Current markers of the Athlete Blood Passport do not flag microdose EPO doping

20 Feb 2011

Current markers of the Athlete Blood Passport do not flag microdose EPO doping / Michael Ashenden, Clare E. Gough, Andrew Garnham, Christopher J. Gore, Ken Sharpe. - (European Journal of Applied Physiology 111 (2011) 9 (September) ; p. 2307-2314).
- PMID: 21336951.
- DOI: 10.1007/s00421-011-1867-6


Abstract:

The Athlete Blood Passport is the most recent tool adopted by anti-doping authorities to detect athletes using performance-enhancing drugs such as recombinant human erythropoietin (rhEPO). This strategy relies on detecting abnormal variations in haematological variables caused by doping, against a background of biological and analytical variability.

Ten subjects were given twice weekly intravenous injections of rhEPO for up to 12 weeks. Full blood counts were measured using a Sysmex XE-2100 automated haematology analyser, and total haemoglobin mass via a carbon monoxide rebreathing test. The sensitivity of the passport to flag abnormal deviations in blood values was evaluated using dedicated Athlete Blood Passport software. Our treatment regimen elicited a 10% increase in total haemoglobin mass equivalent to approximately two bags of reinfused blood. The passport software did not flag any subjects as being suspicious of doping whilst they were receiving rhEPO. We conclude that it is possible for athletes to use rhEPO without eliciting abnormal changes in the blood variables currently monitored by the Athlete Blood Passport.

CAS 2006_A_1162 Fernando Iglesias vs FILA

19 Feb 2007

CAS 2006/A/1162 Fernando Iglesias v/ FILA

On 4 September 2006 the International Wrestling Federation (FILA) decided to impose a 2 year period of ineligibility on the legal minor Argentine wrestler Fernando Iglesias (19) after his sample tested positive for the prohibited substances Hydrochlorothiazide and Methyltestosterone.

Hereafter in September 2006 the Athlete appealed the FILA decision with the Court of Arbitration for Sport (CAS).

The Athlete denied the intentional use of the submstances and requested the Panel to annul the FILA decision of 4 September 2007 on the basis of departures of the International Standard for Testing (IST). Here he contended that he was denied the opportunity to be represented at the sample collection session, a procedural error has been committed which renders the entire sample collection session and the two-year ineligibility sanction null and void.

FILA asserted that the doping test was conducted in compliance with the WADA standards and that the Athlete’s sample was collected in compliance with the WADA procedures. With signing the Doping Control Form the Athlete agreed on the method and the controlling procedure applied on him. Furhter FILA argued that it is the duty of the Athlete to check that food supplements don’t contain prohibited substances.

The Panel holds that the test result establish the presence of prohibited substances and that the Athlete committed an anti-doping rule violation. The Panel tends to agree with the Athlete that a “departure” from the standards set down in the IST has occurred. Having established the fact of this violation, it remains to be determined whether, as a consequence, the adverse analytical finding of the Cologne Laboratory is thus nullified together with any subsequent sanction.

However the Panel concludes that the failure of the Representative to sign the Form did not “cause” the Adverse Analytical Finding of the Cologne Laboratory. FILA, who bears the burden of evidence, has established the absence of any causality between the missing signature and the fact of the adverse analytical finding.

The Panel finds that the Athlete’s entries on the Doping Control Form didn’t contain the slightest indication that the Athlete objected to the absence of his Representative during the Sample Collection Session. As a result the minor Athlete confirmed that the sample collection was conducted in accordance with the relevant procedures for sample collection.

The Panel rules that the failure of the Athlete’s Representative to sign or later ratify the declarations made by his son on the Form cannot result in a nullification or invalidation of the Adverse Analytical Finding pursuant to Article 3.2.1.1 of the FILA Anti-Doping Regulations. Parents, coaches and other representatives must be held to the same standard of responsibility as an adult athlete.

Therefore the Court of Arbitration for Sport decides on 19 February 2007 that:

1.) The appeal filed by Fernando Iglesias on 29 September 2006 is dismissed.
2.) The award is pronounced without costs, except for the Court Office fee of CHF 500 already paid by Fernando Iglesias and which is retained by the CAS.
3.) Each party shall bear its own legal costs and other expenses incurred in connection to the present arbitration.

CAS 2010_A_2083 UCI vs Jan Ullrich & Swiss Olympic

9 Feb 2012

CAS 2010/A/2083 UCI v/ Jan Ullrich & Swiss Olympic
CAS 2010/A/2083 Union Cycliste Internationale (UCI) v. Jan Ullrich & Swiss Olympic

Cycling
Blood doping
Disciplinary proceedings against a rider and Article 75 Swiss Civil Code
Initiation of disciplinary proceedings against a rider who is no longer a UCI licence-holder
Probative value of the evidence leading to the conclusion that the rider engaged in blood doping
Determination of the first or the second infraction according to the 2009 WADC
First or second violation for the calculation of the period of ineligibility
Commencement of the Period of Ineligibility according to the UCI Rules

1. A case of disciplinary proceedings against a rider is not – strictly speaking – one that is situated within the scope of applicability of Article 75 of the Swiss Civil Code, since it is not a member of an association that lodges the appeal against a decision/resolution of an association, but a non-member (that is, however, equally affected by it). Such recourse in favour of a third party is covered by the parties’ autonomy and is not restricted or prevented by Article 75 of the Swiss Code. The parties, therefore, are free to rule and determine who are the proper respondents in a case in which an appeal is lodged by a non-member. The fact that according to Article 282 of the UCI Rules the appeal must be lodged also against the “license-holder” is not arbitrary. If the position under Article 75 of the Swiss Civil Code were otherwise, sporting rules like the UCI Rules and the WADC would not be capable of enforcement under domestic Swiss law, because the athlete could never be a proper defendant. Furthermore, only by being made a party to the proceedings will the athlete’s basic rights be guaranteed.

2. Upon the rider’s resignation, the question arises whether or not such rider can still be considered a “license-holder” within the meaning of the UCI Rules Article 282 of the UCI Rules. According to a judgment of the Supreme Court there is no impediment against actions against former members of an association when there is an interest in doing so. License holders remain subject to the jurisdiction of the relevant disciplinary bodies for acts committed while applying for or while holding a license, even if proceedings are started or continue after they cease to hold a license.

3. The 2009 version of the WADC gives certain guidance as to how certain pre-2009 WADC violations are to be treated when determining a sanction under the 2009 WADC. In principle, pre-2009 violations of antidoping rules may be treated as prior violations for the purposes of determining a period of ineligibility under the 2009 WADC. Under the CAS case law, the purpose of the sporting regulations under which the athlete had been sanctioned in 2003 and the applicable WADC were the same, i.e. the fight against doping in sports. Such objective would be entirely thwarted if one were to ignore the existence of a first offence under the pre-WADC rules in setting the sanction for a second offence under the current rules. Moreover, the fact that the athlete’s first violation may have taken place almost six years subsequent to the second offence has no relevance for the qualification of the latter as a second offense. It is clear from the 2009 WADC and from prior decisions of the CAS that in principle, decisions issued prior to the creation of the WADC can be treated as first violations when assessing the period of ineligibility following an antidoping violation sanctioned under the current WADC or its equivalents.

4. A case where the first violation occurred for ingesting a substance out of competition, which under the current prohibited list are prohibited only in-competition, has not yet been considered by other CAS Panels: Should a previous infraction, which has been finally determined by a sports arbitration tribunal, be treated as a first violation where the same conduct would not constitute a violation under existing antidoping rules? In legal terms, periods of ineligibility involve the application of the substantive law, and the principle of lex mitior requires that the athlete benefit from the least lenient penalty applicable, even if enacted after the commission of the original offence.

5. According to the UCI Rules, where there has been no acceptance or acknowledgement of an athlete’s culpability, periods of ineligibility are set to run from the date of a hearing in an antidoping case. The first instance hearing has to be the one who entered into the merits of the case and not the one that might have dismissed the case for lack of competence. This Panel, however, is of the view that – in principle – the period of ineligibility should only start to run from such hearing date on which a first instance panel looked into the substance of the alleged doping offence.


Jan Ullrich, is a German former professional road cyclist resident in Switzerland. Among other achievements, Ullrich was the winner of the 1997 Tour de France and the gold medalist in the men’s individual road race at the Sydney 2000 Summer Olympic Games. Prior to the events in question in 2006, Ullrich was a member of the T-Mobile professional cycling team, a member of Swiss Cycling, and a UCI license-holder.

In 2004, the Spanish Guardia Civil and the Investigating magistrate no. 31 of Madrid opened an investigation that has come to be known as “Operation Puerto.” Pursuant to this investigation, on May 23, 2006 searches were carried out on two Madrid apartments belonging to a Spanish physician, Dr. Eufemiano Fuentes. Documents and other materials were seized from the apartments, including evidence of possible doping offences by athletes.

The Guardia Civil drafted a report (Report no 116) dated June 27, 2006, which made reference to certain of the materials seized from the apartments and showed that the Athlete had contact with Dr Fuentes. As a consequence of Report no 116 the International Cycling Union (UCI) requested Swiss Cycling to open disciplinary proceedings against the Athlete. In October 2006 the Athlete resigned his membership from Swiss Cycling and announced his retirement from professional cycling.

However on 30 January 2010 the Disciplinary Chamber of Swiss Olympic decided to close the case and the investigations against the Athlete because Ullrich was no longer member of the Swiss Cycling and they had no jurisdiction after he retired.

Hereafter in March 2010 the UCI appealed the decision of Swiss Olympic with the Court of Arbitration for Sport (CAS). The UCI requested the Panel to annul and reform the decision of 30 January 2010 and to impose a lifetime ineligibility on the Athlete.

Supported with evidence from the Operation Puerto investigation, the UCI alleges that the Athlete violated the UCI Rules in the matter of the “use or attempted use of a prohibited substance or a prohibited method.” In particular, the UCI alleges that the Athlete engaged in blood doping (a prohibited method) and used several prohibited substances, including growth hormones, IGF-1, testosterone patches (PCH), EPO and a masking substance referred to as “magic power” that is said to destroy EPO in urine samples. The UCI also alleges that through the same actions, he violated the UCI Rules regarding “Tampering, or Attempted to tamper, with any part of Doping Control.”

The documentary evidence presented by the UCI shows that:
(1) Dr. Fuentes was engaged in the provision of doping services to athletes;
(2) Ullrich travelled in the vicinity of Dr. Fuentes' operations on multiple occasions, and evidence in Dr. Fuentes’ possession suggested that Ullrich was in personal contact with him on certain of those occasions;
(3) Ullrich paid Dr. Fuentes very substantial sums of money for services that have not been particularized; and
(4) a DNA analysis has confirmed that Ullrich’s genetic profile matches blood bags that appear to have been for doping purposes found in the possession of Dr. Fuentes. The evidence has been obtained from multiple sources and is internally consistent despite differences in its provenance. The evidence is probative and directly related to the question of whether an antidoping violation has occurred.

Given the volume, consistency and probative value of the evidence presented by the UCI, and the failure of Ullrich to raise any doubt about the veracity or reliability of such evidence, this Panel is satisfied beyond its comfortable satisfaction that Ullrich engaged at least in blood doping in violation of Article 15.2 of the UCI Rules.

Therefore the Court of Arbitration for Sport decides on 9 February 2012 that:

1.) The appeal filed on 22 March 2010 by the International Cycling Union is partially upheld.
2.) The decision of the Disciplinary Chamber of Swiss Olympic dated January 30, 2010 is annulled.
3.) All cycling results achieved by Mr. Jan Ullrich on or after May 1, 2005 until his retirement are disqualified.
4.) Mr. Jan Ullrich shall be declared ineligible for a period of two (2) years to participate in any Event, as more particularly described in Article 320 of Part 14 (Anti-Doping) of the International Cycling Union’s Cycling Regulations, starting from August 22, 2011.
5.) This award is rendered with no other costs, except for the Court Office fee of CHF 500, which has already been paid by the International Cycling Union and which is to be retained by the Court of Arbitration for Sport.
6.) Mr. Jan Ullrich is ordered to pay a contribution to the legal costs of the International Cycling Union in the sum of CHF 10,000 (ten thousand Swiss francs).
7.) All other motions or prayers for relief are dismissed.

CAS 2011_A_2384 UCI vs Alberto Contador Velasco & RFEC

6 Feb 2012

CAS 2011/A/2384 Union Cycliste Internationale (UCI) v. Alberto Contador Velasco & Real Federación Española de Ciclismo (RFEC) & CAS 2011/A/2386 World Anti-Doping Agency (WADA) v. Alberto Contador Velasco & RFEC

Related case:
CAS 2012/A/3055 Riis Cycling vs Licence Commission of the UCI
October 11, 2013

Cycling
Doping (clenbuterol)
Food supplement contamination
Admissibility of the testimony of a protected witness
Admissibility of the polygraph examination
New evidence
Adverse analytical finding
Burden of proof (principle)
Balance of probability standard
Proof of negative fact
Meat contamination
Disciplinary sanction
Starting point of the period of ineligibility

1. The admission of anonymous witnesses potentially infringes upon both the right to be heard and the right to a fair trial of a party guaranteed by the European Convention of Human Rights and the Swiss Constitution since personal data, record of a witness and the right to ask questions are important elements of information to have in hand when testing the witness’ credibility. However, with respect to anonymous witness statements the Swiss Federal Tribunal stressed that their admission does not necessarily violate the right to a fair trial. According to the Swiss Federal Tribunal, if the applicable procedural code provides for the possibility to prove facts by witness statements, it would infringe the principle of the court’s power to assess the witness statements if a party was prevented from the outset from relying on anonymous witness statements. According to the Swiss Federal Court the right of a party to use anonymous witness statements must be nevertheless subject to strict conditions namely the witness must be concretely facing a risk of retaliations by the party he is testifying against if his identity was known, the witness must be questioned by the court itself which must check his identity and the reliability of his statements; and the witness must be cross-examined through an “audiovisual protection system”.

2. Based on the Panel’s powers to administrate proof under Art. 184 PILA, given the Appellants acceptance that the polygraph examination is admissible as evidence per se and taking into consideration the entry into force of the WADC, the results of the polygraph examination undergone by the athlete are admissible in the particular case,
the credibility of which must nonetheless be verified in light of all the other elements of proof adduced.

3. Under Article R51 of the CAS Code, an expert testimony on a specific issue requested by the Appellant has to be mentioned in the expert opinion included in the Appellant’s written submissions. Addressing questions to an expert on a specific issue not included in the expert opinion at the stage of the hearing is not allowed in principle under Article R56 of the CAS Code.

4. Considering that clenbuterol is a non threshold prohibited substance, the fact that the concentration is extremely low does not have any effect on the result. It is therefore undisputed given the analytical reports made by the Laboratory and the confirmation of the adverse analytical finding by the B Sample that the athlete has committed an anti-doping rule violation and that the Appellants have met the standard of proof.

5. Pursuant to the UCI ADR and according to the established CAS jurisprudence, once an adverse analytical finding has been established the burden of proof shifts to the athlete who has to establish on the balance of probabilities in order to escape a sanction or to obtain a reduction of the sanction, how the prohibited substance entered his/her system and that he/she in an individual case bears no fault or negligence, or no significant fault or negligence.

6. For the Panel to be satisfied that a means of ingestion is demonstrated on a balance of probability simply means, in percentage terms, that it is satisfied that there is a 51% chance of it having occurred. The athlete thus needs to show that one specific way of ingestion is marginally more likely than not to have occurred.

7. Under Art. 8 of the Swiss Civil Code (CC), unless the law provides otherwise, each party must prove the facts upon which it is relying to invoke a right, thereby implying that the case must be decided against the party that fails to adduce such evidence. A valid contestation of facts needs to be specific, i.e. it must be directed and attributable to an individual fact submitted by the party bearing the burden of proof. According to the doctrine, the threshold for meeting such an obligation to specify the contestation is – under normal circumstances – rather low, since it must be avoided that the prerequisites for contesting an allegation result in a reversal of the burden of proof. Nevertheless, there are exceptions to this low threshold. The exceptions concern cases in which a party is faced with a serious difficulty in discharging its burden of proof (“état de nécessité en matière de preuve”, “Beweisnotstand”. This is the case whenever a party needs to prove “negative facts”. In this respect, the Swiss Federal Tribunal makes it clear that difficulties in proving “negative facts” result in a duty of cooperation of the contesting party who must cooperate in the investigation and clarification of the facts of the case. However, the above difficulties do not lead to a re-allocation of the risk if a specific fact cannot be established. Instead, this risk will always remain with the party having the burden of proof.

8. The athlete can only succeed in discharging his burden of proof by proving that (1) in his particular case meat contamination was possible and that (2) other sources from which the Prohibited Substance may have entered his body either do not exist or are less likely. The latter involve a form of negative fact that is difficult to prove for the athlete and which requires the cooperation of the Appellants. Thus, it is only if the theory put forward by the Athlete is deemed the most likely to have occurred among several scenarios, or if it is the only possible scenario, that the Athlete shall be considered to have established on a balance of probability how the substance entered his system, since in such situations the scenario he is invoking will have met the necessary 51% chance of it having occurred. Unlike certain other countries, notably outside Europe, Spain is not known to have a contamination problem with clenbuterol in meat. Furthermore, no other cases of athletes having tested positive to clenbuterol allegedly in connection with the consumption of Spanish meat are known. As a result, no established facts that would elevate the possibility of meat contamination to an event that could have occurred on a balance of probabilities has been established.

9. Pursuant to the UCI ADR, the period of ineligibility shall be two years for a first anti-doping rule violation. If none of the conditions for eliminating or reducing the period of ineligibility are applicable – in particular because the exact contaminated supplement is unknown and the circumstances surrounding its ingestion are equally unknown – the period of ineligibility shall not be reduced. Moreover, the athlete is automatically disqualified from the competition in the course of which he was tested. In addition, the results obtained in all competitions the athlete participated as from the date when the ineligibility period is deemed to have begun are also disqualified.

10. According to the UCI ADR where there have been substantial delays in the hearing process or other aspects of Doping Control not attributable to the License-Holder, the Panel is entitled to fix the start of the period of ineligibility at an earlier date commencing as early as the sample collection. In addition the provisional suspension imposed and respected by the licence-holder must be deducted from the period of ineligibility.


In August 2010 the International Cycling Union (UCI) has reported an anti-doping rule violation against the Spanish cyclist Alberto Contador after his A and B samples tested positive for the prohibited substance Clenbuterol in a low concentration.

On 14 February 2011 the Royal Spanish Cycling Federation (RFEC) decided to acquit the Athlete based solely on the notification of the test results and the evidence filed by the Athlete. Here the UCI and the World Anti-Doping Agency (WADA) did not provide the documentary and scientific evidence to the examining judge.

Hereafter in March 2011 both UCI and WADA appealed the RFEC decision with the Court of Arbitration for Sport (CAS). The UCI and WADA requested the Panel to set aside the RFEC decision of 14 February 2011 and to impose a 2 year period of ineligibility on the Athlete.

In this case the Athlete objected to the admission of an anonymous witness statement filed by WADA while WADA objected to the admission of new evidence filed by the Athlete.

The UCI and WADA argued that the Athlete has the burden of proof to establish how the prohibited substance entered his system on a balance of probability.

The Panel notes that it is not in dispute that the UCI and WADA successfully established that the Athlete committed an anti-doping rule violation. Neither is it disputed that in order for the Athlete to escape a two-year sanction, he must establish, on a balance of probability:
- how the Prohibited Substance entered the Athlete’s system; and
- that he bears no fault or negligence, or no significant fault or negligence.

The Panel considered and weighted the evidence in this case and holds that the meat contamination scenario and blood transfusion theory are a possible explanation for the presence of clenbuterol in the Athlete’s Sample. However, in light of all the evidence adduced, the Panel finds it is very unlikely to have occurred. Further the Panel concludes that the Athlete’s positive test for clenbuterol is more likely to have been caused by the ingestion of a contaminated food supplement than by a blood transfusion or the ingestion of contaminated meat. This does not mean that the Panel is convinced beyond reasonable doubt that this scenario of ingestion of a contaminated food supplement actually happened.

Therefore the Court of Arbitration for Sport decides on 6 February 2012 that:

1.) The appeals filed by the Union Cycliste Internationale on 24 March 2011 and by the World Anti-Doping Agency on 29 March 2011 against Mr Contador and the Real Federación Española de Ciclismo concerning the decision of the Comité Nacional de Competicion y Disciplina Deportiva of the Real Federación Española de Ciclismo dated 14 February 2011 are partially upheld.
2.) The decision of the Comité Nacional de Competicion y Disciplina Deportiva of the Real Federación Española de Ciclismo dated 14 February 2011 is set aside.
3.) Mr Contador is sanctioned with a two-year period of ineligibility starting on 25 January 2011. The period of the provisional suspension will be credited.
4.) Mr Contador is disqualified from the Tour de France 2010 with all of the resulting consequences including forfeiture of any medals, points and prizes.
5.) Mr Contador is disqualified of the results of all the competitions he participated in after 25 January 2011 including forfeiture of any medals, points, and prizes.
6.) (…).
7.) All other or further claims save for the fine issue pursuant to Article 326 of the UCI Anti-Doping Regulations which remains to be decided in a separate award, are dismissed.

CAS 2003_A_447 Anna Stylianou vs FINA

30 Jan 2004

CAS 2003/A/447 Anna Stylianou v/ FINA

On 29 August 2002 the Cyprus Amateur Swimming Association decided to impose a 1 year period of ineligibility on the minor Cypriot swimmer Anna Stylianou (16) after her sample tested positive for the prohibited substance 19-norandrosterone (Nandrolone).

After deliberations the case was referered to the International Swimming Federation (FINA) and 19 February 2003 the FINA Doping Panel decided to impose a 4 year period of ineligibility on the Athlete.

Hereafter the Athlete appealed the FINA decision with the Court of Arbitration for Sport (CAS).

The Athlete requested the Panel for a reduced sanction and argued that the FINA decision of 19 February 2003 is bases on a misinterpretation of the FINA Doping Rules. Also the Athlete asserted that the FINA decision is neither substantiated nor clear. She admitted the violation and denied the intentional use of the prohibited substance.

The Athlete explained that she had purchased and used three supplements recommended by her coach and she and her doctor checked the labels of these products before using. Analysis of two supplements revealed no prohibited substance. Analyisis of the third supplement Inosine was not possible due she had used all capsules, the supplement was not available anymore in Cyprus and it was withdrawn from the market. She concluded that these capsules were the source of the positive test.

FINA contended that the Athlete committed the anti-doping rule violation, she acted with negligence and failed to establish that the supplement Inosine was the source of the positive test. In accordance with the new FINA Doping Control Rules FINA accepted to apply in favor of the Athlete and to reduce the sanction from 4 years to a 2 year period of ineligibility.

The Panel holds that Athlete accepted the test results and that a 2 year period of ineligibility is the appropriate sanction in this case. The Panel finds that FINA failed to show cause as to why the Athlete bears No Significant Fault or Negligence. There are no exceptional circumstances in this case, the Athlete acted negligently with her supplements and she failed to establish how the substance entered her system.

The Panel considers that the reduction of the sanction by 2 years is a de jure consequence of the adoption of the Amended Code by FINA. Therefore, the Appellant did not obtain the reduction of her ineligibility by reason of her pleadings.

Therefore the Court of Arbitration for Sport decides on 30 January 2004 that:

1.) The appeal filed by the Athlete on March 17, 2003 is partially upheld.
2.) The decision of FINA dated February 19, 2003 is hereby amended:
- a) A term of ineligibility of two years is imposed on the Athlete, commencing as of June 16, 2002.
- b) All results achieved by the Athlete during the period from June 16, 2002 until July 2, 2002 shall be deemed cancelled.
3.) This award is rendered without costs, except for the Court Office fee of CHF 500.00 (Five Hundred Swiss Francs) already paid by the Appellant, which shall be retained by the CAS.
4.) Each party shall bear its own respective costs.

Inhaled beta2 agonists and performance in competitive athletes

1 Jul 2006

Inhaled beta2 agonists and performance in competitive athletes / W. Kindermann, T Meyer. - (British Journal of Sports Medicine 40 (2006) Supplement 1 (July) ; p. 43-47).
- PMID: 16799103.
- PMCID: PMC2657501.
- DOI: 10.1136/bjsm.2006.027748


Abstract:

OBJECTIVES:
To provide an overview of the current literature on the use of inhaled beta2 agonists in non-asthmatic competitive athletes, and to assess the performance enhancing effect of inhaled beta2 agonists.

METHODS:
Review of the literature.

RESULTS:
Twenty randomised, placebo controlled studies (19 double blind, one single blind) were located. Only three studies reported a performance enhancing effect of inhaled beta2 agonists. However, methodological shortcomings were most likely responsible for these findings (for example, non-elite athletes, inconsistent results in different tests, subgroups with above-average responsiveness).

CONCLUSIONS:
This review reveals that there is no ergogenic potential of inhaled beta2 agonists in non-asthmatic athletes. In view of the epidemiology of asthma in athletes and the considerable workload involved in provision of therapeutic use exemptions the inclusion of inhaled beta2 agonists on the list of prohibited substances should be reconsidered.

Pharmaceutical treatment of asthma symptoms in elite athletes - doping or therapy

11 Dec 2007

Pharmaceutical treatment of asthma symptoms in elite athletes – doping or therapy? / Vibeke Backer, T. Lund, L. Pedersen. - (Scandinavian Journal of Medicine & Science in Sports 17 (2007) 6 (December) ; p. 615-622).
- PubMed PMID: 18093034.
- DOI: 10.1111/j.1600-0838.2007.00711.x


Abstract:

Asthma, exercise‐induced bronchoconstriction, and airway hyper‐responsiveness are often found in elite athletes, perhaps as a consequence of their sport or maybe because asthma is a common disorder in young adults. Inhaled β2‐agonists (IBA) are frequently used in elite athletes, but due to regulations introduced by the International Olympic Committee, the use of anti‐asthmatic therapy might change. Drugs that make ergogenic effect persist are prohibited in all athletes, whether or not they take part in competitions and systemic steroids and β2‐agonists are among such drugs. On the other hand, opinion is more divided about the use of inhaled corticosteroids (ICS) and IBA. In humans, no effect has been found on the oxygen uptake, performance or distance run with therapeutic doses of IBA, either in asthmatics or non‐asthmatics, whereas others report an ergogenic effect and better lung function of high doses of a β2‐agonist in non‐asthmatics. Anti‐asthmatic treatment is necessary for asthmatics, but should not be used by non‐asthmatic elite athletes due to both possible systemic effects and furthermore, side effects of both ICS and IBA.

β₂-Agonists and physical performance: a systematic review and meta-analysis of randomized controlled trials

1 Jan 2011

β₂-Agonists and physical performance: a systematic review and meta-analysis of randomized controlled trials / Babette M. Pluim, Olivier de Hon, J. Bart Staal, Jacqueline Limpens, Harm Kuipers, Shelley E. Overbeek, Aeilko H. Zwinderman, Rob J.P.M. Scholte. - (Sports Medicine 41 (2001) 1 (January) p. 39-57).
- PMID: 21142283.
- DOI: 10.2165/11537540-000000000-00000


Abstract:

Inhaled β₂-agonists are commonly used as bronchodilators in the treatment of asthma. Their use in athletes, however, is restricted by anti-doping regulations. Controversies remain as to whether healthy elite athletes who use bronchodilators may gain a competitive advantage.

The aim of this systematic review and meta-analysis is to assess the effects of inhaled and systemic β₂-agonists on physical performance in healthy, non-asthmatic subjects. To this end, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to August 2009. Reference lists were searched for additional relevant studies. The search criteria were for randomized controlled trials examining the effect of inhaled or systemic β₂-agonists on physical performance in healthy, non-asthmatic subjects. Two authors independently performed the selection of studies, data extraction and risk of bias assessment. Parallel-group and crossover trials were analysed separately. Mean difference (MD) and 95% confidence intervals were calculated for continuous data and, where possible, data were pooled using a fixed effects model.

Twenty-six studies involving 403 participants (age range 7-30 years) compared inhaled β₂-agonists with placebo. No significant effect could be detected for inhaled β₂-agonists on maximal oxygen consumption (VO₂(max)) [MD -0.14 mL · kg⁻¹ · min⁻¹; 95% CI -1.07, 0.78; 16 studies], endurance time to exhaustion at 105-110% VO₂(max) (MD -1.5 s; 95% CI -15.6, 12.6; four studies), 20-km time trial duration (MD -4.4 s; 95% CI -23.5, 14.7; two studies), peak power (MD -0.14 W · kg⁻¹; 95% CI -0.54, 0.27; four studies) and total work during a 30-second Wingate test (MD 0.80 J · kg⁻¹; 95% CI -2.44, 4.05; five studies). Thirteen studies involving 172 participants (age range 7-22 years) compared systemic β₂-agonists with placebo, with 12 studies involving oral and one study involving intravenous salbutamol. A significant effect was detected for systemic β₂-agonists on endurance time to exhaustion at 80-85% VO₂(max) (MD 402 s; 95% CI 34, 770; two studies), but not for VO₂(max) (placebo 42.5 ± 1.7 mL · kg⁻¹ · min⁻¹, salbutamol 42.1 ± 2.9 mL · kg⁻¹ · min⁻¹, one study), endurance time to exhaustion at 70% VO₂(max) (MD 400 s; 95% CI -408, 1208; one study) or power output at 90% VO₂(max) (placebo 234.9 ± 16 W, salbutamol 235.5 ± 18.1 W, one study). A significant effect was shown for systemic β₂-agonists on peak power (MD 0.91 W · kg⁻¹; 95% CI 0.25, 1.57; four studies), but not on total work (MD 7.8 J · kg⁻¹; 95% CI -3.3, 18.9; four studies) during a 30-second Wingate test. There were no randomized controlled trials assessing the effects of systemic formoterol, salmeterol or terbutaline on physical performance.

In conclusion, no significant effects were detected for inhaled β₂-agonists on endurance, strength or sprint performance in healthy athletes. There is some evidence indicating that systemic β₂-agonists may have a positive effect on physical performance in healthy subjects, but the evidence base is weak.

Reporting and managing elevated testosterone/epitestosterone ratios--novel aspects after five years' experience

1 Nov 2010

Reporting and managing elevated testosterone / epitestosterone ratios--novel aspects after five years' experience / Ute Mareck, Hans Geyer, Gregor Fußhöller, Anne Schwenke, Nadine Haenelt, Thomas Piper, Mario Thevis, Wilhelm Schänzer. - (Drug Testing and Analysis 2 (2010) 11-12 (November) ; p. 637-642).

  • PMID: 21204295
  • DOI: 10.1002/dta.234

Abstract:

The testosterone/epitestosterone (T/E) ratio was implemented as an indirect parameter for the detection of testosterone administration with an empirically established threshold value at T/E = 6. In 2005, the T/E reporting threshold was lowered from six to four.

Between 2005 and 2009, 63 510 doping control urine samples were analyzed in the Cologne laboratory. A total of 1442 specimens (2.3%) showed a T/E > 4; 80 (5.5%) of which were tested positive by means of isotope ratio mass spectrometry (IRMS); and most of which (68) originated from strength sport disciplines.

Specimens of high T/E ratio showed a much higher probability for being confirmed to contain exogenous testosterone using IRMS analysis than samples of low T/E values.

Considering the small number of adverse analytical findings triggered by lowering the T/E reporting threshold (978 urine specimens with T/E ratios between 4 and 6 yielded only 4 (0.4%) positive IRMS findings) and the known limitations of the T/E ratio as discriminating parameter (UGT2B17 polymorphism), the currently mandatory approach shows only marginal overall efficiency.

A more effective tool for the detection of the misuse of testosterone would be the implementation of individual reference ranges. Until athlete steroidal passports are available, it is suggested to exceed the threshold level for T/E from 4 to 6 and perform obligatory IRMS analysis for specimens showing T/E > 6. Further conditions triggering IRMS analysis could be suppressed luteinizing hormone (LH) values in males and disproportionate changes of relevant parameters in individual profiles evidently not resulting from ethanol consumption.

From population- to subject-based limits of T/E ratio to detect testosterone abuse in elite sports.

7 May 2007

From population- to subject-based limits of T/E ratio to detect testosterone abuse in elite sports / Pierre-Edouard Sottasa, Christophe Saudana, Carine Schweizer, Norbert Baume, Patrice Mangin, Martial Saugy. - (Forensic Science International 174 (2008) 2-3 ( 30 January) ; p. 166-172)

  • PubMed PMID: 17485185
  • DOI: 10.1016/j.forsciint.2007.04.001

Abstract:

In elite sports, indirect testing of testosterone abuse is mainly based on the testosterone over epitestosterone (T/E) ratio. Since this marker is characterized by a small ratio of intra- to inter-individual variation, it is surprising that current anti-doping strategy uses a screening test based on a population-based limit.

From a database of more than 15,000 steroid profiles obtained from routine controls, the collection of steroids profiles of 11 elite athletes followed during 2 years, and a longitudinal study involving 17 amateur athletes, 8 of which were orally administrated testosterone undecanoate pills, we selected 12 case studies to represent the possible scenarios to which the anti-doping laboratories are confronted.

Various detection strategies at the disposal of the laboratories are employed and discussed, including isotope ratio mass spectrometry (IRMS) analysis and a Bayesian interpretation of the T/E-time profile. The weak sensitivity versus specificity relation of a population-based limit for the T/E ratio is outlined.

As a result, we propose a Bayesian screening test whose T/E threshold progressively evolves from a population basis to a subject basis as the number of individual test results increases. We found that this screening test heightens drastically the capacity to detect testosterone abuse, at no additional financial and administrative expenses for anti-doping authorities.

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