Investigations into the elimination profiles and metabolite ratios of micro-dosed selective androgen receptor modulator LGD-4033 for doping control purposes / Felicitas Wagener, Sven Guddat, Christian Görgens, Yiannis S. Angelis, Michael Petrou, Andreas Lagojda, Dirk Kühne, Mario Thevis. - (Analytical and Bioanalytical Chemistry (2021) 4 November)

• PMID: 34734312
• DOI: 10.1007/s00216-021-03740-7

Abstract

LGD-4033 (ligandrol) is a selective androgen receptor modulator (SARM), which is prohibited in sports by the World Anti-Doping Agency (WADA) and led to 62 adverse analytical findings (AAFs) in 2019. But not only deliberate doping with LGD-4033 constitutes a problem. In the past years, some AAFs that concerned SARMs can be attributed to contaminated dietary supplements (DS). Thus, the urgency to develop methods to differentiate between inadvertent doping and abuse of SARMs to benefit from the performance-enhancing effect of the compound in sports is growing. To gain a better understanding of the metabolism and excretion patterns of LGD-4033, human micro-dose excretion studies at 1, 10, and 50 µg LGD-4033 were conducted. Collected urine samples were prepared for analysis using enzymatic hydrolysis followed by solid-phase extraction and analyzed via LC-HRMS/MS. Including isomers, a total of 15 phase I metabolites were detected in the urine samples. The LC-HRMS/MS method was validated for qualitative detection of LGD-4033, allowing for a limit of detection (LOD) of 8 pg/mL. The metabolite M1, representing the epimer of LGD-4033, was synthesized and the structure elucidated by NMR spectroscopy. As the M1/LGD-4033 ratio changes over time, the ratio and the approximate LGD-4033 concentration can contribute to estimating the time point of drug intake and dose of LGD-4033 in doping control urine samples, which is particularly relevant in anti-doping result management.

The forensic response after an adverse analytical finding (doping) involving a selective androgen receptor modulator (SARM) in human athlete / Pascal Kintz. - (Journal of Pharmaceutical and Biomedical Analysis 207 (2022) January: 114433)

• PMID: 34715583
• DOI: 10.1016/j.jpba.2021.114433

Abstract

Selective androgen receptor modulators (SARMs) are a class of drugs presenting identical anabolic properties to anabolic steroids in addition to marked reduced androgenic effects. These drugs have emerged in the doping area within the early 2000's. Ligandrol, ostarine, RAD-140 and andarine are the most popular agents belonging to this class. According to the world anti-doping agency (WADA) prohibited list, SARMs are prohibited at all times (i.e. in and out-of-competition) and are listed under the section S1.2 (other anabolic agents). The compilation of the WADA testing figures reports from 2015 to 2019 has indicated a regular increase of adverse analytical findings (AAF) due to SARMs, particularly with ostarine and ligandrol. The implementation of highly sensitive chromatographic anti-doping analyses has induced high-profile challenges of anti-doping rules violations as athletes have claimed in numerous occasions that contamination was the reason for their AAF. Since the early 2000's, it has been accepted by the Court of Arbitration for Sports (CAS) in Lausanne (Switzerland) that, under some specific circumstances, unusual explanations can be provided to the Panel to explain an AAF. This was the open door for forensic investigations, as it is done in criminal Courts. A forensic approach can include testing for SARMs in food, drinks, but mostly in dietary supplements. As most anti-doping rules violations are only known several weeks after urine collection, this biological matrix is seldom use for further tests, despite the fact that most SARMs can be detected for several weeks in urine. Luckily, hair or nail testing can be a complement to document the claim of the athlete but of course, it cannot be considered as an alternative to urinalysis. This is because a negative hair or nail result cannot exclude the use of the detected drug and cannot overrule the urine result. To date, all methods for SARMs identification in various matrices involve liquid chromatography coupled to tandem mass spectrometry or high-resolution mass spectrometry. The aim of this paper is to review the scientific literature on the analytical possibilities of testing SARMs in dietary supplements, urine and hair or nail clippings after an AAF to document the claims of an athlete or his/her legal team.

Social Media, Body Image and Resistance Training : Creating the Perfect 'Me' with Dietary Supplements, Anabolic Steroids and SARM's / Luuk Hilkens, Maarten Cruyff, Liesbeth Woertman, Jeroen Benjamins, Catharine Evers. - (Sports Medicine - Open 7 (2021) 1 (10 November); 81)

• PMID: 34757466
• PMCID: PMC8579410
• DOI: 10.1186/s40798-021-00371-1

Abstract

Background: Few studies have assessed the use of dietary supplements, anabolic androgenic steroids (AAS) and selective androgen receptor modulators (SARM) in male gym users. The comparison of physical appearance with others on social media and the exposure to fitness-related content on social media (i.e., image-centric social media use) may have a profound role in using these compounds due to its role in creating negative body images in male gym users.

Objective: Provide contemporary data on the use of dietary supplements, AAS and SARM among young male gym users, and test the hypothesis that social media is associated with the use of dietary supplements, AAS and SARM, as a result of a negative body image.

Methods: In this cross-sectional study, conducted in the Netherlands, male gym users (N = 2269; 24 ± 6 years) completed an online questionnaire including self-reported measures regarding resistance training participation, image-centric social media use, dietary supplement intake, and body image. The prevalence of AAS and SARM use was assessed with randomized response, a technique to ask sensitive questions indirectly.

Results: Of all participants, 83% used ergogenic dietary supplements (mainly protein and creatine), and an estimated 9 versus 2.7% had ever used AAS versus SARM. Image-centric social media use was positively associated with the use of dietary supplements (r = .26; p < 0.01) and AAS (p < 0.05), but not SARM. Image-centric social media use was associated with a more dissatisfied body image (r = .34; p < 0.01). Body image did not mediate the relationship between image-centric social media use and the use of doping compounds.

Conclusions: The use of dietary supplements in young male gym users is exorbitant, with the use of AAS and SARM being substantial. Image-centric social media use is positively associated with the use of dietary supplements and AAS.

Effects of erythropoietin abuse on exercise performance / Paolo Sgrò, Massimiliano Sansone, Andrea Sansone, Francesco Romanelli, Luigi Di Luigi. - (The Physician and Sportsmedicine 46 (2018) 1 (13 November); p. 105-115)

• PMID: 29113535
• DOI: 10.1080/00913847.2018.1402663

Abstract

The present review provides a comprehensive overview on the erythropoietic and non-erythropoietic effects of rHuEpo on human sport performance, paying attention to quantifying numerically how rHuEpo affects exercise performance and describing physiological changes regarding the most important exercise variables. Much attention has been paid to treatment schedules, in particular, to assess the effects of microdoses of rHuEpo and the prolonged effects on sport performance following withdrawal. Moreover, the review takes into account non-erythropoietic ergogenic effects of rHuEpo, including cognitive benefits of rHuEpo. A significant increase in both Vo2max and maximal cycling power was evidenced in studies taken into account for this review. rHuEpo, administered at clinical dosage, may have significant effects on haematological values, maximal and submaximal physiological variables, whereas few reports show positive effects on exercise perfomance. However, the influence of micro-dose rHuEpo on endurance performance in athletes is still unclear and further studies are warranted.

Exploring user narratives of self-medicated black market IPED use for therapeutic & wellbeing purposes / Luke A.Turnock. - (Performance Enhancement & Health (2021) 8 November; 100207)

• DOI: 10.1016/j.peh.2021.100207

Abstract

With the rising use of IPEDs, it is important to understand how user motivations and practices influence harms, in order to formulate effective harm reduction policy. Existing work has consequently developed user typologies to address this need for specific interventions for differing users. Within this, the ‘wellbeing’ user type is one of the most prominent, however this broad category encompasses a range of users with distinct motivations and needs. This paper consequently explores the subcategory of therapeutically-motivated IPED users, whose IPED use is targeted at repair, rehabilitation, and self-medicating for health conditions, and considers the specific needs of this user category.

Findings are drawn from a connective ethnography of gyms in South-West England, and digital fitness platforms, to analyze the motivations of therapeutically-oriented users, and how their behaviors and experiences are important to formulating interventions and broader policy discussions.

Motivations explored include: (1) repair and injury rehabilitation, including those who access IPEDs for repair relating to sporting or competitive endeavors, as well as those whose IPED use is self-medicating for chronic health conditions. (2) General ‘wellbeing’ motivations for which participants self-medicated with IPEDs, including: health-oriented fat loss, rehabilitation for sleep, irritable bowel syndrome, and offsetting the negative health effects of hard sporting training. And (3) self-medicated testosterone replacement therapy (TRT) to offset negative symptoms ascribed to ‘low testosterone’, in both older gym participants whose natural levels were declining and who were looking to offset this, as well as men who experienced mental health difficulties such as depression, and sought to restore wellbeing through use of black market testosterone.

This article demonstrates the breadth of therapeutic motivations for IPED use, and points to the ways in which the specific needs of this user category may be distinct from broader ‘wellbeing’ users. Significantly, participant narratives regarding the medical community's perceived unwillingness to treat them, and their feelings that this pushed them to access illicit IPEDs, indicate the importance of understanding the specific needs in relation to harm reduction policy formation.

Influence of synthetic isoflavones on selected urinary steroid biomarkers : Relevance to doping control / Michele Iannone, Francesca Alberti, Maria Cristina Braganò, Xavier de la Torre, Francesco Molaioni, Francesco Botrè. - (Steroids 174 (2021) October; 108900)

• PMID: 34391799
• DOI: 10.1016/j.steroids.2021.108900

Abstract

In this work we have investigated the influence of the intake of two synthetic isoflavones, methoxyisoflavone and ipriflavone, on the urinary concentration of endogenous steroids, and on their relative ratios, of doping relevance. Specifically, the concentrations of testosterone (T), epitestosterone (E), androsterone (A), etiocholanolone (Etio), 5α-androstan-3α,17α-diol (5αAdiol), 5β-androstan-3α,17α-diol (5βAdiol), and the ratios T/E, A/T, A/Etio, 5αAdiol/5βAdiol, 5αAdiol/E, were considered, in the framework of the Steroidal Module of the Athlete Biological Passport (ABP). The above set of parameters were complemented by the urinary levels of luteinizing hormone (total LH) and the ratio between T and LH (T/total LH), to assess the possible effects on the biosynthesis of the mentioned steroids. Five healthy Caucasian male volunteers were selected for the study. Urine samples were collected before and during the administration of (i) methoxyisoflavone (Methoxyisoflavone, MyProtein) and (ii) ipriflavone (Osteofix ®, Chiesi Farmaceutici). For the analysis of the urinary steroid profile, after enzymatic hydrolysis with β-glucuronidase from Escherichia Coli (E. Coli) and liquid-liquid extraction with tert-buthylmethyl ether, all samples were analyzed by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS), while for the determination of total LH all urine samples were directly analyzed by a chemiluminescent immunometric assay technique (Siemens Immulite 2000 LH). Our results show that the administration of either methoxyisoflavone or ipriflavone causes an alteration of the urinary concentrations and concentration ratios of the investigated steroids, in the range 55-80% from the baseline values. Furthermore, an oversecretion of LH after the daily intake of methoxyisoflavone or ipriflavone was also recorded in all volunteers, corresponding to an increase in the biosynthesis and excretion of T and some of its metabolites. These changes trigger a disregulation in the pattern of urinary excretion of the steroids included in the Steroidal Module of the ABP, which makes more difficult the interpretation of the longitudinal steroid profile based on the definition of individual normality ranges for each athlete. Our data are also consistent with previous evidence regarding the in vitro effects of natural and synthetic isoflavones, suggesting that their monitoring in doping control routine analysis would be very beneficial for the result management activities.

The fight against doping : back on track with blood / Martial Saugy, Neil Robinson, Christophe Saudan. - (Drug Testing and Analysis 1 (2009) 11-12 (November-December); p. 474-478)

• Special Issue: Advances in sports drug testing
• PMID: 20355161
• DOI: 10.1002/dta.93

The efficiency of the fight against doping in the future will evolve drastically in several ways. Although, during the last ten years, testing of urine samples out of competition opened the door for intelligent testing, the real shift toward improvement of the system was the adoption of the blood matrix as the biological sample of choice. When collected properly, blood allows the establishment of individual haematological andhormonal profiles, which are currently the basis of the ‘biological passport’. A simpler collection procedure also permits the evaluation of the prevalence of doping in specific populations of athletes, as is typically done in epidemiology, to establish a risk assessment.

Thanks to modern research tools that combine analytical techniques (mass spectrometry) with informatics, the biological signatures resulting from the administration of a doping substance can indeed be studied atmany differentmolecular levels. Molecular mapping and fingerprinting will certainly be at the heart of all diagnostic sciences in the future and the fight against doping is no exception.

Anabolic androgenic steroids used as performance and image enhancing drugs in professional and amateur athletes : Toxicological and psychopathological findings / Daria Piacentino, Gabriele Sani, Georgios D. Kotzalidis, Simone Cappelletti, Livia Longo, Salvatore Rizzato, Francesco Fabi, Paola Frati, Vittorio Fineschi, Lorenzo Leggio. - (Human Psychopharmacology (2021) 15 September; 2815)

• PMID: 34528289
• DOI: 10.1002/hup.2815

Abstract

Objective: The use of anabolic androgenic steroids (AASs) as performance and image enhancing drugs (PIEDs), once restricted to professional athletes, now includes amateurs and regular gym visitors. AAS use is associated with psychopathology, yet this relationship is complex and not fully understood. We aimed to assess the presence of AASs and other misused substances in athletes' biological samples and link toxicological to psychopathological findings.

Methods: A multicentre, cross-sectional study in fitness centres in Italy recruited 122 professional and amateur athletes training in several sports (84 men; age range = 18-45 years). Athletes completed questionnaires, interviews, and toxicology testing for AASs, other PIEDs, illicit drugs, and non-prescribed psychotropics. Toxicology was conducted in blood, urine, and hair.

Results: Self-reported and toxicologically detected use rates of AASs and other misused substances showed slight-to-fair agreement (Fleiss' κ = 0.104-0.375). There was slight-to-moderate agreement among the three biological samples used for AAS testing (κ = 0.112-0.436). Thirty-one athletes (25.4%) tested positive for AASs. More sport hours/week, narcissistic or antisocial personality disorders, and higher nonplanning impulsiveness scores predicted AAS use (pseudo-R2 = 0.665). AAS users did not differ significantly from non-users in major psychopathology, but their Hypomania Checklist-32 score, which also predicted AAS use, was significantly higher (p < 0.001), suggesting increased odds for cyclothymic disorder or subthreshold hypomania.

Conclusions: Our results have implications for studying AAS users, as they identify a cluster of variables that may be relevant in future understanding of AAS use risks (e.g., personality disorders). Possible disagreements between AAS assessment methods should be considered when implementing harm reduction interventions, such as needle and syringe distribution, health education, and counselling, as well as surveillance programmes.

Codeine and Tramadol Use in Athletes : A Potential for Abuse / Thomas Zandonai, Mónica Escorial, Ana M. Peiró. - (Frontiers in Pharmacology (2021) 10 June; 661781 : p. 1-5)

• PMID: 34177579
• PMCID: PMC8222773
• DOI: 10.3389/fphar.2021.661781

Analgesic use by athletes is common. It has been observed that athletes used analgesics up to four times more often than their age-matched general population. Notably, codeine and tramadol are not included in the WADA list of prohibited substances in sport. Their use could be an attempt to compensate for fatigue, pain, and inflammation caused by injuries or overtraining. It has been described that this abuse can be related to false expectations of performance improvement. To the best of our knowledge, no studies have investigated codeine’s effects on exercise performance. We present an overview evidencing the athletes’ use of codeine and tramadol and their potential abuse and addiction.

Confidence by injection : Male users of anabolic steroids speak of increases in perceived confidence through anabolic steroid use / Mario J. Vassallo, Tracy W. Olrich. - (International Journal of Sport and Exercise Psychology 8 (2010) 1; p. 70-80)

• DOI: 10.1080/1612197X.2010.9671935

Abstract

Research has accumulated concerning the psychological and behavioral effects of anabolic‐androgenic steroids (AAS) in the last decade (Keane, 2005). Despite the proliferation of such work, the reporting of psychological and behavioral effects has often been inaccurate and wildly speculative (Bahrke, 2000). Methodological limitations have also been identified as a problematic issue in this area (Bahrke, 2000). In an attempt to address such limitations, descriptive, qualitative methodologies have begun to be utilized in this area of investigation (Olrich & Ewing, 1999; Olrich & Vassallo, 2002). This study consisted of in‐depth interviews with males (N = 39) who had used AAS. The men were asked several questions concerning the impact of AAS upon perceived psychological functioning. Thirty seven of the 39 participants reported an increase in perceived levels of self‐confidence during the AAS use period. Furthermore, upon cessation of the AAS use cycle, self‐confidence dropped down to, or below, pre‐AAS use levels. The men stated that the drop in confidence levels and the loss of the mental edge were motivating factors contributing to the further use of AAS