Falk R T, Gail M H, Fears T R, Rossi S C, Stanczyk F, Adlercreutz H, Kiura P, Wahala K, Donaldson J L, Vaught J B, Fillmore C M, Hoover R N, Ziegler R G
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Cancer Epidemiol Biomarkers Prev. 1999 Jun;8(6):567-77.
The reproducibility of RIAs of circulating sex hormones has been evaluated as part of recent epidemiological investigations, but none seem to have addressed the reproducibility or validity of RIAs for urinary hormones or their metabolites. As part of a case-control study of breast cancer in Asian-American women, 12-h overnight urine samples were obtained, and a methodological study was conducted to identify laboratories capable of assaying urinary hormones. For the reproducibility component of this study, two laboratories with extensive experience in hormone assays measured urinary estrone, estradiol, estriol, pregnanediol glucuronide, and estrone glucuronide using samples from 15 women (5 midfollicular, 5 midluteal, and 5 postmenopausal). Variance estimates from these measurements were used to calculate the laboratory variability (coefficient of variation) and to assess the magnitude of the biological variability among the women in relation to the total variability (intraclass correlation coefficient). For the validity component, urinary estrone, estradiol, and estriol levels were measured in the same samples by gas chromatography-mass spectroscopy in the laboratory of Dr. Herman Adlercreutz (University of Helsinki, Helsinki, Finland). We found that the degree of assay reproducibility differed between the laboratories, but that laboratory variability was usually low compared with the range of hormone values among women, particularly for the estrogens. Values for estrone and estradiol were well correlated among all of the laboratories. For estriol, the RIAs tended to overestimate levels compared with gas chromatography-mass spectroscopy. In one laboratory, assays for pregnanediol glucuronide and estrone glucuronide were consistently reproduced; in the other, the reproducibility of the RIA for pregnanediol glucuronide was problematic, and estrone glucuronide was not measured. Despite some limitations, urinary hormones and their metabolites can be reliably measured by current RIAs in large investigations attempting to link hormone level to disease risk and may be particularly advantageous for studies of postmenopausal women, where serum concentrations of estrone and estradiol are low and assay measurements are not as dependable.
作为近期流行病学调查的一部分，已对循环性激素放射免疫分析（RIA）的可重复性进行了评估，但似乎没有一项研究涉及尿激素或其代谢物RIA的可重复性或有效性。作为一项针对亚裔美国女性乳腺癌病例对照研究的一部分，采集了12小时过夜尿液样本，并开展了一项方法学研究，以确定有能力检测尿激素的实验室。对于本研究的可重复性部分，两个在激素检测方面有丰富经验的实验室使用15名女性（5名卵泡中期、5名黄体中期和5名绝经后女性）的样本，检测了尿雌酮、雌二醇、雌三醇、孕二醇葡萄糖醛酸苷和雌酮葡萄糖醛酸苷。这些测量的方差估计值用于计算实验室变异性（变异系数），并评估女性之间生物变异性相对于总变异性（组内相关系数）的大小。对于有效性部分，在赫尔曼·阿德勒克鲁茨博士（芬兰赫尔辛基大学）的实验室中，通过气相色谱 - 质谱法对相同样本中的尿雌酮、雌二醇和雌三醇水平进行了测量。我们发现，各实验室之间分析可重复性的程度有所不同，但与女性激素值范围相比，实验室变异性通常较低，尤其是对于雌激素而言。所有实验室中，雌酮和雌二醇的值相关性良好。对于雌三醇，与气相色谱 - 质谱法相比，RIA往往高估了其水平。在一个实验室中，孕二醇葡萄糖醛酸苷和雌酮葡萄糖醛酸苷的检测结果能够持续重现；而在另一个实验室中，孕二醇葡萄糖醛酸苷RIA的可重复性存在问题，且未检测雌酮葡萄糖醛酸苷。尽管存在一些局限性，但在试图将激素水平与疾病风险联系起来的大型调查中，当前的RIA能够可靠地测量尿激素及其代谢物，对于绝经后女性的研究可能特别有利，因为绝经后女性血清中雌酮和雌二醇的浓度较低，分析测量结果不太可靠。
