World Anti-Doping Agency List Research Articles

Probing the hair detectability of prohibited substances in sports: an in vivo-in silico-clinical approach and analytical implications compared with plasma, urine, and faeces

Hair analysis is a crucial method in forensic toxicology with potential applications in revealing doping histories in sports. Despite its widespread use, knowledge about detectable substances in hair is limited. This study systematically assessed the detectability of prohibited substances in sports using a multifaceted approach. Initially, an animal model received a subset of 17 model drugs to compare dose dependencies and detection windows across different matrices. Subsequently, hair incorporation data from the animal experiment were extrapolated to all substances on the World Anti-Doping Agency’s List through in-silico prediction. The detectability of substances in hair was further validated in a proof-of-concept human study involving the consumption of diuretics and masking agents. Semi-quantitative analysis of substances in specimens was performed using ultra-performance liquid chromatography–tandem mass spectrometry. Results showed plasma had optimal dose dependencies with limited detection windows, while urine, faeces, and hair exhibited a reasonable relationship with the administered dose. Notably, hair displayed the highest detection probability (14 out of 17) for compounds, including anabolic agents, hormones, and diuretics, with beta-2 agonists undetected. Diuretics such as furosemide, canrenone, and hydrochlorothiazide showed the highest hair incorporation. Authentic human hair confirmed diuretic detectability, and their use duration was determined via segmental analysis. Noteworthy is the first-time reporting of canrenone in human hair. Anabolic agents were expected in hair, whereas undetectable compounds, such as peptide hormones and beta-2 agonists, were likely due to large molecular mass or high polarity. This study enhances understanding of hair analysis in doping investigations, providing insights into substance detectability.

Self-Declared and Measured Prevalence of Glucocorticoid Use in Polish Athletes

Glucocorticoids (GCs) are included in the list of prohibited substances and methods in sport published annually by the World Anti-Doping Agency (WADA). In its 2022 update, the WADA list prohibits all injectable routes of administration of GCs for use during in-competition periods. Previously, GCs were prohibited in-competition when administered by oral, intravenous, intramuscular, or rectal routes, but local injections (in addition to topical applications) were allowed. This study first investigated the prevalence of GC use by athletes in Poland, declared in 2130 doping control forms, and the related 2130 urine samples analysed at the Polish Anti-Doping Laboratory. Second, the validity of the analytical methodology to detect GCs was evaluated with the updated WADA requirement for substance-specific minimum reporting levels and considering the proposed washout periods. Despite the new regulation in place, the use of 30 different GC preparations were declared in a total of 162 occurrences (8% of the tests) with therapeutic purposes. Laboratory analyses resulted in the presence of GCs in 16 occurrences with only two samples with a concentration triggering an adverse analytical finding. Our study allowed us to confirm that the applied methodology for the determination of GCs in urine samples (ultra-high-performance liquid chromatography–tandem mass spectrometry) remains fully valid after the latter regulation change while the challenge to assess the timing and administration route for GCs persists.

In‐depth gas chromatography/tandem mass spectrometry fragmentation analysis of formestane and evaluation of mass spectral discrimination of isomeric 3‐keto‐4‐ene hydroxy steroids

The aromatase inhibitor formestane (4-hydroxyandrost-4-ene-3,17-dione) is included in the World Anti-Doping Agency's List of Prohibited Substances in Sport. However, it also occurs endogenously as do its 2-, 6- and 11-hydroxy isomers. The aim of this study is to distinguish the different isomers using gas chromatography/electron ionization mass spectrometry (GC/EI-MS) for enhanced confidence in detection and selectivity for determination. Established derivatization protocols to introduce [2 H9 ]TMS were followed to generate perdeuterotrimethylsilylated and mixed deuterated derivatives for nine different hydroxy steroids, all with 3-keto-4-ene structure. Formestane was additionally labelled with H2 18 O to obtain derivatives doubly labelled with [2 H9 ]TMS and 18 O. GC/EI-MS spectra of labelled and unlabelled TMS derivatives were compared. Proposals for the generation of fragment ions were substantiated by high-resolution MS (GC/QTOFMS) and tandem mass spectrometry (MS/MS) experiments. Subclass-specific fragment ions include m/z 319 for the 6-hydroxy and m/z 219 for the 11-hydroxy compounds. Ions at m/z 415, 356, 341, 313, 269 and 267 were indicative for the 2- and 4-hydroxy compounds. For their discrimination the transition m/z 503 → 269 was selective for formestane. In 2-, 4- and 6-hydroxy steroids loss of a TMSO radical takes place as cleavage of a TMS-derived methyl radical and a neutral loss of (CH3 )2 SiO. Further common fragments were also elucidated. With the help of stable isotope labelling, the structures of postulated diagnostic fragment ions for the different steroidal subclasses were elucidated. 18 O-labelling of the other compounds will be addressed in future studies to substantiate the obtained findings. To increase method sensitivity MS3 may be suitable in future bioanalytical applications requiring discrimination of the 2- and 4-hydroxy compounds.

Identification of S22 (ostarine) in human nails and hair using LC‐HRMS. Application to two authentic cases

Ostarine, also known as S22 or MK2866 and enobosarm, is a selective androgen receptor modulator (SARM). It has high anabolic potency, in addition to limited androgenic effects. At this time, ostarine has no therapeutic use, but can be abused for performance-enhancing purposes using the oral route, at dosages of 10-25 mg per day. As the drug can easily be obtained via the Internet or some fitness centers, athletes and more and more amateurs can use it without undergoing the deleterious physiological side effects that are generally associated with testosterone-related compounds. Since 2008, the World Anti-Doping Agency (WADA) has prohibited SARMs at-all-times in the category of "other anabolic agents" under section S1.2 of the WADA List. In a case of trafficking/abuse, ostarine was identified in nail (subject 1) and hair (subject 2) by LC/HRMS after incubation of 50 mg of matrix in a pH 9.5 buffer, followed by extraction with organic solvents. The drug was quantitated by LC-MS/MS. Ostarine tested positive at 61 pg/mg (toenails) and 111 pg/mg (fingernails) for subject 1. Ostarine was present at 146, 168, 93, and 101 pg/mg in the 4 × 3 cm hair sections of subject 2, clearly demonstrating long-term use.

Urinary excretion studies of meldonium after multidose parenteral application

Meldonium is a drug exhibiting cardioprotective and anti-ischemic effects. Due to its potential performance-enhancing benefit in sports, meldonium was added to the World Anti-Doping Agency list of prohibited substances in 2016. Since then, a high number of adverse analytical findings reported on meldonium has questioned meldonium`s detection time in urine. Hence, the objective of the current study was to characterize the pharmacokinetic urinary excretion pattern of meldonium when administered as multiple intravenous injections. Three injections of 250 mg meldonium were given over a time period of five days to six healthy volunteers and urine samples were collected for eight months after the last injection of the drug. For the quantification of meldonium in urine, a liquid chromatography-tandem mass spectrometry method was fully validated according to the World Anti-Doping Agency guidelines in terms of specificity, matrix interferences, intra- and inter-day precision, accuracy, carry-over, robustness, linearity, limit of detection, and limit of quantification. The assay was successfully applied to the pharmacokinetic study. A three-compartment model was found to best describe the pharmacokinetics of meldonium with average alpha, beta, and gamma half-lives of 1.4 h, 9.4 h, and 655 h, respectively. The detection time in urine varied between 94 and 162 days.

Effects of short-term DHEA intake on hormonal responses in young recreationally trained athletes: modulation by gender.

Dehydroepiandrosterone (DHEA) figures on the World Anti-Doping Agency list of prohibited substances in sport because it is assumed that athletes expect a significant increase in testosterone through DHEA administration. The literature on the hormonal effects of DHEA intake nevertheless appears to be very scant in healthy young subjects, especially women. We examined the effects of DHEA on adrenal and gonadal hormones, IGF1 and free T3 in healthy young male and female recreationally trained volunteers. The study followed a double-blind, randomized-order crossover design. Lean healthy young men (n = 10) and women (n = 11), with all women using oral contraceptives, were treated daily with 100 mg of DHEA and placebo for 4 weeks. DHEA, DHEA-sulfate (DHEA-S), androstenedione, total testosterone (Tes), dihydrotestosterone (DHT), SHBG, estrone, cortisol, IGF1, and free T3 were measured before, in the middle and at the end of each treatment, as were blood glucose, liver transaminases and lipid status. We observed a significant increase in DHEA, DHEA-S, androstenedione, Tes, DHT, and estrone in both men and women in the middle and at the end of DHEA treatment, but the increase in Tes was more marked in women (p < 0.001) than men (p < 0.05). No changes were found in the other parameters, irrespective of gender. In young athletes, DHEA administration induces significant blood hormonal changes, some modulated by gender, which can be used as biomarkers of doping.

Phosphodiesterase Type 5 Inhibitors, Sport and Doping.

Phosphodiesterase type 5 inhibitors (PDE5i) (e.g., sildenafil, tadalafil, vardenafil, and avanafil) are drugs commonly used to treat erectile dysfunction, pulmonary arterial hypertension, and benign prostatic hyperplasia. PDE5i are not prohibited by the World Anti-Doping Agency (WADA) but are alleged to be frequently misused by healthy athletes to improve sporting performance. In vitro and in vivo studies have reported various effects of PDE5i on cardiovascular, muscular, metabolic, and neuroendocrine systems and the potential, therefore, to enhance performance of healthy athletes during training and competition. This suggests well-controlled research studies to examine the ergogenic effects of PDE5i on performance during activities that simulate real sporting situations are warranted to determine if PDE5i should be included on the prohibited WADA list. In the meantime, there is concern that some otherwise healthy athletes will continue to misuse PDE5i to gain an unfair competitive advantage over their competitors.

Pharmacokinetics and pharmacodynamics of meldonium in exercised thoroughbred horses.

Although developed as a therapeutic medication, meldonium has found widespread use in human sports and was recently added to the World Anti-Doping Agency's list of prohibited substances. Its reported abuse potential in human sports has led to concern by regulatory authorities about the possible misuse of meldonium in equine athletics. The potential abuse in equine athletes along with the limited data available regarding the pharmacokinetics and pharmacodynamics of meldonium in horses necessitates further study. Eight exercised adult thoroughbred horses received a single oral dose of 3.5, 7.1, 14.3 or 21.4 mg/kg of meldonium. Blood and urine samples were collected and analyzed using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were determined using non-compartmental analysis. Maximum serum concentrations ranged from 440.2 to 1147 ng/mL and the elimination half-life from 422 to 647.8 h. Serum concentrations were below the limit of quantitation by days 4, 7, 12 and 12 for doses of 3.5, 7.1, 14.3 and 21.4 mg/kg, respectively. Urine concentrations were below the limit of detection by day 44 following administration of 3.5 mg/kg and day 51 for all other dose groups. No adverse effects were observed following meldonium administration. While the group numbers were small, changes in heart rate were observed in the 3.5 mg/kg dose group (n = 1). Glucose concentrations changed significantly in all dose groups studied (n = 2 per dose group). Similar to that reported for humans, the detection time of meldonium in biological samples collected from horses is prolonged, which should allow for satisfactory regulation in performance horses. Copyright © 2017 John Wiley & Sons, Ltd.

Terbutaline Accumulates in Blood and Urine after Daily Therapeutic Inhalation.

This study investigated pharmacokinetics of terbutaline after single and seven consecutive days of inhalation in exercising trained men. Twelve healthy trained men underwent two pharmacokinetic trials comparing single dose (2 mg) and seven consecutive days (2 mg·d) of inhaled terbutaline. After inhalation of terbutaline at each trial, subjects performed 90 min of bike ergometer exercise at 55%-65% of maximal oxygen consumption after which they stayed inactive. Blood and urine samples were collected before and after inhalation of terbutaline. Samples were analyzed by high-performance liquid chromatography-tandem mass spectrometry. Maximum serum concentration of terbutaline (Cmax) (6.4 ± 1.2 vs 4.9 ± 1.2 ng·mL, P = 0.01) (mean ± 95% confidence interval) and area under serum concentration-time curve from 0 to 4 h after inhalation (AUC0-4) (16 ± 3 vs 13 ± 2 ng·mL·h, P ≤ 0.005) were higher after 7 d of inhalation compared with the first day. Seven days of terbutaline inhalation resulted in accumulation of terbutaline in urine, in which total urine excretion of terbutaline was higher after 7 d of inhalation compared with the first day (274 ± 43 vs 194 ± 33 μg, P ≤ 0.001). These differences were partly attributed to systemic accumulation of terbutaline after consecutive days of inhalation, in that baseline serum and urine samples revealed incomplete elimination of terbutaline. Terbutaline accumulates in serum and urine after consecutive days of inhalation. For doping control purposes, these observations are of relevance if a urine threshold and decision limit is to be introduced for terbutaline on the World Anti-Doping Agency's list of prohibited substances because asthmatic athletes may use their bronchorelievers for consecutive days.

Carnitine and γ-Butyrobetaine Stimulate Elimination of Meldonium due to Competition for OCTN2-mediated Transport.

Meldonium (3-(2,2,2-trimethylhydrazinium)propionate) is the most potent clinically used inhibitor of organic cation transporter 2 (OCTN2). Inhibition of OCTN2 leads to a decrease in carnitine and acylcarnitine contents in tissues and energy metabolism optimization-related cardioprotective effects. The recent inclusion of meldonium in the World Anti-Doping Agency List of Prohibited Substances and Methods has raised questions about the pharmacokinetics of meldonium and its unusually long elimination time. Therefore, in this study, the rate of meldonium washout after the end of the treatment was tested with and without administration of carnitine, γ-butyrobetaine (GBB) and furosemide to evaluate the importance of competition for OCTN2 transport in mice. Here, we show that carnitine and GBB administration during the washout period effectively stimulated the elimination of meldonium. GBB induced a more pronounced effect on meldonium elimination than carnitine due to the higher affinity of GBB for OCTN2. The diuretic effect of furosemide did not significantly affect the elimination of meldonium, carnitine and GBB. In conclusion, the competition of meldonium, carnitine and GBB for OCTN2-mediated transport determines the pharmacokinetic properties of meldonium. Thus, due to their affinity for OCTN2, GBB and carnitine but not furosemide stimulated meldonium elimination. During long-term treatment, OCTN2-mediated transport ensures a high muscle content of meldonium, while tissue clearance depends on relatively slow diffusion, thus resulting in the unusually long complete elimination period of meldonium.

The use of performance-enhancing substances (doping) by athletes in Saudi Arabia.

BACKGROUND:Data on doping violation in Saudi Arabia are scarce. Our aim was to investigate the Saudi experience of anti-doping and review all positive samples and adverse analytical findings (AAFs) of Saudi athletes.MATERIALS AND METHODS:This study analyzed databases of the Saudi Arabian Anti-Doping Committee from 2008 to May 2016. The samples originated from various sporting events and were collected in and outside sport competitions. The substances investigated were those included in the annual lists of prohibited substances produced by the World Anti-Doping Agency (WADA). All urine samples were tested in laboratories accredited by the WADA. Samples were declared positive if they contained any prohibited substance on the WADA list for that year.RESULTS:In 4482 urine samples tested, 141 positive samples (3.1%) and 195 AAFs of prohibited substances were detected. The prevalence of positive samples was highest in 2012 (6.6%) and lowest in 2015 (1%). The most prevalent prohibited substances detected were anabolic steroids (32.8%) and stimulants (27.6%). The most frequently detected compounds were amphetamines (22%) and tetrahydrocannabinol (12.8%). The highest prevalence of AAFs was in bodybuilders.CONCLUSION:The prevalence of doping in Saudi Arabia seems to be higher than western countries, but this needs to be confirmed with further research.

Immunoextraction-tandem mass spectrometry method for measuring intact human chorionic gonadotropin, free β-subunit, and β-subunit core fragment in urine.

Human chorionic gonadotropin (hCG) stimulates testosterone production by the testicles. Because of the potential for abuse, hCG is banned (males only) in most sports and has been placed on the World Anti-Doping Agency list of prohibited substances. Intact hCG, free β-subunit (hCGβ), and β-subunit core fragment (hCGβcf) are the major variants or isoforms in urine. Immunoassays are used by antidoping laboratories to measure urinary hCG. Cross-reactivity with isoforms differs among immunoassays, resulting in widely varying results. We developed a sequential immunoextraction method with LC-MS/MS detection for quantification of intact hCG, hCGβ, and hCGβcf in urine. hCG isoforms were immunoextracted with antibody-conjugated magnetic beads and digested with trypsin, and hCGβ and hCGβcf unique peptides were quantified by LC-MS/MS with the corresponding heavy peptides as internal standard. hCG isoform concentrations were determined in urine after administration of hCG, and the intact hCG results were compared to immunoassay results. The method was linear to 20 IU/L. Total imprecision was 6.6%-13.7% (CV), recovery ranged from 91% to 109%, and the limit of quantification was 0.2 IU/L. Intact hCG predominated in the urine after administration of 2 hCG formulations. The window of detection ranged from 6 to 9 days. Mean immunoassay results were 12.4-15.5 IU/L higher than LC-MS/MS results. The performance characteristics of the method are acceptable for measuring hCG isoforms, and the method can quantify intact hCG and hCGβ separately. The limit of quantification will allow LC-MS/MS hCG reference intervals to be established in nondoping male athletes for improved doping control.

ASSESSING NUTRITIONAL KNOWLEDGE AND SUPPLEMENTATION PRACTICES IN ELITE BADMINTON PLAYERS

Badminton is an “intermittent” racquet sport, requiring technical skill and sport-specific-fitness. This study aimed to assess the nutritional knowledge of badminton players to shape the delivery of future support, and...

A population study of urine glycerol concentrations in elite athletes competing in North America

Glycerol is an endogenous substance that is on the World Anti-Doping Agency's list of prohibited threshold substances due to its potential use as a plasma volume expansion agent. The WADA has set the threshold for urine glycerol, including measurement uncertainty, at 1.3 mg/mL. Glycerol in circulation largely comes from metabolism of triglycerides in order to meet energy requirements and when the renal threshold is eclipsed, glycerol is excreted into urine. In part due to ethnic differences in postprandial triglyceride concentrations, we investigated urine glycerol concentrations in a population of elite athletes competing in North America and compared the results to those of athletes competing in Europe. 959 urine samples from elite athletes competing in North America collected for anti-doping purposes were analyzed for urine glycerol concentrations by a gas chromatography mass-spectrometry method. Samples were divided into groups according to: Timing (in- or out-of-competition), Class (strength, game, or endurance sports) and Gender. 333 (34.7%) samples had undetectable amounts of glycerol (<1 μg/mL). 861 (89.8%) of the samples had glycerol concentrations ≤20 μg/mL. The highest glycerol concentration observed was 652 μg/mL. Analysis of the data finds the effects of each category to be statistically significant. The largest estimate of the 99.9(th) percentile, from the in-competition, female, strength athlete samples, was 1813 μg/mL with a 95% confidence range from 774 to 4251 μg/mL. This suggests a conservative threshold of 4.3 mg/mL, which would result in a reasonable detection window for urine samples collected in-competition for all genders and sport classes.

Special considerations for adolescent athletic and asthmatic patients

Asthma is defined as a chronic inflammatory disorder of the airways with bronchial hyperresponsiveness and variable bronchoconstriction, and is one of the most common diseases in childhood and adolescence. Exercise-induced asthma-like symptoms and asthma are also frequently seen in highly trained athletes. Exercise-induced asthma (EIA) and exercise-induced bronchoconstriction (EIB) are found in 8%–10% of healthy school-aged children and in 35% of children with asthma. Highly increased ventilation, inhalation of cold, dry air and air pollutants (eg, chlorine) are thought to be important triggers for EIA and EIB. EIA is often experienced concurrently with vocal cord dysfunction, which needs to be considered during the differential diagnosis. The pharmacological treatment of EIA is similar to the treatment of asthma in nonexercising adolescents. The therapy is based on anti-inflammatory drugs (eg, inhaled glucocorticosteroids) and bronchodilators (eg, β2-agonists). The treatment of EIB is comparable to the treatment of EIA and leukotriene modifiers offer a new and promising treatment option, particularly in EIB. Generally, athletes may not use β2-agonists according to the prohibited list of the World Anti-Doping Agency (WADA). However, the WADA list contains specific β2-agonistic substances that are permitted to be used by inhalation.

Ultra high performance liquid chromatography tandem mass spectrometry determination and profiling of prohibited steroids in human biological matrices. A review

The use of doping agents, once restricted to professional athletes, has nowadays become a problem of public health, since it also concerns young people and non-competing amateurs in different sports. The use is also diffused in social life for improving physical appearance and enhancing performance and even dietary supplements assumed to improve performance often contain anabolic steroids. While decades ago the so-called "classical doping agents" (like stimulants and narcotics) were used, to-day anabolic steroids are more widely diffused. Anabolic steroids are synthetic substances prepared by introducing modifications in the molecular structure of testosterone, the main natural androgenic anabolic steroid that forms in testes interstitial cells. The first report concerning the use of anabolic steroids by an athlete who searched for increased weight and power dates 1954. In 1974 the misuse of anabolic steroids in sports was banned by the International Olympic Committee and control tests were implemented in 1976 Montreal Olympic Games through radioimmunoassay analysis: the technique, however, only allows for unspecific detection of a limited number of exogenous steroids. Over the years, always new doping substances are synthesized and, as a consequence, the list of prohibited compounds is continuously updated and new suitable analytical methods for their detection and determination in biological matrices are continuously required. In doping control analysis the knowledge of steroid metabolism pathway in human body is of primary importance and the analytical methods must permit the simultaneous detection and determination not only of the forbidden precursor agents but also of their metabolites. In addition, the potential presence and amount in the biological samples of species that can interfere in the analysis should be evaluated. Also the several anabolic steroids, specifically designed to circumvent doping control, put on the market have been incorporated in the list of the prohibited substances of the World Anti-Doping Agency (WADA). In WADA list steroids figure in three main classes, namely anabolic steroids, corticosteroids and substances with anti-estrogenic properties. It must be strongly reminded that assumption of doping agents not only leads to athletes the possible failing of doping tests but causes important health risk and WADA prohibited list establishes criteria to highlight the alteration of the natural steroid profile caused by exogenous administration. Doping control analyses are generally performed in urine, a matrix that provides a prolonged detection time window, and less often in blood, serum, plasma, hair, saliva, and nails. To identify the chemical structures of anabolic steroids the use of mass spectrometry detection is very advantageous. Gas chromatography-mass spectrometry (GC-MS) techniques allowed for the development of comprehensive screening methods. GC-MS methods are sensitive and robust but present the disadvantages of time-consuming sample pretreatment, that is often based on hydrolysis and derivatisation reactions. Liquid chromatography-mass spectrometry (LC-MS) methods have been successfully used to identify and determinate steroids in different matrices, as well as to study their metabolisms. Nowadays, automatic rapid ultra high performance liquid chromatography (UHPLC) tandem mass spectrometry has become the technique of choice for steroid analysis. Due to its generally higher speed, sensitivity, reproducibility and specificity with respect to HPLC, it can be used to simultaneously separate and determinate multi component steroid mixtures. The technique is of huge interest to separate conjugates anabolic androgenic steroids, as it allows efficiency enhancement due to the small particle (sub-2μm) column packing, which provides high peak capacity within analysis times even 5-10 fold shorter than conventional HPLC methods. Modern multiplex instruments can analyze thousands of samples per month so that, notwithstanding the generally high instrumental costs, the cost of the individual assay is affordable. In addition, the improved specificity and resolution offered by time-of-flight or quadrupole time-of-flight mass spectrometry allow their application in doping control analysis or in steroid profiling for accurate and sensitive full mass range acquisition. Aim of the present review is to consider, compare and discuss the applications of the UHPLC/MS methods present in literature for the identification and determination of forbidden steroids and their metabolites in human biological matrices.

A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance–Part 34

Part 34 is dominated by a review of prohormones, or more specifically, testosterone prohormones, which cause concern in sports nutrition related to their direct use or inadvertent intake as contaminants...

Analytical Challenges in The Detection of Peptide Hormones For Anti-Doping Purposes

Although significant progress has been achieved during the past few years with the introduction of new assays and analytical methodologies, the detection and quantification of protein analytes, in particular of peptide hormones, continues to pose analytical challenges for the World Anti-Doping Agency-accredited anti-doping laboratories. In this article, the latest achievements in the application of MS-based methodologies and specific biochemical and immunological assays to detect some of the prohibited substances listed in section S2 of the World Anti-Doping Agency List of Prohibited Substances and Methods are reviewed. In addition, we look towards the future by focusing on some of the most promising analytical approaches under development for the detection of so-called 'biomarkers of doping'.

London 2012: prescribing for athletes in ophthalmology

Prescribing for athletes requires an up-to-date knowledge of the World Anti-Doping Agency's list of prohibited substances. As the London 2012 Olympic Games attract athletes from around the world, we review the current guidelines with respect to all medications licensed for ophthalmic use in the United Kingdom. We describe the process that an ophthalmologist can use to check for permissible medications and also highlight treatments that are contraindicated. We systematically reviewed all 77 drugs listed in Section 11 of the British National Formulary (Issue 63) for use in the treatment of ophthalmic conditions, and referenced these against the 2012 Prohibited List published by the World Anti-Doping Agency. The majority of ophthalmic preparations are suitable for use in- and out-of-competition. Some preparations, such as glucocorticoids, are prohibited when administered systemically but permitted for topical administration. Beta-blockers are prohibited in-competition and oral carbonic anhydrase inhibitors are prohibited in- and out-of competition. The 2012 Prohibited List has important implications for the pharmacological treatment of ophthalmic conditions in athletes. Clinicians prescribing for athletes have a duty to familiarize themselves with the list in order to avoid causing significant damage to their patient's career and reputation.

Skeletal and Cardiac Muscle Ergogenics and Side Effects of Clenbuterol Treatment

Well known, well detected and still used by athletes, clenbuterol is one of the β 2 -agonists which has no authorization for therapeutic use, contrarily to salbutamol, salmeterol and formoterol in the 2012 World Anti-Doping Agency list. However, clenbuterol is still detected in athletes’ antidoping test samples. Its ability to induce muscle hypertrophy but also its strong lipolytic action and the absence of androgenic effects have made it a prized substances by athletes, specially females, without scruples whose performance requires significant muscle strength. Like the effects of clenbuterol on the heart, the effects of clenbuterol on skeletal muscle are dependent on the doses used and duration of the treatment. If there is a consensus concerning the clenbuterol action on the phenotypic conversion from slow to fast type fibers and on the hypertrophy, there is, to our knowledge, no consensus concerning the effects of clenbuterol on the slow type fibers and slow profile muscles. There is also no consensus concerning the clenbuterol effects on performance. We will shortly reviewing the known operating mode, side and benefits effects of short and long term β-agonists, and specially clenbuterol, treatment on mammals