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? / Vibeke Backer, T. Lund, L. Pedersen. - (Scandinavian Journal of Medicine & Science in Sports 17 (2007) 6 (December) ; p. 615-622).

• 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 / 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 / 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 / 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)

• 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.

Performance characteristics of a carbon isotope ratio method for detecting doping with testosterone based on urine diols : controls and athletes with elevated testosterone / epitestosterone ratios / Rodrigo Aguilera, Thomas Edward Chapman, Borislav Starcevic, C.K. Hatton, D.H. Catlin. - (Clinical Chemistry 47 (2001) 2 (February) ; p. 292-300)

• PMID: 11159778

Abstract

Background: Carbon isotope ratio methods are used in doping control to determine whether urinary steroids are endogenous or pharmaceutical.

Methods: Gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) was used to determine the delta(13)C values for 5 beta-androstane-3 alpha,17 beta-diyl diacetate (5 beta A), 5 alpha-androstane-3 alpha,17 beta-diyl diacetate (5 alpha A), and 5 beta-pregnane-3 alpha,20 alpha-diyl diacetate (5 beta P) in a control group of 73 healthy males and 6 athletes with testosterone/epitestosterone ratios (T/E) >6.

Results: The within-assay precision SDs for 5 beta A, 5 alpha A, and 5 beta P were +/- 0.27 per thousand, +/- 0.38 per thousand, and +/- 0.28 per thousand, respectively. The between-assay precision SDs ranged from +/- 0.40 per thousand to +/- 0.52 per thousand. The system suitability and batch acceptance scheme is based on SDs. For the control group, the mean delta(13)C (SD) values were -25.69 per thousand (+/- 0.92 per thousand), -26.35 per thousand (+/- 0.68 per thousand), and -24.26 per thousand (+/- 0.70 per thousand), for 5 beta A, 5 alpha A, and 5 beta P, respectively. 5 beta P was greater than 5 beta A and 5 alpha A (P <0.01), and 5 beta A was greater than 5 alpha A (P <0.01). The means - 3 SD were -28.46 per thousand, -28.39 per thousand, and -26.37 per thousand for 5 beta A, 5 alpha A, and 5 beta P, respectively. The maximum difference between 5 beta P and 5 beta A was 3.2 per thousand, and the maximum 5 beta A/5 beta P was 1.13. Three athletes with chronically elevated T/Es had delta(13)C values consistent with testosterone administration and three did not.

Conclusions: This GC-C-IRMS assay of urine diols has low within- and between-assay SDs; therefore, analysis of one urine sample suffices for doping control. The means, SDs, +/-3 SDs, and ranges of delta(13)C values in a control group are established. In comparison, testosterone users have low 5 beta A and 5 alpha A, large differences between 5 beta A or 5 alpha A and 5 beta P, and high 5 beta A/5 beta P and 5 alpha A/5 beta P ratios.

The 2008 Prohibited List International Standard : The World Anti-Doping Code / World Anti-Doping Agency (WADA). - Montreal : WADA, 2007.

- The official text of the Prohibited List shall be maintained by WADA and shall be published in English and French. In the event of any conflict between the English and French versions, the English version shall prevail.
- This List shall come into effect on 1 January 2008

The 2009 Prohibited List International Standard : The World Anti-Doping Code / World Anti-Doping Agency (WADA). - Montreal : WADA, 2008.

- The official text of the Prohibited List shall be maintained by WADA and shall be published in English and French. In the event of any conflict between the English and French versions, the English version shall prevail.
- This List shall come into effect on 1 January 2009

The 2010 Prohibited List International Standard : The World Anti-Doping Code / World Anti-Doping Agency (WADA). - Montreal : WADA, 2009.

- The official text of the Prohibited List shall be maintained by WADA and shall be published in English and French. In the event of any conflict between the English and French versions, the English version shall prevail.
- This List shall come into effect on 1 January 2010

CAS 2008/A/1608 International Association of Athletics Federations v/ Athletic Federation of Slovenia & Ms Helena Javornik

In April 2008 the International Association of Athletics Federations (IAAF) has reported an anti-doping rule violation against the Slovenian Athlete Helena Javornik after her A and B samples tested positive for the prohibited substance recombinant human erythropoietin (rhEPO).

However on 19 June 2008 the Athletic Federation of Slovenia (AFS) decided that the Athlete had not committed an anti-doping rule violation and that the imposed provisional suspension was invalid.

In first instance the AFS deemed that the analytical results of the Athlete’s sample did not establish the presence of a prohibited substance, since they didn’t fulfil the criteria set in the WADA Technical Document TD2007EPO.

Hereafter in July 2008 the IAAF appealed the Slovenian decision with the Court of Arbitration for Sport (CAS). The IAAF requested the Panel to set aside the Appealed Decision and to impose a 2 year period of ineligibility on the Athlete.

The IAAF rejected the grounds to declare the Athlete not guilty for a doping offence and considers the AFS decision to be erroneous and procedurally unsound. The IAAF contended that the tests results were valid, in accordance with the ISL and the relevant WADA Technical Document.

The Panel assessed and addressed the evidence in this case and concludes that the IAAF has established, to the comfortable satisfaction of the Panel, that the anti-doping rule violation has been committed. The Panel concludes that the analyses of the A sample and of the B sample of the Athlete’s urine show positive results. Such results cannot be held to amount to falsely positive results.

Further the Panel finds that no departures occurred and, in any case, that the validity of the analytical findings in the Athlete’s sample was not undermined. Also the Panel holds, in any case, that it has been demonstrated that the collection, storage and transport conditions of the Athlete’s sample did not undermine the validity of adverse analytical finding established in the Seibersdorf Lab.

Therefore the Court of Arbitration for Sport decides on 13 March 2009 that:

1.) The appeal filed by the International Association of Athletics Federations against the decision issued on 19 June 2008 by the Antidoping Commission of the Athletic Federation of Slovenia is upheld.

2.) The decision adopted on 19 June 2008 by the Antidoping Commission of the Athletic Federation of Slovenia is set aside.

3.) Ms Helena Javornik is found guilty of an anti-doping rule violation under IAAF Competition Rule 32.2(a) and is declared ineligible for a period of 2 years commencing on 11 June 2008.

4.) All other prayers for relief are dismissed.

5.) This award is pronounced without costs, except for the court office fee of CHF 500 (five hundred Swiss Francs) paid by the International Association of Athletics Federations, which is retained by the CAS.

6.) Each party shall bear its own costs.