Estrogen replacement therapy and cardioprotection: mechanisms and controversies.
Estrogen replacement therapy and cardioprotection: mechanisms and controversies.
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DOI：
10.1590/s0100-879x2002000300001
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发表时间：
2002-03
期刊：
影响因子：
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通讯作者：
M.T.R. Subbiah
中科院分区：
文献类型：
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作者：
M.T.R. Subbiah
流行病学和病例对照研究表明，雌激素替代疗法在冠心病一级预防方面可能是有益的。雌激素的这种有益作用最初被认为是由于低密度脂蛋白（LDL）的减少和高密度脂蛋白（HDL）的增加。最近的研究表明，雌激素可以防止氧化应激并降低低密度脂蛋白氧化。雌激素直接作用于动脉组织，通过一氧化氮和前列腺素的合成调节血管反应性。虽然雌激素对血管组织的许多影响被认为是由雌激素受体α和β介导的，但有证据表明存在“直接的非基因组”影响。高密度脂蛋白在与17 -雌二醇相互作用中的作用，包括其酯化和酯化雌激素向低密度脂蛋白的转移，正在开始被阐明。尽管雌激素有积极作用，但最近在冠心病妇女中进行的两项安慰剂对照临床试验并未发现雌激素治疗对总体冠状动脉事件有任何有益影响。事实上，一些女性的冠心病发病率有所增加。在一个妇女亚群中的血栓形成基因突变（因子V Leiden，凝血酶原突变等）可能在这一意想不到的发现中发挥作用。因此，雌激素的心脏保护作用似乎比原先认为的更复杂，需要更多的研究。
Epidemiological and case-controlled studies suggest that estrogen replacement therapy might be beneficial in terms of primary prevention of coronary heart disease (CHD). This beneficial effect of estrogens was initially considered to be due to the reduction of low density lipoproteins (LDL) and to increases in high density lipoproteins (HDL). Recent studies have shown that estrogens protect against oxidative stress and decrease LDL oxidation. Estrogens have direct effects on the arterial tissue and modulate vascular reactivity through nitric oxide and prostaglandin synthesis. While many of the effects of estrogen on vascular tissue are believed to be mediated by estrogen receptors alpha and beta, there is evidence for 'immediate non-genomic' effects. The role of HDL in interacting with 17beta-estradiol including its esterification and transfer of esterified estrogens to LDL is beginning to be elucidated. Despite the suggested positive effects of estrogens, two recent placebo-controlled clinical trials in women with CHD did not detect any beneficial effects on overall coronary events with estrogen therapy. In fact, there was an increase in CHD events in some women. Mutations in thrombogenic genes (factor V Leiden, prothrombin mutation, etc.) in a subset of women may play a role in this unexpected finding. Thus, the cardioprotective effect of estrogens appears to be more complicated than originally thought and requires more research.