Herrington D M, Brosnihan K B, Pusser B E, Seely E W, Ridker P M, Rifai N, MacLean D B
Department of Internal Medicine/Cardiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
J Clin Endocrinol Metab. 2001 Sep;86(9):4216-22. doi: 10.1210/jcem.86.9.7799.
Although increased levels of C-reactive protein have been linked to E therapy, the significance of this finding and whether it occurs with the selective ER modulators are unknown. Thirty-five healthy postmenopausal women were enrolled in a placebo-controlled, two-period cross-over design trial to evaluate the effects of 0.625 mg oral conjugated E and 60 mg droloxifene, a structural analog of tamoxifen, on serum levels of C-reactive protein, IL-6, and endothelial cell adhesion molecules. E treatment resulted in 65.8% higher levels of C-reactive protein (P = 0.0002) and 48.1% higher levels of IL-6 (P < 0.001), but also resulted in a 10.9% reduction in soluble E-selectin (P = 0.002) and borderline reductions in vascular cell adhesion molecule-1. In contrast, droloxifene had no effect on C-reactive protein and IL-6, but did produce a significant 11% reduction in E-selectin (P < 0.00001). However, droloxifene also resulted in an 11.6% increase in vascular cell adhesion molecule-1 (P < 0.007). These data provide additional evidence of a proinflammatory effect of E that may have adverse cardiovascular consequences. However, these changes were also accompanied by a reduction in E-selectin, suggesting an antiinflammatory effect at the level of the endothelium. The net clinical impact of these changes is not yet well established. In contrast, droloxifene had little or no proinflammatory effects on C-reactive protein and IL-6 and had mixed effects on endothelial adhesion molecules. This observation provides additional rationale for continuing to evaluate the potential cardiovascular benefits of selective ER modulators.
尽管C反应蛋白水平升高与雌激素（E）治疗有关，但这一发现的意义以及它是否会在选择性雌激素受体调节剂（SERMs）治疗时出现尚不清楚。35名健康的绝经后女性参与了一项安慰剂对照、两阶段交叉设计试验，以评估0.625毫克口服共轭雌激素和60毫克屈洛昔芬（他莫昔芬的结构类似物）对C反应蛋白、白细胞介素-6（IL-6）和内皮细胞粘附分子血清水平的影响。雌激素治疗使C反应蛋白水平升高了65.8%（P = 0.0002），IL-6水平升高了48.1%（P < 0.001），但也使可溶性E选择素降低了10.9%（P = 0.002），血管细胞粘附分子-1也有临界性降低。相比之下，屈洛昔芬对C反应蛋白和IL-6没有影响，但确实使E选择素显著降低了11%（P < 0.00001）。然而，屈洛昔芬也使血管细胞粘附分子-1增加了11.6%（P < 0.007）。这些数据为雌激素的促炎作用提供了额外证据，这种作用可能会产生不良心血管后果。然而，这些变化也伴随着E选择素的降低，表明在内皮水平存在抗炎作用。这些变化的净临床影响尚未完全明确。相比之下，屈洛昔芬对C反应蛋白和IL-6几乎没有促炎作用，对内皮粘附分子有混合作用。这一观察结果为继续评估选择性雌激素受体调节剂的潜在心血管益处提供了额外的理论依据。
