Clarkson Thomas B
Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, USA.
Menopause. 2007 May-Jun;14(3 Pt 1):373-84. doi: 10.1097/GME.0b013e31803c764d.
The past several years have been marked by confusion and controversy concerning whether estrogens are cardioprotective. The issue is of utmost public health importance because coronary heart disease (CHD) remains the leading cause of death among postmenopausal women. Fortunately, a unifying hypothesis has emerged that reproductive stage is a major determinant of the effect of estrogens on atherosclerosis progression, complications, and plaque vulnerability. PREMENOPAUSAL YEARS: Premenopausal atherosclerosis progression seems to be an important determinant of postmenopausal atherosclerosis and thus the risk for CHD. Clearly, plasma lipids/lipoproteins influence this progression; however, estradiol deficiency seems to be the major modulator. Both monkeys and women with premenopausal estrogen deficiency develop premature atherosclerosis, an effect that can be prevented in both species by estrogen-containing oral contraceptives. PERIMENOPAUSAL/EARLY POSTMENOPAUSAL YEARS: During this stage, there are robust estrogen benefits. Monkeys given estrogens immediately after surgical menopause have a 70% inhibition in coronary atherosclerosis progression. Estrogen treatment prevented progression of atherosclerosis of women in the Estrogen in the Prevention of Atherosclerosis Trial. A meta-analysis of women younger than 60 years given hormone therapy had reduced total mortality (relative risk = 0.61, 95% CI: 0.39-0.95). LATE POSTMENOPAUSAL YEARS: This stage is one in which there are no or possible deleterious estrogen effects. Monkeys lose CHD benefits of estrogens when treatment is delayed. The increase in CHD events associated with initiating hormone therapy 10 or more years after menopause seems to be related to up-regulation of the plaque inflammatory processes and plaque instability and may be down-regulated by statin pretreatment.
在过去几年中，关于雌激素是否具有心脏保护作用一直存在困惑和争议。这个问题具有极其重要的公共卫生意义，因为冠心病（CHD）仍然是绝经后女性的主要死因。幸运的是，一个统一的假说已经出现，即生殖阶段是雌激素对动脉粥样硬化进展、并发症和斑块易损性影响的主要决定因素。绝经前几年：绝经前动脉粥样硬化进展似乎是绝经后动脉粥样硬化的一个重要决定因素，因此也是冠心病风险的重要决定因素。显然，血浆脂质/脂蛋白会影响这种进展；然而，雌二醇缺乏似乎是主要的调节因素。绝经前雌激素缺乏的猴子和女性都会出现过早的动脉粥样硬化，含雌激素的口服避孕药可以在这两个物种中预防这种情况。围绝经期/绝经后早期：在这个阶段，雌激素有显著益处。手术绝经后立即给予雌激素的猴子，冠状动脉粥样硬化进展受到70%的抑制。在“雌激素预防动脉粥样硬化试验”中，雌激素治疗阻止了女性动脉粥样硬化的进展。对60岁以下接受激素治疗的女性进行的一项荟萃分析显示，总死亡率降低（相对风险 = 0.61，95%可信区间：0.39 - 0.95）。绝经后期：在这个阶段，雌激素没有作用或可能产生有害作用。如果延迟治疗，猴子会失去雌激素对冠心病的益处。绝经后10年或更长时间开始激素治疗与冠心病事件增加相关，这似乎与斑块炎症过程的上调和斑块不稳定有关，他汀类药物预处理可能会下调这种情况。
