ABSTRACT:This Consensus statement provides an update to the 1996 American College of Sports Medicine Position Stand: The Use of Blood Doping as an Ergogenic Aid. Red blood cell (RBC) mass directly influences exercise performance because RBCs are critical to the transport of oxygen to skeletal muscle, as well as their role in maintaining acid-base status and regulating blood flow. Blood doping is defined as the practice of artificially increasing RBC volume for the purpose of improving exercise performance. Blood doping methods have classically included reinfusion of stored blood as well as administration of pharmaceutical agents such as recombinant human erythropoietin, hypoxia-inducible factor stabilizers or nonpharmaceutical substances, like cobalt or xenon, which stimulate the erythropoietic pathway. It is clear through scientific consensus that other methods to naturally increase hemoglobin, such as hypoxic or hyperoxic exposure, are not considered blood doping. More recently, emerging blood doping threats through gene manipulation have received new attention. In the last 25 yr, the science and technology surrounding oxygen sensing and erythropoiesis, pharmacological intervention, and doping detection has advanced substantially, dictating this updated review. It is the position of the American College of Sports Medicine that any blood doping procedure used with the actual or potential to improve athletic performance is unethical and unfair and exposes the athlete to unwarranted and potentially serious health risks.
Abstract Background Determining the prevalence of doping within an elite athlete population is challenging due to the extreme sensitivity of the topic; however, understanding true doping prevalence is important when designing anti-doping programs and measuring their effectiveness. The objective of this study was to estimate the prevalence of doping among Olympic, Paralympic, World, and National-level competitive athletes in the United States subject to the World Anti-Doping Code. All athletes who were subject to the U.S. Anti-Doping Agency’s Protocol for Olympic and Paralympic Movement Testing, a World Anti-Doping Code (“Code”)-compliant anti-doping program, were invited to complete a web-delivered survey. Using a direct questioning approach, the survey items asked athletes whether they had used each specific category of banned substance / method on the World Anti-Doping Agency’s Prohibited List. Multiple strategies to encourage honest reporting (e.g., protecting anonymity by collecting minimal demographic information; using an outside organization to administer the survey) and to detect inconsistent responses were used. Results Depending on the method of calculation, 6.5–9.2% of the 1,398 respondents reported using one or more prohibited substances or methods in the 12 months prior to survey administration. Specific doping prevalence rates for each individual substance / method categories ranged from 0.1% (for both diuretics / masking agents and stem cell / gene editing) to 4.2% for in-competition use of cannabinoids. Conclusion Determining the prevalence of doping within different athlete populations is critical so that sport governing bodies can evaluate their anti-doping efforts and better tailor their programming. By measuring doping prevalence of specific categories of substances and methods, rather than just the overall prevalence of doping, this study also highlights where sport governing bodies should focus their future educational and detection efforts.
Blood collection is an important facet of anti-doping testing, forming the basis of the hematological module of the athlete biological passport (ABP). Presently, whole blood is collected via venepucture under standardized conditions, in accordance with the World Anti-doping Agency's International Standard for Testing and Investigations (ISTI). Advances in capillary whole blood collection technology now afford the ability to collect microvolumetric capillary whole blood from the upper arm (or other suitable vascular location such as the abdomen) that is "needle-free" and virtually painless. Previous work has demonstrated the suitability and feasibility of capillary whole blood compared with venous using the Tasso+ device. Recently, other microcapillary devices have received FDA approval increasing the options available to the anti-doping community. The present study extends previous work, by collecting microliter capillary whole blood samples via two different FDA approved devices (RedDrop and the Tasso+ device) to compare with venous blood collected simultaneously. Ten participants provided three matched blood samples (2× capillary and 1× venous) in accordance with WADA ABP guidelines for blood sample collection, for a total of 30 samples. Capillary samples from both devices showed excellent laboratory agreement with venous blood for all CBC parameters, with the exception of platelets. Excellent laboratory agreement was also observed between the two microcapillary collection devices. Irrespective of the device, microcapillary blood collection provides a valid alternative to venous blood collection for ABP purposes.
Roxadustat (FG-4592), an orally active hypoxia-inducible factor prolyl hydroxylase stabilizer, has been shown to enhance erythropoiesis by increasing endogenous erythropoietin. It is indicated for the treatment of anemia and chronic kidney disease and is approved for clinical use in several countries, including the European Union, Japan and others. Due to its reasonably anticipated performance-enhancing effect in athletes, roxadustat is prohibited for use in sports at all times. A few cases of adverse analytical findings in routine doping controls have been reported worldwide, some of which were claimed to be the result of contaminated dietary supplements. The present study offers new data demonstrating the long-term excretion pattern of roxadustat. Even after a single-dose administration, roxadustat can remain detectable in urine for 8 months, albeit at very low concentrations (<10 pg/mL). Following three times a week treatment with 70 to 100 mg of roxadustat, the drug was still detectable in the urine of anemic patients for between 9 and 18 months after treatment was discontinued. Lastly, an athlete who admitted use of roxadustat for almost a year (50 mg 3 to 5 times a week) has now tested positive multiple times over the course of 15 months (the first test being 12 months after the drug was discontinued), with an estimated concentration of roxadustat between 3 and 8 pg/mL. Altogether, these findings indicate the unusually prolonged terminal excretion kinetics of roxadustat, a property that testing authorities should consider in their results management process.
Abstract Background: Determining the prevalence of doping within an elite athlete population is challenging due to the extreme sensitivity of the topic, however understanding true doping prevalence is important when designing anti-doping programs and measuring their effectiveness. The objective of this study was to estimate the prevalence of doping among Olympic, Paralympic, World and National-level competitive athletes in the United States subject to the World Anti-Doping Agency (WADA) Prohibited List. This study used a web-delivered survey and direct questioning approach to collect data from athletes in the United States Anti-Doping Agency (USADA) Registered Testing Pool or Clean Athlete Program. For the first time, a prevalence survey of elite athletes used the WADA Prohibited List to assess prevalence in each specific category of banned substance / method. Results: Of 1,425 respondents, overall doping prevalence among U.S. elite athletes in the 12 months prior to survey administration ranged from an estimated 6.7-9.2% depending on the method of calculation. Specific doping prevalence rates for each individual substance category ranged from 0.1% (diuretics or masking agents) to 4.1% for cannabinoids (in-competition). Conclusion: By measuring doping prevalence down to specific performance enhancing substances and methods, as well as coupling with individual athlete personality characteristics such as attitudes, motivators and norms, a clearer picture of the use of specific prohibited substances in- and out of-competition, attitudes toward doping, beliefs about testing and most effective deterrents can be identified. By understanding doping prevalence, anti-doping programs can be tailored to increase deterrence and overall program effectiveness.
Abstract Background: Determining the prevalence of doping within an elite athlete population is challenging due to the extreme sensitivity of the topic, however understanding true doping prevalence is important when designing anti-doping programs and measuring their effectiveness. The objective of this study was to estimate the prevalence of doping among Olympic, Paralympic, World and National-level competitive athletes in the United States subject to the World Anti-Doping Agency (WADA) Prohibited List. This study used a web-delivered survey and direct questioning approach to collect data from athletes in the United States Anti-Doping Agency (USADA) Registered Testing Pool or Clean Athlete Program. For the first time, a prevalence survey of elite athletes used the WADA Prohibited List to assess prevalence in each specific category of banned substance / method. Results: Of 1,425 respondents, overall doping prevalence among U.S. elite athletes in the 12 months prior to survey administration ranged from an estimated 6.7-9.2% depending on the method of calculation. Specific doping prevalence rates for each individual substance category ranged from 0.1% (diuretics or masking agents) to 4.1% for cannabinoids (in-competition). Conclusion: By measuring doping prevalence down to specific performance enhancing substances and methods, as well as coupling with individual athlete personality characteristics such as attitudes, motivators and norms, a clearer picture of the use of specific prohibited substances in- and out of-competition, attitudes toward doping, beliefs about testing and most effective deterrents can be identified. By understanding doping prevalence, anti-doping programs can be tailored to increase deterrence and overall program effectiveness.
Capromorelin is a growth hormone secretagogue. Despite promising results to alleviate muscle-wasting in the elderly, it has not advanced further in human development. Subsequent studies demonstrated capromorelin's ability to increase food intake in animals, leading to approval in the United States and Europe as an appetite stimulant for cats (Elura) and dogs (Entyce). Capromorelin is prohibited in sports due to its ability to stimulate growth hormone production and enhance performance. However, given that its veterinary preparation is formulated as a highly concentrated solution (20 or 30 mg/mL) delivered orally, incidental ingestion or dermal absorption may result in an adverse analytical finding (AAF) by way of direct exposure during oral administration to a pet. An administration study was conducted by either oral or transdermal application of capromorelin solution to mimic the scenario of inadvertent exposure to the drug. Ingestion of 30 μg of capromorelin orally (equivalent to 1 μL of Entyce) resulted in detectable amounts of capromorelin in urine for up to 48 h after administration with a maximum urinary concentration of 7 ng/mL. Importantly, when applied directly to the skin on the hands in larger quantities mimicking a pet administration exposure scenario (30 mg or 1 mL of Entyce), capromorelin was also detected reaching a maximum urinary concentration of 0.7 ng/mL. Athletes and testing authorities should be aware of the risk of an AAF arising due to incidental exposure to veterinary preparations of capromorelin. To our knowledge, before 2022, no positive test for capromorelin had ever been reported.
Blood collection is an important facet of anti-doping testing, forming the basis of the Athlete Biological Passport (ABP). Traditional blood collection via venipuncture can be uncomfortable for athletes, especially those who are tested frequently or close to competition. Athletes may also have negative perceptions of venipuncture due to past experiences or the risks of adverse health events such as bruising, hematomas, syncope, and general discomfort that has the potential to affect performance. Advances in capillary whole blood collection technology now affords the ability to collect micro-volumetric capillary whole blood from the upper arm (or other suitable vascular location such as the abdomen) that is "needle-free" and virtually painless using devices such as the Tasso+. The present study extends previous work, by collecting microliter capillary whole blood samples via the Tasso+ EDTA device in an official anti-doping setting prior to competition, as well as requiring temperature-monitored cold chain shipping by air to the laboratory before analysis. Fifty-eight matched capillary and venous blood samples were collected under official doping control conditions by certified Doping Control Officers. No impact of sample shipment by air under cool conditions was observed on sample integrity. Provided that no visible clots were identified prior to analysis, capillary and venous blood samples showed excellent laboratory agreement for all CBC parameters, with the exception of platelets. Micro capillary blood collection provides a valid alternative to venous blood collection for ABP purposes, with the advantage of providing a more athlete-friendly experience, particularly close to competition.
19-Norandrosterone (19NA) is the preferred urinary target compound to identify doping with nandrolone or related 19-norsteroids. At concentrations between 2.5 and 15 ng/mL, isotope ratio mass spectrometry (IRMS) is required to establish exogenous origin of urinary 19NA. An absolute difference of 3‰ between urinary 19NA and an endogenous reference compound (ERC) constitutes a finding for exogenous origin of 19NA. Over the last 3 years, 77 samples containing urinary 19NA between 2.5 and 15 ng/mL were analyzed at our laboratory. The measured δ13 C values for 19NA ranged from -29.5‰ to -16.8‰. In comparison, the δ13 C values for the corresponding urinary ERCs ranged from -22.4‰ to -16.2‰. Due to the considerable overlap in values between the target compound and the natural range of urinary ERCs, it can be challenging to distinguish between endogenous and exogenous origins of urinary 19NA. In addition, it is well known that consumption of offal from non-castrated pigs can produce 19NA in urine. To determine whether this could cause a positive IRMS finding under the current IRMS positivity criteria, meat from non-castrated boars fed a mixture of corn and soy was consumed by 13 volunteers. Two volunteers produced 19NA findings above 2.5 ng/mL, and the measured isotope values, while inconsistent with documented 19-norsteroid preparations, did meet IRMS positivity criteria. However, these increases in 19NA urinary concentrations were short-lived due to rapid elimination. Timely follow-up collections may help support a claim for dietary exposure when low urinary concentrations of 19NA with pseudo-endogenous isotope values are observed.
The hematological module of the Athlete Biological Passport (ABP) represents an important tool in the pursuit to detect blood doping in athletes. Currently, collecting blood samples for ABP analysis can be cumbersome, invasive, and expensive, involving a venous blood draw performed by a trained phlebotomist followed by cold-chain monitored shipping to the analysis laboratory. Developing innovative methods to collect and transport ABP blood samples while adhering to strict preanalytical and analytical requirements has the potential to greatly increase testing frequency and, consequently, the effectiveness of the ABP program globally. The focus of this study was to compare venous blood collections with capillary blood collections to determine if capillary samples could be used for ABP analysis without sacrificing the analytical integrity required for antidoping testing procedures. In this study, capillary blood was collected using the Tasso+ EDTA device (Tasso, Inc.), a novel microvolumetric device that collects liquid, whole blood from skin capillaries on the upper arm. Excellent laboratory agreement was observed between venous and capillary blood samples for the three main ABP parameters: HGB, RET%, and OFF-Score. Additionally, the stability of capillary samples after storage at 4°C, similar to what would be required during transport, was acceptable for up to 72 h following collection. Finally, we generated individual ABP profiles using the adaptive model for 10 participants and observed excellent agreement between venous and capillary profiles. These results indicate capillary blood collection is a viable alternative to venous blood collections for ABP analysis.
The popularity of regenerative medicine has recently increased, with many athletes turning to orthobiologic therapies that utilize complex milieus of biological substances, such as stem cells and natural growth factors, to heal sports injuries faster. Commonly derived from donor and non-donor harvested tissues, these include umbilical cord blood, amniotic fluid, placental allografts, connective and adipose tissue. Many of these products are not well characterized and their safety and efficacy has not been proven. Orthobiologics, generally are not prohibited in sport if no exogenous growth factors or other prohibited substances are added after harvesting or during the administration process, and as long as they only return normal functioning of the affected area and do not enhance it. Use of these treatments by professional athletes, presents an ethical dilemma for anti-doping governance due to the unproven efficacy, possible health risks and potential to contravene the Spirit of Sport. The US Anti-doping Agency (USADA) adopted an orthobiologics Declaration of Use (DOU) policy in 2020 for the Ultimate Fighting Championship (UFC). PURPOSE: Document the use of orthobiologics within the UFC in order to assist in evaluating such products and provide an anti-doping status to athletes. METHODS: DOU were submitted to USADA in advance of treatment, including: Date of procedure, Product, Injury, and Course of treatment and reviewed by USADA. RESULTS: Over 50 stem cell DOU were submitted in 1y including over 15 individual products. Treatment was requested primarily for joint injuries sustained during competition or arising from overuse. The most common orthobiologic was umbilical cord derived Wharton’s Jelly following or in conjunction with surgical intervention. Despite the high amounts of growth factors and cytokines present, all but one DOU was approved since growth factors were not added post-harvesting. No adverse analytical findings were associated with orthobiologic use. CONCLUSIONS: The use of orthobiologics has exploded in UFC athletes. USADA continues to monitor the evolving field through a DOU process. More detailed studies are needed to characterize these products, ensure that the constituents lack the potential for performance enhancement, evaluate treatment efficacy and monitor their safety.
This paper describes nine instances of positive anti-doping tests that could be accounted for by the use of permitted generic prescription drugs contaminated with diuretics, which are prohibited in sport at all times under the WADA Prohibited List. The contamination levels found in the medications are reported and were below FDA limits for manufacturers that are based primarily on safety considerations. These cases demonstrate that great care must be taken to identify the source of low-level anti-doping positives for diuretics reported by WADA-accredited laboratories, and possibly other prohibited substances as well, in order to avoid sanctioning innocent athletes. An evaluation of the cases in this paper supports an approach which establishes a laboratory minimum reporting level (MRL) for diuretics found most commonly in medications. A global consensus after extensive review of similar anti-doping cases has resulted in implementation of a recently announced solution regarding potential diuretic contamination cases.
Similar to the general population, elite athletes are exposed to a complex set of environmental factors including chemicals and radiation and also biological and physical stressors, which constitute an exposome that is, unlike for the general population, subjected to specific scrutiny for athletes due to applicable antidoping regulations and associated (frequent) routine doping controls. Hence, investigations into the athlete's exposome and how to distinguish between deliberate drug use and different contamination scenarios has become a central topic of antidoping research, as a delicate balance is to be managed between the vital and continually evolving developments of sensitive analytical techniques on the one hand, and the risk of the athletes' exposome potentially causing adverse analytical findings on the other.
Rationale: Chlorphenesin is an approved biocide frequently used in cosmetics, and its carbamate ester is an approved skeletal muscle relaxant in certain countries for the treatment of discomfort related to skeletal muscle trauma and inflammation. A major urinary metabolite is 4-chlorophenoxy acetic acid (4-CPA), also known as para-chlorophenoxyacetate, which is also employed as a target analyte in sports drug testing to detect the use of the prohibited nootropic stimulant meclofenoxate. To distinguish between 4-CPA resulting from chlorphenesin, chlorphenesin carbamate, and meclofenoxate, urinary metabolite profiles of chlorphenesin after legitimate use were investigated. Methods: Human administration studies with commercially available sunscreen containing 0.25% by weight of chlorphenesin were conducted. Six study participants dermally applied 8 g of sunscreen and collected urine samples before and up to 7 days after application. Another set of six study participants applied 8 g of sunscreen on three consecutive days, and urine samples were also taken for up to 5 days after the last dosing. Urine specimens were analyzed using liquid chromatography-high resolution (tandem) mass spectrometry, and urinary metabolites were identified in accordance with literature data by accurate mass analysis of respective precursor and characteristic product ions. Results: In accordance with literature data, chlorphenesin yielded the characteristic urinary metabolites, chlorphenesin glucuronide, chlorphenesin sulfate, and 3-(4-chlorophenoxy)-2-hydroxypropanoic acid (4-CPP), as well as the common metabolite 4-CPA. 4-CPA and 4-CPP were observed at similar abundances, with urinary concentrations of 4-CPA reaching up to similar to 1500 and 2300 ng/mL after single and multiple sunscreen applications, respectively. Conclusion: 4-CPA is a common metabolite of meclofenoxate, chlorphenesin, and chlorphenesin carbamate. Monitoring the diagnostic urinary metabolites of chlorphenesin provides conclusive supporting evidence of whether chlorphenesin or the prohibited nootropic meclofenoxate was administered.
Family physicians may be surprised to learn the number of their patients who use performance-enhancing drugs, either deliberately to improve athletic performance or unknowingly through contaminated dietary supplements.
Protecting the integrity of sport & the doping control processThe recent global COVID-19 pandemic is an unprecedented global health crisis with far-reaching impacts on sport.With world sporting events canceled or postponed to limit the spread of infectious disease among athletes and the public and athletes adapting their training programs within the safety and protection of their own homes, global anti-doping programs face the challenge of protecting the health and wellbeing of athletes and sample collection personnel while continuing to pursue the detection and deterrence value of anti-doping testing programs.These uncertain and exceptional circumstances require innovation and flexibility within the current anti-doping system to protect the rights of clean athletes and the integrity of sport.The World Anti-Doping Code governs global anti-doping programs across Olympic and Paralympic sport.This aims to achieve global standards and harmonization of the operational aspects of anti-doping programs including sample collection and analysis, the results management process, protection of privacy and personal information, the list of prohibited substances and methods, the Therapeutic Use Exemption process, the athlete whereabouts system, intelligence and investigations practices and Code signatories' rights and responsibilities with code compliance.Within the International Standard for Testing and Investigations (ISTI), specific details with respect to the process of sample collection must be strictly followed to uphold the integrity of the sample and the chain of custody [1].Some important aspects of the sample collection process, designed to minimize the likelihood of sample manipulation, tampering and to prevent athletes from exploiting loopholes in the system include no-advance notice testing, physically present sample collectors performing in-person sample collection with directly observed urine and blood sample provision and the need for tamper-evident sample collection equipment that ensures the security, suitability and chain of custody of the samples from the time of collection, until laboratory receipt and analysis.Compliance with the current sample collection standards and procedures protect athletes, as well as ensuring that legal challenges to the sample collection process are minimized in cases of a positive test.As addressed in the current ISTI, witnessing and verifying the provision of the sample is critical to prevent tampering and any attempt to falsify a urine specimen.There have been instances of athletes attempting to use commercially available penile prostheses, urine substitutes, chemical additives that detoxify the sample or attempt to interfere with chemical testing and warming devices to maintain the sample at body temperature [2].Several commercially available technologies have been developed that can be used to alleviate the invasive nature of a witnessed urine collection that can also identify urine as coming from a specific athlete.One solution is PEGs given orally prior to urination and consequently urine samples can be traced to the donor by analysis of the known urinary PEGs previously ingested [3].Practical limitations to this approach include requiring elite athletes to ingest a foreign substance and the delay between ingestion and urinary excretion of the PEGs. Virtual drug testing as an innovative alternative to complement traditional in-person doping controlVirtual sport drug testing via remote sample collection personnel has been piloted by the United States Anti-Doping Agency (USADA) in order to maintain strict physical distancing and protect the health of elite Olympic
Globally exists an ongoing battle between increasingly advanced doping methods and limited resources available to anti-doping organizations. Therefore, the developments of new tools for identifying athletes who may be doping are needed. Recognizing which athletes are at the highest risk of doping allows an anti-doping organization to distribute those limited resources in the most effective manner. Presented below is a comparison of multiple machines and statistical learning approaches, combined with resampling techniques, to identify which athletes are at the highest risk of doping. The results presented indicate that support vector classification and logistic regression, combined with oversampling, may provide an effective tool to aid anti-doping organizations in most effectively distributing scarce resources. Adoption and implementation of these methods may both enhance the deterrence effect of anti-doping, as well as increases the likelihood of catching athletes doping. Future research should be conducted to explore the feasibility of combining these performance-based measures with biological measures such as the Athlete Biological Passport to enhance anti-doping efforts.
Current anti-doping testing is primarily conducted in urine and blood. Recently, due to confounding factors with urine and blood collections such as invasiveness, cost, and stringent shipping conditions, there has been a push for the use of alternative sample matrices to ameliorate these issues. Gaining support within the anti-doping field is the use of oral fluid, and more recently exhaled breath, as viable alternative or complementary matrices to traditional urine and blood for drug testing. Thus, we designed a first-in-field study with the purpose of investigating the utility of oral fluid and exhaled breath testing, and the preference of athlete participants, comparative to conventional anti-doping methods of urine testing. To accomplish this, 521 total matched samples, consisting of exhaled breath, oral fluid, and urine samples, were collected and analyzed, and the results compared across matrices. Participants in this study preferred the exhaled breath collection (rated 4.90 +/- 0.34 out of 5, mean SD) over the oral fluid collection procedure (4.29 +/- 0.85), and most preferred both over urine collections. Exhaled breath resulted in the shortest collection time (2.58 +/- 1.00 min, mean +/- SD), followed by urine (3.08 +/- 1.50 min), and finally oral fluid (4.14 +/- 1.94 min). Prohibited substances from the drug categories of stimulants, narcotics, cannabinoids, diuretics, glucocorticoids, beta-blockers, and others, were analyzed in this study for a comparison of testing efficacy. Of the total findings 49% were detectable in only urine, 38% in urine + oral fluid, and 9% in all three matrices. Of the unique findings 3% were detectable in only oral fluid, 1% in oral fluid + breath, and 0% of unique findings were present only in exhaled breath. The findings from this study provide a strong foundation for the future use of oral fluid and exhaled breath as viable alternative or complementary matrices for in-competition anti-doping testing. (C) 2019 Elsevier B.V. All rights reserved.
The presence of performance-enhancing drugs in dietary supplements poses serious anti-doping and health risks to athletes and military service members. A positive drug test, suboptimal health, or adverse event can ruin a career in either setting. These populations need to be certain in advance that a product is of high quality and free from performance-enhancing drugs and other banned substances. However, no regulatory authority conducts or mandates a quality review before dietary supplements are sold. Under the Food Drug and Cosmetic Act, the Food and Drug Administration does not have a role in the premarket safety review of dietary supplements. Due to the increasing demand for high-quality, properly labeled dietary supplements, multiple companies have stepped into this void by offering testing and quality review programs for dietary supplements. Each of these third-party programs has its own quality assurance program with varying testing components. It is difficult for consumers in the sport and military settings to assess whether a particular certification program reduces the risks enough so that they can use a product with confidence. This article puts forward the consensus of the authors on current best practices for third-party certification programs for dietary supplements consumed by athletes and military service members. Also discussed are important ways that third-party programs can develop in the future to improve access to safe, high-quality dietary supplements for these populations.
1 Endurance Research Group, University of Kent, Chatham, United Kingdom, 2 Aspetar Orthopaedic and Sports Medicine Hospital, Doha, Qatar, United States Anti-Doping Agency, Colorado Springs, CO, United States, 4 Anti-Doping Denmark, Brøndby, Denmark, 5 LMAHESS Nice, France and Monaco Institute of Sports Medicine and Surgery, University Cote d’Azur, Monaco, France, 6 KIHU—Research Institute for Olympic Sports, Jyvaskyla, Finland, World Anti-Doping Agency, Lausanne,