WADA ... Olympics ...

[Michael Scally MD]

Cooper ER, McGrath KC, Heather AK. In vitro androgen bioassays as a detection method for designer androgens. Sensors (Basel) 2013;13(2):2148-63. Sensors | Free Full-Text | In Vitro Androgen Bioassays as a Detection Method for Designer Androgens

Androgens are the class of sex steroids responsible for male sexual characteristics, including increased muscle mass and decreased fat mass. Illicit use of androgen doping can be an attractive option for those looking to enhance sporting performance and/or physical appearance. The use of in vitro bioassays to detect androgens, especially designer or proandrogens, is becoming increasingly important in combating androgen doping associated with nutritional supplements. The nutritional sports supplement market has grown rapidly throughout the past decade. Many of these supplements contain androgens, designer androgens or proandrogens. Many designer or proandrogens cannot be detected by the standard highly-sensitive screening methods such as gas chromatography-mass spectrometry because their chemical structure is unknown. However, in vitro androgen bioassays can detect designer and proandrogens as these assays are not reliant on knowing the chemical structure but instead are based on androgen receptor activation. For these reasons, it may be advantageous to use routine androgen bioassay screening of nutraceutical samples to help curb the increasing problem of androgen doping.

 

[pumpingiron22]

Thanks for the info. Its always great to stay in the know.

 

[Michael Scally MD]

Velloso CP, Aperghis M, Godfrey R, et al. The effects of two weeks of recombinant growth hormone administration on the response of IGF-I and N-terminal pro-peptide of collagen type III (P-III-NP) during a single bout of high resistance exercise in resistance trained young men. Growth Horm IGF Res. ScienceDirect.com - Growth Hormone & IGF Research - The effects of two weeks of recombinant growth hormone administration on the response of IGF-I and N-terminal pro-peptide of collagen type III (P-III-NP) during a single bout of high resistance exer

OBJECTIVE: Recombinant human growth hormone (rhGH) is used by some athletes and body builders with the aim of enhancing performance, building muscle and improving physique. Detection of the misuse of rhGH has proved difficult for a number of reasons. One of these is the effect of preceding exercise. In this randomised, double blind placebo-controlled study, we determined the effects of rhGH administration in male amateur athletes on two candidate markers of rhGH abuse, IGF-I and N-terminal pro-peptide of collagen type III (P-III-NP), following a bout of weightlifting exercise.

DESIGN: Sixteen men entered a four-week general weight training programme to homogenise their activity profile. They then undertook repeated bouts of standardised leg press weightlifting exercise (AHRET-acute heavy resistance exercise test). Blood samples were taken before and up to one hour after the AHRET. After the first laboratory visit (Test 1), the subjects were randomly assigned to receive daily injections of either rhGH (0.1IUkg(-1)day(-1)) or placebo for two weeks. The AHRET was repeated after the two-week dosing period (Test 2) and a further test was undertaken following a one-week washout (Test 3).

RESULTS: There was no effect of exercise on either IGF-I or P-III-NP in any test. Both markers were markedly elevated at Test 2 (p<0.001), with P-III-NP remaining elevated at Test 3 in the GH administration group (p<0.05). Application of the GH-2000 discriminant function positively identified GH administration in 17 of 40 blood samples taken at Test 2 from the rhGH group and none from the placebo group.

CONCLUSION: The data show that rhGH results in elevated levels of IGF-I and P-III-NP in well-trained individuals and that leg press weightlifting exercise does not affect these markers. The GH-2000 discriminant function identified four of eight subjects taking rhGH with no false positive results.

 

[Michael Scally MD]

Fabregat A, Pozo OJ, Marcos J, Segura J, Ventura R. The use of LC-MS/MS for the open detection of steroid metabolites conjugated with glucuronic acid. Anal Chem. The use of LC-MS/MS for the open detection of steroid metabolites conjugated with glucuronic acid - Analytical Chemistry (ACS Publications)

In humans, conjugation with glucuronic acid is the most important phase II metabolic reaction of steroidal compounds. Glucuronoconjugated metabolites have been conventionally studied by using beta-glucuronidase enzymes to release the phase I metabolites. It is well known that hydrolysis with beta-glucuronidase presents some limitations that may result on the underestimation of some conjugates. The aim of the present work was to develop and to evaluate liquid chromatography-tandem mass spectrometry (LC-MS/MS) scan methods for the open detection of steroid glucuronides in urine samples. The mass spectrometric behavior of thirteen representative steroid glucuronides, used as a model compounds, was studied. Characteristic ionization and collision induced dissociation behaviors were observed depending of the steroid glucuronide structure. Neutral loss (NL of 176, 194, 211 and 229 Da) and precursor ion (PI of m/z 141, 159 and 177, in positive mode; and m/z 75, 78 and 113, in negative mode) scan methods were evaluated. The NL scan method was chosen for the open detection of glucuronoconjugated steroids due to its sensitivity and the structural information provided by this method. The application of the NL scan method to urine samples collected after testosterone (T) undecanoate administration revealed the presence of two testosterone T metabolites which remain conjugated as glucuronides after an enzymatic hydrolysis of the urine. 3alpha,6beta-dihydroxy-5alpha-androstan-17-one (6beta-hydroxyandrosterone) glucuronide and 3alpha,6beta-dihydroxy-5beta-androstan-17-one (6beta-hydroxyetiocholanolone) glucuronide were established as the structures for these metabolites, by comparing the structure of the steroids released after chemical hydrolysis with reference materials. An increase of 50-300 folds of these metabolites after an oral administration of T undecanoate was observed, proving that their determination can be useful in the doping control field. Moreover, these results exemplify that significant information might be missed, unless direct methods for the direct determination of steroid glucuronides are employed.

 

[Michael Scally MD]

Aqai P, Cevik E, Gerssen A, Haasnoot W, Nielen MW. High-throughput bioaffinity mass spectrometry for screening and identification of designer anabolic steroids in dietary supplements. Anal Chem 2013;85(6):3255-62. High-Throughput Bioaffinity Mass Spectrometry for Screening and Identification of Designer Anabolic Steroids in Dietary Supplements - Analytical Chemistry (ACS Publications)

A generic high-throughput bioaffinity liquid chromatography-mass spectrometry (BioMS) approach was developed and applied for the screening and identification of known and unknown recombinant human sex hormone-binding globulin (rhSHBG)-binding designer steroids in dietary supplements. For screening, a semi-automated competitive inhibition binding assay was combined with fast ultrahigh-performance-LC-electrospray ionization-triple-quadrupole-MS (UPLC-QqQ-MS). 17beta-Testosterone-D3 was used as the stable isotope label of which the binding to rhSHBG-coated paramagnetic microbeads was inhibited by any other binding (designer) steroid. The assay was performed in a 96-well plate and combined with the fast LC-MS, 96 measurements could be performed within 4 h. The concentration-dependent inhibition of the label by steroids in buffer and dietary supplements was demonstrated. Following an adjusted bioaffinity isolation procedure, suspect extracts were injected into a chip-UPLC(NanoTile)-Q-time-of-flight-MS system for full-scan accurate mass identification. Next to known steroids, 1-testosterone was identified in three of the supplements studied and the designer steroid tetrahydrogestrinone was identified in a spiked supplement. The generic steroid-binding assay can be used for high-throughput screening of androgens, estrogens, and gestagens in dietary supplements to fight doping. When combined with chip-UPLC-MS, it is a powerful tool for early warning of unknown emerging rhSHBG bioactive designer steroids in dietary supplements.

 

[Michael Scally MD]

Badoud F, Boccard J, Schweizer C, Pralong F, Saugy M, Baume N. Profiling of steroid metabolites after transdermal and oral administration of testosterone by ultra-high pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. J Steroid Biochem Mol Biol. Profiling of steroid metabolites after transdermal and oral administration of testosterone by ultra-high pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometry

The screening of testosterone (T) misuse for doping control is based on the urinary steroid profile, including T, its precursors and metabolites. Modifications of individual levels and ratio between those metabolites are indicators of T misuse. In the context of screening analysis, the most discriminant criterion known to date is based on the T glucuronide to epitestosterone glucuronide (EG) ratio (TG/EG).

Following the World Anti-Doping Agency (WADA) recommendations, there is suspicion of T misuse when the ratio reaches 4 or beyond. While this marker remains very sensitive and specific, it suffers from large inter-individual variability, with important influence of enzyme polymorphisms. Moreover, use of low dose or topical administration forms makes the screening of endogenous steroids difficult while the detection window no longer suits the doping habit.

As reference limits are estimated on the basis of population studies, which encompass inter-individual and inter-ethnic variability, new strategies including individual threshold monitoring and alternative biomarkers were proposed to detect T misuse.

The purpose of this study was to evaluate the potential of ultra-high pressure liquid chromatography (UHPLC) coupled with a new generation high resolution quadrupole time-of-flight mass spectrometer (QTOF-MS) to investigate the steroid metabolism after transdermal and oral T administration. An approach was developed to quantify 12 targeted urinary steroids as direct glucuro- and sulfo-conjugated metabolites, allowing the conservation of the phase II metabolism information, reflecting genetic and environmental influences.

The UHPLC-QTOF-MSE platform was applied to clinical study samples from 19 healthy male volunteers, having different genotypes for the UGT2B17 enzyme responsible for the glucuroconjugation of T. Based on reference population ranges, none of the traditional markers of T misuse could detect doping after topical administration of T, while the detection window was short after oral TU ingestion.

The detection ability of the 12 targeted steroids was thus evaluated by using individual thresholds following both transdermal and oral administration. Other relevant biomarkers and minor metabolites were studied for complementary information to the steroid profile, including sulfoconjugated analytes and hydroxy forms of glucuroconjugated metabolites. While sulfoconjugated steroids may provide helpful screening information for individuals with homozygotous UGT2B17 deletion, hydroxy-glucuroconjugated analytes could enhance the detection window of oral T undecanoate doping.

 

[Michael Scally MD]

Highlights

• Analysis of 22 anabolic steroids and related compounds in horse hair.
• Detection of stanozolol and testosterone and boldenone esters in real world samples.
• Sensitive UHPLC–MS/MS instrumentation provides exceptional detection capability.
• Segmental analysis may provide greater understanding of the timing of administration.
• Increasing the information available to Racing Regulators.

Gray BP, Viljanto M, Bright J, Pearce C, Maynard S. Investigations into the feasibility of routine ultra high performance liquid chromatography-tandem mass spectrometry analysis of equine hair samples for detecting the misuse of anabolic steroids, anabolic steroid esters and related compounds. Anal Chim Acta 2013;787:163-72. Investigations into the feasibility of routine ultra high performance liquid chromatography–tandem mass spectrometry analysis of equine hair samples for detecting the misuse of anabolic steroids, anabolic steroid esters and related compounds

The detection of the abuse of anabolic steroids in equine sport is complicated by the endogenous nature of some of the abused steroids, such as testosterone and nandrolone. These steroids are commonly administered as intramuscular injections of esterified forms of the steroid, which prolongs their effects and improves bioavailability over oral dosing. The successful detection of an intact anabolic steroid ester therefore provides unequivocal proof of an illegal administration, as esterified forms are not found endogenously.

Detection of intact anabolic steroid esters is possible in plasma samples but not, to date, in the traditional doping control matrix of urine. The analysis of equine mane hair for the detection of anabolic steroid esters has the potential to greatly extend the time period over which detection of abuse can be monitored.

Equine mane hair samples were incubated in 0.1M phosphate buffer (pH 9.5) before anabolic steroids (testosterone, nandrolone, boldenone, trenbolone and stanozolol), anabolic steroid esters (esters of testosterone, nandrolone, boldenone and trenbolone) and associated compounds (fluticasone propionate and esters of hydroxyprogesterone) were extracted by liquid-liquid extraction with a mix of hexane and ethyl acetate (7:3, v:v). Further sample clean up by solid phase extraction was followed by derivatisation with methoxylamine HCL and analysis by UHPLC-MS/MS.

Initial method development was performed on a representative suite of four testosterone esters (propionate, phenylpropionate, isocaproate and decanoate) and the method was later extended to include a further 18 compounds. The applicability of the method was demonstrated by the analysis of mane hair samples collected following the intramuscular administration of 500mg of Durateston((R)) (mixed testosterone esters) to a Thoroughbred mare (560kg).

The method was subsequently used to successfully detect boldenone undecylenate and stanozolol in hair samples collected following suspicious screening findings from post-race urine samples. The use of segmental analysis to potentially provide additional information on the timing of administration was also investigated.

 

[Michael Scally MD]

Guha N, Cowan DA, Sonksen PH, Holt RI. Insulin-like growth factor-I (IGF-I) misuse in athletes and potential methods for detection. Anal Bioanal Chem. Insulin-like growth factor-I (IGF-I) misuse in athletes and potential methods for detection - Online First - Springer

To athletes, insulin-like growth factor-I (IGF-I) is an attractive performance-enhancing drug, particularly as an alternative to growth hormone (GH) because IGF-I mediates many of the anabolic actions of GH. IGF-I has beneficial effects on muscle protein synthesis and glycogen storage that could enhance performance in several sporting disciplines. Recombinant human IGF-I (rhIGF-I) is used in clinical practice, but a variety of IGF-I compounds and IGF-I analogues are also advertised on the internet and many have been available on the black market for several years. Although methods for detecting GH misuse are now well established and there have been several cases in which athletes have tested positive for GH, no test is yet in place for detecting IGF-I misuse. The GH-2004 research group has been investigating methods for detection of IGF-I misuse and a test is being developed on the basis of the principles of the successful GH-2000 marker method, in which markers from the IGF axis and markers of collagen and bone turnover are used to detect GH misuse. Commercial immunoassays for these markers have been validated for anti-doping purposes but new methods, including IGF-I measurement by use of mass spectrometry, should improve the performance of the tests and help in the detection of athletes who are doping with these peptide hormones.

 

[Michael Scally MD]

What were the pills?

Ryder suspended over diet pills
Ryder suspended over diet pills | Otago Daily Times Online News : Otago, South Island, New Zealand & International News

 

[Michael Scally MD]

Sanchis-Gomar F, Galeano HP, Brioche T, Martinez-Bello V, Lippi G. Altitude exposure in sports: the Athlete Biological Passport standpoint. Drug Testing and Analysis. Altitude exposure in sports: the Athlete Biological Passport standpoint - Sanchis-Gomar - 2013 - Drug Testing and Analysis - Wiley Online Library

The Athlete Biological Passport (ABP) is principally founded on monitoring an athlete's biological variables over time, to identify abnormal biases on a longitudinal basis. Several factors are known to influence the results of these markers. However, the manner in which the altitude factor is taken into account still needs to be standardized. Causal relationships between haematological variables should be correctly integrated into ABP software. In particular, modifications of haematological parameters during and after exposure to different altitudes/hypoxic protocols need to be properly included within detection models.

 

[Michael Scally MD]

Athletes' biological passports will track steroid use
Athletes' biological passports will track steroid use - life - 31 December 2013 - New Scientist

SPORTS cheats beware. As of 1 January, professional athletes became subject to routine checks on steroid concentrations in their urine. These tests won't be used to spot specific drugs, but to form a baseline by which to detect any future suspicious deviations from the athlete's normal physiology. The checks have been added to the World Anti-Doping Agency's "biological passport", a procedure for monitoring every athlete's metabolic profile.

 

[Michael Scally MD]

Zhang L, Thevis M, Piper T, et al. Carbon isotope ratio analysis of steroids by high temperature liquid chromatography - isotope ratio mass spectrometry. Anal Chem. Carbon isotope ratio analysis of steroids by high temperature liquid chromatography - isotope ratio mass spectrometry - Analytical Chemistry (ACS Publications)

Generally, compound-specific isotope analysis of steroids is carried out by gas chromatography combined with isotope ratio mass spectrometry. Thus, a derivatization of the steroids prior the measurement is compulsory and a correction of the isotopic data is often necessary. To overcome this limitation, we present a new approach of high-temperature liquid chromatography coupled with photodiode array detection and isotope ratio mass spectrometry (HT-LC/PDA/IRMS) for the carbon isotope ratio analysis of unconjugated steroids. A steroid mixture containing 19-norandrosterone, testosterone, epitestosterone, androsterone, 5beta-pregnane-3alpha,17alpha,20alpha-triol was fully separated on a C4 column under high-temperature elution with water as sole eluent. The accuracy for isotope analysis (+/-0.5 per thousand) were around 20 microg g-1 for testosterone, epitestosterone (79 ng steroid absolute on column), and 30 microg g-1 for 19-norandrosterone, androsterone and 5beta-pregnane-3alpha,17alpha,20alpha-triol (119 ng steroid absolute on column). The applicability of the method was tested by measuring a pharmaceutical gel containing testosterone. With this work, the scope of LC/IRMS applications has been extended to non-polar compounds.

 

[Michael Scally MD]

New Doping Substance May Be Circulating in Sochi - Mechano Growth Factor (MGF).
New Doping Substance May Be Circulating in Sochi | Science/AAAS | News

A new substance may be in the mix: On 2 February, television reporters for the German WDR network broadcast their undercover investigation of a Russian scientist willing to sell them 100 milligrams of something called “full-size MGF” for $100,000.

The reporters brought a sample to anti-doping expert Mario Thevis, a forensic chemist at the Center for Preventive Doping Research at the German Sport University Cologne.

He confirmed the sample contained mechano growth factor (MGF), a variant of the human insulin-like growth factor-1 (IGF-1) protein, which can prompt muscle growth.

It would be undetectable by current testing methods.

Thevis spoke with ScienceInsider from Sochi.

 

[Michael Scally MD]

Breathe it in
An obscure gas improves athletes’ performance
Athletic enhancement: Breathe it in | The Economist

XENON is one of the shyest members of the periodic table of the elements. Chemically, it is almost inert, and physically, it makes up only 0.000009% of the atmosphere, so it is not surprising that it was among the last of the naturally occurring elements to be identified, in 1898. Biologically, however, it is not shy at all. In some countries, notably Russia, it is used as an anaesthetic. It is also known to protect body tissues from the effects of low temperatures, lack of oxygen and even physical trauma. In particular, it increases levels of erythropoietin, also known as EPO, a hormone that encourages the formation of red blood cells.

Xenon's protective and EPO-boosting properties mean it is being investigated as a treatment for babies whose brains have accidentally been starved of oxygen during birth, and of adults who have had heart attacks. But it is also, in Russia, being used as a way to improve athletic performance.

Xenon works its magic by activating production of a protein called Hif-1 alpha. This acts as a transcription factor: a chemical switch that turns on production of a variety of other proteins, one of which is EPO. Artificially raising levels of EPO, by injecting synthetic versions of the hormone or by taking so-called Hif stabilisers (drugs that discourage the breakdown of Hif-1 alpha), is illegal under the rules of the World Anti-Doping Agency (WADA). Other methods of boosting the hormone, however, are permissible--and that fact has not gone unnoticed by the Russian sports authorities. Athletes are allowed to live or train at altitude, or sleep in a low-oxygen tent, in order to stimulate red-cell production. If xenon treatment is merely replicating low-oxygen environments by replacing oxygen with xenon, then its use to enhance athletic performance is permissible.

The use of xenon by athletes certainly has government blessing. A document produced in 2010 by the State Research Institute of the Ministry of Defence sets out guidelines for the administration of the gas to athletes. It advises using it before competitions to correct listlessness and sleep disruption, and afterwards to improve physical recovery. The recommended dose is a 50:50 mixture of xenon and oxygen, inhaled for a few minutes, ideally before going to bed. The gas's action, the manual states, continues for 48-72 hours, so repeating every few days is a good idea. And for last-minute jitters, a quick hit an hour before the starting gun can help.

The benefits, the manual suggests, include increasing heart and lung capacity, preventing muscle fatigue, boosting testosterone and improving an athlete's mood. Similar benefits have been noted in papers in Russian scientific journals, and in conference presentations describing tests of xenon on mountain climbers, paddlers, soldiers and pilots.

And the gas appears to have been used in past Olympics. The website of Atom Medical Centre, a Russian medical-xenon producer, cites national honours the company received for its efforts in preparing athletes for the 2004 summer Olympics and the 2006 winter games.

Something the published Russian reports do not go into, however, are measurements of EPO or Hif-1 alpha. Yet animal studies elsewhere have demonstrated xenon's dramatic effects on both. One such, carried out in 2009 by Mervyn Maze at Imperial College, London, found that exposing mice to a mixture of 70% xenon and 30% oxygen for two hours more than doubled the animals' EPO levels a day later. Another, by Xiaoqiang Ding of Fudan University in Shanghai, found that Hif-1 alpha levels in mice stayed high for up to 48 hours after treatment. By contrast, mice put in a low-oxygen enclosure saw an EPO increase that lasted less than two hours.

Similar physiological effects may take place in people. In healthy adults, two hours in a low-oxygen chamber raises EPO levels by 50%, and the effect disappears (as in mice) within a few hours. The Russian manual indicates, by contrast, that xenon's benefits last for days--as might be expected if they were caused by the sort of Hif-1 alpha response seen in mice.

Whether xenon treatment will pass muster if and when WADA scrutinises it remains to be seen--and will no doubt depend on the finer points of the gas's biological action, many of which are still muddy. In the meantime, sports trainers around the world might be tempted to follow Russia's example, and reap xenon's benefits before the regulators catch up.

 

[Michael Scally MD]

Cheat Sheet: The Tyson Gay File
Cheat Sheet: The Tyson Gay File - ProPublica

Last July, U.S. sprinter Tyson Gay held the fastest 100-meter time in the world. He appeared primed to give world record holder Usain Bolt a run for the crown at the 2013 world championships in Moscow the following month.

But instead of discussing his acceleration phase, Gay struggled through sobs as he told reporters that he’d failed a drug test.

People with knowledge of USADA’s ongoing investigation have told ProPublica that the sprinter tested positive for a steroid or steroid precursor believed to have come from a cream given to him by Atlanta chiropractor and anti-aging specialist Clayton Gibson III.

The saga of the nation’s top sprinter likely done in by an obscure cream delivered by an anti-aging practitioner provides a view of the slipshod medical underworld of top-level sport, in which athletes risk their reputations in the enduring hunt for any competitive edge.

The label on the cream Gay is believed to have used starkly says “Testosterone/DHEA Crème,” and lists testosterone and DHEA among its ingredients.

Was this the cream?

 

[Michael Scally MD]

[Old News Recycled] Bodybuilders Take Breast Cancer Drug
http://www.the-scientist.com/?artic...7/title/Bodybuilders-Take-Breast-Cancer-Drug/

Tamoxifen, an endocrine therapy for women with breast cancer, is found in a supplement marketed to bodybuilders.

For decades, some bodybuilders who’ve taken steroids to help increase their muscle mass have illegally purchased the breast cancer drug tamoxifen to prevent breast enlargement.

But according to new research from Liverpool John Moores University in the U.K., others may simply have bought the dietary supplement Esto Suppress, which was found to contain the drug in three out of four samples tested by the investigators, who published their results last week (February 13) as a letter in the British Medical Journal (BMJ). Is the breast cancer drug tamoxifen being sold as a bodybuilding dietary supplement? | BMJ

 

[Michael Scally MD]

Advances in the Detection of Designer Steroids in Anti-Doping
[For Full-Text Email mscally@alum.mit.edu (Include Title)]

The abuse of unknown designer androgenic anabolic steroids (AAS) is considered to be an issue of significant importance, as AAS are the choice of doping preference according to World Anti-doping Agency statistics.

In addition, unknown designer AAS are preferred since the World Anti-doping Agency mass spectrometric identification criteria cannot be applied to unknown molecules.

Consequently, cheating athletes have a strong motive to use designer AAS in order to both achieve performance enhancement and to escape from testing positive in anti-doping tests.

To face the problem, a synergy is required between the anti-doping analytical science and sports anti-doping regulations.

This Review examines various aspects of the designer AAS.

First, the structural modifications of the already known AAS to create new designer molecules are explained. A list of the designer synthetic and endogenous AAS is then presented.

Second, we discuss progress in the detection of designer AAS using: mass spectrometry and bioassays; analytical data processing of the unknown designer AAS; metabolite synthesis; and, long-term storage of urine and blood samples.

Finally, the introduction of regulations from sports authorities as preventive measures for long-term storage and reprocessing of samples, initially reported as negatives, is discussed.

Abushareeda W, Fragkaki A, Vonaparti A, et al. Advances in the detection of designer steroids in anti-doping. Bioanalysis 2014;6(6):881-96. http://www.future-science.com/doi/abs/10.4155/bio.14.9 (An Error Occurred Setting Your User Cookie)

 

[Michael Scally MD]

Dvorak J, Saugy M, Pitsiladis YP. Challenges and threats to implementing the fight against doping in sport. Br J Sports Med 2014;48(10):807-9. Challenges and threats to implementing the fight against doping in sport -- Dvorak et al. 48 (10): 807 -- British Journal of Sports Medicine

Prominent doping cases in certain sports have recently raised public awareness of doping and reinforced the perception that doping is widespread. Efforts to deal with doping in sport have intensified in recent years, yet the general public believes that the 'cheaters' are ahead of the testers. Therefore, there is an urgent need to change the antidoping strategy. For example, the increase in the number of individual drug tests conducted between 2005 and 2012 was approximately 90 000 and equivalent to an increase of about 50%, yet the number of adverse analytical findings remained broadly the same. There is also a strikingly different prevalence of doping substances and methods in sports such as a 0.03% prevalence of anabolic steroids in football compared to 0.4% in the overall WADA statistics. Future efforts in the fight against doping should therefore be more heavily based on preventative strategies such as education and on the analysis of data and forensic intelligence and also on the experiences of relevant stakeholders such as the national antidoping organisations, the laboratories, athletes or team physicians and related biomedical support staff. This strategy is essential to instigate the change needed to more effectively fight doping in sport.


Dvorak J, Baume N, Botre F, et al. Time for change: a roadmap to guide the implementation of the World Anti-Doping Code 2015. Br J Sports Med 2014;48(10):801-6. Time for change: a roadmap to guide the implementation of the World Anti-Doping Code 2015 -- Dvorak et al. 48 (10): 801 -- British Journal of Sports Medicine

A medical and scientific multidisciplinary consensus meeting was held from 29 to 30 November 2013 on Anti-Doping in Sport at the Home of FIFA in Zurich, Switzerland, to create a roadmap for the implementation of the 2015 World Anti-Doping Code. The consensus statement and accompanying papers set out the priorities for the antidoping community in research, science and medicine. The participants achieved consensus on a strategy for the implementation of the 2015 World Anti-Doping Code. Key components of this strategy include: (1) sport-specific risk assessment, (2) prevalence measurement, (3) sport-specific test distribution plans, (4) storage and reanalysis, (5) analytical challenges, (6) forensic intelligence, (7) psychological approach to optimise the most deterrent effect, (8) the Athlete Biological Passport (ABP) and confounding factors, (9) data management system (Anti-Doping Administration & Management System (ADAMS), (10) education, (11) research needs and necessary advances, (12) inadvertent doping and (13) management and ethics: biological data. True implementation of the 2015 World Anti-Doping Code will depend largely on the ability to align thinking around these core concepts and strategies. FIFA, jointly with all other engaged International Federations of sports (Ifs), the International Olympic Committee (IOC) and World Anti-Doping Agency (WADA), are ideally placed to lead transformational change with the unwavering support of the wider antidoping community. The outcome of the consensus meeting was the creation of the ad hoc Working Group charged with the responsibility of moving this agenda forward.

 

[Michael Scally MD]

Anabolic steroids are mainly excreted through the urinary route, requiring modifications of their hydrophobic chemical structures. Phase I and phase II metabolic reactions are responsible for, respectively, functionalisation and addition of conjugates (ie, glucuronides or sulfates) to steroids, thereby increasing their hydrophilicity and allowing their dissolution and elimination in urine mixture.

Since steroid conjugates analysis is not compatible with GC-MS, the only analytical technique recognised by WADA for endogenous steroids quantification in urine, deconjugation of the conjugated moiety by enzymatic hydrolysis (?-glucuronidase) is a crucial step during sample preparation and prior to GC-MS measurement.

Kuuranne T, Saugy M, Baume N. Confounding factors and genetic polymorphism in the evaluation of individual steroid profiling. Br J Sports Med 2014;48(10):848-55. Confounding factors and genetic polymorphism in the evaluation of individual steroid profiling -- Kuuranne et al. 48 (10): 848 -- British Journal of Sports Medicine

In the fight against doping, steroid profiling is a powerful tool to detect drug misuse with endogenous anabolic androgenic steroids. To establish sensitive and reliable models, the factors influencing profiling should be recognised.

We performed an extensive literature review of the multiple factors that could influence the quantitative levels and ratios of endogenous steroids in urine matrix. For a comprehensive and scientific evaluation of the urinary steroid profile, it is necessary to define the target analytes as well as testosterone metabolism.

The two main confounding factors, that is, endogenous and exogenous factors, are detailed to show the complex process of quantifying the steroid profile within WADA-accredited laboratories. Technical aspects are also discussed as they could have a significant impact on the steroid profile, and thus the steroid module of the athlete biological passport (ABP).

The different factors impacting the major components of the steroid profile must be understood to ensure scientifically sound interpretation through the Bayesian model of the ABP. Not only should the statistical data be considered but also the experts in the field must be consulted for successful implementation of the steroidal module.

Target analytes of the steroid profile, their interindependence and metabolic pathway.
5?-/5?-diol, 5?/5?-androstane-3?,17?-diol;
DHEA, dehydroepiandrosterone;
DHT, dihydrotestosterone.

 

[Michael Scally MD]

Raschka C, Chmiel C, Preiss R, Boos C. [Recreational athletes and doping--a survey in 11 gyms in the area of Frankfurt/Main]. MMW Fortschr Med 2014;155 Suppl 2:41-3. http://www.ncbi.nlm.nih.gov/pubmed/24930320

BACKGROUND: Doping no longer concerns exclusively competitive sports, but also recreational sports.

METHOD: Survey of 484 recreational athletes in 11 gyms in the area of Frankfurt/Main.

RESULTS: 12.9% of the men and 3.6% of the women reported to take anabolic drugs. They consumed anabolic steroids (100%; 35% p.o., 71% parenterally), stimulants (14%) and growth hormone (5%). Suppliers were friends (39%), sports mates (28%), physicians (28%) and coaches (6%).

The acquisition costs amounted to an average intake over 9 weeks to 175 Euro.

Information about doping side effects came from literature (67%), physicians (38%), sports mates and the so-called Black Book (14% respectively), coaches, friends and Internet (5% respectively).

2% of the athletes with abuse of doping substances were smokers, 11% had a drink several times a week, 3% also consumed other drugs, 35% had consumed other drugs in the past.

Abusers of doping substances primarily intended to increase muscle size (86%) and strength (61%).

CONCLUSION: From a sports medical point of view it is concerning that the proportion of doping drugs prescribed by physicians has doubled in the decade after the publication of the predecessor study in Northern Germany despite optimized sports medical and legal education measures.