In October 2018 the Japan Anti-Doping Agency (JADA) has reported an anti-doping rule violation against the Athlete J-5977 after his A and B samples tested positive for the prohibited substance Clomiphene. After notification a provisional suspension was ordered. The Athlete filed a statement in his defence and he was heard for the Japan Anti-Doping Disciplinary Panel (JADDP). The Athlete accepted the test results and denied the intentional use of the prohibited substance. He assumed that one of the supplements he had used was the source of the positive test and he had mentioned these supplements on the Doping Control Form. He could not demonstrate with evidence how the substance entered his system since he already had deposed the containers of these supplements after they were depleted. He had already retired from athletics. The Panel accepts that the violation was not intentional and that he failed to establish how the substance entered his system. Therefore the JADDP decides on 12 February 2019 to impose a 2 year period of ineligibility on the Athlete starting on the date of the provisional suspension, i.e. on 11 October 2018.

In October 2018 the Japan Anti-Doping Agency (JADA) has reported an anti-doping rule violation against the bodybuilder J-5976 after his sample tested positive for the prohibited substance Clomiphene. After notification the Athlete admitted the violation, waived his right to be heard, accepted the test result, a provisional suspension and the sanction proposed by JADA. JADA accepts that the violation was not intentional in this case and decides on 18 December 2018 to impose a 2 year period of ineligibility on the Athlete J-5976 starting on the date of the provisional suspension, i.e. on 10 October 2018.

Related case: JADDP 2018-003 JADA vs J-5975 November 19, 2018 In June 2018 the Japan Anti-Doping Agency (JADA) has reported an anti-doping rule violation against the cyclist J-5975 after his sample tested positive for the prohibited substance Vilanterol. After notification a provisional suspension was ordered in September 2018. The Athlete applied for a TUE, filed a statement in his defence and he was heard for the Japan Anti-Doping Disciplinary Panel (JADDP). The Athlete gave a prompt admission, accepted the test result and denied the intentional use of the substance. He explained that he had used the medication Revlar as treatment for his asthma attacks in May 2018 prescribed by his mother and physician and he mentioned this on the Doping Control Form. The physician testified that she erroneously believed that for this prescribed medication the TUE would be granted automatically. However instead the physician had to apply for a TUE and explain why this medication was used and not the regular substances Salbutamol, Formoterol or Salmeterol. Further the TUE application made afterwards in June 2018 for this medication was denied by the JADA TUEC and this rejection was again confirmed by the Japan Sports Arbitration Agency on 6 September 2018 when appealed by the Athlete J-5975. Considering the circumstances the Panel finds that the anti-doping rule violation was not intentional, that the Athlete gave a prompt admission and that he established No Siginificant Fault or Negligence in this case. Therefore the JADDP decides on 19 November 2018 to impose a 3 month period of ineligibility on the Athlete J-5975 starting on the date of the provisional suspension, i.e. on 6 September 2018 until the date of this decision.

In August 2018 the Japan Anti-Doping Agency (JADA) has reported an anti-doping rule violation against the wrestler J-5974 after his A and B samples tested positive for the prohibited substance Acetazolamide. After notification a provisional suspension was ordered. The Athlete filed a statement in his defence and he was heard for the Japan Anti-Doping Disciplinary Panel (JADDP). The Athlete accepted the test results and denied the intentional use of the prohibited substance. He believed that the positive test result was caused by a contaminated medication he had used prescribed by the team physician. Analysis of this medication confirmed that it contained the prohibited substance while the substance was not listed as ingredient on the label of this product. Considering the evidence in this case the Panel accepts that the positive test was the result of a prescribed contaminated medication the Athlete had used and that he established No Fault or Negligence. Therefore the JADDP decides on 22 February 2019 to lift the provisional suspension and to acquit the Athlete J-5974 without imposing any period of ineligibility.

In July 2018 the Japan Anti-Doping Agency (JADA) has reported an anti-doping rule violation against the cyclist J-5973 after his sample tested positive for the prohibited substances Clomiphene and Methandienone. After notification the Athlete admitted the violation, waived his right to be heard, accepted the test result, a provisional suspension and the sanction proposed by JADA. JADA considers that the Ahtlete could not explain how the prohibited substance entered his system nor that the violation was not intentional. Therefore JADA decides on 31 July 2018 to impose a 4 year period of ineligibility on the Athlete J-5973 starting on the date of the provisional suspension, i.e. on 11 July 2018.

In March 2015 the International Cycling Union (UCI) reported an anti-doping rule violation against the (already retired) Spanish cyclist Juan José Cobo Acebo after an UCI expert panel concluded unanimously in July 2014, in December 2014, in November 2015 and again in May 2016 in their Experts Reports, that the Athlete’s hematological profile “highly likely” showed that he used a prohibited substance or a prohibited method: the use of EPO or Blood doping in 2009 and in 2011. This conclusion of the UCI expert panel is based on assessment of blood samples, collected in the period from 2 December 2007 until 2 May 2013 reported in the Athlete’s Biological Passport (ABP). Previously the Athlete submitted 3 explanations to the UCI about the circumstances surrounding the collected samples which were rejected by the Expert Panel in their Experts Reports submitted in July 2014, in November 2015 and in May 2016. After notification the Athlete waived an Acceptance of Consequences, he failed to file a statement in his defence nor did he attend the hearing of the UCI Anti-Doping Tribunal. The Sole Arbitrator settled the case based on the written submissions of the parties. In his explanations the Athlete argued: • The Expert Panel had made inconsistent definitions of what was normal and abnormal; • The ABP assessment was based on a “comparison with an unknown population of athletes”; • The variances in his blood values could be due to inter-laboratory variation; • His OFF-score marker did not breach his individual limits and that the variances in the RET values were in line with publically available data on cyclists; • The samples taken during the 2009 World Championships could have been affected by a traumatic humerus fracture which occurred in August 2009; • General analytical issues (such as absence of duplicate analyses and temperature variation) could have impacted his profile; and • His profile during the 2011 Vuelta was “similar to the profile described in large samples of cyclists”. • The Athlete compared his ABP with the alleged haematological data of a “model cyclist”, in order to conclude that his profile was normal; • The Athlete further argued that in addition to his humerus fracture, he had been treated with corticosteroids in 2009, following a tendon injury and that prior to the World Championships, he underwent intermittent hypoxic training. • As argued in his first explanation, the haemoglobin variation could be due to inter-laboratory variation; • The Expert Panel had arbitrarily analysed the ABP and had not relied on appropriate studies to do so; • That one of his samples, sample 32, had been affected by high temperature variations. UCI contended that the Expert Panel had carefully addressed all of the arguments raised by the Athlete in his 3 explanations and dismissed them in full. The Sole Arbitrator finds that the arguments raised by the Athlete during the results management process before the UCI have been correctly addressed by the Expert Panel. Further based on the UCI’s petition and on the Athlete’s explanations submitted to the UCI, and taking into consideration that the Athlete failed to dispute the Expert Panel’s 4th and final Report and/or answer to the UCI’s petition in any way, the Sole Arbitrator concludes that the Athlete did not set forth any legal basis on which his arguments may rely. As a result the Sole Arbitrator does not find any evidence allowing him to depart from the Expert Panel’s four reports on file. In evaluating the Athlete’s explanation and the UCI’s petition and all the evidence before him, and applying the standard of proof in the context of the assessment of evidence before him, the Sole Arbitrator is comfortably satisfied that the Athlete committed an anti-doping rule violation of Article 21.2. UCI ADR 2009, in fact the Use of a Prohibited Substance or a Prohibited Method. The Sole Arbitrator deems that there are aggravating circumstances in this case and that there were substantial delays in this case not attributed to the UCI. Therefore the UCI Anti-Doping Panel decides on 13 June 2019 to impose a fine and a 3 year period of ineligibility on the Athlete starting on the date of the decision. The UCI legal costs, the costs for the results management and the ABP documentation package shall be borne by the Athlete.

Annual banned-substance review: analytical approaches in human sports drug testing / Mario Thevis, Tiia Kuuranne, Hans Geyer, . – (Drug testing and analysis 11 (2019) 1 (January); p. 8-26). - PMID: 30488582. - DOI: 10.1002/dta.2549 _________________________________________________ Contents: - Introduction - Non-Approved Substances - Anabolic Agents • Anabolic-androgenic steroids • Initial testing procedures: Comprehensive screening, metabolism studies, and new target analytes • Steroid profiling • Confirmatory testing procedures – IRMS • Other anabolic agents - Peptide Hormones, Growth Factors, Related Substances, and Mimetics • Erythropoietin-receptor agonists • Hypoxia-inducible factor stabilizers and activators • Transforming growth factor-beta (TGR- β) inhibitors • Growth hormone, its fragments and releasing factors, and chorionic gonadotrophin - β2‐Agonists - Hormone and Metabolic Modulators - Diuretics and other Masking Agents, Stimulants, Narcotics, and Glucocorticoids - Chemical and Physical Manipulation / Gene Doping - Monitoring Program - Conclusion Abstract A number of high profile revelations concerning anti‐doping rule violations over the past 12 months have outlined the importance of tackling prevailing challenges and reducing the limitations of the current anti‐doping system. At this time, the necessity to enhance, expand, and improve analytical test methods in response to the substances outlined in the World Anti‐Doping Agency (WADA) Prohibited List represents an increasingly crucial task for modern sports drug testing programs. The ability to improve analytical testing methods often relies on the expedient application of novel information regarding superior target analytes for sports drug testing assays, drug elimination profiles, and alternative sample matrices, together with recent advances in instrumental developments. This annual banned‐substance review evaluates literature published between October 2017 and September 2018 offering an in‐depth evaluation of developments in these arenas and their potential application to substances reported in WADA's 2018 Prohibited List.

In October 2018 the United States Anti-Doping Agency (USADA) has reported an anti-doping rule violation against the Paralympic Athlete Striley Jones after his A and B samples tested positive for the prohibited substance Stanozolol. After notification a provisional suspention was ordered. The Athlete filed a statement with evidence in his defence and he was heard for the American Arbitration Association (AAA) Commercial Arbitration Tribual. The Paralympic Athlete accepted the test result, denied the intentional use of the prohibited substance and requested the Panel for a reduced sanction. The Athlete claimed that one of his supplements he used was contamined and they were sent to a Lab for testing. Analysis of these supplements in question revealed that the supplement Nitro Tech Whey Protein was contaminated with Stanozolol which was recommended by the Athlete’s nutritionist. Reanalysis in the WADA Salt Lake City Lab confirmed the presence of Stanozolol. USADA was able to obtain an unopened case of six sealed containers from the manufacturer from the same lot number as the supplement in question, which, when tested, did not contain Stanozolol. As a result USADA contended that the Athlete failed to establish that the positive test was caused by a contaminated product and requested the Panel to impose a 4 year period of ineligibility on the Athlete. The Panel considered the facts and circumstances in this case and accepts that this is a different inquiry entirely from the requirements on ameliorating a sanction on the basis of fault or lack thereof, which analysis expressly requires the athlete to meet the balance of probabilities burden on source. It is entirely possible for an Athlete to prevail on the finding of lack of intention only to fail to establish source to get a further reduction; such a result is not logically inconsistent and is in fact possible under the very different tests provided by the IPC ADC. A majority of the Panel concludes that there was insufficient proof of lack of intention while the minority of the Panel concludes that there was sufficient proof of lack of intention. Consequently the Athlete did not establish by a balance of probability to the satisfaction of the majority of the Panel that the ingestion of the Stanozolol was unintentional. Unanimously, the Panel does not believe that the Athlete was a cheater and the Panel would have welcomed additional evidence to support that belief. Unfortunately, under the existing rules, that belief alone is insufficient and adducing such evidence is acknowledged by the Panel as being difficult to accomplish; the majority is of the view that its hands are tied to issue a sanction of 4 years ineligibility. Therefore by a Majority the Arbitration Tribunal decides on 17 June 2019 to impose a 4 year period of ineligibility on the Athlete starting on the date of the provisional suspension, i.e. on 17 October 2018.

A next-generation sequencing method for gene doping detection that distinguishes low levels of plasmid DNA against a background of genomic DNA / Eddy N. de Boer, Petra E. van der Wouden, Lennart F. Johansson, Cleo C. van Diemen, Hidde J. Haisma. - (Gene Therapy (2019) 11 July; p. 1-9). - https://doi.org/10.1038/s41434-019-0091-6 _________________________________________________ Abstract Gene doping confers health risks for athletes and is a threat to fair competition in sports. Therefore the anti-doping community has given attention on its detection. Previously published polymerase chain reaction-based methodologies for gene doping detection are targeting exon–exon junctions in the intron-less transgene. However, because these junctions are known, it would be relatively easy to evade detection by tampering with the copyDNA sequences. We have developed a targeted nextgeneration sequencing based assay for the detection of all exon–exon junctions of the potential doping genes, EPO, IGF1, IGF2, GH1, and GH2, which is resistant to tampering. Using this assay, all exon–exon junctions of copyDNA of doping genes could be detected with a sensitivity of 1296 copyDNA copies in 1000 ng of genomic DNA. In addition, promotor regions and plasmid-derived sequences are readily detectable in our sequence data. While we show the reliability of our method for a selection of genes, expanding the panel to detect other genes would be straightforward. As we were able to detect plasmidderived sequences, we expect that genes with manipulated junctions, promotor regions, and plasmid or virus-derived sequences will also be readily detected.

Effects of Anabolic Androgenic Steroids on the Reproductive System of Athletes and Recreational Users : A Systematic Review and Meta-Analysis / Maria A. Christou, Panagiota A. Christou, Georgios Markozannes, Agathocles Tsatsoulis, George Mastorakos, Stelios Tigas. - (Sports Medicine 47 (2017) 9 (September); p. 1869-1883). - PMID: 28258581. - DOI: 10.1007/s40279-017-0709-z ___________________________________________________ Abstract BACKGROUND: Anabolic androgenic steroids (AAS) are testosterone derivatives used by athletes and recreational users to improve athletic performance and/or enhance appearance. Anabolic androgenic steroids use may have serious and potentially irreversible adverse effects on different organs and systems, including the reproductive system. OBJECTIVE: This systematic review and meta-analysis aimed to critically assess the impact of AAS use on the reproductive system of athletes and recreational users. METHODS: An electronic literature search was conducted using the databases MEDLINE, CENTRAL, and Google Scholar. Studies were included when the following criteria were fulfilled: participants were athletes or recreational users of any age, sex, level or type of sport; AAS use of any type, dose, form or duration; AAS effects on the reproductive system were assessed as stated by medical history, clinical examination, hormone and/or semen analysis. Random-effects meta-analysis was performed to assess the weighted mean difference (WMD) of serum gonadotropin (luteinizing hormone, follicle-stimulating hormone) and testosterone levels compared with baseline, during the period of AAS use, as well as following AAS discontinuation. RESULTS: Thirty-three studies (three randomized clinical trials, 11 cohort, 18 cross-sectional, and one non-randomized parallel clinical trial) were included in the systematic review (3879 participants; 1766 AAS users and 2113 non-AAS users). The majority of the participants were men; only six studies provided data for female athletes. A meta-analysis (11 studies) was conducted of studies evaluating serum gonadotropin and testosterone levels in male subjects: (1) prior to, and during AAS use (six studies, n = 65 AAS users; seven studies, n = 59, evaluating gonadotropin and testosterone levels respectively); (2) during AAS use and following AAS discontinuation (four studies, n = 35; six studies, n = 39, respectively); as well as (3) prior to AAS use and following AAS discontinuation (three studies, n = 17; five studies, n = 27, respectively). During AAS intake, significant reductions in luteinizing hormone [weighted mean difference (WMD) -3.37 IU/L, 95% confidence interval (CI) -5.05 to -1.70, p < 0.001], follicle-stimulating hormone (WMD -1.73 IU/L, 95% CI -2.67 to -0.79, p < 0.001), and endogenous testosterone levels (WMD -10.75 nmol/L, 95% CI -15.01 to -6.49, p < 0.001) were reported. Following AAS discontinuation, serum gonadotropin levels gradually returned to baseline values within 13-24 weeks, whereas serum testosterone levels remained lower as compared with baseline (WMD -9.40 nmol/L, 95% CI -14.38 to -4.42, p < 0.001). Serum testosterone levels remained reduced at 16 weeks following discontinuation of AAS. In addition, AAS abuse resulted in structural and functional sperm changes, a reduction in testicular volume, gynecomastia, as well as clitoromegaly, menstrual irregularities, and subfertility. CONCLUSION: The majority of AAS users demonstrated hypogonadism with persistently low gonadotropin and testosterone levels, lasting for several weeks to months after AAS withdrawal. Anabolic androgenic steroid use results in profound and prolonged effects on the reproductive system of athletes and recreational users and potentially on fertility. KEYWORDS: DHEAS; Female Athlete; Luteinizing Hormone; Testosterone; Testosterone Level