Soy Isoflavone Distribution in Biological Fluids as Markers of Prostate Exposure

描述（由申请人提供）：食用富含异黄酮的大豆已被建议降低前列腺癌的风险。大豆中的异黄酮被认为是造成这种效果的原因。因此，大豆异黄酮目前正在流行病学和临床研究中调查其在预防前列腺癌方面的可能作用。在这些研究中，准确估计个体的异黄酮暴露量是极其重要的。鉴于饮食方法的不足，生物体液被认为是异黄酮暴露的更可靠的指标。在设计这些研究时，研究人员通常假设血浆和24小时尿液异黄酮浓度准确反映前列腺组织暴露。然而，目前还没有关于这一假设的有效性的信息。因此，本应用程序的主要目的是通过比较血液和尿液浓度与前列腺暴露的更直接测量来评估血浆和尿液异黄酮水平的可靠性。为了实现这一目标，该研究将比较血浆和24小时尿液中的异黄酮水平与表达前列腺分泌（EPS）中的异黄酮水平，EPS是被广泛接受的前列腺组织暴露的标志。此外，将测定精液和按摩后尿液中的异黄酮水平，并与EPS进行比较，以确定这些液体是否比血液或尿液更准确，在临床或流行病学研究中是否比EPS更容易获得。该项目的具体目的是评估食用大豆异黄酮后血液、24小时尿液、精液、按摩后尿液和EPS中的异黄酮（染料木黄酮、大豆黄酮、马雌酚、ODMA、糖苷和二氢大豆黄酮）浓度。一项随机双盲平行对照研究将在50名年轻男性中进行，他们被分配服用含有30或60毫克异黄酮的片剂，为期4天。测量治疗前后24小时尿液、血浆、EPS、按摩后尿液和精液的植物雌激素浓度。将24小时尿液、血浆、按摩后尿液和精液浓度与EPS进行比较，将使我们能够评估血液、尿液和精液作为前列腺组织植物雌激素暴露预测因子的有效性。比较两个治疗组将使我们能够评估剂量依赖性对植物雌激素分布的影响。虽然EPS比前列腺组织更容易获得，但手术过程不舒服，需要训练有素的人员。如果精液或按摩后尿液浓度与EPS有良好的相关性，这些收集将更实用于估计流行病学和干预研究中的组织暴露。如果血液和24小时尿液浓度与EPS有良好的相关性，则其有效性将得到证实，我们将证明其他液体的收集是不必要的。这项研究的结果将有助于确定哪种生物液体最能反映前列腺暴露于异黄酮，并可能有助于改进未来关于异黄酮和前列腺癌风险降低的流行病学和干预研究的设计。

DESCRIPTION (provided by applicant): Consumption of isoflavone-rich soy has been suggested to lower prostate cancer risk. The soy components thought to be responsible for this effect are the isoflavones. As a result, soy isoflavones are currently being investigated in epidemiological and clinical studies for their possible roles in prostate cancer prevention. It is extremely important in these studies to have an accurate estimate of isoflavone exposure in individuals. Given the inadequacy of dietary methodologies, biological fluids are considered more reliable indicators of isoflavone exposure. In designing these studies, researchers have generally assumed that plasma and 24- hr urine isoflavone concentrations accurately reflect prostate tissue exposure. However at this time, no information is available on the validity of this assumption. Thus, the main objective of this application is to evaluate the reliability of plasma and urinary isoflavone levels by comparing blood and urine concentrations to more direct measurements of prostate exposure. To accomplish this, the proposed study will compare isoflavone levels in plasma and 24-hr urine with those in expressed prostatic secretion (EPS), a widely accepted marker of prostatic tissue exposure. In addition, isoflavone levels in semen and post-massage urine will be determined and compared with EPS, in order to determine whether these fluids are more accurate than blood or urine and more easily obtainable than EPS in clinical or epidemiological studies. The specific aims of this project are to assess concentrations of isoflavones (genistein, daidzein, equol, ODMA, glycitein and dihydrodaidzein) in blood, 24-hr urine, semen, post-massage urine and EPS after soy isoflavone consumption. A randomized double-blind parallel arm study will be performed in 50 young men assigned to receive a tablet containing either 30 or 60 mg of isoflavones for a period of four days. Before and after the treatment period phytoestrogen concentrations 24-hr urine, plasma, EPS, post-massage urine and semen will be measured. Comparing 24-hr urine, plasma, post-massage urine and semen concentrations with those in EPS will enable us to assess the validity of blood, urine, and semen as predictors of prostate tissue phytoestrogen exposure. Comparing the two treatment groups will allow us to assess dose-dependant effects on phytoestrogen distribution. Although EPS is easier to obtain than prostate tissue,,the procedure is uncomfortable and requires trained personnel. If semen orposf-massage urine concentrations correlate well with EPS, these collections would be more practical for estimating tissue exposure in epidemiological and intervention studies. If blood and 24-hr urine concentrations correlate well with EPS, their validity will be confirmed and we will show that collection of the other fluids is unnecessary. The results of this study will help determine which biological fluid best reflects prostate exposure to isoflavones and may help improve the design of future epidemiological and intervention studies on isoflavones and prostate cancer risk reduction.