Multidimensional Separations of Intact Phase II Steroid Metabolites Utilizing LC-Ion Mobility-HRMS

28 Jul 2021

Multidimensional Separations of Intact Phase II Steroid Metabolites Utilizing LC-Ion Mobility-HRMS / Don E. Davis Jr, Katrina L. Leaptrot, David C. Koomen, Jody C. May, Gustavo de A. Cavalcanti, Monica C. Padilha, Henrique M.G. Pereira, John A. McLean. - (Analytical Chemistry 93 (2021) 31 (10 August); p. 10990-10998)

  • PMID: 34319704
  • DOI: 10.1021/acs.analchem.1c02163


Abstract

The detection and unambiguous identification of anabolic-androgenic steroid metabolites are essential in clinical, forensic, and antidoping analyses. Recently, sulfate phase II steroid metabolites have received increased attention in steroid metabolism and drug testing. In large part, this is because phase II steroid metabolites are excreted for an extended time, making them a potential long-term chemical marker of choice for tracking steroid misuse in sports. Comprehensive analytical methods, such as liquid chromatography-tandem mass spectrometry (LC-MS/MS), have been used to detect and identify glucuronide and sulfate steroids in human urine with high sensitivity and reliability. However, LC-MS/MS identification strategies can be hindered by the fact that phase II steroid metabolites generate nonselective ion fragments across the different metabolite markers, limiting the confidence in metabolite identifications that rely on exact mass measurement and MS/MS information. Additionally, liquid chromatography-high-resolution mass spectrometry (LC-HRMS) is sometimes insufficient at fully resolving the analyte peaks from the sample matrix (commonly urine) chemical noise, further complicating accurate identification efforts. Therefore, we developed a liquid chromatography-ion mobility-high resolution mass spectrometry (LC-IM-HRMS) method to increase the peak capacity and utilize the IM-derived collision cross section (CCS) values as an additional molecular descriptor for increased selectivity and to improve identifications of intact steroid analyses at low concentrations.

Multiple hepatocellular adenomas and renal cell carcinoma associated with anabolic androgenic steroids

9 Jan 2021

Множественные гепатоцеллюлярные аденомы и почечноклеточный рак, ассоциированные с приемом бодибилдером анаболических андрогенных стероидов [Multiple hepatocellular adenomas and renal cell carcinoma associated with anabolic androgenic steroids] / M.M. Morozova, E.I. Ivanova, N.K. Chardarov, O.V. Dolzhanskiy, G.A. Shatveryan, Yu.R. Kamalov. - (Khirurgiya (2021) 10; p. 105-109

  • PMID: 34608788
  • DOI: 10.17116/hirurgia2021101105
  • Article in Russian


Abstract in English

The authors report a rare case of combination of chromophobe renal cell carcinoma Grade 2 pT2aN0 with multiple hepatocellular adenomas in a 31-year-old bodybuilder who received anabolic androgenic steroids at high doses for 8 years. According to MRI data, over 15 liver adenomas and tumor in the lower segment of the right kidney were detected. The patients underwent laparascopic resection of the right kidney and liver segments 2, 3 and 4 with large adenomas. Histological study and immunohistochemistry revealed no malignancy signs in hepatocellular adenomas. Nuclear β-catenin expression was absent. Kidney tumor had a structure of chromophobe renal cell carcinoma. The patient is currently being followed-up due to residual small liver adenomas. In our opinion, liver adenomatosis and renal cancer have the same cause in this case (chronic toxic effect of androgens).


Abstract in Russian

Приведен редкий случай сочетания хромофобного рака почки Grade 2 (pT2aN0 по системе TMN) со множественными гепатоцеллюлярными аденомами печени у 31-летнего бодибилдера, который на протяжении 8 лет в больших дозах принимал анаболические андрогенные стероиды. При МРТ выявлено более 15 аденом печени, а также образование в нижнем сегменте правой почки. Больному проведена одномоментная операция: лапараскопическая резекция правой почки и резекция II, III и IV сегментов печени с наиболее крупными образованиями. При гистологическом и иммуногистохимическом исследованиях гепатоцеллюлярные аденомы не имели признаков малигнизации, ядерная β-катениновая экспрессия отсутствовала, образование почки расценено как хромофобный почечноклеточный рак. В настоящее время пациент находится под динамическим контролем онколога и хирурга в связи с необходимостью наблюдения за сохранившимися в паренхиме печени аденомами. Сочетанное поражение печени в виде аденоматоза и рака почки у данного пациента следует рассматривать как единый этиопатологический процесс, обусловленный хроническим токсическим влиянием андрогенов.

Multiple incidence of the prescription diuretic hydrochlorothiazide in compounded nutritional supplements

18 Oct 2018

Multiple incidence of the prescription diuretic hydrochlorothiazide in compounded nutritional supplements / Donata Favretto, Sindi Visentin Salvatore Scrivano, Emanuele Roselli, Fabio Mattiazzi, Roberto Pertile, Susanna Vogliardi, Marianna Tucci, Massimo Montisci. - (Drug Testing and Analysis 11(2018) 3 (March) ; 512-522)

  • PMID: 30194914.
  • DOI: 10.1002/dta.2499

Abstract

Diuretic agents are prohibited in sports in- and out-of-competition according to the regulations of the World Anti-Doping Agency (WADA) because of their possible masking effects on other doping agents in urine samples, and their ability to produce fast acute weight losses. Despite previous studies reported adverse analytical findings (AAFs) resulting from contaminations at ppm level (μg/g) of medicinal products, and recommended to introduce reporting limits for diuretics in doping controls, these are not adopted in analyses performed by WADA-accredited laboratories. We report the case of an athlete with two AAFs for hydrochlorothiazide (HCTZ) at low urinary concentrations (<10 ng/mL), who declared the use of nutritional supplements prepared in a compounding pharmacy. His nutritional supplements were analyzed revealing HCTZ presence in different concentrations, at the ppm level (μg/g and ng/mL). With the aim of testing the plausibility of the observed urinary HCTZ concentrations with the nutritional supplement ingestion, a urinary excretion study with three healthy volunteers was performed. HCTZ-contaminated powder (6.4 μg/g of HCTZ) was administered to each subject in different dosages, reproducing the possible ingestion pattern occurred. Urine specimens were collected before and after ingestion of the powder, up to 24 hours, and underwent liquid-liquid extraction and liquid chromatography-tandem mass spectrometry determination. Post-administration specimens were found to contain HCTZ at concentrations of 5-230 ng/mL, which supported the accidental inadvertent intake of the prohibited substance by the athlete. This study makes the argument that the introduction of reporting limits for diuretics are warranted in doping control samples, in order to protect against inadvertent AAFs due to contaminated products.

Multivariate interpretation of the urinary steroid profile and training-induced modifications. The case study of a Marathon runner

15 Jul 2019

Multivariate interpretation of the urinary steroid profile and training-induced modifications : The case study of a Marathon runner / Eleonora Amante, Serena Pruner, Eugenio Alladio, Alberto Salomone, Marco Vincenti, Rasmus Bro. - (Drug Testing and Analysis 11 (2019) 10 (October); p. 1556-1565).

  • PMID: 31307117.
  • DOI: 10.1002/dta.2676

Abstract

The steroidal module of the athlete biological passport (ABP) introduced by the World Anti-Doping Agency (WADA) in 2014 includes six endogenous androgenic steroids and five of their concentration ratios, monitored in urine samples collected repeatedly from the same athlete, whose values are interpreted by a Bayesian model on the basis of intra-individual variability. The same steroid profile, plus dihydrotestosterone (DHT) and DHEA, was determined in 198 urine samples collected from an amateur marathon runner monitored over three months preceding an international competition. Two to three samples were collected each day and subsequently analyzed by a fully validated gas chromatography-mass spectrometry protocol. The objective of the study was to identify the potential effects of physical activity at different intensity levels on the physiological steroid profile of the athlete. The results were interpreted using principal component analysis and Hotelling's T2 vs Q residuals plots, and were compared with a profile model based on the samples collected after rest. The urine samples collected after activity of moderate or high intensity, in terms of cardiac frequency and/or distance run, proved to modify the basal steroid profile, with particular enhancement of testosterone, epitestosterone, and 5α-androstane-3α,17β-diol. In contrast, all steroid concentration ratios were apparently not modified by intense exercise. The alteration of steroid profiles seemingly lasted for few hours, as most of the samples collected 6 or more hours after training showed profiles compatible with the "after rest" model. These observations issue a warning about the ABP results obtained immediately post-competition.

Munich Court of Appeal 2015 Speed-Skater vs District Court Munich

15 Jan 2015

Oberlandgericht München January 15, 2015 Az. U 1110/14 Kart

Facts
Speed-skater athlete appeals against the decision of the District Court Munich of February 26, 2014. The Court of Arbitration for Sport (CAS) in Lausanne had followed an ISU judgment on 25 November 2009 and had confirmed the two-year ban for reticulocyte fluctuating blood values without doping test. The athlete had always denied doping and carries an inherited blood anomaly as a reason for their increased values up to the present time. In the Munich compensation process, the Berliner has the ISU therefore sued for wrongs to 4.4 million euros. Also the monopolistic position of the International Skating Union (ISU) for letting only one athlete per country taking part in international competition was an issue, this ruling goes against the antitrust law. The reason for this lies in the perception that an athlete takes part in an economic activity, consisting of offering goods for services on a (sport)market.
Also the ISU had required that the athlete signed an arbitration clause but the athlete refused.
The Higher Regional Court overturned the decision of the Landgericht München I that the award of the CAS must be recognized. The German courts were not bound in the compensation question to the CAS ruling.

Decison
The claim of the athlete partially upheld, the complaint is admissible but not ready for a decision at this moment.

Munich District Court 37_O_28331_12 Claudia Pechstein vs DESG & ISU

26 Feb 2014

Landgericht München I
Urteil Az. 37 O 28331/12 Claudia Pechstein vs DESG & ISU

On 1 July 2009 the International Skating Union (ISU) imposed a 2 year period of ineligibility on the German Athlete Claudia Pechstein. On basis of all evidence presented in this case the ISU Disciplinary Commission ruled that the Athlete has applied the prohibited method of blood doping.

The Athlete denied the doping allegations and appealed with the Court of Arbitration for Sport (CAS) and the Swiss Federal Supreme Court. All 4 appeals were dismissed and the ban was upheld.

Hereafter the Athlete started proceedings with the German District Court in Munich (Landgericht München I) against the ISU and the Deutsche Eisschnelllauf-Gemeinschaft (DESG). The Athlete claimed damages suffered as a result of a doping ban.

On 26 February 2014 the Munich District Court dismissed the Athlete’s claim but also ruled that the arbitration clause contained in the athletes’ agreement between Pechstein and both the ISU and DESG to be invalid.

The Munich court found that at the time the Athletes‘ agreements with ISU and DESG were entered into, a structural disbalance (strukturelles Ungleichgewicht) existed between Pechstein and the sport federations, who formed a monopoly. Pechstein did not enter into the agreement voluntarily, but only because she had no choice. Had she not signed the agreements, she would not have been able to enter competitions and hence, unable to pursue her career as a professional athlete.

On that basis, the court found that it had jurisdiction to hear the damages claims, and the defendants could not invoke the arbitration clauses. However, the court held that it could not revisit and review the legality of the ban. As it was bound by the CAS findings that the ban was legal, the Athlete’s damages claims were unfounded.

On the issue of the legality of the ban, the arbitral award of the CAS was final, and its finality was to be respected by the Munich court. Pechstein could have, and should have challenged the jurisdiction of the CAS during the arbitral proceedings.

At the time she appealed the ban to the CAS, the structural disbalance did no longer play a role. Still, Pechstein, in full knowlegde of all the circumstances, did appeal to the CAS. At that point in time, she should have invoked that she did not enter into the arbitration agreement voluntarily.

The same was true for other procedural challenges to the CAS proceedings. The fact that the arbitration agreement is void (Nichtigkeit der Schiedsvereinbarung) does not preclude the recognition of the arbitral award in the Munich proceedings.

Munich Higher District Court U_1110_14 Claudia Pechstein vs DESG & ISU

15 Jan 2015

Oberlandesgericht München Teil-Urteil AZ. U 1110/14 Claudia Pechstein vs DESG & ISU

On 1 July 2009 the International Skating Union (ISU) imposed a 2 year period of ineligibility on the German Athlete Claudia Pechstein. On basis of all evidence presented in this case the ISU Disciplinary Commission ruled that the Athlete has applied the prohibited method of blood doping.

The Athlete denied the doping allegations and appealed with the Court of Arbitration for Sport (CAS) and the Swiss Federal Supreme Court. All 4 appeals were dismissed and the ban was upheld.

The Athlete started proceedings with the Geman District Court in Munich (Landgericht München I) against the ISU and the Deutsche Eisschnelllauf-Gemeinschaft (DESG). The Athlete claimed damages suffered as a result of a doping ban.

On 26 February 2014 the Munich District Court dismissed the Athlete’s claim but also ruled that the arbitration clause contained in the athletes’ agreement between Pechstein and both the ISU and DESG to be invalid.

The court found that it had jurisdiction to hear the damages claims, and the defendants could not invoke the arbitration clauses. However, the court held that it could not revisit and review the legality of the ban. As it was bound by the CAS findings that the ban was legal, the Athlete’s damages claims were unfounded.

Hereafter the Athlete filed a new appeal against the ISU with the Higher Distict Court in Munich (Oberlandesgericht München).

The Court ruled that international sports federations are monopolists. German doctrine refers to this as the Ein-Platz-Prinzip, which stipulates that in each sport there can be only one federation per geographical level. At least in speed skating, if an athlete wants to make a living from this sport, there is no alternative to the international competitions organised by the governing bodies.

This puts the ISU, organiser of the World Speed Skating Championships, in a dominant position pursuant to the German Act against Restraints of Competition. If athletes want to compete at the international level, they have no other choice but to put up with an arbitration clause that the organising federations include in their registration forms.

Having athletes sign a compulsory arbitration agreement is not per se an abuse of a dominant position because there are good reasons for such an agreement.

The German Court held, however, that the problem lies in a structural imbalance of the CAS. In 2009, when Pechstein signed the arbitration agreement, the CAS Code then in force provided that 3 out of 5 arbitrators were chosen by the sport’s governing bodies, with only two among those persons independent from those bodies.

Furthermore, the court noted that in disputes in which the parties don’t agree on a name, the president of an arbitral tribunal is directly nominated by the president of the CAS Appeals Division, who is himself nominated by the International Council of Arbitration for Sport (ICAS), a body highly dependent on sports associations.

Forcing an athlete to accept an imbalanced arbitral court’s jurisdiction is what constitutes an abuse of market power (and not the arbitration agreement itself).
Accordingly, the Oberlandesgericht refused to recognise the CAS award based on Art. V (2) (b) New York Convention because it violates German cartel law, which is part of the ordre public.

Hence, no res iudicata effect of the CAS award hinders Pechstein from bringing forward claims for damages before German state courts. Therefore the Oberlandesgericht Munich rules on 15 January 2015 that the arbitration agreement was void and the arbitral award could not be recognized.

The Court of Arbitration for Sport (CAS) noted in response that, accourding to the Higher District Court in Munich, the fact that the decisions of the CAS and of the Swiss Federal Tribunal (SFT) were final in Switzerland did not prevent the athlete from bringing a claim for damages before the German courts, in the light of the principles of German competition law which forms part of German public policy.

However, the CAS has also noted that the Higher Court did not consider that making the Athletes’ participation in competitions contingent on their agreement to arbitration in general was an abuse of a dominant position. The Higher Court also mentioned that CAS arbitration does not breach Article 6 para. 1 of the European Convention for Human Rights and recognized the need to have a specialized international tribunal, instead of state courts, ensuring the uniform adjudication of sports-related disputes.

The CAS noted that the findings of the Munich Higher Court are based on the CAS rules and organization in force in 2009, when Claudia Pechstein appealed before CAS, and do not take into account the changes leading to the current organization, with amended procedural rules regarding the nomination of arbitrators, development of the legal aid program and the appointment of new ICAS Members not active in or connected to sports-bodies.

If, like in the Pechstein/ISU case, arbitration agreements were to be considered as invalid by state courts, even when not challenged at any stage during the arbitration, then the basic principles of international arbitration would be compromised.

(SportsAndTaxation.com & Court of Arbitration for Sport)

Muscle building supplement use in Australian adolescent boys : relationships with body image, weight lifting, and sports engagement

26 Feb 2020

Muscle building supplement use in Australian adolescent boys : relationships with body image, weight lifting, and sports engagement / Zali Yager, Siân McLean. - (BMC Pediatrics 20 (2020) 89 (26 February); 1-9).

  • DOI: 10.1186/s12887-020-1993-6.
  • PMCID: PMC7043030.
  • PMID: 32101154


Abstract

Background
The extent and implications of muscle building protein supplement use among adolescents is relatively unknown. This study aimed to describe the prevalence of protein powder, creatine, and anabolic steroid use in a sample of 14–16 year-old boys in Australia, and the predictors of actual use, and intentions to use protein powder.

Methods
Data were obtained from questionnaires with Australian adolescent boys aged 14–16 years from one independent boy’s school in Melbourne (N = 237). Hierarchical linear and logistic regressions were used to determine the predictors of intentions, and actual use of protein powder.

Results
49.8% of boys reported current use of, and 62% intended to use protein powder; 8.4% used creatine, and 4.2% used anabolic steroids. Higher levels of drive for muscularity, participation in weight training, and playing a greater number of sports were significant predictors of higher current use and intentions to use protein powder, but age, BMI, body esteem, and ethnicity were not.

Conclusions
Prevalence of muscle building supplement use was relatively high among this adolescent population. This research has implications for intervention and prevention programs to educate young boys about muscle building supplements to reduce negative physical and psychological health effects of their use.

Muscle Dysmorphia Among Current and Former Steroid Users

1 Mar 2011

Muscle Dysmorphia Among Current and Former Steroid Users / Rebecca Davies, Dave Smith, Kevan Collier. - (Journal of Clinical Sport Psychology 5 (2011) 1 (March) ; p. 77-94)

  • DOI: 10.1123/jcsp.5.1.77


Abstract

This study examined the presence and experience of muscle dysmorphia among current and former steroid-using recreational bodybuilders. The Muscle Dysmorphia Inventory was given to 60 male participants, with 9 of these being interviewed to examine the predisposing factors, characteristics, and negative consequences of muscle dysmorphia comprising Lantz, Rhea, and Mayhew’s (2001) conceptual model. Quantitative results from the MDI data showed no significant differences between current and former steroid users in their experiences of muscle dysmorphia. In contrast, interviews suggested that former users appeared to be more susceptible to some of the characteristics of muscle dysmorphia, including physique protection and body distortion/dissatisfaction, which suggests perhaps a limitation in the amount of information that can be extracted from a questionnaire. These preliminary findings also raise concerns about the lack of a diagnostic tool available for the condition and are discussed in relation to Lantz et al.’s (2001) conceptual model.

Muscle Dysmorphia and anabolic steroid abuse: Can we trust the data of online research?

20 Dec 2017

Muscle Dysmorphia and anabolic steroid abuse: Can we trust the data of online research? / Michele Settanni, Laura Elvira Prino, Matteo Angelo Fabris, Claudio Longobardi

  • Psychiatry Research 263 (May 2018), p. 288
  • PMID: 29290483
  • DOI: 10.1016/j.psychres.2017.12.049

 

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