The World Anti-Doping Agency : Guardian of Elite Sport's Credibility / Maarten van Bottenburg, Arnout Geeraert, Olivier de Hon

Published in: Guardians of Public Value : How Public Organisations Become and Remain Institutions / Arjen Boin (ed), et al. - Springer, 2020. - Chapter 8; p. 185-210

• ISBN: 978-3-030-51700-7
• ISBN: 978-3-030-51701-4
• DOI: 10.1007/978-3-030-51701-4

Contents:

• Introduction
• A Moral Crisis in Elite Sport
• A Global Public–Private Body
• Establishing Performance and Reputation
• Mission Mystique in a Challenging Environment
  • Mission
  • Passion and Commitment
  • Transparency, Autonomy and Renewal
• An Institutional Crisis
• Challenges to Institutional Resilience
• WADA’s Experience in Perspective
• Questions for Discussion

Development of models to predict anabolic response to testosterone administration in healthy young men / Linda J. Woodhouse, Suzanne Reisz-Porszasz, Marjan Javanbakht, Thomas W. Storer, Martin Lee, Hrant Zerounian, Shalender Bhasin. - (American Journal of Physiology-Endocrinology and Metabolism 284 (2003) 5 (1 May); p. E1009-E1017)

• PMID: 12517741
• DOI: 10.1152/ajpendo.00536.2002

Abstract

Considerable heterogeneity exists in the anabolic response to androgen administration; however, the factors that contribute to variation in an individual's anabolic response to androgens remain unknown. We investigated whether testosterone dose and/or any combination of baseline variables, including concentrations of hormones, age, body composition, muscle function, and morphometry or polymorphisms in androgen receptor could explain the variability in anabolic response to testosterone. Fifty-four young men were treated with a long-acting gonadotropin-releasing hormone (GnRH) agonist and one of five doses (25, 50, 125, 300, or 600 mg/wk) of testosterone enanthate (TE) for 20 wk. Anabolic response was defined as a change in whole body fat-free mass (FFM) by dual-energy X-ray absorptiometry (DEXA), appendicular FFM (by DEXA), and thigh muscle volume (by magnetic resonance imaging) during TE treatment. We used univariate and multivariate analysis to identify the subset of baseline measures that best explained the variability in anabolic response to testosterone supplementation. The three-variable model of TE dose, age, and baseline prostate-specific antigen (PSA) level explained 67% of the variance in change in whole body FFM. Change in appendicular FFM was best explained (64% of the variance) by the linear combination of TE dose, baseline PSA, and leg press strength, whereas TE dose, log of the ratio of luteinizing hormone to testosterone concentration, and age explained 66% of the variation in change in thigh muscle volume. The models were further validated by using Ridge analysis and cross-validation in data subsets. Only the model using testosterone dose, age, and PSA was a consistent predictor of change in FFM in subset analyses. The length of CAG tract was only a weak predictor of change in thigh muscle volume and lean body mass. Hence, the anabolic response of healthy, young men to exogenous testosterone administration can largely be predicted by the testosterone dose.

Cathinonen in webshops : vrij verkrijgbare experimentele harddrugs = Cathinones in web shops : Freely available experimental hard drugs / Michiel Olijhoek, Willem Koert, Edwin van den Worm. - (TSG - Tijdschrift voor gezondheidswetenschappen (2020) 18 November; p. 1-6)

• Abstract in English
• DOI: 10.1007/s12508-020-00287-3

Samenvatting

Webwinkels die zich richten op Nederlandse consumenten van recreatieve drugs, verkopen een snelgroeiend assortiment van synthetische drugs die door hun experimentele karakter op dit moment legaal kunnen worden verkocht. In een verkennend onderzoek, dat zich beperkte tot de onder de stimulantia vallende cathinonen, werden in deze winkels 26 cathinonen aangetroffen. Van geen van deze middelen is de toxiciteit goed onderzocht. Een trendanalyse van de cathinonen die onlangs in dit circuit zijn gelanceerd doet vrezen dat de bedenkers van deze middelen, in hun streven om nieuwe drugs te produceren die de regelgeving ontwijken, waarschijnlijk onbedoeld steeds verslavender drugs op de markt brengen.

Abstract

Web shops targeting Dutch consumers of recreational drugs sell a fast-growing range of synthetic drugs which can currently be legally sold due to their experimental nature. In an exploratory study, limited to the cathinones – a group of drugs with stimulant biological effects – 26 cathinones were found in these stores. The toxicity of none of these agents has been properly studied. A trend analysis of the cathinones recently launched in this circuit suggested that the inventors of these drugs, in their quest to manufacture new drugs that avoid regulation, may introduce substances with an increasingly addictive potential.

Δ-4-Androstene-3,17-Dione Binds Androgen Receptor, Promotes Myogenesis in Vitro, and Increases Serum Testosterone Levels, Fat-Free Mass, and Muscle Strength in Hypogonadal Men / Ravi Jasuja, Pandurangan Ramaraj, Ricky Phong Mac, Atam B. Singh, Thomas W. Storer, Jorge Artaza, Aria Miller, Rajan Singh, Wayne E. Taylor, Martin L. Lee, Tina Davidson, Indrani Sinha-Hikim, Nestor Gonzalez-Cadavid, Shalender Bhasin. - (Journal of Clinical Endocrinology & Metabolism 90 (2005) 2 (1 February); p. 855-863)

• PMID: 15522925
• DOI: 10.1210/jc.2004-1577

Abstract

Previous studies of Delta 4-androstene-3,17-dione (4-androstenedione) administration in men have not demonstrated sustained increments in testosterone levels, fat-free mass (FFM), and muscle strength, and failure to demonstrate androstenedione's androgenic/anabolic effects has stifled efforts to regulate its sales. To determine whether 4-androstenedione has androgenic/anabolic properties, we evaluated its association with androgen receptor (AR) and its effects on myogenesis in vitro. Additionally, we studied the effects of a high dose of 4-androstenedione on testosterone levels, FFM, and muscle strength in hypogonadal men. We determined the dissociation constant (K(d)) for 4-androstenedione using fluorescence anisotropy measurement of competitive displacement of fluorescent androgen from AR ligand-binding domain. AR nuclear translocation and myogenic activity of androstenedione were evaluated in mesenchymal, pluripotent C3H10T1/2 cells, in which androgens stimulate myogenesis through an AR pathway. We determined effects of a high dose of androstenedione (500 mg thrice daily) given for 12 wk on FFM, muscle strength, and hormone levels in nine healthy, hypogonadal men. 4-Androstenedione competitively displaced fluorescent androgen from AR ligand-binding domain with a lower affinity than dihydrotestosterone (K(d), 648 +/- 21 and 10 +/- 0.4 nm, respectively). In C3H10T1/2 cells, 4-androstenedione caused nuclear translocation of AR and stimulated myogenesis, as indicated by a dose-dependent increase in myosin heavy chain II+ myotube area and up-regulation of MyoD protein. Stimulatory effects of 4-androstenedione on myosin heavy chain II+ myotubes and myogenic determination factor expression were attenuated by bicalutamide, an AR antagonist. Administration of 1500 mg 4-androstenedione daily to hypogonadal men significantly increased serum androstenedione, total and free testosterone, estradiol, and estrone levels and suppressed SHBG and high-density lipoprotein cholesterol levels. 4-androstenedione administration was associated with significant gains in FFM (+1.7 +/- 0.5 kg; P = 0.012) and muscle strength in bench press (+4.3 +/- 3.1 kg; P = 0.006) and leg press exercises (+18.8 +/- 17.3 kg; P = 0.045). 4-androstenedione is an androgen that binds AR, induces AR nuclear translocation, and promotes myogenesis in vitro, with substantially lower potency than dihydrotestosterone. 4-androstenedione administration in high doses to hypogonadal men increases testosterone levels, FFM, and muscle strength, although at the dose tested, the anabolic effects in hypogonadal men are likely because of its conversion to testosterone.

Mass spectrometric characterization of different norandrosterone derivatives by low-cost mass spectrometric detectors using electron ionization and chemical ionization / Douwe de Boer, E.G. de Jong, R.A. Maes. - (Rapid Communications in Mass Spectrometry 4 (1990) 6 (June); p. 181-185)

• PMID: 2134345
• DOI: 10.1002/rcm.1290040604

Abstract

The abuse of nortestosterone in sport is an important problem in doping-control analysis. In order to detect the main urinary metabolite of nortestosterone, norandrosterone (NA), sensitive and specific methodology is necessary. In this context the use of a low-cost mass spectrometric detector such as the Finnigan MAT ion-trap detector (ITD) was studied. The electron ionization (EI) and positive-ion chemical ionization (PICI) mass spectra of the methoxime-trimethylsilyl, trimethylsilyl-enol trimethylsilyl ether and pentafluoropropionic ester derivatives of NA are described. The limits of detection of these derivatives are compared with those obtained by the Hewlett-Packard mass selective detector (MSD), another low-cost mass spectrometric detector and operating only in the EI mode. For the derivatives of the reference standard of NA the ITD has in the EI mode the same limit of detection, in the range of 0.5 to 1 ng injected on the column, as the MSD. However, under these conditions the ITD provides more spectrometric information, because it gives full scan data. Moreover, with the same or even improved limits of detection the ITD can operate in the PICI mode. On the other hand, for the analysis of NA isolated from urine samples, the performance of the MSD was better than that of the ITD. The ion trapping technique is probably limited when the chemical background is high.

The methyl-5 alpha-dihydrotestosterones mesterolone and drostanolone; gas chromatographic/mass spectrometric characterization of the urinary metabolites / Douwe de Boer, E.G. de Jong, R.A. Maes, J.M. van Rossum. - (Journal of Steroid Biochemistry and Molecular Biology 42 (1992) 3-4 (May); p. 411-419)

• PMID: 1606052
• DOI: 10.1016/0960-0760(92)90146-a

Abstract

Before including the detection of the methyl-5 alpha-dihydrotestosterones mesterolone (1 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one) and drostanolone (2 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one) in doping control procedures, their urinary metabolites were characterized by gas chromatography/mass spectrometry. Several metabolites were found after enzymatic hydrolysis and conversion of the respective metabolites to their trimethylsilyl-enol-trimethylsilyl ether derivatives. The major metabolites of mesterolone and drostanolone were identified as 1 alpha-methyl-androsterone and 2 alpha-methyl-androsterone, respectively. The parent compounds and the intermediate 3 alpha,17 beta-dihydroxysteroid metabolites were detected as well. The reduction into the corresponding 3 beta-hydroxysteroids was a minor metabolic pathway. All metabolites were found to be conjugated to glucuronic acid.

The analysis of trenbolone and the human urinary metabolites of trenbolone acetate by gas chromatography/mass spectrometry and gas chromatography/tandem mass spectrometry / Douwe de Boer, M.E. Gainza Bernal, R.D. van Ooyen, R.A. Maes. - (Biological Mass Spectromety 20 (1991) 8 (August); p. 459-466)

• PMID: 1768702
• DOI: 10.1002/bms.1200200805

Abstract

The electron impact mass spectrometric properties of trimethylsilyl ether and fluoroacyl ester derivatives of trenbolone, combined or not combined with a methoxime group, are presented. Some derivatization problems were observed and were due to the formation of enol derivatives at the 3C-position in several tautomeric forms, which in their turn were not stable and lost two or four hydrogens under the conditions studied. The enolization could be minimized by carefully selecting the reaction conditions or could be prevented by the introduction of a methoxime group at the 3C-position. The limits of detection and identification of the methoxime heptafluorobutyryl ester and the methoxime trimethylsilyl ether derivative of trenbolone were determined using a mass selective detector in the electron impact mode and a triple-stage quadrupole in the methane positive chemical ionization mode. Selected reaction monitoring in tandem mass spectrometry did not improve the limit of detection, but because of the gain in selectivity did improve the limit of identification. The glucuronides of trenbolone and epitrenbolone could be identified in three urine specimens out of 200 samples in routine doping control.

Doping control of testosterone and human chorionic gonadotrophin : a case study / Douwe de Boer, E.G. de Jong, J.M. van Rossum, R.A. Maes. - (International Journal of Sports Medicine 12 (1991) 1 (February); p. 46-51)

• PMID: 2030059
• DOI: 10.1055/s-2007-1024654

Erratum in:

• Int J Sports Med 1991 Aug;12(4):430. De Jong EG [corrected to de Jong EG]

Abstract

Doping control for testosterone and human Chorionic Gonadotrophin (hCG) requires special attention as a difference must be made between the endogenous and exogenous origin of both substances. The detection of exogenous testosterone is based on the ratio of testosterone- to epitestosterone-glucuronide (T/E) in urine. The problems with this ratio are discussed. For hCG analysis in urine the utilization of sandwich-type hCG specific assays instead of hCG/hCG beta competitive assays is recommended. A case study in which an athlete self-administered testosterone and hCG before a competition is described. The T/E ratio and hCG concentration in urine were followed during this period of self-administration. The results demonstrate the relevance of the T/E ratio and of the selected hCG assay. The ratio of testosterone to human Luteinizing Hormone (T/hLH) in serum also indicated the use of hormones. Although the athlete's urine was negative for exogenous testosterone directly after competition, he would have been found positive for hCG.

The detection of danazol and its significance in doping analysis / Douwe de Boer, E.G. de Jong, R.A. Maes. - (Journal of Analytical Toxicology 16 (1992) 1 (January-February); p. 14-18)

• PMID: 1640693
• DOI: 10.1093/jat/16.1.14

Abstract

The use of anabolic steroids and related compounds in sport is forbidden by the International Olympic Committee (IOC). Because danazol (17 alpha-pregna-2,4-dien-20-yno[2,3-D] isoxazol-17 beta-ol) is structurally related to the anabolic steroid stanozolol, its use should be questioned. Therefore, the detection and the significance of danazol in doping analysis are discussed. A urine specimen suspected of containing danazol metabolites was analyzed in order to characterize the metabolites. After isolation and conversion into three different derivatives, the metabolites were subjected to gas chromatography/mass spectrometry (GC/MS) in the electron impact (EI) mode. The structure assignment was based on the molecular ions, fragmentation patterns observed for the three different derivatives, and the possible metabolite structures given in the literature. Ethisterone was identified as a nonconjugated metabolite. 2-Hydroxymethylethisterone was observed in two stereoisomeric forms. One stereoisomer was found mainly in the nonconjugated steroid fraction and the other in the conjugated fraction. The results were confirmed by analyzing urine specimens of a volunteer who was known to have taken danazol. Derivatization methods and GC/MS data are given to implement danazol detection in routine screening and confirmation procedures.

Why do doping control labs need a tandem mass spectrometer? / E.G. de Jong, R.A. Maes, J.M. van Rossum. - (Biomedical & Environmental Mass Spectrometry 16 (1988) 1-12 (October); p. 75-80)

• PMID: 3242711
• DOI: 10.1002/bms.1200160115

Abstract

The International Olympic Committee requires a confirmation by gas chromatography/mass spectrometry for all positive doping cases. Because of the severe consequences involved they should be more specific about the required information and determine the differences allowed. The use of tandem mass spectrometry in dope control should be required before the Olympic Games in Barcelona in 1992. This article shows the power of tandem mass spectrometry in the definite identification of a drug.