Effect of Lower Dose of Oral Conjugated Equine Estrogen on Size and Oxidative Susceptibility of Low-Density Lipoprotein Particles in Postmenopausal Women
Effect of Lower Dose of Oral Conjugated Equine Estrogen on Size and Oxidative Susceptibility of Low-Density Lipoprotein Particles in Postmenopausal Women
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DOI：
10.1161/01.cir.0000084552.54277.64
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发表时间：
2003-08
期刊：
影响因子：
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通讯作者：
A. Wakatsuki;Y. Okatani;N. Ikenoue;K. Shinohara;Kazushi Watanabe;T. Fukaya
中科院分区：
文献类型：
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作者：
A. Wakatsuki;Y. Okatani;N. Ikenoue;K. Shinohara;Kazushi Watanabe;T. Fukaya
背景：雌激素替代疗法（ERT）具有抗氧化作用，可以阻止LDL的氧化。然而，口服ert诱导的血浆甘油三酯增加与LDL大小降低有关，这可能抵消这种抗氧化作用。由于低剂量口服雌激素不影响血浆甘油三酯浓度，LDL大小可能不会改变，雌激素的抗氧化作用可能被保留。我们研究了低剂量口服雌激素是否可以消除高剂量口服ERT对绝经后妇女LDL大小和氧化易感性的不良影响。方法与结果：绝经后妇女不接受治疗或口服共轭马雌激素（CEE） 0.625或0.3125 mg/d，疗程3个月。剂量为0.625 mg/d的CEE显著增加了血浆甘油三酯浓度，降低了LDL直径，但LDL衍生的硫代巴比妥酸反应物质（TBARS）浓度和共轭二烯形成的滞后时间没有变化。相反，0.3125 mg CEE不影响血浆甘油三酯浓度或LDL直径，显著降低LDL来源的TBARS浓度，显著延长LDL滞后时间。雌激素诱导的LDL直径变化与血浆甘油三酯（r = - 0.44, P <0.01）和LDL来源的TBARS （r = - 0.57, P <0.001）的变化呈负相关，但与LDL滞后时间的变化呈正相关（r =0.42, P <0.01）。结论-由于口服CEE 0.3125 mg/d剂量不会升高血浆甘油三酯，导致LDL颗粒大小不变，具有抗氧化性，因此雌激素的抗氧化作用得以保留。
Background—Estrogen replacement therapy (ERT) has an antioxidant effect that opposes the oxidation of LDL. Oral ERT-induced increases in plasma triglyceride, however, are associated with decreased LDL size, which may counteract this antioxidant effect. Because lower doses of oral estrogen do not affect plasma triglyceride concentrations, LDL size might not change, and the antioxidant effect of estrogen might be preserved. We investigated whether a lower dose of oral estrogen could eliminate the adverse effects of high-dose oral ERT on the size and oxidative susceptibility of LDL in postmenopausal women. Methods and Results—Postmenopausal women received no treatment or were treated with oral conjugated equine estrogen (CEE) 0.625 or 0.3125 mg/d for 3 months. CEE at a dose of 0.625 mg/d significantly increased plasma triglyceride concentrations and decreased LDL diameter, but the concentrations of LDL-derived thiobarbituric acid reactive substances (TBARS) and lag time for conjugated diene formation did not change. In contrast, 0.3125 mg of CEE did not affect plasma triglyceride concentrations or LDL diameter and significantly decreased LDL-derived TBARS concentrations and significantly prolonged LDL lag time. Estrogen-induced changes in LDL diameter correlated negatively with changes in plasma triglyceride (r =−0.44, P <0.01) and LDL-derived TBARS (r =−0.57, P <0.001) but positively with changes in LDL lag time (r =0.42, P <0.01). Conclusions—Because oral CEE at a dose of 0.3125 mg/d does not elevate plasma triglyceride, resulting in unchanged size of LDL particles that are resistant to oxidation, the antioxidant effect of estrogen can be preserved.