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一项基于受试者的综合类固醇谱分析的试点研究:用于检测体育运动中睾酮滥用的新型生物标志物。

A pilot study on subject-based comprehensive steroid profiling: novel biomarkers to detect testosterone misuse in sports.

作者信息

Van Renterghem Pieter, Van Eenoo Peter, Sottas Pierre-Edouard, Saugy Martial, Delbeke Frans

机构信息

Docolab, Department of Clinical Chemistry, Microbiology and Immunology, University of Ghent, Zwijnaarde, BelgiumSwiss Laboratory for Doping Analysis, Université de Lausanne, Epalinges, Switzerland.

出版信息

Clin Endocrinol (Oxf). 2011 Jul;75(1):134-40. doi: 10.1111/j.1365-2265.2011.03992.x.

DOI:10.1111/j.1365-2265.2011.03992.x
PMID:21521264
Abstract

CONTEXT

Until now, the testosterone/epitestosterone (T/E) ratio is the main marker for the detection of testosterone (T) misuse in athletes. As this marker can be influenced by a number of confounding factors, additional steroid profile parameters indicating T misuse can provide substantiating evidence of doping with endogenous steroids. The evaluation of a steroid profile is currently based upon population statistics. As large inter-individual variations exist, a paradigm shift towards subject-based references is ongoing in doping analysis.

OBJECTIVE

Proposition of new biomarkers for the detection of testosterone in sports using extensive steroid profiling and an adaptive model based upon Bayesian inference.

SUBJECTS

Six healthy male volunteers were administered with testosterone undecanoate. Population statistics were performed upon steroid profiles from 2014 male Caucasian athletes participating in official sport competition.

DESIGN

An extended search for new biomarkers in a comprehensive steroid profile combined with Bayesian inference techniques as used in the athlete biological passport resulted in a selection of additional biomarkers that may improve detection of testosterone misuse in sports.

RESULTS

Apart from T/E, 4 other steroid ratios (6α-OH-androstenedione/16α-OH-dehydroepiandrostenedione, 4-OH-androstenedione/16α-OH-androstenedione, 7α-OH-testosterone/7β-OH-dehydro-epiandrostenedione and dihydrotestosterone/5β-androstane-3α,17β-diol) were identified as sensitive urinary biomarkers for T misuse. These new biomarkers were rated according to relative response, parameter stability, detection time and discriminative power.

CONCLUSION

Newly selected biomarkers were found suitable for individual referencing within the concept of the Athlete's Biological Passport. The parameters showed improved detection time and discriminative power compared to the T/E ratio. Such biomarkers can support the evidence of doping with small oral doses of testosterone.

摘要

背景

到目前为止,睾酮/表睾酮(T/E)比值是检测运动员滥用睾酮(T)的主要指标。由于该指标会受到多种混杂因素的影响,其他表明T滥用的类固醇谱参数可为内源性类固醇兴奋剂使用提供确凿证据。目前对类固醇谱的评估基于群体统计数据。由于个体间存在较大差异,兴奋剂检测分析正在朝着基于个体参考的模式转变。

目的

利用广泛的类固醇谱分析和基于贝叶斯推理的自适应模型,提出用于检测体育赛事中睾酮的新生物标志物。

对象

对6名健康男性志愿者给予十一酸睾酮。对2014名参加官方体育比赛的男性白种人运动员的类固醇谱进行群体统计。

设计

在综合类固醇谱中广泛寻找新生物标志物,并结合运动员生物护照中使用的贝叶斯推理技术,从而筛选出可能改善体育赛事中睾酮滥用检测的其他生物标志物。

结果

除T/E外,还确定了4种其他类固醇比值(6α-羟基雄烯二酮/16α-羟基脱氢表雄酮、4-羟基雄烯二酮/16α-羟基雄烯二酮、7α-羟基睾酮/7β-羟基脱氢表雄酮和双氢睾酮/5β-雄甾烷-3α,17β-二醇)作为T滥用的敏感尿液生物标志物。根据相对反应、参数稳定性、检测时间和鉴别能力对这些新生物标志物进行了评级。

结论

新筛选出的生物标志物被认为适用于运动员生物护照概念中的个体参考。与T/E比值相比,这些参数的检测时间和鉴别能力有所提高。此类生物标志物可支持小剂量口服睾酮兴奋剂使用的证据。

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