Confounding factors and genetic polymorphism in the evaluation of individual steroid profiling

Kuuranne, Tiia; Saugy, Martial; Baume, N

doi:10.1136/bjsports-2014-093510

Cited by 87 publications

(96 citation statements)

References 144 publications

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“…[17,18] With this in mind, exogenous testosterone use by the subjects enrolled in this study was only detected in 70% of samples using these established screening thresholds, and was detected in 0% of samples collected greater than 24h after the last use. We first analyzed the effect that administration had on markers typical to an initial steroid screening method that would be used by anti-doping laboratories.…”

Section: Discussionmentioning

confidence: 91%

Intranasal delivery of Natesto® testosterone gel and its effects on doping markers

Miller

Nair²,

Morrison³

et al. 2016

Drug Testing and Analysis

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The laboratory profile of intranasal testosterone gel has not been previously reported from an anti-doping perspective. Because intranasal testosterone gel is newly available as a commercial product, we sought to examine the laboratory parameters following administration of this formulation, with particular attention to anti-doping guidelines. Five healthy and active male subjects were administered testosterone intranasal gel three times daily for four weeks, using a pattern of five consecutive days on, two days off. Urine was collected after each five-day round of drug administration and analyzed using a full steroid screen and isotope ratio mass spectrometry (IRMS). Windows of detection for elevated testosterone/epitestosterone (T/E) and other steroid ratios, World Anti-Doping Agency (WADA) athlete biological passport (ABP) findings, and IRMS results were analyzed in this study. In the 0-24 h window post-administration, 70% of samples were flagged with a suspicious steroid profile and 85% were flagged as atypical passport findings according to the WADA ABP steroid module. In the 24-48 h window, 0% of samples displayed suspicious steroid profiles while 40% resulted in atypical passport findings. IRMS testing confirmed the presence of exogenous testosterone in 90% and 40% of samples in the 0-24 h and 24-48 h windows post-administration, respectively. Additionally, IRMS data were analyzed to determine commonalities in the population changes in δ C values of testosterone, androsterone, etiocholanolone, 5αAdiol, and 5βAdiol. Though no discernible metabolic trend of the route of administration was identified, we discovered that intranasal gel testosterone is detectable using conventional anti-doping tests. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 91%

Intranasal delivery of Natesto® testosterone gel and its effects on doping markers

Miller

Nair²,

Morrison³

et al. 2016

Drug Testing and Analysis

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“…Despite these efforts to improve the discriminating power of the threshold values and to incorporate as many markers as possible for EAAS administration, a number of exogenous variability factors can occur in a very unpredictable manner and may lead to atypical passport findings [8,31]. Among these, several confounding factors are already considered in a specific WADA Technical Document [32].…”

Section: Introductionmentioning

confidence: 99%

Drug-drug interactions and masking effects in sport doping: influence of miconazole administration on the urinary concentrations of endogenous anabolic steroids

et al. 2016

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We have investigated the influence of oral\ud miconazole administration on the urinary concentrations of\ud endogenous anabolic androgenic steroids of doping relevance,\ud specifically considering all these compounds routinely monitored in doping control analysis, in the framework of the\ud steroidalmodule of the ‘‘athlete biologicalpassport’’, and other\ud steroids, including dehydroepiandrosterone, 5a-dihydrotestosterone, and the hydroxylated metabolites recently\ud proposed as additional markers of the intake of testosteronerelated steroids (16a-hydroxy-androsterone, 16a-hydroxyetiocholanolone, 6b-hydroxy-androsterone, 6b-hydroxy-etiocholanolone, 7a-hydroxy-dehydroepiandrosterone, and 7bhydroxy-dehydroepiandrosterone). Urinary concentrations of\ud the final metabolic products of the glucocorticoid biosynthetic\ud pathways (11b-hydroxy-androsterone and 11b-hydroxy-etiocholanolone, the formerly used as an endogenous reference\ud compound for the gas chromatography–combustion-isotope\ud ratio mass spectrometry confirmation analysis) were also\ud monitored. Two healthy Caucasian volunteers exhibiting\ud physiologically high testosterone/epitestosterone ratios and\ud elevated concentrations of the main target steroids were\ud selected for the study. Miconazole was administered orally\ud (500 mg/day) for 1 week. Multiple urine samples were\ud collected for 1 week before and during the treatment, and\ud analyzed according to a validated analytical procedure based\ud on gas chromatography–electron ionization-mass spectrometry in selected ion monitoring mode. Our results indicated that\ud oral administration of miconazole decreased the urinary concentrations of androsterone, and to a lesser extent, of etiocholanolone (both detected as the sum of free and glucuronated\ud steroids), and consequently the androsterone/testosterone and\ud androsterone/etiocholanolone ratios. Furthermore, the urinary\ud concentrations of 16a-hydroxy-etiocholanolone, 16a-hydroxy-androsterone, 7b-hydroxy-dehydroepiandrosterone,\ud 6b-hydroxy-etiocholanolone, 7a-hydroxy-dehydroepiandrosterone, 6b-hydroxy-androsterone, 11b-hydroxy-androsterone,\ud and 11b-hydroxy-etiocholanolone were significantly suppressed. This evidence suggests the potential intake of\ud miconazole whenever the urinary steroid profile is characterized by abnormally low concentrations of the above-mentioned steroids

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“…[11][12][13] The stability of the IRMS parameters of healthy individuals in terms of short (1month), intermediate (6months) and long-term (1year) variability was studied in our laboratory [14] and observed by others. It is known that the SP is influenced by endogenous factors including but not limited to ethnicity, gender, age and genetic polymorphisms and exogenous factors including medications, diet, and matrix composition [15][16][17][18] ; while the IRMS data are almost exclusively based on the 13 C isotopic composition of the diet. It is known that the SP is influenced by endogenous factors including but not limited to ethnicity, gender, age and genetic polymorphisms and exogenous factors including medications, diet, and matrix composition [15][16][17][18] ; while the IRMS data are almost exclusively based on the 13 C isotopic composition of the diet.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal evaluation of the isotope ratio mass spectrometric data: towards the ‘isotopic module’ of the athlete biological passport?

Jardines

Botrè

Colamonici

et al. 2016

Drug Testing and Analysis

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The detection of the abuse of pseudo-endogenous steroids (testosterone and/or its precursors) is currently based on the application of the steroid module of the World Anti-Doping Agency (WADA) Athletes' Biological Passport (ABP), implemented through ADAMS. Diagnostic metabolites are monitored for every athlete and statistically evaluated with a predictive Bayesian approach. In the case of suspicious samples, the data of the ABP are confirmed and the isotope ratio mass spectrometry (IRMS) test is activated. We have previously demonstrated that IRMS enables confirmation of the non-endogenous origin of pseudo-endogenous steroids in otherwise non-suspicious samples, after a longitudinal evaluation of the ABP, even after the inclusion of additional long-term diagnostic hydroxylated metabolites, and that the delta values of the parameters obtained during the IRMS confirmation process presented much less variability compared to the parameters of the ABP. The aim of the present work is to evaluate the application of the same methodology used for the evaluation of the ABP, on the delta values of the pseudo-endogenous steroids monitored. The effectiveness of the proposed model has been assessed on samples obtained after controlled administrations of oral androstenedione and transdermal testosterone. The results support the conclusion that, if applied, the longitudinal evaluation of the IRMS data allows the detection of positive samples that otherwise will be reported as atypical findings (ATF), improving the efficacy of the fight against doping in sport. This approach, by narrowing the individual acceptable range, could possibly improve the detection of the intake of preparations of synthetic origin with delta values close to or overlapping those of endogenously produced steroids. Copyright © 2016 John Wiley & Sons, Ltd.

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Confounding factors and genetic polymorphism in the evaluation of individual steroid profiling

Cited by 87 publications

References 144 publications

Intranasal delivery of Natesto® testosterone gel and its effects on doping markers

Intranasal delivery of Natesto® testosterone gel and its effects on doping markers

Drug-drug interactions and masking effects in sport doping: influence of miconazole administration on the urinary concentrations of endogenous anabolic steroids

Longitudinal evaluation of the isotope ratio mass spectrometric data: towards the ‘isotopic module’ of the athlete biological passport?

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