Prestwood Karen M, Unson Christine, Kulldorff Martin, Cushman Mary
Center on Aging, University of Connecticut Health Center, 265 Farmington Ave., Farmington, CT 06030-5215, USA.
J Gerontol A Biol Sci Med Sci. 2004 Aug;59(8):827-32. doi: 10.1093/gerona/59.8.m827.
The authors evaluated the effect of 3 doses (0.25 mg/day, 0.5 mg/day, and 1 mg/day) of micronized 17beta-estradiol (E2) on C-reactive protein (CRP), interleukin-6 (IL-6), and lipids, compared with placebo, in healthy older women participating in an osteoporosis study.
This randomized, double-blind, placebo-controlled study was conducted in a University clinical research center. Participants were healthy, community-living women older than 65 years. The primary outcome measure of the study was bone metabolism as estimated by serum and urine markers of bone turnover. For this analysis, the authors measured serum markers of CRP, IL-6, lipids, intracellular adhesion molecule-1, and E-selectin at baseline, after 12 weeks of treatment, and after 12 weeks with no treatment.
A significant dose-response effect of estrogen occurred on CRP levels. After 12 weeks of treatment, CRP decreased 59% in the 0.25 mg/day E2 group and increased 65% in the 1 mg/day E2 group, compared with placebo. The CRP level continued to be elevated (92%), compared with placebo, 12 weeks after treatment was discontinued in the 1 mg/day E2 group. High-density lipoprotein (HDL) and HDL2 cholesterol increased and low-density lipoprotein (LDL) cholesterol decreased at 12 weeks in the 1 mg/day E2 group, with a significant dose-response effect. E-selectin decreased significantly in the 1 mg/day E2 group 12 weeks after discontinuation of treatment (-7%), and there was a significant dose-response effect at this time. The 2 lower doses did not affect any of these parameters. Total and HDL3 cholesterol, triglycerides, lipoprotein(a), intracellular adhesion molecule-1, and IL-6 did not change with any dose of E2.
C-reactive protein, an inflammation marker associated with increased risk for cardiovascular disease, decreased in women taking the lowest estrogen dose but increased in women assigned to the highest estrogen dose, suggesting decreased inflammation with lower dose E2. However, with 3 months of treatment, 0.25 or 0.5 mg/day E2 did not have the same beneficial effects on HDL or LDL cholesterol as did 1 mg/day E2. These data suggest that estradiol doses have differential short-term effects on markers of cardiovascular disease. Low-dose E2 decreased CRP, an important marker of inflammation, but did not affect lipid parameters, whereas the highest dose increased CRP and had a beneficial effect on lipid parameters. The long-term consequences of these effects are unknown, but it is possible that estradiol dose should be considered when risk:benefit ratios are evaluated for individual women before estrogen replacement therapy is initiated.
作者评估了在参与一项骨质疏松症研究的健康老年女性中，3种剂量（0.25毫克/天、0.5毫克/天和1毫克/天）的微粉化17β-雌二醇（E2）对C反应蛋白（CRP）、白细胞介素-6（IL-6）和血脂的影响，并与安慰剂进行比较。
这项随机、双盲、安慰剂对照研究在一所大学临床研究中心进行。参与者为65岁以上健康的社区居住女性。该研究的主要结局指标是通过骨转换的血清和尿液标志物估计的骨代谢。对于此次分析，作者在基线、治疗12周后以及停药12周后测量了CRP、IL-6、血脂、细胞间黏附分子-1和E-选择素的血清标志物。
雌激素对CRP水平产生了显著的剂量反应效应。治疗12周后，与安慰剂相比，0.25毫克/天E2组的CRP下降了59%，而1毫克/天E2组的CRP增加了65%。在1毫克/天E2组停药12周后，与安慰剂相比，CRP水平仍持续升高（92%）。1毫克/天E2组在12周时高密度脂蛋白（HDL）和HDL2胆固醇升高，低密度脂蛋白（LDL）胆固醇降低，具有显著的剂量反应效应。在停药12周后，1毫克/天E2组的E-选择素显著下降（-7%），此时存在显著的剂量反应效应。较低的2种剂量对这些参数均无影响。总胆固醇、HDL3胆固醇、甘油三酯、脂蛋白（a）、细胞间黏附分子-1和IL-6在任何剂量的E2作用下均未改变。
C反应蛋白是一种与心血管疾病风险增加相关的炎症标志物，在服用最低雌激素剂量的女性中降低，而在分配到最高雌激素剂量的女性中升高，这表明较低剂量的E2可减轻炎症。然而，经过3个月的治疗，0.25或0.5毫克/天的E2对HDL或LDL胆固醇的有益作用不如1毫克/天的E2。这些数据表明，雌二醇剂量对心血管疾病标志物具有不同的短期影响。低剂量E2降低了CRP，CRP是一种重要的炎症标志物，但不影响血脂参数，而最高剂量则增加了CRP并对血脂参数产生有益作用。这些效应的长期后果尚不清楚，但在开始雌激素替代治疗前为个体女性评估风险效益比时，可能应考虑雌二醇剂量。
