OBJECTIVES:To determine if low dose conjugated equine estrogens (CEE) result in a reduction of coronary artery atherosclerosis progression, and to relate these findings to previous studies using the traditional dose. METHODS:Adult female monkeys (Macaca fascicularis) were fed an atherogenic diet for 10 months, to induce fatty streaks and small plaques comparable to those present in early postmenopausal women, and then ovariectomized and treated orally with: CEE (0.30 mg/day women's equivalent dose, n=28) or placebo (n=25) daily for 24 months. Body weight and estradiol were measured at 3, 6, 12 and 18 months and plasma lipids were measured at baseline and every 6 months. RESULTS:Despite the lack of effect on plasma lipid profiles, monkeys treated with low dose CEE had marked reductions in coronary artery atherosclerosis plaque extent (intimal area) in all three main coronary arteries: left anterior descending artery (52% less, 0.044 mm(2) versus 0.091 mm(2), p=0.04); left circumflex artery (62% less, 0.045 mm(2) versus 0.119 mm(2), p=0.006) and right circumflex artery (42% less, 0.018 mm(2) versus 0.031 mm(2), p=0.20). The overall mean coronary atherosclerosis extent was 52% lower in CEE treated animals (0.042 mm(2) versus 0.088 mm(2), p=0.02). CONCLUSION:Low dose CEE (0.30 mg/woman/day equivalent) was effective in reducing coronary atherosclerosis and the magnitude of the protection was comparable to previously reported studies using doses equivalent to 0.625 mg/woman/day. This study provides an experimental basis for the assumption that low dose CEE may be as effective as the traditional dose in inhibiting coronary atherosclerosis progression in early postmenopausal subjects.

译文

目的:确定低剂量的共轭马雌激素(CEE)是否会导致冠状动脉粥样硬化进程的减少,并将这些发现与以前使用传统剂量的研究相关联。
方法:成年雌性猴子(Macaca fascicularis)进行动脉粥样硬化饮食10个月,以诱发与绝经后早期女性相当的脂肪条纹和小斑块,然后进行卵巢切除并口服:CEE(0.30 mg /日女性当量剂量,n = 28)或安慰剂(n = 25),持续24个月。在第3、6、12和18个月测量体重和雌二醇,在基线和每6个月测量一次血浆脂质。
结果:尽管对血浆脂质谱没有影响,但低剂量CEE治疗的猴子在所有三个主要冠状动脉中均显着降低了冠状动脉粥样斑块程度(内膜面积):左前降支(减少52%,0.044 mm( 2)与0.091 mm(2),p = 0.04);左旋支动脉(少62%,0.045 mm(2)对0.119 mm(2),p = 0.006)和右旋支动脉(少42%,0.018 mm(2)对0.031 mm(2),p = 0.20)。在CEE治疗的动物中,总体平均冠状动脉粥样硬化程度降低了52%(0.042 mm(2)对0.088 mm(2),p = 0.02)。
结论:低剂量CEE(0.30 mg /妇女/天)可有效减轻冠状动脉粥样硬化,其保护程度可与先前报道的等效于0.625 mg /妇女/天的研究相媲美。这项研究为以下假设提供了实验依据:低剂量的CEE在抑制绝经后早期受试者的冠状动脉粥样硬化进展中可能与传统剂量一样有效。

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