WADA ... Olympics ...

[Michael Scally MD]

Thevis M, Kuuranne T, Walpurgis K, Geyer H, Schanzer W. Annual banned-substance review: analytical approaches in human sports drug testing. Drug Test Anal. Annual banned-substance review: analytical approaches in human sports drug testing - Thevis - 2016 - Drug Testing and Analysis - Wiley Online Library

The aim of improving anti-doping efforts is predicated on several different pillars, including, amongst others, optimized analytical methods.

These commonly result from exploiting most recent developments in analytical instrumentation as well as research data on elite athletes' physiology in general, and pharmacology, metabolism, elimination, and downstream effects of prohibited substances and methods of doping, in particular.

The need for frequent and adequate adaptations of sports drug testing procedures has been incessant, largely due to the uninterrupted emergence of new chemical entities but also due to the apparent use of established or even obsolete drugs for reasons other than therapeutic means, such as assumed beneficial effects on endurance, strength, and regeneration capacities.

Continuing the series of annual banned-substance reviews, literature concerning human sports drug testing published between October 2014 and September 2015 is summarized and reviewed in reference to the content of the 2015 Prohibited List as issued by the World Anti-Doping Agency (WADA), with particular emphasis on analytical approaches and their contribution to enhanced doping controls.

 

[Michael Scally MD]

 

[Michael Scally MD]

IAAF Investigates Letter Alleging Doping In Chinese Athletics
IAAF investigates letter alleging doping in Chinese athletics - BBC News

The body that governs world athletics has said it is investigating a letter alleging historic state-backed doping in the sport in China.

The previously unseen letter was apparently written by Chinese Olympic medallist Wang Junxia in 1995, but only published in state media this week.

Wang still holds two world records.

...

Wang broke the world record for 10,000m and 3,000m in 1993. No athlete is yet to come within 20 seconds of her time on the 10,000m. She also won the 5,000m at the 1996 Olympics, finishing second in the 10,000m.

 

[Michael Scally MD]

Exclusive: WADA President Sir Craig Reedie On Athletics’ Doping Crisis, Part One
http://www.newsweek.com/exclusive-w...eedie-athletics-doping-crisis-part-one-423460

These are interesting times to be sport’s most powerful figure in the fight against doping.

Since December 2014, Sir Craig Reedie, president of the World Anti-Doping Organization, the body charged with coordinating the anti-doping effort across the globe, has watched the fallout from a scandal that has once again shaken the public’s faith in the integrity of professional sport.

An investigation by ARD, the German broadcaster, entitled ‘Doping–Top Secret: The Shadowy World of Athletics’ alleged widespread cheating in Russian athletics. WADA commissioned an independent report to look into the claims, the scope of which widened in August 2015.

In conjunction with ARD, The Sunday Times alleged, using results from a leaked database of athletes’ blood values, that a third of medals from Olympics and World Championships between 2001 and 2012 were won by athletes with suspicious blood values that should have been flagged up by the IAAF, international athletics’ governing body.

The aftermath was bloody, in literal and metaphorical senses. Lord Sebastian Coe, the IAAF president, claimed a “declaration of war” against athletics. A criminal investigation was opened by Interpol into Lamine Diack, Coe’s predecessor as president. Diack’s son, Papa Massata, was banned for life by the IAAF for alleged cover-ups of positive Russian drugs tests, as was the organization’s former head of anti-doping, Gabriel Dolle.

Amid the recriminations, WADA released its first Independent Report, chaired by former President Dick Pound, with the recommendation, since implemented, that Russia be suspended from athletic competition until it has proved its approach to anti-doping has changed.

The second report, released in January, focused more on the IAAF, suggesting that the council, of which Coe is a member, “could not have been unaware” of illicit practices under the presidency of Diack.

With athletics engaged in an existential fight, Reedie spoke exclusively to Newsweek on the difficulties his organization faces in the struggle to restore public faith in sport.

 

[Michael Scally MD]

Atypical Excretion Profile and GC/C/IRMS Findings May Last for Nine Months After a Single Dose of Nandrolone Decanoate

Highlights

• There were large inter-individual variation in the urinary excretion profile of nandrolone and its metabolites 19-norandrosterone and 19-noretiocholanolone after the administration of a single dose of nandrolone decanoate.
• Six and three of eleven individuals were identified as adverse analytical findings 120 and 270 days after the injection of only one single dose nandrolone decanoate.
• GC/C/IRMS confirmed the presence of exogenous 19-norandrosterone long time after the administration, even in a sample below the WADA Decision Limit.

Palonek E, Ericsson M, Garevik N, Rane A, Lehtihet M, Ekstrom L. Atypical excretion profile and GC/C/IRMS findings may last for nine months after a single dose of nandrolone decanoate. Steroids. Atypical excretion profile and GC/C/IRMS findings may last for nine months after a single dose of nandrolone decanoate

The use of the anabolic androgenic steroid nandrolone and its prohormones is prohibited in sport. A common route of nandrolone administration is intramuscular injections of a nandrolone ester.

Here we have investigated the detection time of nandrolone and 19-norandrosterone and 19-noretiocholanolone metabolites in eleven healthy men after the administration of a 150mg dose of nandrolone decanoate. The urinary concentrations of nandrolone and the metabolites were monitored by GC-MS/MS for nine months and in some samples the presence of 19-norandrosterone was confirmed by GC/C/IRMS analysis. The participants were genotyped for polymorphisms in PDE7B1 and UGT2B15 genes previously shown to influence the activation and inactivation of nandrolone decanoate.

There were large inter-individual variations in the excretion rate of nandrolone and the metabolites, although not related to genetic variations in the UGT2B15 (rs1902023) and PDE7B1 (rs7774640) genes. After the administration, 19-norandrosterone was found at 2-8-fold higher concentrations than 19-noretiocholanolone.

We showed that nandrolone doping can be identified 4 and 9months after the injection of only one single dose in six and three individuals, respectively. We also noted that GC/C/IRMS confirms the presence of exogenous 19-norandrosterone in the urine samples, showing delta13 values around -32 per thousand. This was true even in a sample that was not identified as an atypical finding after the GC-MS/MS analysis further showing the power of using GC/C/IRMS in routine anti-doping settings.

 

[Michael Scally MD]

The Edge - The War against Cheating and Corruption in the Cutthroat World of Elite Sports [By Roger Pielke, SImon Kuper]
http://search.perseusbooksgroup.com/book/paperback/the-edge/9781938901577 (book : The Edge)

Sport is about securing an edge—over history, over an opponent, over what has been done before. Pushing limits and exceeding them is a defining characteristic of sport and a fulfillment of what it means to be human. At the same time, pushing boundaries inevitably results in sometimes going over the edge, beyond what is acceptable, allowable, or ethical. Navigating this boundary is no easy feat. But sport depends upon it.

We think we know the difference between cheating and not cheating, “clean” and “dirty,” in sports—but we don’t. Rapid developments in the 21st century and outdated sports governance have left sport in a state of crisis. Increasingly, athletes and teams seek a competitive edge in the world of elite sport and go over the edge in their pursuit of one.

THE EDGE is about the tension between the performance edge and the ethical edge, and how sport tries to manage the boundary between the two. Drawing on controversies straight out of the headlines, Roger Pielke Jr. explores that edge and offers the reader a provocative but clear new understanding of 21st-century sport.

 

[Michael Scally MD]

The Truth About Knud: Revisiting An Anti-Doping Myth
The truth about Knud: revisiting an anti-doping myth - Sports Integrity Initiative

The anti-doping movement may have been initiated on the basis of a myth.

In ‘A brief history of doping’ on its website, the World Anti-Doping Agency (WADA) mention Knud Enemark Jensen’s death, involving ‘traces of amphetamine’, as one of the key events which caused sporting authorities to introduce drug testing.

Dr. Paul Dimeo, a senior lecturer in sports policy at the University of Stirling, explains that there is no evidence that Jensen had even taken amphetamine, less still died as a result of such ingestion.

Dr Dimeo explains how the myth came about and was gradually perpetuated to suit the objectives of sport’s anti-doping regulators.

He also examines the dangers that continuing to support such an inaccuracy holds for the anti-doping community, especially in today’s environment.

...



http://l.facebook.com/l.php?u=http%3A%2F%2Fwww.sportsintegrityinitiative.com%2Fthe-truth-about-knud-revisiting-an-anti-doping-myth%2F&h=TAQEkFcYw&enc=AZPaJb7bu6heA4RaL9nhmxqeQPAYRAbaN0S-oGcV-cZikYKUVtjjSREFgIWk2hGliYh_oIXBf6VIWcb9mJplvmI1ZnzUGyD-XNKkHAfg-xdux_b6PiqMeILjmAbDf1yJcADS3ZMh9uGO0YzMTTWRgDhdTNIreu_aIRVbtwPL6u0APXasZXHmPHICzkkCDTsfiYE&s=1

 

[Michael Scally MD]

 

[Millard]

"...in 724 of 4316 urine samples, the Moscow researchers found meldonium - that means 17% positive tests - in other words, almost 1 in 5 Russian athletes had traces of meldonium in their bodies."

 

[Michael Scally MD]

[Open Access] Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs

Testosterone (T) and related androgens are performance enhancing drugs (PEDs) abused by some athletes to gain competitive advantage. To monitor unauthorized androgen abuse, doping control programs use mass spectrometry (MS) to detect androgens, synthetic anabolic-androgenic steroids (AASs) and their metabolites in an athlete's urine. AASs of unknown composition will not be detected by these procedures.

Since AASs achieve their anabolic effects by activating the Androgen Receptor (AR), cell-based bioassays that measure the effect of a urine sample on AR activity are under investigation as complementary, pan-androgen detection methods.

We evaluated an AR BioAssay as a monitor for androgen activity in urine pre-treated with glucuronidase, which releases T from the inactive T-glucuronide that predominates in urine. AR BioAssay activity levels were expressed as 'T-equivalent' concentrations by comparison to a T dose response curve.

The T-equivalent concentrations of androgens in the urine of hypogonadal participants supplemented with T (in whom all androgenic activity should arise from T) were quantitatively identical to the T measurements conducted by MS at the UCLA Olympic Analytical Laboratory (0.96 +/- 0.22).

All 17 AASs studied were active in the AR BioAssay; other steroids were inactive. 12 metabolites of 10 commonly abused AASs, which are used for MS monitoring of AAS doping because of their prolonged presence in urine, had reduced or no AR BioAssay activity.

Thus, the AR BioAssay can accurately and inexpensively monitor T, but its ability to monitor urinary AASs will be limited to a period immediately following doping in which the active AASs remain intact.

Bailey K, Yazdi T, Masharani U, Tyrrell B, Butch A, Schaufele F. Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs. PLoS One 2016;11(3):e0151860. Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs

 

[master.on]

I heard that every doping test costs $10k
Thus why only a few random athletes are tested at major events.

 

[Michael Scally MD]

[Open Access] Longitudinal Monitoring of Endogenous Blood Steroids as a Tool to Detect Testosterone Abuse in Sport

Results of this work show how the future implementation of a longitudinal follow-up of endogenous steroids in the blood matrix could increase the capabilities of antidoping laboratories for detecting exogenous testosterone administration.

Ponzetto F, Boccardb J, Baume N, Rudazb S, Saugya M, Nicolia R. Longitudinal Monitoring of Endogenous Blood Steroids as a Tool to Detect Testosterone Abuse in Sport. Chimia (Aarau) 2016;70(3):208. http://www.ingentaconnect.com/contentone/scs/chimia/2016/00000070/00000003/art00010

 

[Michael Scally MD]

Salamin O, Jaggi L, Baume N, Robinson N, Saugy M, Leuenberger N. Circulating microRNA-122 as Potential Biomarker for Detection of Testosterone Abuse. PLoS One 2016;11(5):e0155248. Circulating microRNA-122 as Potential Biomarker for Detection of Testosterone Abuse

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and thus influence many cellular and physiological processes. miRNAs are also present in cell-free body fluids such as plasma or serum, and these circulating miRNAs are very stable, sensitive, and specific biomarkers of pathophysiological states.

In this study, we investigated whether circulating miRNAs could serve as biomarkers of exogenous testosterone administration. Misuse of testosterone as a performance-enhancing drug is thought to be widespread in sports. Detection of testosterone through the urinary steroid profile of the Athlete Biological Passport faces several obstacles, indicating that new biomarkers are required.

To this end, we analyzed plasma miRNA levels by high-throughput quantitative real-time PCR. Plasma samples were obtained before and at several time points after transdermal and oral testosterone administration.

Screening identified three potential candidate miRNAs that were altered by both routes of testosterone administration. Longitudinal monitoring of these candidates revealed that variation in two of them (miR-150 and miR-342), relative to the corresponding levels in control samples, was testosterone-independent. However, levels of the liver-specific miR-122 increased 3.5-fold 1 day after drug intake.

Given that testosterone is metabolized by the liver, this observation suggests that miR-122 in cell-free fluids may be used as a sensitive biomarker of testosterone misuse via multiple dosing routes and could therefore be integrated into a blood-based multiparametric follow-up.

 

[Redrum42]

My opinion differs to most. I think pros should be able to use PEDs under strict dr supervision. However I can't imagine the feeling of being a gold medal winner for years, suddenly having it stripped, and your name dragged through the mud.

I would imagine that feels infinitely worse than finishing 3rd. Unless we are talking IFBB athletes or other sports that are "we may test for PED if we feel the need.. wink wink" I'd absolutely tell this athlete to not fuck around and risk losing everything. Their detection methods these days are getting scary good

 

[Michael Scally MD]

Doping and an Olympic Crisis of Idealism
Doping and an Olympic Crisis of Idealism - The New Yorker

When Thomas Hicks, an American runner, faltered near the end of the 1904 Olympic marathon, in St. Louis, his assistants gave him shots of strychnine (which is now commonly used as rat poison) and brandy to revive him. Hicks crossed the finish line after another American, Fred Lorz—but was declared the winner when it was discovered that Lorz had ridden eleven miles of the marathon in his coach’s car. The perception was that Lorz had cheated, and Hicks had not.

I thought of Hicks on Sunday, when the International Olympic Committee announced that all Russian athletes would have to appeal to the international federation of their sport in order to gain eligibility to compete at next month’s Rio Olympic Games. For anti-doping officials and for many athletes, the announcement was disappointing; they had been seeking a ban on all Russian athletes. Last week, the World Anti-Doping Agency released an independent report, which ran nearly a hundred pages, offering proof of a Russian state-sponsored doping system that gave athletes performance-enhancing drugs and then covered up their test results. The methods are the stuff of a spy thriller—a secret laboratory for replacing samples in the laboratory at the Sochi Olympics, actual cocktails of steroids dissolved in alcohol (“Chivas for the men and vermouth for the women”)—but the extent of the scheme is even more incredible. According to the report, Russian athletes cheated in more than thirty sports. The I.O.C. determined that “Russian athletes in any of the 28 Olympic summer sports have to assume the consequences of what amounts to a collective responsibility.” What is at stake, the I.O.C. said, is nothing less than the “credibility of the Olympic competitions.”

That performance-enhancing drugs represent a threat to the integrity of sport seems obvious. Gaining an unfair advantage is the definition of cheating. But that hasn’t always been the case. Otherwise, Hicks’s result would have been thrown out along with Lorz’s. So what happened? The answer has something to do with the sophistication of doping now, but it also has something to do with the changing way we understand sports. The current doping crisis is also a crisis about idealism. It’s related to the gradual erosion of faith in the original idea of the Olympic Games.

The modern Olympics were founded in 1896 by Pierre de Coubertin, a French baron who thought that his country was getting soft. He looked to Britain’s sporting culture—and the fad for all things ancient—to revive the Olympic Games, hoping that sporting competition would encourage the making of champions and the building of character. The point of a game is to win, and the Olympics would be no different. But that wasn’t enough for de Coubertin, whose idea of the Games was pseudo-religious. “The important thing in life is not the triumph, but the fight; the essential thing is not to have won, but to have fought well,” he famously said. The Olympics were an elaborate ritual constructed around the idea that a running race—or a wrestling match, or a ski jump—could tell you something about the virtue of its competitors.

For the 1920 Summer Games, in Antwerp, de Coubertin wrote an oath, which amounted to a mission statement for the Games. First delivered by the Belgian fencer Victor Boin, it read, “We swear that we are taking part in the Olympic Games as loyal competitors, observing the rules governing the Games, and anxious to show a spirit of chivalry, for the honor of our countries and for the glory of sport.” The word “chivalry” sounded archaic even then; the point was to revive a better, more noble world, where excellence was pursued for its own sake. Maybe there was something even noble about pushing yourself to the point of death to complete a race. In their view, a real sportsman pursued excellence for its own sake.

For most of the twentieth century, the existential threat to sport wasn’t doping. It was professionalism. If an athlete competed for material gain, the spirit of sport—sportsmanship—would be tainted. The classic example of this idea is Jim Thorpe, one of the greatest athletes in the history of the modern era. Thorpe bounced around Native American boarding schools. His twin brother died when he was nine, his mother died a few years later, and his father died when he was sixteen. Thorpe went on to win the pentathlon and the decathlon at the 1912 Olympic Games. But the following year it was reported that he had played semi-professional baseball before competing in the Olympics. It didn’t matter that he had earned as little as two dollars per game—about fifty dollars today—or that he had desperately needed the money. The I.O.C. made a unanimous decision to strip him of his medals. Thorpe’s ethnicity and his impoverished background surely made him an easier target. But, for decades, even in the face of blatant violations of the amateur ideal, the I.O.C. maintained that its decision to strip Thorpe of his medals—and to restrict the Olympics to amateurs—was intended to protect sport from corruption. “If we water down the rules now, the games will be destroyed in eight years,” a supporter of Avery Brundage, then the I.O.C. president, said, according to a 1960 Sports Illustrated article about the amateur debate. Brundage and his followers took the amateur ideal seriously—even metaphysically. One of his colleagues called it “a question of the soul.”

The use of performance-enhancing drugs was understood to be a problem, but only insofar as it was a symptom of the corruption of the amateur ideal. In the nineteen-fifties, speed skaters took amphetamine sulfate until they were sick. Cyclists took vasodilators; in 1960, one crashed and died. When an American weightlifting coach guessed that the Soviet lifters who were crushing records were chemically altering their bodies, he didn’t cry foul; instead, he started experimenting with testosterone injections and commercially available anabolic steroids himself, and then encouraged athletes to take them as well.

In the seventies, East Germany developed a program, called State Plan 14.25, in which athletes were given little blue pills and were told they were vitamins. They were, in fact, Oral Turinabol, a steroid. Women—for whom steroids were especially effective—started developing facial hair and low voices. Men grew breasts. Both sexes developed extreme acne. Records started to fall. “The training motto at the pool was, ‘You eat the pills, or you die,’ ” one swimmer later testified. “It was forbidden to refuse.” But even in countries where doping wasn’t forced, it was done. An American track-and-field athlete, Harold Connolly, told a congressional inquiry, in 1973, that “the overwhelming majority of the international track-and-field athletes I have known would take anything and do anything short of killing themselves to improve their athletic performance.”

The I.O.C. was slow to act. It formed a committee in 1962 and started developing a list of banned substances, protocols, and eventually tests. (The first athlete to fail was popped for alcohol.) But it wasn’t until the 1988 Summer Olympics, in Seoul, that a doping scandal rocked the Games, when the men’s hundred-metre champion, Ben Johnson, failed a test. This was, as it happens, the first Summer Olympics at which professionals were allowed to compete. In reality, of course, athletes had been compensated in various ways for decades. American athletes were subsidized by schools; athletes within the Soviet bloc were supported by the government, allowed to train full time and given salaries for bogus jobs. What really changed things, of course, was the introduction of television, and the fantastic amounts of money that flooded the Games, flowing around the athletes but not to them—and the public’s desire to see the best athletes, the dream teams, compete.

The belief that amateurism was necessary for real sportsmanship was over at the Olympics. (It continues, of course, in another organization, founded around the same time as the I.O.C.: the N.C.A.A.) But the anxiety behind it—how could sport maintain its idealism in the face of the intense pressures of commercialism? what ideals do the Olympics and the idea of sport itself represent?—had not disappeared. The problem was merely transformed. It was not a question of the soul anymore but, rather, a question of the unadulterated body. The crisis had become about drugs.

In the nineties, the I.O.C. began a rearguard fight against the widespread use of performance-enhancing drugs, culminating in the creation of the World Anti-Doping Agency, in 1999. In 2000, for the first time since 1960, the I.O.C. even changed the Olympic oath. On August 5th, when the Rio Games begin, a Brazilian will hold a corner of the Olympic flag and recite, “In the name of all the competitors, I promise that we shall take part in these Olympic Games, respecting and abiding by the rules which govern them, committing ourselves to a sport without doping and without drugs, in the true spirit of sportsmanship, for the glory of sport and the honor of our teams.” In place of “a spirit of chivalry,” we have a body that is uncontaminated by doping and drugs.

The vast majority of athletes, of course, are “clean.” (Even the word is telling.) But, ultimately, doping has become so sophisticated and hard to police, and the rewards so significant, that it is impossible to eradicate. A recent retesting of samples from the London and Beijing Games uncovered forty-five positive tests—twenty-three of which came from medalists. And testing may not be the most effective way to uncover the use of performance-enhancing drugs. Most of the major anti-doping success stories—the cases of Lance Armstrong; balco; and, now, the Russian Olympic team—relied on whistle-blowers and methods more commonly associated with criminal investigations. Doping is a problem in the N.F.L., N.B.A., M.L.B., N.C.A.A., in tennis, in horse racing, in Nascar—everywhere the rewards far exceed the punishment. But it is a particular challenge for the Olympics, because the Olympics are supposed to mean something more than an athletic competition.

The distance between the ideal and the reality has never seemed greater. The bribery scandal during the bidding for the 2002 Salt Lake City Winter Games exposed an organization rotted by corruption. The price of hosting an Olympics has become so astronomical that few cities, especially in democratic countries, are willing to do it. In the cities that do, the residents who are least prepared to bear the costs often end up bearing the most. The runaway spending during the 2004 Athens Games—much of which was public debt—became a symbol of what was wrong with Greece’s economy when it went bust a few years later. In Beijing, the magnificent “Bird’s Nest” stadium sits underused and rusting. The risk of terrorism has led to draconian surveillance and security measures. Right after the Sochi Olympics, the host nation forcefully annexed Crimea.

And now Rio seems to be a catastrophe even before it begins. The water is polluted, the country is in a deep recession, the government is in the midst of political scandal, and the city is facing rising crime rates. Then came the Russian doping scandal.

In the end, the real question may not be whether the I.O.C. made the right decision on the Russian athletes. It is, instead, about what ideals the Olympics really represent.

 

[Redrum42]

Sucks how many times "let's make an example" has ruined an athletes career and personal life.

It's kind of like the business world, where you are taught "get ahead at all costs. Don't scam people *wink wink*" everyone does it, just some more than others.

In the end I feel it comes down to insecurity. Someone who is stronger and better is cheating! With arbitrarily drawn lines as to what is "advanced training /nutrition/supplementation" and what is "performance enhancement"

 

[Michael Scally MD]

[OA] Tsitsimpikou C, Tsarouhas K, Spandidos DA, Tsatsakis AM. Detection of stanozolol in the urine of athletes at a pg level: The possibility of passive exposure. Biomed Rep 2016;5(6):665-6. Detection of stanozolol in the urine of athletes at a pg level: The possibility of passive exposure

Stanozolol is a synthetic heterocyclic steroid with anabolic and androgenic properties, which has been abused by several high-profile professional athletes. Stanozolol is also used in veterinary medicine to increase appetite, cause weight gain and treat certain types of anemia.

The detection of stanozolol metabolites in human urine for doping control purposes depends on the analytical method applied.

The most commonly applied methods in the World Anti-Doping Agency (WADA)-accredited doping control laboratories are gas chromatography/high-resolution mass spectrometry (GC/HRMS) or gas chromatography-mass spectrometry (GC/MS/MS).

Recently, a new method has been published and validated that makes the detection of 3'-hydroxystanozolol glucuronide in urine possible in a concentration >50-fold less compared to the above-mentioned commonly used methods.

It is common practice to administer breeding animals with steroid hormones in order to enhance their growth. Athletes who consume meat containing such hormone residues may be at risk of failing a sports drug test.

A randomized study in the general population consuming meat should be conducted, monitoring the levels of 3'-OH-stanozolol glucoronide in human urine, in order to determine the threshold levels of passive exposure, if any, and therefore guarantee that any adverse analytical findings reported in the urine of athlete at a pg level correspond to stanozolol abuse for enhancing performance.

 

[Michael Scally MD]

Strategies That Athletes Use to Avoid Detection of Androgenic-Anabolic Steroid Doping and Sanctions

Highlights

• The abuse of androgenic-anabolic steroids is a major public health problem.
• Athletes use masking agents and other drugs to avoid detection of anabolic steroids.
• Serial monitoring of individual athlete's steroid profile allow detection of doping.
• Use of epitestosterone, hCG and diuretics obscure detection of anabolic steroid use.
• Therapeutic Use Exemptions grant prohibited medication use when properly indicated.

Androgenic-anabolic steroids (AAS) are potent and widely used performance-enhancing substances (PES). Since the International Olympic Committee (IOC) began testing athletes for AAS in the 1970s, athletes and their teams have endeavored to beat the system to avoid doping violations and/or sanctions derived from positive test results.

This review will discuss the strategies used to avoid detection based on the pharmacology, biochemistry, and genetics of AAS metabolism and testing principles. Another strategy used is to dope with testosterone under the guise that the athlete has a true medical condition that requires testosterone treatment, using the therapeutic use exemption (TUE) mechanism.

Misrepresentation in TUE applications is extending to amateur athletes, as testosterone prescription outside of FDA guidance increases and sport organizations broaden their efforts to police doping at all levels of competition. Strict criteria are enforced under which a TUE for testosterone use may be granted, to maintain the integrity of sport.

The challenge of upholding a zero-tolerance policy for AAS abuse, despite popular misconceptions of androgen physiology and pervasive attempts to dope among athletes and physicians, remains a daunting and evolving task for the anti-doping community.

Alquraini H, Auchus RJ. Strategies that athletes use to avoid detection of androgenic-anabolic steroid doping and sanctions. Molecular and Cellular Endocrinology. https://www.sciencedirect.com/science/article/pii/S0303720717300412

 

[Michael Scally MD]

Erythropoietin as A Performance-Enhancing Drug: Its Mechanistic Basis, Detection, And Potential Adverse Effects

Highlights

• Cheating athletes now use microdoses of erythropoiesis-stimulating agents that are difficult to detect with current validated methods.
• The development of new substances able to correct anemia in patients provide potential agents for doping purposes.
• Markers originating from transcriptomics or ironomics could be introduced in the Athlete Biological Passport to ameliorate ESAs detection.

Erythropoietin (EPO) is the main hormone regulating red blood cell (RBC) production. The large-scale production of a recombinant human erythropoietin (rHuEPO) by biotechnological methods has made possible its widespread therapeutic use as well as its misuse in sports.

Since the marketing of the first epoetin in 1989, the development has progressed to the third-generation analogs. However, the production of rHuEPO is costly, and the frequent administration of an injectable formula is not optimal for compliance of therapeutic patients.

Hence, pharmaceutical industries are currently developing alternative approaches to stimulate erythropoiesis, which might offer new candidates for doping purposes. The hypoxia inducible factors (HIF) pathway is of particular interest.

The introduction of new erythropoiesis-stimulating agents (ESAs) for clinical use requires subsequent development of anti-doping methods for detecting the abuse of these substances.

The detection of ESAs is based on two different approaches, namely, the direct detection of exogenous substances and the indirect detection, for which the effects of the substances on specific biomarkers are monitored. Omics technologies, such as ironomics or transcriptomics, are useful for the development of new promising biomarkers for the detection of ESAs.

Finally, the illicit use of ESAs associates with multiple health risks that can be irreversible, and an essential facet of anti-doping work is to educate athletes of these risks.

The aim of this review is to provide an overview of the evolution of ESAs, the research and implementation of the available detection methods, and the side effects associated with the misuse of ESAs.

Salamin O, Kuuranne T, Saugy M, Leuenberger N. Erythropoietin as a performance-enhancing drug: Its mechanistic basis, detection, and potential adverse effects. Mol Cell Endocrinol. https://www.sciencedirect.com/science/article/pii/S030372071730045X

 

[Michael Scally MD]

Clark B, Woolford SM, Eastwood A, Sharpe K, Barnes PG, Gore CJ. Temporal changes in physiology and haematology in response to high- and micro-doses of recombinant human erythropoietin. Drug Testing and Analysis. http://onlinelibrary.wiley.com/doi/10.1002/dta.2176/abstract

Temporal Changes in Physiology and Haematology In Response to High- and Micro-Doses of Recombinant Human Erythropoietin

There is evidence to suggest athletes have adopted recombinant human erythropoietin (rHuEPO) dosing regimens that diminish the likelihood they will be caught by direct detection techniques.

However, the temporal response in physiology, performance and athlete biological passport (ABP) parameters to such regimens is not clearly understood.

Participants were assigned to a

• high dose only group (HIGH, n = 8, six rHuEPO doses of 250 IU/kg over two weeks), a
• combined high micro-dose group (COMB, n = 8, high dose plus nine rHuEPO micro-doses over a further three weeks), or
• one of two placebo control groups who received saline in the same pattern as the HIGH (HIGH-PLACEBO, n = 4) or COMB (COMB-PLACEBO, n = 4) groups.

Temporal changes in physiology and performance were tracked by graded exercise test (GXT) and haemoglobin mass assessment at baseline, after high dose, after micro-dose (COMB and COMB-PLACEBO only) and after a four week washout.

Venous blood samples were collected throughout the baseline, rHuEPO administration and washout periods to determine the haematological and ABP response to each dosing regimen.

Physiological adaptations induced by a two week rHuEPO high dose were maintained by rHuEPO micro-dosing for at least three weeks.

HOWEVER, ALL PARTICIPANTS ADMINISTERED RHUEPO REGISTERED AT LEAST ONE SUSPICIOUS ABP VALUE DURING THE ADMINISTRATION OR WASHOUT PERIODS.

These results indicate there is sufficient sensitivity in the ABP to detect use of high rHuEPO doping regimens in athletic populations and they provide important empirical examples for use by anti-doping experts.