Swiss Laboratory for Doping Analyses, University Center of Legal Medecine, Geneva and Lausanne, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Ch. des Croisettes 22, 1066 Epalinges, Switzerland.
Forensic Sci Int. 2011 Dec 10;213(1-3):62-72. doi: 10.1016/j.forsciint.2011.07.002. Epub 2011 Jul 27.
Since it is established that human chorionic gonadotropin (hCG) affects testosterone production and release in the human body, the use of this hormone as a performance enhancing drug has been prohibited by the World Anti-Doping Agency. Nowadays, the only validated biomarker of a hCG doping is its direct quantification in urine. However, this specific parameter is subjected to large inter-individual variability and its determination is directly dependent on the reliability of hCG immunoassays used. In order to counteract these weaknesses, new biomarkers need to be evidenced. To address this issue, a pilot clinical study was performed on 10 volunteers submitted to 3 subsequent hCG injections. Blood and urine samples were collected during two weeks in order to follow the physiological effects on related compounds such as the steroid profile or hormones involved in the hypothalamo-pituitary axis. The hCG pharmacokinetic observed in all subjects was, as expected, prone to important inter-individual variations. Using ROC plots, level of testosterone and testosterone on luteinizing hormone ratio in both blood and urine were found to be the most relevant biomarker of a hCG abuse, regardless of inter-individual variations. In conclusion, this study showed the crucial importance of reliable quantification methods to assess low differences in hormonal patterns. In regard to these results and to anti-doping requirements and constraints, blood together with urine matrix should be included in the anti-doping testing program. Together with a longitudinal follow-up approach it could constitute a new strategy to detect a hCG abuse, applicable to further forms of steroid or other forbidden drug manipulation.
由于已经确定人绒毛膜促性腺激素(hCG)会影响人体的睾酮产生和释放,因此世界反兴奋剂机构已禁止将该激素用作兴奋剂。如今,hCG 兴奋剂的唯一有效生物标志物是尿液中 hCG 的直接定量。然而,该特定参数受到个体间差异的影响很大,其测定直接取决于所使用的 hCG 免疫分析的可靠性。为了克服这些弱点,需要证明新的生物标志物。为了解决这个问题,对 10 名志愿者进行了一项初步的临床研究,这些志愿者接受了 3 次后续的 hCG 注射。在两周内采集了血液和尿液样本,以跟踪与相关化合物(如类固醇谱或参与下丘脑-垂体轴的激素)的生理效应。所有受试者中观察到的 hCG 药代动力学均如预期的那样,容易出现重要的个体间差异。使用 ROC 图,发现血液和尿液中的睾酮水平和黄体生成素与睾酮的比值是 hCG 滥用的最相关生物标志物,而与个体间差异无关。总之,这项研究表明,可靠的定量方法对于评估激素模式的微小差异至关重要。关于这些结果以及反兴奋剂的要求和限制,血液和尿液基质都应包含在反兴奋剂检测计划中。结合纵向随访方法,它可以构成一种新的策略来检测 hCG 滥用,适用于进一步的类固醇或其他禁用药物的操纵。