WADA ... Olympics ...

[Michael Scally MD]

Metabolism of Steroids and Sport Drug Testing

Anabolic androgenic agents (AAS) belong to the most frequently reported group of prohibited substances in sports [1] and have been misused in sports for several decades. The ongoing misuse of AAS challenges doping control laboratories to find new markers and more sensitive analytical methods for detection. This might seem like a never-ending story and leads to the question: what makes AAS so interesting for athletes, and how can doping control laboratories improve their approach in detecting these compounds? …

Nowadays, the most significant target for AAS detection is not always the most abundant metabolite, but metabolites which can be detected in urine for the longest period of time after administration of the steroid, so-called long-term metabolites (LTM). The discovery of LTM of AAS, along with the progress in analytical instrumentation, has led to a significant improvement of AAS testing in sports. Considering the fact, that LTM sometimes can be detected in urine for several weeks after application, this is an important achievement in the doping control field.

In this paper, three examples demonstrate the progress in detection of some AAS using their LTMs.

Stojanovic BJ, Göschl L, Forsdahl G, Günter G. Metabolism of steroids and sport drug testing [published online ahead of print, 2020 May 15]. Bioanalysis. 2020;10.4155/bio-2020-0077. doi:10.4155/bio-2020-0077 https://www.future-science.com/doi/10.4155/bio-2020-0077

 

[Michael Scally MD]

[OA] Are nutritional supplements a gateway to doping use in competitive team sports? The roles of achievement goals and motivational regulations.

Objectives: The study investigated the moderating role of achievement goals and motivation regulations on the association between self-reported nutritional supplement (NS) use, doping likelihood, and self-reported doping behaviour among competitive athletes.

Method: Four hundred and ninety seven competitive team sport athletes (64% males; M age=23.54 years, SD=5.75) completed anonymous questionnaires measuring self-reported use of prohibited substances and licit NS; beliefs about the "gateway" function of NS; achievement goals; and motivational regulations.

Results: Hierarchical linear regression analysis showed that self-reported doping was associated (Adjusted R2=33%) with NS use, a stronger belief that NS use acts as a gateway to doping, amotivation, controlled motivation, mastery approach, and performance avoidance goals. Higher likelihood to use doping substances in the future was associated (Adjusted R2=41.7%) with current NS use, stronger belief that NS act as a gateway to doping, autonomous motivation, and performance avoidance goals.

A series of moderated regression analyses showed that NS use significantly interacted with mastery approach, mastery avoidance, performance avoidance goals, autonomous motivation controlled motivation, and with amotivation in predicting self-reported doping. Finally, NS use significantly interacted with mastery approach goals, performance avoidance goals, and controlled motivation in predicting future doping likelihood.

Conclusions: Achievement goals and motivational regulations are differentially associated with both doping likelihood and self-reported doping, and may account for the observed association between self-reported NS use and doping substances; thus, providing an alternative explanation to the "gateway hypothesis" that emphasizes the role of motivation.

Barkoukis V, Lazuras L, Ourda D, Tsorbatzoudis H. Are nutritional supplements a gateway to doping use in competitive team sports? The roles of achievement goals and motivational regulations. J Sci Med Sport. 2020;23(6):625‐632. doi:10.1016/j.jsams.2019.12.021 https://www.jsams.org/article/S1440-2440(19)31239-3/fulltext

 

[Michael Scally MD]

McLaren Independent Weightlifting Investigation
Independent Investigator Report to The Oversight and Integrity Commission of International Weightlifting Federation
https://mclarenweightliftingenquiry.com/wp-content/themes/mclarenweightlifitingenquiry/assets/mclaren-independent-investigator-report-iwf-final.pdf

Key Findings

1. Dr. Aján’s autocratic authoritarian leadership of the International Weightlifting Federation resulted in a dysfunctional, ineffective oversight of the organisation by the Executive Board, which had an ill-informed understanding of the organisation. This was achieved through various control mechanisms. As a consequence, Dr. Aján disabled anyone other than himself from understanding the overall affairs of the IWF.

2. The foundational control mechanism used by Dr. Aján was the tyranny of cash. Cash collected, cash withdrawn, and cash unaccounted for, which Dr. Aján was the sole collector. The primary sources of this cash were doping fines paid personally to the President and cash withdrawals of large amounts from the IWF’s accounts, usually withdrawn before major competitions or IWF congresses. It is absolutely impossible to determine how much of the cash collected or withdrawn was used for legitimate expenses. The McLaren Independent Investigation Team has determined that $10.4 million USD is unaccounted for.

3. Weightlifting has a history of use of performance enhancing drugs. Over 600 lifters in the past decade have tested positive. While Dr. Aján has impermissibly interfered with the IWF Anti-Doping Commission, the real problem is the culture of doping that exists in the sport. The investigation uncovered 40 positive Adverse Analytical Findings hidden in the IWF records. This includes gold and silver medalists who have not had their samples dealt with. This information has been passed on to WADA for further investigation.

4. HUNADO is not the cause of doping sample manipulation or hidden results. It has operated in compliance with WADA standards. The investigation found that the procedures followed by Doping Control Officer Barbara Kallo were correct and in accordance with the WADA Code. The source of antidoping issues that have plagued the IWF and sport of weightlifting lie elsewhere. HUNADO and its DCOs are not the cause of the positive testing results or the alleged influence on weightlifters to be tested.

5. The financial records are a jumble of incomplete and inaccurate figures distorted by a failure to accurately record cash expenditures and revenues and disclose hidden bank accounts by Dr. Aján.

6. The two most recent Electoral Congresses were rampant with vote buying for the President and senior level positions of the Executive Board, despite monitoring. Such actions are a fundamental violation of the sport’s By-Laws on Disciplinary and Ethics Procedures.

This Report will explain these key findings.

 

[Michael Scally MD]

McLaren Independent Weightlifting Investigation
Independent Investigator Report to The Oversight and Integrity Commission of International Weightlifting Federation
https://mclarenweightliftingenquiry.com/wp-content/themes/mclarenweightlifitingenquiry/assets/mclaren-independent-investigator-report-iwf-final.pdf

Key Findings

1. Dr. Aján’s autocratic authoritarian leadership of the International Weightlifting Federation resulted in a dysfunctional, ineffective oversight of the organisation by the Executive Board, which had an ill-informed understanding of the organisation. This was achieved through various control mechanisms. As a consequence, Dr. Aján disabled anyone other than himself from understanding the overall affairs of the IWF.

2. The foundational control mechanism used by Dr. Aján was the tyranny of cash. Cash collected, cash withdrawn, and cash unaccounted for, which Dr. Aján was the sole collector. The primary sources of this cash were doping fines paid personally to the President and cash withdrawals of large amounts from the IWF’s accounts, usually withdrawn before major competitions or IWF congresses. It is absolutely impossible to determine how much of the cash collected or withdrawn was used for legitimate expenses. The McLaren Independent Investigation Team has determined that $10.4 million USD is unaccounted for.

3. Weightlifting has a history of use of performance enhancing drugs. Over 600 lifters in the past decade have tested positive. While Dr. Aján has impermissibly interfered with the IWF Anti-Doping Commission, the real problem is the culture of doping that exists in the sport. The investigation uncovered 40 positive Adverse Analytical Findings hidden in the IWF records. This includes gold and silver medalists who have not had their samples dealt with. This information has been passed on to WADA for further investigation.

4. HUNADO is not the cause of doping sample manipulation or hidden results. It has operated in compliance with WADA standards. The investigation found that the procedures followed by Doping Control Officer Barbara Kallo were correct and in accordance with the WADA Code. The source of antidoping issues that have plagued the IWF and sport of weightlifting lie elsewhere. HUNADO and its DCOs are not the cause of the positive testing results or the alleged influence on weightlifters to be tested.

5. The financial records are a jumble of incomplete and inaccurate figures distorted by a failure to accurately record cash expenditures and revenues and disclose hidden bank accounts by Dr. Aján.

6. The two most recent Electoral Congresses were rampant with vote buying for the President and senior level positions of the Executive Board, despite monitoring. Such actions are a fundamental violation of the sport’s By-Laws on Disciplinary and Ethics Procedures.

This Report will explain these key findings.

Moments before powerlifters attempt a superhuman feat of strength, they like to hold a capsule of ammonia to their nose, snort deeply, and feel a huge jolt of adrenaline rip through their bodies. But it is going to take far more than smelling salts to revive weightlifting’s reputation after the publication of a truly eye-bulging independent investigation by the Canadian law professor Richard McLaren. Corruption. Cronyism. Cover-ups. Bribes. An omerta that would impress the five families. It’s all there in a 122-page report that leaves the reader feeling they have bathed in a fetid swamp. https://mclarenweightliftingenquiry.com/wp-content/themes/mclarenweightlifitingenquiry/assets/mclaren-independent-investigator-report-iwf-final.pdf

Think Fifa and double it. The IAAF and quadruple it. McLaren’s investigation found that more than $10m (around £7.9m) was unaccounted for in the books of the International Weightlifting Federation, that 40 doping positives were covered up and vote-buying to ensure the re-election of the former president Dr Tamas Ajan was rampant. And that was just for starters.

The Hungarian, a senior figure in the sport since 1976, also “ran the IWF as if it was his own personal fiefdom”, concluded McLaren, whose team also established that Ajan was “the sole person making all cash deposits into the IWF’s bank accounts” and “millions of dollars in cash withdrawals conducted by Ajan were never recorded”.

A confidential witness told McLaren’s investigation team that at one point Ajan even called up the head of the Albanian weightlifting federation and issued an ultimatum: pay a $100,000 fine for doping offences – in cash – or his team would not go to the Rio Olympics. Cue a comical scene involving four Albanian officials taking $25,000 each in cash on a road trip from Tirana to Budapest. At least Ajan gave them a receipt.

Other countries – including Russia and Romania – did not even get that. No wonder an expert in money laundering quoted in McLaren’s report described Ajan’s modus operandi as apparently “symptomatic of corruption or criminal activity”. Investigators also uncovered a deleted letter addressed to Ajan from the Azerbaijan National Olympic Committee’s president in 2016 – thanking him for delaying the doping suspensions of certain Azeri weightlifters so they could compete. Meanwhile, McLaren’s report notes the 2013 and 2017 presidential elections were “astonishingly bribery prone”, with Ajan securing his presidency “by paying member federations cash bribes ranging from $5,000-30,000 to vote for him and his team of cronies”.

It is astounding stuff. The question is, why did all this take so long to come out? ...

 

[Michael Scally MD]

Gene doping and genomic science in sports: where are we?

The misuse of sport-related gene transfer methods in elite athletes is a real and growing concern. The success of gene therapy in the treatment of hereditary diseases has been most evident since targets in gene therapy products can be used in healthy individuals to improve sports performance. Performing these practices threatens the sporting character of competitions and may pose potential health hazards.

Since the World Anti-Doping Agency pronouncement on the prohibition of such practices in 2003, several researchers have been trying to address the challenge of developing an effective method for the detection of genetic doping.

This review presents an overview of the published methods developed for this purpose, the advantages and limitations of technologies and the putative target genes. At last, we present the perspective related to the application of the detection methods in the doping control field.

López S, Meirelles J, Rayol V, et al. Gene doping and genomic science in sports: where are we? [published online ahead of print, 2020 Jun 19]. Bioanalysis. 2020;10.4155/bio-2020-0093. doi:10.4155/bio-2020-0093 https://www.future-science.com/doi/10.4155/bio-2020-0093

 

[Michael Scally MD]

 

[Michael Scally MD]

Screening for Twenty-Eight Target Anabolic-Androgenic Steroids in Protein Supplements Using QuEChERS

Anabolic-androgenic steroids (AASs) are very potent muscle builders, and professional sportsmen often take protein supplements to improve their performance. Several studies have emphasised that protein supplements may contain undeclared AASs banned by the International Olympic Committee/World Anti-Doping Agency.

The widespread occurrence and abuse of contaminated protein supplements is extremely dangerous because of their side effects. To minimise the chances of an unattended positive doping test or to avoid serious health problems, adequate screening methods for the detection of a wide range of steroids is essential.

To address this requirement, a rapid and effective modified QuEChERS (quick, easy, cheap, effective, rugged and safe) method was developed and validated to screen and quantify the simultaneous analysis of twenty-eight AASs in protein supplements using LC-MS/MS.

The validated method was applied to 198 protein supplements collected from on-line and, off-line markets, and direct purchase from overseas between 2019 and 2020. Of the 198 samples, two samples contained testosterone and stanozolol at concentrations of 0.27 μg/g and 0.023 μg/g, respectively. In addition, 5α-hydroxylaxogenin was detected for the first time in three products purchased in Korea from overseas.

The modified QuEChERS method was established and successfully applied to screen and determine AASs as a measure of continuous control and supervision in protein supplements.

Lee JH, Han JH, Min AY, Kim H, Shin D. Screening for twenty-eight target anabolic-androgenic steroids in protein supplements using QuEChERS extraction followed by liquid chromatography-tandem mass spectrometry [published online ahead of print, 2020 Jun 22]. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2020;1-12. doi:10.1080/19440049.2020.1773543 https://www.tandfonline.com/doi/abs/10.1080/19440049.2020.1773543?journalCode=tfac20

 

[Michael Scally MD]

Evaluation of Longitudinal Steroid Profiling with The Adams Adaptive Model for Detection of Transdermal, Intramuscular, and Subcutaneous Testosterone Administration

The steroidal module of the Athlete Biological Passport (ABP) has been used since 2014 for the longitudinal monitoring of urinary testosterone and its metabolites in order to identify samples suspicious for the use of synthetic forms of Endogenous Anabolic Androgenic Steroids (EAAS). Samples identified by the module may then be confirmed by Isotope Ratio Mass Spectrometry (IRMS) to clearly establish the exogenous origin of testosterone and/or metabolites in the sample.

To examine the detection capability of the steroidal ABP model, testosterone administration studies were performed with various doses and three routes of administration - transdermal, intramuscular and subcutaneous with fifteen subjects for each route of administration. Urine samples were collected before, during, and after administration and steroid profiles were analyzed using the steroidal ABP module in ADAMS. A subset of samples from each mode of administration was also analyzed by IRMS.

The steroidal ABP module was more sensitive to testosterone use than population-based thresholds and with high dose administrations there was very good agreement between the IRMS results and samples flagged by the module. However, with low dose administration the ABP module was unable to identify samples where testosterone use was still detectable by IRMS analysis. The testosterone/ epitestosterone (T/E) ratio was the most diagnostic parameter for longitudinal monitoring with the exception of low testosterone excreters for whom the 5α-androstane-3α, 17β-diol/epitestosterone (5αAdiol/E) ratio may provide more sensitivity.

Nair VS, Husk J, Miller GD, van Eenoo P, Crouch A, Eichner D. EVALUATION OF LONGITUDINAL STEROID PROFILING WITH THE ADAMS ADAPTIVE MODEL FOR DETECTION OF TRANSDERMAL, INTRAMUSCULAR, AND SUBCUTANEOUS TESTOSTERONE ADMINISTRATION [published online ahead of print, 2020 Jun 23]. Drug Test Anal. 2020;10.1002/dta.2885. doi:10.1002/dta.2885 https://onlinelibrary.wiley.com/doi/abs/10.1002/dta.2885

 

[Michael Scally MD]

[OA] Why are placebos not on WADA’s Prohibited List?

Highlights
· Placebos can increase performance.
· Two out of three criteria suffice to include a substance on WADA's Prohibited List: it enhances performance, it carries a health risk and it is against the 'spirit of sport'.
· Placebos respond to all criteria and should therefore be added to the Prohibited List.
· This reductio ad absurdum illustrates the need for a reform of the criteria for inclusion on the Prohibited List.

The placebo effect is a biological response to psychosocial environmental cues surrounding the use of inert or active substances or methods. Placebo effects can be exploited for performance enhancement purposes and their use is not forbidden in sport. WADA’s Code stipulates that at least two out of three criteria must be met to put something on the Prohibited List of substances and methods forbidden in sport.

These criteria are:
· Medical or other scientific evidence, pharmacological effect or experience that the substance or method, alone or in combination with other substances or methods, has the potential to enhance or enhances sport performance;
· Medical or other scientific evidence, pharmacological effect or experience that the use of the substance or method represents an actual or potential health risk to the athlete; and
· WADA’s determination that the use of the substance or method violates the ‘spirit of sport’ described in the introduction to the Code.

By looking at what is on the Prohibited List and by interpreting the discourse surrounding the ‘spirit of sport’ criterion I postulate that substances and methods with documented placebo effects on performance fully meet the inclusion criteria and should therefore be included on the Prohibited List.

Such reductio ad absurdum further illustrates the limits of WADA’s three criteria framework for inclusion of methods and substances on the Prohibited List and reinforces the calls for a change in the way the Prohibited List is established and maintained.

Kayser B. Why are placebos not on WADA’s Prohibited List? Performance Enhancement & Health 2020;8:100163. Why are placebos not on WADA’s Prohibited List? - ScienceDirect

 

[Michael Scally MD]

Evaluation of Epiandrosterone As A Long-Term Marker of Testosterone Use

Identification and evaluation of long-term markers is crucial in prolonging the detection window for anabolic steroid abuse in sport. Recently, sulfoconjugated epiandrosterone was identified as a potential long-term marker for the abuse of certain endogenous anabolic agents, including testosterone, which continues to be widely used as a performance enhancing agent in sport.

To evaluate the applicability of epiandrosterone sulfate as a marker for testosterone use, administration studies were conducted with multiple modes of testosterone administration - transdermal, intramuscular, and subcutaneous. A modified sample preparation method was used to collect both glucuronidated and sulfoconjugated analytes of interest. Carbon isotope ratio measurements from the administration studies are presented here.

Epiandrosterone was less effective than the conventionally used target compounds for detection of the low dose application (transdermal gel). With intramuscular administration, epiandrosterone was more diagnostic than with transdermal administration, but it did not prolong the detection window more than the conventional target compounds.

With subcutaneous administration, the doses administered to the subjects were varied and the effect in the epiandrosterone values was dependent on the magnitude of the dose administered.

Epiandrosterone does not appear to be a useful marker in the detection of low dose testosterone administration. It is responsive to higher dose administration, but it does not provide extension of the detection window relative to conventional target compounds.

Nair VS, Doman CE, Morrison MS, et al. EVALUATION OF EPIANDROSTERONE AS A LONG-TERM MARKER OF TESTOSTERONE USE [published online ahead of print, 2020 Jul 22]. Drug Test Anal. 2020;10.1002/dta.2903. doi:10.1002/dta.2903 Error - Cookies Turned Off

 

[Michael Scally MD]

"Doing What Is Right and Doing It Right": A Mapping Review of Athletes' Perception of Anti-Doping Legitimacy

Highlights
· Legitimacy is an important yet underestimated concept in anti-doping research.
· Mapping review identified 39 empirical studies with athletes on anti-doping legitimacy.
· Better conceptual clarity and a unified framework for legitimacy perception is needed.
· Athletes agreed on the need for rigorous doping control to protect clean sport.
· Athletes questioned the effectiveness and fairness of doping testing and sanctions.
· Attention to implementation, transparency and better communication is warranted.

Background: The creation of the World Anti-Doping Agency in 1999 and the first implementation of the Anti-Doping Code in 2004 established institutional and legal level legitimacy for the anti-doping movement. Subsequently, a distinct line of research examining athletes' perceptions of anti-doping has emerged. This study aims to review the literature on legitimacy via athletes' perceptions of the underpinning values, fairness and effectiveness of anti-doping rules and procedures.

Methods: A systematic mapping review with computerised literature search of seven databases (EBSCOHost, PubMed, Ingenta, ScienceDirect, SCOPUS, SPORTDiscuss and Google Scholar) was used, followed by hand-search of reference lists and relevant journals. Based on Tyler's (2006) psychological components of legitimacy (proper, just, and appropriate), a bespoke conceptual map and analytical framework was developed and employed for retrospective categorisation.

Results: Thirty-nine studies representing 15,434 participants met the inclusion criteria. About half of the eligible studies discussed legitimacy components without identifying them as such.

Identification of studies for legitimacy concepts faced considerable ambiguity in measures and interpretation, particularly in distinguishing between elements of being 'just' and 'appropriate'. Single focus on one aspect was rare but only 11 of the 39 studies included all three elements of perceived legitimacy.

Overall, athletes agreed that anti-doping is 'doing the right thing' to protect clean sport but their views differed on whether the existing anti-doping system is effective and implemented fairly (i.e., 'doing anti-doping in a right way'). Owing to the ad hoc measurements and diverse methodology, quantitative meta-analysis was not feasible.

Conclusion: Legitimacy is an important concept in anti-doping. Attention to globally equal and fair implementation of testing and sanctioning is warranted. Legitimacy perceptions can be improved by better communication from anti-doping organisations to highlight progress with detection, greater transparency and explicit support for athletes who were affected by doping. Future research requires standardised conceptual framework and measures.

Woolway T, Lazuras L, Barkoukis V, Petróczi A. "Doing What Is Right and Doing It Right": A Mapping Review of Athletes' Perception of Anti-Doping Legitimacy [published online ahead of print, 2020 Jul 29]. Int J Drug Policy. 2020;84:102865. doi:10.1016/j.drugpo.2020.102865 “Doing What Is Right and Doing It Right”: A Mapping Review of Athletes' Perception of Anti-Doping Legitimacy - ScienceDirect

 

[Michael Scally MD]

Determination of Anabolic Steroids in Dried Blood Using Microsampling and Gas Chromatography-Tandem Mass Spectrometry: Application to a Testosterone Gel Administration Study

Highlights
· Nine anabolic steroids are separated within 6.4 min and are detectable at 50 fg
· VAMS dried blood exhibits good stability and better recovery over spotting card
· Quantification of testosterone between serum and VAMS dried blood is in agreement
· Doping with micro-dose testosterone can be caught by using 20 μL of dried blood

Anabolic androgenic steroids (AAS) have been the most commonly abused substances taken by not only professional sportsmen but also recreational bodybuilders. The detection of micro-dose testosterone (T) misuse is particularly challenging as it possesses pseudo-endogenous origin and is sometimes impossible to be identified in urine samples.

Dried blood (DB) obtained by finger pricking has been proven to be an alternative matrix for better correlating to physiological responses. Moreover, the introduction of the volumetric absorptive microsampling (VAMS) technology allows overcoming some major limitations of spotting blood onto a filter paper card.

In this work, a fast and sensitive GC-MS/MS method was developed and validated for the quantification of AAS in DB collected by means of VAMS. T and the eight top abused synthetic AAS, namely nandrolone, boldenone, mesterolone, drostanolone, metenolone, metandienone, oxandrolone, and dehydrochloromethyl T were selected as the target analytes.

The method based on VAMS exhibited good precision, accuracy as well as stability, and superior extraction recoveries over the punched DB spots reported in the literature. The chromatographic separation was achieved within 6.4 min and the detection limit is as little as 50 fg (i.e. able to detect 0.10 ng mL−1 in 20 μL of DB).

Confirmed by forty real blood samples, the Deming regression and Bland-Altman analysis revealed that the VAMS DB could be employed for quantifying blood T level in agreement with using the serum specimen. The feasibility of the method was then successfully proven by the analysis of samples collected from a three-arm T administration trial.

Our results highlighted that DB total T was a sensitive indicator for identifying transdermal micro-dosing of T. In the groups of receiving T gel administration, T concentrations could rise up to ten times higher than the baseline at 9 h after the application. As a future step, this approach is being expanded to a large cohort screening of bodybuilders at gym and ultimately may allow universal applications on monitoring sports drug misuse.

Chang WC-W, Cowan DA, Walker CJ, Wojek N, Brailsford AD. Determination of anabolic steroids in dried blood using microsampling and gas chromatography-tandem mass spectrometry: Application to a testosterone gel administration study. Journal of Chromatography A 2020:461445. Determination of anabolic steroids in dried blood using microsampling and gas chromatography-tandem mass spectrometry: Application to a testosterone gel administration study - ScienceDirect

 

[Michael Scally MD]

WADA’s Prohibited List from The Perspective of Elite Athletes

WADA’s Prohibited List is a cornerstone of the World Anti-Doping Code and the key to managing “doping” in sport. The List potentially plays a role in all competitive athletes’ lives. Athletes are personally responsible for not consuming any prohibited substances, and the proportion of inadvertent/unintentional doping cases is significant.

The article provides insight into 645 elite athletes’ perceptions and understandings of the List and how the personal responsibility for not consuming any prohibited substances affects athletes’ daily lives. Results showed that almost all elite athletes supported the compilation of a prohibited list.

Simultaneously, a majority reported not knowing exactly what was included, while some athletes were not satisfied with the selection of substances on the List. It is illustrated how many athletes worried about unintentionally consuming prohibited substances. Particularly female athletes and athletes frequently tested were more likely to worry often about what substances they consumed.

The article discusses ambivalences; differences between athletes; legitimacy; and unintended effects. Further, it discusses limitations of the results and how subsequent global policy developments might contribute to an increase in athletes’ worries while other initiatives or developments might significantly reduce these worries. Prospective adjustments with the 2021 WADA Code are also considered.

The study suggests that most athletes support anti-doping as a principle. However, for some athletes the List induces worries of unintentional doping. It is concluded that the compilation of a prohibited list in sport has legitimacy among athletes, but its unintended effects raise some concerns.

Overbye M. WADA’s Prohibited List from the perspective of elite athletes. Performance Enhancement & Health 2020:100165. WADA’s Prohibited List from the perspective of elite athletes - ScienceDirect

 

[Michael Scally MD]

[OA] Risk and Enabling Environments in Sport: Systematic Doping as Harm Reduction

Doping and the use of performance enhancing drugs (PEDs) are often considered and discussed as a separate issue from other types of substance use, by sporting bodies, politicians, the media, and athletes who use drugs themselves.

However, perceptions and understandings of substance use in the sport and fitness world are directly related to those of substance use in the non-sport world. One way the gap between sport and non-sport substance use research can be bridged is to consider sport risk and enabling environments.

Similar to non-sport contexts and drug use, it is important to analyse the environments in which doping occurs. This approach allows us to examine the dynamic interplay between risk and enabling factors, as the enabling environment shifts in response to changes produced in the risk environment, and vice versa. There are models of sport environments that have proven effective at both enabling doping by athletes and reducing harms to athletes: systematic doping.

This article will use secondary literature in order to review and analyse known cases of systematic doping through the risk and enabling environment frameworks. We argue that these systems responded to anti-doping in ways that protected athletes from the risk factors established by anti-doping policy and that athletes suffered most when these systems were revealed, exposing athletes to the full range of doping harms. Further, we argue that risks within these systems (i.e. extortion, bullying) resulted from the broader prohibitive sport environment that forces doping underground and allows such abuses to occur.

Henning A, McLean K, Andreasson J, Dimeo P. Risk and enabling environments in sport: Systematic doping as harm reduction [published online ahead of print, 2020 Aug 4]. Int J Drug Policy. 2020;102897. doi:10.1016/j.drugpo.2020.102897 Risk and enabling environments in sport: Systematic doping as harm reduction - ScienceDirect

 

[Michael Scally MD]

[OA] Perspectives and Strategies for Anti-Doping Analysis

Current doping testing in sports provides identification, often followed by quantitation, of banned substances and methods from biological samples collected from athletes in- and out-of-competition. The compounds (approximately 250) and methods included into the World Anti-Doping Agency (WADA) list of prohibited substances and methods [1] as part of the World Anti-Doping Code [2] are classified in the S0–S9 and M1–M3 categories, respectively, while alcohol (P1) and β-blockers (P2) are forbidden in selected sports.

Compounds are divided into non-threshold substances, for which identification is sufficient to provide an adverse analytical finding (AAF), and threshold substances prohibited above a certain level. To harmonize the results obtained from WADA-accredited laboratories, minimum required performance levels for analytical methods have been established, defining the minimum sensitivity requirements for the analysis of non-threshold substances [3].

Urine, and in some cases also hematic matrices (whole blood, serum, plasma), are considered the biological specimens of choice for routine anti-doping analysis. Advantages of urine samples include non-invasive collection and relatively large volumes available, whereas blood collection invasive and yields a limited volume. Mainly for these reasons, most anti-doping analyses are still performed in urine, even if the prevalence of blood testing is recently increasing.

Thus, investigations on the presence of a banned compound in urine are routinely carried out by means of a common workflow, starting with an initial screening followed by a confirmation procedure. The screening step should be fast, selective and sensitive enough to avoid false-negative and false-positive results. In the case of a positive screening result, it must be confirmed by targeting the identified compound and its metabolites [4].

To achieve this workflow on such a wide range of compounds included in the WADA prohibited list, accredited anti-doping laboratories should use multiple analytical methodologies and first of all MS-based ones (GC–MS/MS and LC–MS/MS), considered reference methods due to their higher selectivity and sensitivity.

In order to investigate the constantly evolving illicit doping practices in sports, direct screening and confirmation strategies should be continuously updated, by including the monitoring of additional substances with potential doping properties and new metabolites of known compounds with increased detection windows; by taking into account alternative biological matrices to obtain complementary data; by optimizing all the pre-analytical steps to enhance sample stability and maximize result soundness and reliability.

Protti M, Mandrioli R, Mercolini L. Perspectives and strategies for anti-doping analysis. Bioanalysis. 2019;11(3):149-152. doi:10.4155/bio-2018-0290 https://www.future-science.com/doi/10.4155/bio-2018-0290

 

[Michael Scally MD]

[OA] No Standarisation or Harmonisation in Anti-Doping Testing Frequency

The use of performance-enhancing drugs (PEDs) has undermined the credibility of sports for many years, with cycling and athletics, especially badly hit.

The World Anti-Doping Agency has been tasked with leading the fight against the use of PEDs in sport and has been largely successful in achieving standardisation and harmonisation in terms of rules and regulations but has not addressed the question of testing frequency to any meaningful extent.

This study, which focuses on athletics, shows vast differences in testing rates around the world with some of the most successful countries in athletics doing very little testing compared to many other countries.

Cuddihy B. No standarisation or harmonisation in anti-doping testing frequency. BMJ Open Sport Exerc Med. 2020 Sep 23;6(1):e000739. doi: 10.1136/bmjsem-2020-000793. PMID: 33062299; PMCID: PMC7525253. No standarisation or harmonisation in anti-doping testing frequency

 

[Michael Scally MD]

Annual Banned-Substance Review-Analytical Approaches In Human Sports Drug Testing 2019/2020

Analytical chemistry-based research in sports drug testing has been a dynamic endeavor for several decades, with technology-driven innovations continuously contributing to significant improvements in various regards including analytical sensitivity, comprehensiveness of target analytes, differentiation of natural/endogenous substances from structurally identical but synthetically derived compounds, assessment of alternative matrices for doping control purposes, etc.

The resulting breadth of tools being investigated and developed by anti-doping researchers has allowed to substantially improve anti-doping programs and data interpretation in general. Additionally, these outcomes have been an extremely valuable pledge for routine doping controls during the unprecedented global health crisis that severely affected established sports drug testing strategies.

In this edition of the annual banned-substance review, literature on recent developments in anti-doping published between October 2019 and September 2020 is summarized and discussed, particularly focusing on human doping controls and potential applications of new testing strategies to substances and methods of doping specified the World Anti-Doping Agency's 2020 Prohibited List.

Thevis M, Kuuranne T, Geyer H. Annual banned-substance review-analytical approaches in human sports drug testing 2019/2020. Drug Test Anal. 2020 Nov 12. doi: 10.1002/dta.2969. Epub ahead of print. PMID: 33185038. https://onlinelibrary.wiley.com/doi/10.1002/dta.2969

 

[Michael Scally MD]

[OA] Nandrolone Decanoate: Use, Abuse and Side Effects

Background and Objectives: Androgens play a significant role in the development of male reproductive organs. The clinical use of synthetic testosterone derivatives, such as nandrolone, is focused on maximizing the anabolic effects and minimizing the androgenic ones. Class II anabolic androgenic steroids (AAS), including nandrolone, are rapidly becoming a widespread group of drugs used both clinically and illicitly.

The illicit use of AAS is diffused among adolescent and bodybuilders because of their anabolic proprieties and their capacity to increase tolerance to exercise. This systematic review aims to focus on side effects related to illicit AAS abuse, evaluating the scientific literature in order to underline the most frequent side effects on AAS abusers' bodies.

Materials and Methods: A systematic review of the scientific literature was performed using the PubMed database and the keywords "nandrolone decanoate". The inclusion criteria for articles or abstracts were English language and the presence of the following words: "abuse" or "adverse effects". After applying the exclusion and inclusion criteria, from a total of 766 articles, only 148 were considered eligible for the study.

Results: The most reported adverse effects (found in more than 5% of the studies) were endocrine effects (18 studies, 42%), such as virilization, gynecomastia, hormonal disorders, dyslipidemia, genital alterations, and infertility; cardiovascular dysfunctions (six studies, 14%) such as vascular damage, coagulation disorders, and arteriosus hypertension; skin disorders (five studies, 12%) such as pricking, acne, and skin spots; psychiatric and mood disorders (four studies, 9%) such as aggressiveness, sleep disorders and anxiety; musculoskeletal disorders (two studies, 5%), excretory disorders (two studies, 5%), and gastrointestinal disorders (two studies, 5%).

Conclusions: Based on the result of our study, the most common adverse effects secondary to the abuse of nandrolone decanoate (ND) involve the endocrine, cardiovascular, skin, and psychiatric systems. These data could prove useful to healthcare professionals in both sports and clinical settings.

Patanè FG, Liberto A, Maria Maglitto AN, Malandrino P, Esposito M, Amico F, Cocimano G, Rosi GL, Condorelli D, Nunno ND, Montana A. Nandrolone Decanoate: Use, Abuse and Side Effects. Medicina (Kaunas). 2020 Nov 11;56(11):E606. doi: 10.3390/medicina56110606. PMID: 33187340. https://www.mdpi.com/1010-660X/56/11/606/htm

 

[Michael Scally MD]

'Clean Athlete Status' Cannot Be Certified: Calling for Caution, Evidence and Transparency In 'Alternative' Anti-Doping Systems

Highlights

Attempts to certificate ‘clean athlete status’ are scrutinised on multiple grounds.

The need for transparency, evidence and scientific scrutiny is highlighted.

Clean sport and anti-doping are discussed in the broader scope of sport integrity.

Instituting ways to show due diligence in compliance with anti-doping is recommended.


Athletes, sponsors and sport organisations all have a vested interest in upholding the values of clean sport. Despite the considerable and concerted efforts of the global anti-doping system over two decades, the present system is imperfect.

Capitalising upon consequent frustrations of athletes, event organisers and sponsors, alternative anti-doping systems have emerged outside the global regulatory framework. The operating principles of these systems raise several concerns, notably including accountability, legitimacy and fairness to athletes.

In this paper, we scrutinise the Clean Protocol™, which is the most comprehensive alternative system, for its shortcomings through detailed analysis of its alleged logical and scientific merits.

Specifically, we draw the attention of the anti-doping community - including researchers and practitioners - to the potential pitfalls of using assessment tools beyond the scope for which they have been validated, and implementing new approaches without validation.

Further, we argue that whilst protecting clean sport is critically important to all stakeholders, protocols that put athletes in disadvantageous positions and/or pose risks to their professional and personal lives lack legitimacy.

We criticise the use of anti-doping data and scientific research out of context, and highlight unintended harms that are likely to arise from the widespread implementation of such protocols in parallel with - or in place of - the existing global anti-doping framework.

Petróczi A, Backhouse SH, Boardley ID, Saugy M, Pitsiladis Y, Viret M, Ioannidis G, Ohl F, Loland S, McNamee M. 'Clean athlete status' cannot be certified: Calling for caution, evidence and transparency in 'alternative' anti-doping systems. Int J Drug Policy. 2020 Nov 26:103030. doi: 10.1016/j.drugpo.2020.103030. Epub ahead of print. PMID: 33250439. ‘Clean athlete status’ cannot be certified: Calling for caution, evidence and transparency in ‘alternative’ anti-doping systems

 

[Michael Scally MD]

Russia’s four-year ban from global sports has been cut in half by a court in Switzerland, a decision that could signal the end of its yearslong battle with antidoping regulators who had accused the country of running one of the most sophisticated doping schemes in history in pursuit of sporting glory and Olympic medals.

The decision by the Court of Arbitration for Sport in Switzerland, the final arbiter on global sports disputes, means Russia will not be able to enter teams in the next two Olympics — the rescheduled Tokyo Games next summer and the 2022 Winter Games in Beijing — or have its anthem, its flag or even its name represented at other high-profile competitions. Some Russian athletes will still be allowed to compete at events, but only as neutrals.

The court’s decision was confirmed by a person familiar with the ruling, which will be announced later Thursday.

The ruling will be viewed as a victory by the World Anti-Doping Agency, the global doping regulator, which was responsible for issuing Russia’s ban last year. And it will mean relief and a degree of satisfaction for officials at the organization who had feared that new rules created in the wake of the Russian scandal, and designed to punish nations involved in state-sponsored doping conspiracies, would not be able to survive the sort of legal onslaught Russia had employed to fight them.