Mullen Jenny, Börjesson Annica, Hopcraft Oscar, Schulze Jenny J, Ericsson Magnus, Rane Anders, Lehtihet Mikael, Ekström Lena
Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet at Huddinge, Huddinge, Sweden.
Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden.
Drug Test Anal. 2018 May;10(5):839-848. doi: 10.1002/dta.2341. Epub 2017 Dec 28.
Micro-doping with testosterone (T) is challenging to detect with the current doping tests. Today, the methods available to detect T are longitudinally monitoring of urine biomarkers in the Athlete Biological Passport (ABP) and measuring the isotopic composition of excreted biomarkers to distinguish the origin of the molecule. In this study, we investigated the detectability of a single dose of 100 mg T gel in 8 healthy male subjects. We also studied which biomarkers were most sensitive to T gel administration, including blood biomarkers. The ABP successfully detected T gel administration in all 8 subjects. The most sensitive ratio was 5αAdiol/E, however, all ratios showed atypical findings. Isotope ratio mass spectrometry (IRMS) was performed on 5 subjects and only 2 met all the criteria for a positive test according to the rules set by the World Anti-Doping Agency (WADA). The other 3 showed inconclusive results. Other markers that were affected by T gel administration, not used for this detection today, were serum dihydrotestosterone (DHT) and T as well as reticulocyte count and percentage in whole blood. miRNA-122 was not significantly affected by the single T dose. A single dose of 100 mg T gel is possible to detect with today's doping tests. Since a single dose of T gel has an impact on some hematological biomarkers, access to both modules of the ABP when evaluating the athletes' profiles will increase the possibility to detect micro-doses of T. In addition, serum DHT and T may be a useful addition to the future endocrine module of the ABP.
使用目前的兴奋剂检测方法很难检测出睾酮（T）的微量使用。如今，可用于检测T的方法包括纵向监测运动员生物护照（ABP）中的尿液生物标志物，以及测量排泄生物标志物的同位素组成以区分分子来源。在本研究中，我们调查了8名健康男性受试者单次服用100毫克T凝胶的可检测性。我们还研究了哪些生物标志物对T凝胶给药最为敏感，包括血液生物标志物。ABP成功检测出了所有8名受试者服用了T凝胶。最敏感的比率是5α雄甾二醇/雌二醇（5αAdiol/E），然而，所有比率均显示出非典型结果。对5名受试者进行了同位素比率质谱分析（IRMS），根据世界反兴奋剂机构（WADA）制定的规则，只有2名受试者的检测结果符合阳性检测的所有标准。另外3名受试者的结果不明确。其他受T凝胶给药影响但目前未用于此检测的标志物包括血清双氢睾酮（DHT）和T，以及全血中的网织红细胞计数和百分比。miRNA-122未受到单次T剂量的显著影响。使用当今的兴奋剂检测方法可以检测出单次服用100毫克T凝胶的情况。由于单次服用T凝胶会对一些血液学生物标志物产生影响，因此在评估运动员的档案时使用ABP的两个模块将增加检测微量T的可能性。此外，血清DHT和T可能会成为未来ABP内分泌模块的有用补充。
