Adams M R, Register T C, Golden D L, Wagner J D, Williams J K
Comparative Medicine Clinical Research Center, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1040, USA.
Arterioscler Thromb Vasc Biol. 1997 Jan;17(1):217-21. doi: 10.1161/01.atv.17.1.217.
Although estrogen replacement therapy is associated with reduced risk of coronary heart disease and reduced extent of coronary artery atherosclerosis, the effects of combined (estrogen plus progestin) hormone-replacement therapy are uncertain. Some observational data indicate that users of combined hormone replacement consisting of continuously administered oral conjugated equine estrogens (CEE) and oral sequentially administered (7 to 14 days per month) medroxyprogesterone acetate (MPA) experience a reduction in risk similar to that of users of CEE alone. However, the effects of combined, continuously administered CEE plus MPA (a prescribing pattern that has gained favor) on the risk of coronary heart disease or atherosclerosis are not known. We studied the effects of CEE (monkey equivalent of 0.625 mg/d) and MPA (monkey equivalent of 2.5 mg/d), administered separately or in combination, on the extent of coronary artery atherosclerosis (average plaque size) in surgically postmenopausal cynomolgus monkeys fed atherogenic diets and treated with these hormones for 30 months. Treatment with CEE alone resulted in atherosclerosis extent that was reduced 72% relative to untreated (estrogen-deficient) controls (P < .004). Atherosclerosis extent in animals treated with CEE plus MPA or MPA alone did not differ from that of untreated controls. Although treatment had marked effects on plasma lipoprotein patterns, statistical adjustment for variation in plasma lipoproteins did not alter the between-group relationships in atherosclerotic plaque size, suggesting that these factors do not explain substantially the atheroprotective effect of estrogen or the MPA-associated antagonism. Although the mechanism(s) remains unclear, we conclude that oral CEE inhibits the initiation and progression of coronary artery atherosclerosis and that continuously administered oral MPA antagonizes this atheroprotective effect.
尽管雌激素替代疗法与冠心病风险降低及冠状动脉粥样硬化程度减轻相关，但联合（雌激素加孕激素）激素替代疗法的效果尚不确定。一些观察性数据表明，连续口服结合马雌激素（CEE）并每月序贯口服（7至14天）醋酸甲羟孕酮（MPA）的联合激素替代疗法使用者，其风险降低程度与单独使用CEE的使用者相似。然而，连续联合使用CEE加MPA（一种已受青睐的处方模式）对冠心病或动脉粥样硬化风险的影响尚不清楚。我们研究了单独或联合给予CEE（相当于0.625mg/d的猴剂量）和MPA（相当于2.5mg/d的猴剂量），对接受致动脉粥样硬化饮食喂养并接受这些激素治疗30个月的手术绝经食蟹猴冠状动脉粥样硬化程度（平均斑块大小）的影响。单独使用CEE治疗导致动脉粥样硬化程度相对于未治疗（雌激素缺乏）对照组降低了72%（P < 0.004）。接受CEE加MPA或单独使用MPA治疗的动物的动脉粥样硬化程度与未治疗对照组无异。尽管治疗对血浆脂蛋白模式有显著影响，但对血浆脂蛋白变化进行统计调整并未改变动脉粥样硬化斑块大小的组间关系，这表明这些因素并不能充分解释雌激素的抗动脉粥样硬化作用或与MPA相关的拮抗作用。尽管机制尚不清楚，但我们得出结论，口服CEE可抑制冠状动脉粥样硬化的发生和发展，而连续口服MPA可拮抗这种抗动脉粥样硬化作用。
