Differential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal women.
Differential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal women.
复制标题
口服与透皮雌激素替代疗法对绝经后妇女 C 反应蛋白的不同影响。
DOI：
10.1016/s0735-1097(03)00156-6
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发表时间：
2003
影响因子：
24
通讯作者：
Jialal,Ishwarlal
中科院分区：
文献类型：
--
作者：
Vongpatanasin,Wanpen;Tuncel,Meryem;Wang,Zhongyun;Arbique,Debbie;Mehrad,Borna;Jialal,Ishwarlal
目的探讨雌激素替代治疗(ET)途径是否为绝经后妇女C反应蛋白(CRP)的主要决定因素。因为CRP是在肝脏中合成的，所以我们假设雌激素诱导的CRP升高与首次通过的肝脏代谢有关。方法在21名绝经后妇女中，我们进行了一项随机、交叉、安慰剂对照研究，比较了透皮和口服ET对CRP和炎症细胞因子的影响。我们在服用透皮雌二醇(100μg/天)、口服结合雌激素(0.625 mg/天)或安慰剂8周前后检测C反应蛋白、白介素1-β、白介素6和肿瘤坏死因子-α。同时检测肝源性合成多肽胰岛素样生长因子-1(IGF-1)。相比之下，口服结合雌激素八周后，同一组女性的CRP水平增加了两倍多，而IGF-1水平显著降低(p<；0.01)。C反应蛋白的升高幅度与胰岛素样生长因子-1的降低程度呈负相关(r=−0.49，p=0.008)。无论是经皮给药还是口服CEE，对促进CRP合成的细胞因子的血浆浓度均无影响。结论绝经后妇女口服ET而不是经皮给药可通过首过肝效应升高CRP。C反应蛋白水平的升高伴随着一种抗炎生长因子IGF-1的减少。由于在其他方面健康的绝经后妇女中，CRP是预测不良预后的有效指标，因此给药途径可能是将ET对心血管结局的不良影响降至最低的重要因素。
ObjectivesWe investigated whether the route of estrogen replacement therapy (ET) is the major determinant of C-reactive protein (CRP) in postmenopausal women.BackgroundRecent studies demonstrated that oral ET causes a sustained increase in CRP, implicating a proinflammatory effect. Because CRP is synthesized in the liver, we hypothesized that estrogen-induced CRP elevation is related to first-pass hepatic metabolism.MethodsIn 21 postmenopausal women, we conducted a randomized, crossover, placebo-controlled study to compare the effects of transdermal versus oral ET on CRP and inflammatory cytokines. We measured CRP, interleukin (IL)-1-beta, IL-6, and tumor necrosis factor-alpha before and after eight weeks of transdermal estradiol (E2) (100 μg/day), oral conjugated estrogen (CEE) (0.625 mg/day), or placebo. Insulin-like growth factor-1 (IGF-1), a hepatic-derived anabolic peptide, was also measured.ResultsTransdermal E2had no effect on CRP or IGF-1 levels. In contrast, eight weeks of oral conjugated estrogens caused a more than twofold increase in CRP and a significant reduction in IGF-1 (p < 0.01) in the same women. The magnitude of increase in CRP was inversely correlated to the decrease in IGF-1 (r = −0.49, p = 0.008). Neither transdermal E2nor oral CEE had any effects on the plasma concentrations of cytokines that promote CRP synthesis.ConclusionsIn postmenopausal women, oral but not transdermal ET increased CRP by a first-pass hepatic effect. An increase in CRP levels is accompanied by a reduction in IGF-1, an anti-inflammatory growth factor. Because CRP is a powerful predictor of an adverse prognosis in otherwise healthy postmenopausal women, the route of administration may be an important consideration in minimizing the adverse effects of ET on cardiovascular outcomes.