Reproducibility of fifteen urinary estrogens and estrogen metabolites over a 2- to 3-year period in premenopausal women.
Reproducibility of fifteen urinary estrogens and estrogen metabolites over a 2- to 3-year period in premenopausal women.
复制标题
DOI：
10.1158/1055-9965.epi-09-0591
复制
发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
Hankinson SE
中科院分区：
文献类型：
--
作者：
Eliassen AH;Ziegler RG;Rosner B;Veenstra TD;Roman JM;Xu X;Hankinson SE
内源性雌激素在乳腺癌、子宫内膜癌和可能的卵巢癌的病因学中起着不可或缺的作用。雌激素代谢产生的产物具有潜在的雌激素性和遗传毒性，但在流行病学研究中对个体代谢模式的探索才刚刚开始。在护士健康研究II中，我们研究了110名绝经前妇女三年内收集的三个黄体期尿液样本中15种尿雌激素和雌激素代谢产物（EM）的可重复性。EM测量最近开发的高效液相色谱-串联质谱法（LC-MS 2）具有高灵敏度，特异性和精密度。我们评估了三个样本的斯皮尔曼相关性和组内相关系数（ICC）。尿雌酮或雌二醇与雌激素代谢产物之间的相关性仅为适度（r=0.1-0.5）。2-和4-羟基化途径高度相关（r=0.9），但与16-羟基化途径呈弱负相关（r=-0.2）。随着时间的推移，三种途径的女性生殖能力相当高，ICC范围从0.52（16-羟基化途径）到0.72（2-羟基化途径）。2-儿茶酚和单个儿茶酚的ICC相似地高（ICC =0.58-0.72）。甲基化2-儿茶酚的个体和分组具有相当高的ICC（0.51-0.62），但甲基化4-儿茶酚的ICC较低（0.14-0.27）。这些数据表明，在一般情况下，尿EM水平差异很大，个体之间相比，intrinindividual变异。随着时间的推移，大多数EM指标的人内生殖能力与经过充分审查的生物标志物（如血浆胆固醇和绝经后妇女的雌二醇）相当或更好。
Endogenous estrogens play an integral role in the etiology of breast, endometrial, and possibly ovarian cancer. Estrogen metabolism yields products that are potentially both estrogenic and genotoxic, yet individual metabolic patterns are just beginning to be explored in epidemiologic studies. Within the Nurses’ Health Study II, we examined reproducibility of 15 urinary estrogens and estrogen metabolites (EM) among 110 premenopausal women with three luteal phase urine samples collected over three years. EM were measured by a recently developed high-performance liquid chromatography-tandem mass spectrometry (LC-MS2) method with high sensitivity, specificity, and precision. We assessed Spearman correlations and intraclass correlation coefficients (ICCs) across the three samples. Correlations between urinary estrone or estradiol and the estrogen metabolites were only modest (r=0.1–0.5). The 2- and 4-hydroxylation pathways were highly correlated (r=0.9) but weakly inversely correlated with the 16-hydroxylation pathway (r=−0.2). Reproducibility within woman over time was fairly high for the three pathways, with ICCs ranging from 0.52 (16-hydroxylation pathway) to 0.72 (2-hydroxylation pathway). ICCs were similarly high for 2-catechols and the individual catechols (ICCs=0.58–0.72). Individual and grouped methylated 2-catechols had fairly high ICCs (0.51–0.62), but ICCs were low for the methylated 4-catechols (0.14–0.27). These data indicate that, in general, urinary EM levels vary substantially among individuals compared with intraindiviual variability. Reproducibility within person over time for most EM measures is comparable to or better than well-vetted biomarkers like plasma cholesterol and, in postmenopausal women, estradiol.