therapy (HT) combination designed to have fewer side effects than cyclical therapies and therapies using medroxyprogesterone acetate (MPA), could improve vascular endothelial function in postmenopausal women with risk factors for cardiovascular disease (CVD).
Eighteen postmenopausal women (mean age 62 +/- 11 years) participated in a randomized, placebo-controlled, crossover design trial of 10 microg estradiol/1 mg norethindrone acetate given once daily for 3 months, with a 1-month washout period between placebo and active treatment phases. Vascular reactivity was assessed at each phase of the study using high-frequency brachial artery ultrasound in response to flow-mediated hyperemia, cold pressor testing, and sublingual nitroglycerin. Markers of cardiovascular risk, including cholesterol levels, inflammatory markers, fibrinolytic markers, and solubilized adhesion molecules, were also measured at each phase.
We found no significant difference in vascular reactivity measurements during active treatment with ethinyl estradiol/norethindrone acetate vs. placebo. C-reactive protein (CRP) levels increased significantly during active treatment, and high-density lipoprotein (HDL) levels decreased significantly. Vascular cell adhesion molecule-1 (VCAM-1) levels declined during active treatment. Plasminogen activator inhibitor-1 (PAI-1) levels were inversely correlated with flow-mediated hyperemic vascular reactivity, independent of active treatment or placebo phases.
In this older postmenopausal population with at least one cardiovascular risk factor, treatment with combined continuous ethinyl estradiol and norethindrone acetate failed to improve vascular endothelial function. The agent's proinflammatory effect or subclinical atherosclerosis in this population may have contributed to this finding.
本研究旨在确定联合使用炔雌醇和醋酸炔诺酮（一种绝经后激素疗法[HT]组合，设计用于比周期性疗法和使用醋酸甲羟孕酮[MPA]的疗法具有更少的副作用）是否能改善有心血管疾病（CVD）风险因素的绝经后女性的血管内皮功能。
18名绝经后女性（平均年龄62±11岁）参与了一项随机、安慰剂对照、交叉设计试验，每天服用一次10微克雌二醇/1毫克醋酸炔诺酮，持续3个月，在安慰剂和积极治疗阶段之间有1个月的洗脱期。在研究的每个阶段，使用高频肱动脉超声评估血管反应性，以应对血流介导的充血、冷加压试验和舌下含服硝酸甘油。还在每个阶段测量心血管风险标志物，包括胆固醇水平、炎症标志物、纤溶标志物和可溶性粘附分子。
我们发现，与安慰剂相比，在使用炔雌醇/醋酸炔诺酮进行积极治疗期间，血管反应性测量没有显著差异。在积极治疗期间，C反应蛋白（CRP）水平显著升高，高密度脂蛋白（HDL）水平显著降低。在积极治疗期间，血管细胞粘附分子-1（VCAM-1）水平下降。纤溶酶原激活物抑制剂-1（PAI-1）水平与血流介导的充血性血管反应性呈负相关，与积极治疗或安慰剂阶段无关。
在这个至少有一个心血管风险因素的老年绝经后人群中，联合使用连续炔雌醇和醋酸炔诺酮治疗未能改善血管内皮功能。该药物在此人群中的促炎作用或亚临床动脉粥样硬化可能导致了这一结果。
