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Discussion in 'Steroid Forum' started by Michael Scally MD, May 1, 2011.
Kim VJ, Okano CK, Osborne CR, Frank DM, Meana CT, Castaneto MS. Can synthetic urine replace authentic urine to “beat” workplace drug testing? Drug Testing and Analysis 2018;0. https://doi.org/10.1002/dta.2497
Synthetic urine (SU), which was primarily utilized by drug testing laboratories as matrix for quality control preparations, are now commercially sold and can be used to “fool” a positive drug test. To determine if SU can pass as authentic urine, we challenged Army urine drug testing collection and testing procedures using eight different commercial SU products. Adulteration (Sciteck AdultaCheck® 6) and Onsite SU (Synthetic UrineCheckTM) test strips were also evaluated. Five of the eight SU were identified by physical observation. All SU products screened negative in the drug immunoassay and additionally passed the SVT as authentic urine. Furthermore, SU was not detected as adulterated with the adulteration test strips (Sciteck AdultaCheck® 6) but was successfully detected as synthetic urine with the On‐site synthetic urine (Synthetic UrineCheckTM). To deter SU use, direct observation, as utilized by the military may be recommended during the collection process.
Three years after Russia’s drug-testing agency was banned over one of the largest and most egregious state-sponsored doping schemes in the history of sport, it’s back in business, authorized by the World Anti-Doping Agency to certify that the same Russian athletes it so recently helped cheat are clean. It’s hard to know where to start on how outrageous that is.
After negotiating with the Russians over the summer, WADA announced last Thursday that it was, in effect, lifting its major conditions for Russia’s reinstatement — a full admission of the cheating and access to its stored urine samples — in exchange for a pledge to grant access to those samples by year’s end.
Faced with a deluge of outrage, much of it from athletes, WADA’s president, Craig Reedie, claimed this was the best way to get access to the samples WADA says it needs to complete its investigation into Russian doping. “My question to athletes is: What, in practice, is the alternative action to all the statements you have made?” he asked in a conference call with reporters on Monday.
Well, Sir Craig, let’s start with this alternative: Maintain the suspension until Russia fully acknowledges the government’s central role in the widespread cheating that was first laid bare by the former head of the Russian testing lab, Grigory Rodchenkov, and then confirmed in a report commissioned by WADA.
HPT-Axis Effects and Urinary Detection Following clomiphene Administration
Context: Clomiphene is a commonly abused performance-enhancing drug by males in sport, but the extent to which testosterone increases in healthy males following its use is unknown. Additionally, evidence has suggested that clomiphene, a mixture of cis- and trans-isomers zuclomiphene and enclomiphene, is detectable in urine for months following use; the isomer-specific urinary detection window has yet to be characterized in a controlled study.
Objective: To determine the effect of a once daily, 30-day clomiphene treatment on serum testosterone and gonadotropins in the subject population studied, and the urinary clearance and detection window of clomiphene isomers following administration for anti-doping purposes. Participants and Design: Twelve healthy males aged 25 to 38, representing a recreational athlete population, participated in this open-label, single-arm study.
Intervention: Oral clomiphene citrate (50 mg) was self-administered once daily for 30 days. Serum and urine samples were collected at baseline and at Day 7, 14, 21, 28, 30, 32, 35, 37, 44, 51, and 58; urine collections continued periodically up to Day 261.
Results: Testosterone, LH, and FSH increased 146% (+/- 23% SEM), 177% (+/- 34%), and 170% (+/- 33%), respectively, during treatment compared to baseline. Serum drug concentrations and urinary excretion were non-uniform amongst individuals as isomeric concentrations varied. The zuclomiphene urinary detection window ranged from 121 to greater than 261 days.
Conclusions: Clomiphene significantly raises serum testosterone and gonadotropins in healthy men and thus can be abused as a performance-enhancing drug. Such abuse is detectable in urine for four months or greater following short-term use.
Miller GD, Moore C, Nair V, et al. HPT-Axis Effects and Urinary Detection Following Clomiphene Administration in Males. The Journal of clinical endocrinology and metabolism 2018. https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/jc.2018-01159/5115462
An Overview of Doping in Sports
The history of doping field can be outlined in three major stages:
(1) early stage in which drug abuse took place during sports performance and competition and gas chromatography was used for its detection;
(2) approximately in the 1970s when androgenic anabolic steroids were introduced;
(3) In the recent era when the fields of biochemistry, physiology, toxicology, genomics, genetics, immunology, and molecular biology were integrated and applied routinely.
Advanced omics technology and gene doping age may be applied in near future. This review will discuss commonly abused materials, both their adverse and harmful effects, and the alleged benefits in conjunction with the current standards in doping.
Five prime areas should be targeted:
(1) substances misused in strength sports;
(2) metabolic modulators/hormones;
(3) blood doping in aerobic sports;
(4) structurally diverse masking agents; and
(5) gene doping.
Sanchis-Gomar F, Martinez Bello V, Pareja-Galeano H, Brioche T, Gómez-Cabrera MC. Chapter 16 - An Overview of Doping in Sports. In: Bagchi D, Nair S, Sen CK, eds. Nutrition and Enhanced Sports Performance (Second Edition): Academic Press; 2019:189-202. https://www.sciencedirect.com/science/article/pii/B9780128139226000163
Guimarães-Ferreira L, Cholewa JM, Dantas WS, Murai I, Duncan MJ, Zanchi NE. Chapter 3 - Performance-Enhancing Drugs and Sports Supplements for Resistance Training. In: Bagchi D, Nair S, Sen CK, eds. Nutrition and Enhanced Sports Performance (Second Edition): Academic Press; 2019:31-47. https://www.sciencedirect.com/science/article/pii/B9780128139226000035
In general, nutritional sports ergogenics are designed to enhance energy production and/or improve body composition, promoting muscle growth and decreasing body fat. Many of the nutritional supplements and pharmacological substances have been used during resistance training without knowledge about the effects on human metabolism caused by their chronic administration.
Before the usage or prescription of any ergogenic aid, it is important to consider some questions about that substance:
Is it effective?
Is it safe?
Is it legal and ethical?
In this chapter we will discuss the most widely used drugs and supplements among individuals engaged in resistance training—testosterone, growth hormone and insulin growth factor-1, creatine, beta-hydroxy beta-methylbutyrate and caffeine—focusing on their effects on strength and body composition, the safety of their usage, and the mechanisms of action.
[OA] Development of Doping in Sports: Overview and Analysis
Doping is a public health issue and not simply a problem inside the professional sports community It is a complex and ancient phenomenon considering the vast variety of substances, supplied through both legal and illegal trading routes. It occurs in elite athletes but also affects amateur athletes and was generally considered as dangerous and unhealthy.
Furthermore, it involves athletes’ friends and relatives, medical staff, managers, chemists, biologists and pharmacists, pharmaceutical industries, clandestine laboratories and criminal organizations. Over time, doping has shown a great ability to discover and always use new substances and appropriated the new scientific discoveries.
Unfortunately, new discoveries for the human health are been used in distorted way by the athletes. In fact, the athletes may be able to use gene therapy to re-engineer their bodies for better performances.
Drug dependence depends on several factors: the socio-environmental context of the subject and what effects have the substance in the body.
We will agree that sport is essentially under the current anti-doping campaign executed by a coordinated alliance between the World Anti-Doping Agency (WADA), law enforcement authorities, sports organizers and the media.
This paper explores comprehensive description of the state of doping and its regulation in the modern Olympic Movement.
Mazzeo F, Altavilla G, D’elia F, Raiola G. Development of Doping in sports: overview and analysis. J. Phys. Educ. Sport (Online). 2018;18(3):1669-77. https://efsupit.ro/images/stories/september2018/Art 244.pdf
The Use and Misuse of testosterone in Sport: The Challenges and Opportunities in Doping Control
Testosterone and anabolic androgenic steroids (AASs) have been widely used to enhance sport performance throughout the last 50years. The German Democratic Republic used a notoriously comprehensive programme of steroid doping across all major Olympic sports throughout the 1970s and 1980s, and in more recent years, a somewhat similar state-sponsored doping regime has been shown to have operated in Russian sport.
The first part of this review summarizes some major examples of testosterone and AAS use in sport. Following on from this is an overview of the main methods used by global antidoping organizations to detect the prohibited use of synthetic testosterone and AASs and a brief look at the emerging methods that represent the new frontier of doping detection.
Shelley J, Moir HJ, Petróczi A. Chapter 48 - The Use and Misuse of Testosterone in Sport: The Challenges and Opportunities in Doping Control. In: Bagchi D, Nair S, Sen CK, eds. Nutrition and Enhanced Sports Performance (Second Edition): Academic Press; 2019:571-80. https://www.sciencedirect.com/science/article/pii/B9780128139226000485
[OA] Anabolic Androgenic Steroids: Searching New Molecular Biomarkers
Even if anabolic androgenic steroid (AAS) abuse is clearly associated with a wide spectrum of collateral effects, adolescents and athletes frequently use a large group of synthetic derivatives of testosterone, both for aesthetic uses and for improving performance. Over the last few years, the development of MicroRNA (miRNA) technologies has become an essential part of research projects and their role as potential molecular biomarkers is being investigated by the scientific community. The circulating miRNAs detection as a diagnostic or prognostic tool for the diagnosis and treatment of several diseases is very useful, because with a minimal quantity of sample (peripheral blood), miRNAs are very sensitive. Even more, miRNAs remain stable both at room temperature and during freeze-thaw cycles.
These characteristics highlight the important role of miRNAs in the near future as new tools for anti-doping. The article provides a systematic review and meta-analysis on the role of miRNAs as new potential molecular biomarkers of AAS use/abuse. Particularly, this paper analyzed the "miRNA signature" use as biomarkers for health disorders, focusing on the organ damages which are related to ASS use/abuse. Moreover, this review aims to provide a future prospect for less invasive or noninvasive procedures for the detection of circulating miRNA biomarkers as doping assumption signaling.
Sessa F, Salerno M, Di Mizio G, et al. Anabolic Androgenic Steroids: Searching New Molecular Biomarkers. Frontiers in Pharmacology 2018;9:1321. Anabolic Androgenic Steroids: Searching New Molecular Biomarkers
[OA] Faiss R, Saugy M, Passfield L, Hopker J. Editorial: Performance Modeling and Anti-doping. Front Physiol. 2019;10:169. Editorial: Performance Modeling and Anti-doping
Medals shine under the spotlight for the winning athletes. In the context of global sport, athletic performance is scrutinized more than ever and the fight against doping is often considered as the shady side of the medal.
The Athlete's Biological Passport (ABP) was developed in an attempt to impede athletes' use of substances identical to those naturally produced by the human body (Sottas et al., 2011). Since its progressive implementation, the APB has become a strong tool for the indirect detection of doping (in blood) (Saugy et al., 2014; Zorzoli et al., 2014).
Athletes aim to improve athletic performance via doping, but these practices may also influence biomarkers measured longitudinally as part of the ABP. However, numerous confounding factors (e.g., exercise training, hypoxic exposure, heat stress) are also known to alter these ABP parameters (Bouchard, 2015).
There is therefore a need to gather additional information on athletes to strengthen the ABP, and provide a more forensic style intelligence led approach to anti-doping. One such approach is afford by the recent growth of technology in sports affording the ability to analyse and large volumes of data from both training and performance.
Indeed, experts and scientists have gathered rudimentary performance data for decades to better understand the mechanisms underlying performance production (Faria et al., 2005; Borresen and Lambert, 2009; Sweeting et al., 2017), and with the aim of objectifying successes and failures of training strategies (Jobson et al., 2009; Passfield et al., 2017).
The potential use of performance data for anti-doping purposes has only relatively recently been proposed (Schumacher and Pottgiesser, 2009), but has led to heightened interest in the area.
The objective of this Research Topic is to discuss the potential for scientific evidence-based models of athletic performance to provide a cost effective tool that can be used by anti-doping organizations in the fight against doping in sports. …
Indirect Clinical Markers for The Detection of Anabolic Steroid Abuse Beyond The Conventional Doping Control In Athletes
Growing analytical challenges have arisen for the detection of misuse of androgenic anabolic steroids (AAS) in athletes the last years. Therefore, consideration of additional indirect markers can substantially aid the efforts to detect AAS abuse in athletes. Moreover, this approach can also help physicians to suspect AAS abuse when treating athletes.
Laboratory markers highly indicative of AAS abuse in athletes include the considerable downregulation of high density lipoprotein-cholesterol, elevation of haematocrit or serum γ-glutamyl transpeptidase levels and for males reduced serum levels of both luteinizing hormone and follicle-stimulating hormone.
Moreover, physical signs suggestive of current AAS abuse are hypertension, apparent changes in behaviour making the athlete more irritable and aggressive and the sudden appearance of acne vulgaris in an adult athlete with no recent history of acne, while testicular atrophy and gynecomastia raise suspicion of current or past AAS abuse in male athletes.
Christou GA, Christou MA, Žiberna L, Christou KA. Indirect clinical markers for the detection of anabolic steroid abuse beyond the conventional doping control in athletes. European Journal of Sport Science 2019:1-11. https://doi.org/10.1080/17461391.2019.1587522
[OA] The Unethicality of Doping in Sports
Performance enhancing drug use in sport arguably constitutes a crisis, and as such, targeted measures are needed in order to stem it. Substance abuse in professional sports and competitions has besmirched many world-class athletes' reputations and standing, in addition to jeopardizing their health.
Furthermore, there are many instances of amateur athletes and school-aged competitors who have taken to using such substances as well, significantly exacerbating the overall picture.
The widespread acknowledgement of the potentially life-threatening consequences of performance-enhancing drug use has prodded sports organizations and governments into cooperating on many different levels to preserve the ethical grounding and soundness of sport competitions; unlawful substance abuse is in fact liable to undermine the very core of fairness in competition.
Doping, along with various forms of cheating, has been recorded throughout the history of sport: prohibition in itself is all but ineffective without reliable and systematic detection strategies and enforcement of sanctions.
Palmi I, Berretta P, Tini A, Ricci G, Marinelli S. The unethicality of doping in sports. La Clinica terapeutica 2019;170:e100-e1. The unethicality of doping in sports | La Clinica Terapeutica
The history of doping is as old as sport itself. From ancient times, athletes try to win at any cost, using all the resources they can discover.
The WADA launches every year a List of forbidden substances and methods because a new year is an opportunity of improving the drugs or methods to achieve performances in sports which are not fair and can harm the athlete’s health.
Besides the List, doping has become so sophisticated that athletes have to be controlled by a biological passport that can figure out if they are cheating about improving hemoglobin or steroids and so being checked in their “physiologic values, not so physiologic after all.”
Cascais MJ. Doping. In: Rocha Piedade S, Imhoff AB, Clatworthy M, Cohen M, Espregueira-Mendes J, eds. The Sports Medicine Physician. Cham: Springer International Publishing; 2019:439-46. Doping
Anti-doping: CAS accepts a new method to detect prohibited substances
Anti-doping: CAS accepts a new method to detect prohibited substances - LawInSport
On 29 March 2019, the Court of Arbitration for Sport (CAS) issued its decision in the appeal arbitration procedures involving two Ukrainian track-and-field athletes (the Athletes). https://www.athleticsintegrity.org/...y-process/en/CAS-Arbitral-Award-5654-5655.pdf
Both athletes were convicted of using a prohibited substance based on the detection of non-physiological levels of testosterone in their blood serum samples following analysis in the WADA-accredited laboratories in Lausanne, Switzerland, and Seibersdorf, Austria.
The case is of significant importance for the fight against doping as it was for the first time athletes were convicted of anti-doping rule violations (the ADRVs) based on the steroidal values in their blood serum. This article reviews the decision.
Implementation and Performance of The Gas Chromatography/Combustion/Isotope Ratio Mass Spectrometry-Based Method for The Confirmatory Analysis of Endogenous Anabolic Steroids
Carbon isotope ratio (CIR) confirmation is one of the most complex and delicate analysis in doping control field, due to the nature of the molecules to be confirmed, normally present in urinary samples as a consequence of an endogenous production. The requirements for method validation established by the World Anti-Doping Agency (WADA) have been pushing the accredited laboratories to improve their methods. The choice of the method is always a cost benefit ratio involving a hard-working and time-consuming analysis and the guarantee of reporting of reliable results.
This work presents the method fully validated by the Brazilian Doping Control Laboratory as part of the preparation for the Rio de Janeiro Summer Olympic and Paralympic Games 2016. Sample preparation encompassed solid phase extraction, liquid-liquid extraction, enzymatic hydrolysis, acetylation and purification by preparative high-performance liquid chromatography, and analyses were per-formed by gas chromatography/combustion/isotope ratio mass spectrometry.
This proved to be a robust method to CIR confirmation in a big event, as demonstrated by the analysis of 179 samples during the Games 2016, from clearly negative results and adverse findings for testosterone (T) and related substances, boldenone and metabolite, 19-norandrosterone and formestane. Two atypical findings were also reported for T and metabolites.
de Oliveira FA, Casilli A, Piper T, et al. Implementation and performance of the gas chromatography/combustion/isotope ratio mass spectrometry-based method for the confirmatory analysis of endogenous anabolic steroids during the Rio de Janeiro Olympic and Paralympic Games 2016. Analytical chemistry 2019. https://pubs.acs.org/doi/10.1021/acs.analchem.9b02341
Effects of Transdermal Administration of testosterone Gel on The Urinary Steroid Profile in Hypogonadal Men: Implications in Antidoping Analysis
· A single dose of testosterone gel was administered transdermally to hypogonadal subjects.
· Results were different between “late onset” and “non-late onset” subjects.
· Testosterone glucuronide increased in all subjects.
· Epitestosterone glucuronide increased mostly in non-late onset subjects.
· Testosterone sulfate and epitestosterone sulfate also increased in non-late onset subjects.
· Criteria based on the testosterone/epitestosterone ratio for detection of testosterone doping should be reconsidered for non-late onset hypogonadal athletes.
Testosterone is one of the most abused pseudo-endogenous anabolic steroids in sport doping. The current method adopted to detect the abuse of testosterone and other pseudo-endogenous steroids (endogenous steroids when administered exogenously) is first based on the longitudinal monitoring of several urinary biomarkers, which constitute the so called "steroidal module" of the Athlete Biological Passport (ABP): atypical samples undergo a confirmation analysis based on the measurement of the (13)C/(12)C isotopic ratio of selected target compounds, to distinguish their endogenous or exogenous origin.
At the same time, testosterone administration can be allowed in athletes diagnosed with hypogonadism, provided they are granted a therapeutic use exemption by the relevant medical authority. In this pilot study we have investigated whether the approach based on the preliminary determination of the urinary steroid profile, in the format considered in the steroidal module of the ABP, also integrated with the inclusion of the sulfo-conjugates and of additional target steroids, can retain its validity also in the case of hypogonadal athletes.
We have studied the effects of a single low dose (40 mg) of testosterone gel (T-gel) on the urinary concentration of the markers of steroidal module of the ABP, as well as on some additional steroid markers.
The study was based on the analysis of urinary samples from 19 non-hospitalized hypogonadal men, 10 of them with late-onset hypogonadism (LOH), collected before, after 4 hours and after 24 hours the transdermal self-administration of 40 mg of T-gel. None of the patient had any co-morbidities possibly affecting the urinary excretion of the steroidal markers.
The steroidal markers were quantified by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) after the enzymatic hydrolysis of the respective glucuro-conjugates and the chemical hydrolysis of the respective sulfo-conjugates. Targeted GC-MS/MS analysis was carried out operating in electron impact (EI) ionization mode, with acquisition in multiple reaction monitoring (MRM) mode.
Our preliminary results show that, as expected, the treatment with T-gel leads, in all hypogonadal men, to an increase of the urinary concentration of the glucuro-conjugate metabolites of testosterone and its main metabolites, with special relevance to those with 5alpha-reduction. Furthermore, samples collected from non-LOH hypogonadal men showed an increase also in the levels of epitestosterone glucuronide, testosterone sulfate and epitestosterone sulfate.
Apart from their biochemical and pharmacological relevance, these outcomes could be leveraged to refine the analytical strategy currently followed in the antidoping field for the analysis of the urinary steroidal markers, with potential implications also in other forensic and/or clinical investigations.
Iannone M, Palermo A, de la Torre X, et al. Effects of transdermal administration of testosterone gel on the urinary steroid profile in hypogonadal men: implications in antidoping analysis. Steroids 2019:108491. https://www.sciencedirect.com/science/article/pii/S0039128X19301813?via%3Dihub
[OA] The 36th Manfred Donike Workshop On Doping Analysis
Sports drug testing has been subjected to continual change. The underlying dynamics have been manifold, spanning new technological options addressing formerly unsolved analytical challenges to the implementation of newly identified drugs and/or corresponding (long‐term) metabolites for comprehensiveness and doping control retrospectivity.
The presentation, discussion, and dissemination of research in anti‐doping science is critical and since 1983 a central venue has been the Manfred Donike Workshop on Doping Analysis.1 The 36th workshop was held in Cologne, Germany, April 22–27, 2018.
Over 130 international representatives from all of the World Anti‐Doping Agency (WADA)‐accredited laboratories attended the meeting where current issues and solutions, future aspects and new methods, as well as data on most diverse aspects of sports drug testing were thematized.
The collection of articles compiled in this special issue mirrors the substantial breadth of research topics of the 2018 conference. Error - Cookies Turned Off
Taken together, this compilation of papers mirrors and highlights the multifaceted nature of doping controls and related topics. While expanding test methods plays a major role in anti‐doping research, a trend toward studies aimed at identifying situations that could affect doping controls is recognized.
Thevis M. The 36th Manfred Donike workshop on doping analysis. Drug testing and analysis 2018;10:1633-4. Error - Cookies Turned Off
Analytical Approaches in Human Sports Drug Testing: Recent Advances, Challenges, and Solutions
Technical innovations are continuously offering new options to research and routine applications in various arenas of analytical chemistry. In combination with a concomitantly increasing knowledge in physiology and pharmacology and a steadily growing supply of new drug candidates and potential therapeutic approaches, sports drug testing laboratories have been urged to develop and refine numerous test methods and strategies in order to provide best-possible levels of information to testing authorities in support of decision-making processes in anti-doping.
Thevis M, Walpurgis K, Thomas A. Analytical Approaches in Human Sports Drug Testing: Recent Advances, Challenges, and Solutions. Analytical chemistry 2019. https://doi.org/10.1021/acs.analchem.9b04639
The Use of Prohibited Substances for Therapeutic Reasons in Athletes Affected by Endocrine Diseases and Disorders: The Therapeutic Use Exemption (TUE) in Clinical Endocrinology
To protect sporting ethics and athletes' health, the World Anti-Doping Agency (WADA) produced the World Anti-Doping Code and The Prohibited List of substances and methods forbidden in sports.
In accordance with the International Standards for Therapeutic Use Exemption (ISTUE), to avoid rule violations and sanctions, athletes affected by different endocrine diseases and disorders (e.g., adrenal insufficiency, diabetes, male hypogonadisms, pituitary deficit, thyroid diseases, etc.) who need to use a prohibited substance for therapeutic reasons (e.g., medical treatments, surgical procedures, clinical diagnostic investigations) must apply to their respective Anti-Doping Organizations (ADOs) to obtain a Therapeutic Use Exemption (TUE), if specific criteria are respected.
The physicians who treat these athletes (i.e., endocrinologists, andrologists and diabetologists) are highly involved in these procedures and should be aware of their specific role and responsibility in applying for a TUE, and in adequately monitoring unhealthy athletes treated with prohibited substances.
In this paper, the prohibited substances commonly used for therapeutic reasons in endocrine diseases and disorders (e.g., corticotropins, beta-blockers, glucocorticoids, hcg, insulin, GnRH, rhGH, testosterone, etc.), the role of physicians in the TUE application process and the general criteria used by ADO-Therapeutic Use Exemption Committees (TUECs) for granting a TUE are described.
Di Luigi L, Pigozzi F, Sgro P, Frati L, Di Gianfrancesco A, Cappa M. The use of prohibited substances for therapeutic reasons in athletes affected by endocrine diseases and disorders: the therapeutic use exemption (TUE) in clinical endocrinology. Journal of endocrinological investigation 2019. The use of prohibited substances for therapeutic reasons in athletes affected by endocrine diseases and disorders: the therapeutic use exemption (TUE) in clinical endocrinology