The pseudoendogenous anabolic steroid 1,4-androstadiene-3,17-dione does not occur naturally in Rhodiola rosea L. radix and rhizome / Juan Da, Lin Yang, Wan-Ying Wu, De-an Guo, Alexander G. Panossian. - (Phytochemistry Letters
23 (2018) February; p. 155-163)

• DOI:10.1016/j.phytol.2017.12.007

Abstract

Background:

Rhodiola rosea L. roots and rhizome (RRR) extracts are used as dietary supplements for temporary relief of symptoms of stress, such as fatigue, sensation of weakness, and for improvement of mental and cognitive function. RRR containing products are also of interest to sports nutrition experts and antidoping authorities. It has been suggested that nutritional supplements containing Rhodiola rosea extracts be examined for the presence of (pseudo-) endogenous steroids, specifically for the presence of 1,4-androstadiene-3,17-dione (ADD) which can potentially lead to adverse analytical findings (AAFs) in doping controls.

Aim of the study:

The aim of the present study was to detect and quantify ADD in Rhodiola roots and rhizomes collected in various geographical locations of North America, Europe, and Asia.

Results:

ADD was not found in RRR by any of three methods used in this study. No peaks corresponding to ADD in chromatograms of RRR extract were detected at the limit of quantification corresponding to 1.6 ng/g of ADD in dry rhizomes of Rhodiola rosea.

Conclusion:

The anabolic steroid 1,4-androstadiene-3,17-dione was not detectable in the Rhodiola rosea roots and rhizomes, at least not present in amounts which may be a concern for athletes who want to avoid the consumption of this anabolic agent with Rhodiola dietary supplementation.

SARM-S4 and metabolites detection in sports drug testing: a case report / Elia Grata, Laurent Perrenoud, Martial Saugy, Norbert Baume. - (Forensic Science International 213 (2011) 1-3 (10 December); p. 104-108)

• PMID: 21816554
• DOI: 10.1016/j.forsciint.2011.07.014

Abstract

Recently, pharmaceutical industry developed a new class of therapeutics called Selective Androgen Receptor Modulator (SARM) to substitute the synthetic anabolic drugs used in medical treatments. Since the beginning of the anti-doping testing in sports in the 1970s, steroids have been the most frequently detected drugs mainly used for their anabolic properties. The major advantage of SARMs is the reduced androgenic activities which are the main source of side effects following anabolic agents' administration. In 2010, the Swiss laboratory for doping analyses reported the first case of SARMs abuse during in-competition testing. The analytical steps leading to this finding are described in this paper. Screening and confirmation results were obtained based on liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses. Additional information regarding the SARM S-4 metabolism was investigated by ultra high-pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS).

Studies of the pharmacology of 17α-ethynyl-androst-5-ene-3β,7β,17β-triol, a synthetic anti-inflammatory androstene / Clarence N. Ahlem, Michael R. Kennedy, Theodore M. Page, Christopher L. Reading, Steven K. White, John J. McKenzie, Phaedra I. Cole, Dwight R. Stickney, James M. Frincke. - (International Journal of Clinical and Experimental Medicine 4 (2011) 2 (23 April); 119-135)

• PMID: 21686136
• PMCID: PMC3113500

Abstract

17α-Ethynyl-androst-5ene-3β, 7β, 17β-triol (HE3286) is an orally bioavailable analogue of androst-5-ene-3β,7β,17β-triol, a non-glucocorticoid anti-inflammatory metabolite of the adrenal steroid, dehydroepiandrosterone. The pharmacology of HE3286 was characterized in preparation for clinical trials in type 2 diabetes mellitus and other diseases of inflammation. Interactions with nuclear hormone receptors and P450 enzymes were measured in vitro. Drug metabolism was studied preclinically in mice, rats, dogs, and monkeys. Neurological and cardiopulmonary safety and dose-ranging and chronic toxicity studies were conducted in rats and dogs in accordance with FDA guidelines. Pharmacokinetics and metabolites were measured in Phase I clinical trials. HE3286 was differentially metabolized between species. HE3286 and metabolites did not bind or transactivate steroid binding nuclear hormone receptors or inhibit P450 enzymes. There were no adverse effects in safety pharmacology and canine toxicology studies. Although HE3286 did not elicit systemic toxicity in rats, mild estrogenic effects were observed, but without apparent association to hormonal changes. Safety margins were greater than 20-fold in rats and dogs with respect to the most commonly used clinical dose of 10 mg/day. The terminal half-life in humans was 8 hours in males and 5.5 hours in females. HE3286 is the first derivative of the DHEA metabolome to undergo a comprehensive pharmacological and safety evaluation. The results of these investigations have shown that HE3286 has a low potential for toxicity and possesses pharmacological properties generally suitable for use in human medicine. The favorable profile of HE3286 warrants further exploration of this new class of anti-inflammatory agents.

Keywords: HE3286; Toxicology; androstene; metabolism; pharmacokinetics; pharmacology.

Mass spectrometry of selective androgen receptor modulators / Mario Thevis, Wilhelm Schänzer. - (Journal of Mass Spectrometry 43 (2008) 7 (July); p. 865-876)

• PMID: 18521833
• DOI: 10.1002/jms.1438

Abstract

Nonsteroidal selective androgen receptor modulators (SARMs) are an emerging class of drugs for treatment of various diseases including osteoporosis and muscle wasting as well as the correction of age-related functional decline such as muscle strength and power. Several SARMs, which have advanced to preclinical and clinical trials, are composed of diverse chemical structures including arylpropionamide-, bicyclic hydantoin-, quinoline-, and tetrahydroquinoline-derived nuclei. Since January 2008, SARMs have been categorized as anabolic agents and prohibited by the World Anti-Doping Agency (WADA). Suitable detection methods for these low-molecular weight drugs were based on mass spectrometric approaches, which necessitated the elucidation of dissociation pathways in order to characterize and identify the target analytes in doping control samples as well as potential metabolic products and synthetic analogs. Fragmentation patterns of representatives of each category of SARMs after electrospray ionization (ESI) and collision-induced dissociation (CID) as well as electron ionization (EI) are summarized. The complexity and structural heterogeneity of these drugs is a daunting challenge for detection methods.

In March 2021 the Athletics Integrity Unit (AIU) of World Athletics has reported an an anti-doping rule violation against the Kuwaiti Athlete Yousef Karam after his sample tested positive for the prohibited substance Ibutamoren.

After notification the Athlete gave a prompt admission, waived his right for a hearing, accepted a provisional suspension and the sanction proposed by AIU. 

Therefore the AIU decides on 18 August 2021 to impose a 3 year period of ineligibility on the Athlete starting on the date of the provisional suspension, i.e. on 30 March 2021.

CAS 2021/O/7977 World Athletics v. Shelby Houlihan

In January 2021 the Athletics Integrity Unit (AIU) for World Athletics has reported an anti-doping rule violation against the American Athlete Shelby Houlihan after her A and B samples tested positive for the prohibited substance 19-norandrosterone (Nandrolone).

After notification a provisional suspension was ordered. In May 2021 the case was referred to the Court of Arbitration for Sport (CAS) for a first instance hearing panel. Previously the Athlete's request to lift the imposed provisional suspension was rejected by the AIU as by CAS.

The Athlete denied the intentional use of the substance and  argued that the 19-norandrosterone entered her body by eating a burrito from a food truck containing pork offal and that the burrito was the only possible source of the 19-norandrosterone in the Sample.

The Athlete disputed the test results and asserted, supported by an expert witness, that the analytical results of the Montreal Lab should haven been reported as an Atypical Finding. Further she argued that TD2021NA applies since this document was approved and published and because of the application of the principle of lex mitior.

The Panel establishes that the TD2021NA is applicable in this matter and a majority of the Panel finds that the Athlete failed to demonstrate that the Adverse Analytical Finding (AAF) was not properly reported pursuant to the ISL, neither that the anti-doping rule violation was not properly managed, asserted and notified pursuant to the ISRM.

Considering the evidence in the case the Panel:

• finds it possible but unlikely that the Athlete’s burrito contained boar offal;
• finds it possible but unlikely that the ingestion of boar offal would have resulted in the urinary concentration of 19-norandrosterone found in the Athlete’s A and B samples;
• finds it possible but not probable that the ingestion of boar offal would have resulted in the Athlete’s reported urinary concentration of 19-NA or her carbon isotope ratio of -23‰;
• finds that neither the hair analysis nor the polygraph results are sufficient for the Athlete to satisfy her burden of proving that the anti-doping rule violation was not intentional.

Finally the Panel concludes that the Athlete has not satisfied her burden of proof on the balance of probabilities that the anti-doping rule violation was unintentional, and that the violation must be deemed intentional.

Therefore the Court of Arbitration for Sport decides on 27 August 2021 that:

1. The request for arbitration filed by World Athletics on 18 May 2021 against Shelby Houlihan is upheld.
2. Shelby Houlihan is found to have committed an anti-doping rule violation pursuant to Rule 2.1 and Rule 2.2 of the World Athletics Anti-Doping Rules.
3. Shelby Houlihan is subject to a period of ineligibility of four (4) years starting on 14 January 2021.
4. All competitive results obtained by Shelby Houlihan from 15 December 2020 through to 14 January 2021 are disqualified, including forfeiture of any titles, awards, medals, points and prize and appearance money obtained during this period.
5. (…).
6. (…).
7. All other motions or requests for relief are dismissed.
8. The present decision is confidential, unless the President of the CAS Ordinary Arbitration Division decides that it should be made public.

Related cases:

CAS 2019_A_6319 Maria Guadalupe Gonzalez Romero vs IAAF
July 2, 2020

IAAF 2018 IAAF vs María Guadalupe González Romero
May 9, 2019

On 9 May 2019 the IAAF (now: World Athletics) Disciplinary Tribunal decided to impose a 4 year period of ineligibility on the Mexican Athlete María Guadalupe González Romero after her A and B samples tested positive for the prohibited substance Trenbolone.

In First Instance the Sole Arbitrator deemed that the explanation together with the evidence produced by the Athlete were not convincing, contradicting and unreliable. Consequently her explanation was rejected for lack of credibility since she failed to establish that her violation was not intentional.

The Athlete appealed in June 2020 with the Court of Arbitration for Sport (CAS). However on 2 July 2020 the CAS Panel confirmed the Appealed IAAF Decision of 9 May 2019. During the CAS hearing the Athlete acknowledged that she had provided false statements and evidence.

Hereafter in July 2020 the Athletics Integrity Unit (AIU) for World Athletics reported a new anti-doping rule violation against the Athlete for Tampering because of the false statements, fabricated evidence and false documents she had provided to the AIU.

Regarding the Athlete's Tampering the AIU contended that:

• the Athlete provided two contradictory sets of facts with regards to her consumption of meat in the days before the sample collection;
• the hospital report submitted by the Athlete was forged;
• the receipts for the restaurants in question were also forged;
• the Athlete acknowledged that she had asked her friend to provide false testimony to support her story about eating beef at the restaurant in question.

The Athlete argued that she never had the intention to manipulate evidence or to lie during the proceedings neither before the First Instance Proceedings before the Disciplinary Tribunal, nor before CAS. Indeed, the Athlete discharged any possible responsibility on her first lawyers, who did not disclose or inform her about any falsification or manipulation of documents and even forged her signature.

The Sole Arbitrator finds the conclusions reached by both, the First Decision and the CAS decision of the utmost relevance, since they are convincing and persuasive enough to conclude that the Athlete indeed lied and presented fabricated evidence during the First Instance Proceedings.

The Sole Arbitrator rejects the Athletes arguments alleging that she was unaware of the content, evidence and documents filed in her defence. Whereas he concludes that the Athlete's conduct shall be qualified as Tampering pursuant to the definition established in the ADR.

Considering the principle of lex mitior and the application of Article 10.9.3(c) of the ADR 2021 the Sole Arbitrator deems that the Athlete committed a stand-alone first violation with the imposition of a 4 year period of ineligibility (instead of 8 years).

Therefore on 30 July 2021 the Sole Arbitrator decides that the Athlete has committed an anti-doping rule violation for Tampering and to impose a 4 year period of ineligibility.

This new sanction shall run consecutively to the period of ineligibility already imposed on the Athlete unitl 15 November 2022, thus starting on 16 November 2022 until 15 November 2026.

• CAS 2020/A/7526 World Athletics v. Salwa Eid Naser
• CAS 2020/A/7559 World Anti-Doping Agency (WADA) v. World Athletics & Salwa Eid Naser

Related case:

World Athletics 2020 WA vs Salwa Eid Naser
October 14, 2020

On 14 October 2020 the World Athletics Disciplinary Tribunal decided to dismiss the 2 charges against the Athlete Salwa Eid Naser for the reported Whereabouts Filing failures and Missed Tests within a 12 month period.

In first instance the Panel deemed that there was a Missed Test committed on 24 January 2020 but concluded that the Missed Test on 12 April 2019 could not be attributed to the Athlete. As a result the anti-doping rule violation (ADRV) has not been established for 3 Missed Tests to the comfortable satisfaction of the Panel. The January 2020 Missed Test still stands against the Athlete. 

Hereafter in November 2020 World Athletics (WA) and the World Anti-Doping Agency (WADA) appealed the Decision of 14 October 2020 with the Court of Arbitration for Sport (CAS).

Both WA and WADA requested the Panel to set aside the Appealed Decision, contending that the 12 April 2019 Missed Test should be confirmed and that thus the Athlete violated Article 2.4 ADR based either on the First Charge or on the Second Charge. As to the consequences for such violation,

WA and WADA contended that the Athlete shall be sanctioned with (i) the standard two-year period of ineligibility, which does not deserve reductions based on the Athlete's degree of fault and (ii) disqualification of her results since the date of the third Whereabouts Failure, 12 April 2019.

The Athlete, seeked full confirmation of the Appealed Decision, asserting that on 12 April 2019 there was no Whereabouts Failure. Leaving aside the recharacterization as a Failing Failure, this alleged Whereabouts Failure is crucial to both the First Charge and the Second Charge as, without it, the Athlete would not incur three such failures within a twelve-month period and she could not be charged with any ADRV.

Alternatively, should the Panel find that Athlete did perpetrate an ADRV, the Athlete requested (i) that any imposed period of ineligibility be reduced, taking into account the circumstances of the case at hand, including the delays in the proceedings that led to the Notice of Charge and the Athlete's dyslexia and ADHD, and (ii) that her results be disqualified only from 4 October 2019.

The Panel finds that the 2 separate reported ADRVs against the Athlete must be considered as only one single ADRV for sanctioning purposes and that there are insufficient grounds for backdating the ineligibility period.

Further the Panel concludes that the Athlete, in all three Whereabouts Failures, has shown an unacceptable degree of nonchalance and a worryingly lackadaisical approach to her whereabouts obligations under the ADR, thereby deserving no reduction of her ineligibility period.

Therefore the Court of Arbitration for Sport decides on 30 June 2021 that:

1. The appeal filed by World Athletics on 12 November 2020 against Ms Salwa Eid Naser with respect to the decision issued by the World Athletics Disciplinary Tribunal on 14 October 2020 is partially upheld.
2. The appeal filed by the World Anti-Doping Agency on 30 November 2020 against World Athletics and Ms Salwa Eid Naser with respect to the decision issued by the World Athletics Disciplinary Tribunal on 14 October 2020 is partially upheld.
3. The decision rendered by the World Athletics Disciplinary Tribunal on 14 October 2020 in the matter of Ms Salwa Eid Naser is set aside.
4. Ms Salwa Eid Naser is sanctioned with a period of ineligibility of two years, commencing on the date of notification of this award, with credit given for the period of provisional suspension already served between 4 June 2020 and 14 October 2020.
5. All competitive results obtained by Ms Salwa Eid Naser from 25 November 2019 through to the date of notification of this award shall be disqualified, with all of the resulting consequences, including forfeiture of any medals, titles, ranking points and prize and appearance money.
6. The present award is pronounced without costs, except for the CAS Court Office fees of CHF 1,000 each, already paid by World Athletics and by the World Anti-Doping Agency, which are retained by the CAS.
7. Ms Salwa Eid Naser shall pay CHF 5,000 (five thousand Swiss francs) to World Athletics and CHF 5,000 (five thousand Swiss francs) to the World Anti-Doping Agency as contribution towards their costs incurred in connection with these arbitration proceedings.
8. All other or further motions or prayers for relief are dismissed.

CAS OG 20/12 Nazar Kovalenko v. World Athletics & Athletics Integrity Unit

Mr Nazar Kovalenko is a Ukrainian athlete competing in the 20 km race walk discipline. He served a 3 year period of ineligibility, resumed his sporting activitity in March 2020 and started his preparatons for the qualifications for the upcoming Olympic Games.

Previously the Athletics Integrity Unit (AIU) of World Athletics (WA) had placed the Ukrainian Athletic Federation (UAF) into the category A with the highest risk of doping. Consequently  their national team athletes had to undergo at least 3 out-of-competition doping tests in the 10 months before a World Championship or Olympic Games.

This case is about the question of whether the Athlete is eligible to participate as an athlete in the 20 km Race Walk at Tokyo 2020, although it is undisputed that the Athlete failed to meet the Mandatory Testing Requirements which are issued for all athletes belonging to Category A Federations under the WA AD Rule 15.5.1 c.

In this matter the Panel believes that three main questions are presented before it:

• Whether the ineligibility of the Athlete decided by the AIU for the failure to comply with AR Rule 15 is an unenforceable sanction;
• Whether the Athlete has, in practice, complied with the testing requirements and therefore his ineligibility would be a disproportionate, unfair and illegal measure taken against him;
• Whether the Athlete has demonstrated exceptional circumstances that would allow an exemption to the strict application of AD Rule 15.

The Panel finds that the AIU decision is not a sanction and that the imposition of ineligibility is not disproportionate for the failure of a Category A Member Federation to perform sufficient regular anti-doping tests. Further the Panel deems that there are no grounds to conclude that there are exceptional circumstances to allow an exemption.

Therefore on 3 August 2021 the CAS AD Hoc Division decides:

1. The application filed by Mr. Nazar Kovalenko on 1 August 2021 is rejected.

2. The Parties bear their own costs.

In January 2020 the Fédération Internationale de l'Automobile (FIA) has reported an anti-doping rule violation against the French karting driver Leo Payen after his sample tested positive for the prohibited substance Cannabis.

After notification the Athlete admitted the violation and FIA accepted that the violation was not intentional. The parties reached an agreement which was approved by the FIA Anti-Doping Disciplinairy Committee. Here the Panel considered that there were delays in the proceedings not attributed to the Athlete.

Therefore the FIA Anti-Doping Disciplinary Committee decides on 4 June 2021 to impose a 2 year period of ineligibiltiy on the Athlete, starting on the date of the sample collection, i.e. on 28 September 2019.