False negative results in testosterone doping in forensic cases: Sensitivity of the urinary detection criteria T/E and T/LH,Drug Testing and Analysis

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False negative results in testosterone doping in forensic cases: Sensitivity of the urinary detection criteria T/E and T/LH
Drug Testing and Analysis ( IF 2.6 ) Pub Date : 2021-07-06 , DOI: 10.1002/dta.3125
Yvonne Lood _{1,

2} , Elisabeth Aardal ₃ , Sara Gustavsson ₁ , Ilya Prasolov ₄ , Martin Josefsson _{5,

6} , Johan Ahlner ₂

Affiliation

At the Swedish national forensic toxicology laboratory, a measured testosterone/epitestosterone (T/E) ratio ≥ 12 together with testosterone/luteinizing hormone (T/LH) in urine > 400 nmol/IU is considered as a proof of exogenous testosterone administration. However, according to the rules of the World Anti-Doping Agency (WADA), samples with T/E ratio > 4 are considered suspicious and shall be further analysed by gas chromatography–combustion–isotope ratio mass spectrometry (GC-C-IRMS) to confirm the origin of testosterone and its metabolites. The aim of this study was to investigate the possibility of false negative results and to estimate the frequency of negative results using the current criteria for detection of abuse of testosterone in forensic investigations. Urine and serum samples were collected by the police at suspected infringement of the doping law in Sweden. Fifty-eight male subjects were included in the study. Urinary testosterone was determined by gas chromatography–mass spectrometry (GC–MS), serum testosterone and LH—by immunoassay. The origin of testosterone and its metabolites was confirmed by means of GC-C-IRMS. Twenty-six of the 57 analysed subjects tested positive for exogenous testosterone using the criteria T/E ≥ 12 combined with T/LH > 400 nmol/IU. The IRMS analyses confirmed 47 positives; thus, 21 were considered false negatives. Negative predictive value was 32% (95% confidence interval [CI]: 16%–50%) and sensitivity 55%. No false positive subjects were found. The number of false negative cases using the current criteria for the detection of testosterone abuse and hence the low sensitivity indicates a need to discuss introduction of new strategies in forensic doping investigations.

中文翻译：

法医病例中睾酮兴奋剂的假阴性结果：尿液检测标准 T/E 和 T/LH 的敏感性

在瑞典国家法医毒理学实验室，测得的睾酮/表睾酮 (T/E) 比率 ≥ 12 以及尿液中的睾酮/促黄体生成素 (T/LH) > 400 nmol/IU 被认为是外源性睾酮给药的证据。但是，根据世界反兴奋剂机构 (WADA) 的规定，T/E 比 > 4 的样本被视为可疑样本，应通过气相色谱-燃烧-同位素比质谱 (GC-C-IRMS) 进一步分析确认睾酮及其代谢物的来源。本研究的目的是调查假阴性结果的可能性，并使用目前在法医调查中检测睾酮滥用的标准来估计阴性结果的频率。警方在瑞典收集了涉嫌违反兴奋剂法的尿液和血清样本。该研究包括 58 名男性受试者。尿睾酮通过气相色谱-质谱 (GC-MS)、血清睾酮和 LH-通过免疫测定来确定。睾酮及其代谢物的来源通过 GC-C-IRMS 得到证实。使用标准 T/E ≥ 12 结合 T/LH > 400 nmol/IU，57 名分析对象中有 26 名外源性睾酮检测呈阳性。IRMS 分析证实了 47 个阳性；因此，有 21 个被认为是假阴性。阴性预测值为 32%（95% 置信区间 [CI]：16%–50%），敏感性为 55%。没有发现假阳性受试者。

更新日期：2021-07-06

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