A robust test for growth hormone doping : present status and future prospects / Anne E Nelson. Ken K Ho. - (Asian journal of andrology 10 (2008) 3 (May); p. 416-425).

• PMID: 18385903.
• DOI: 10.1111/j.1745-7262.2008.00395.x

Abstract

Although doping with growth hormone (GH) is banned, there is anecdotal evidence that it is widely abused. GH is reportedly used often in combination with anabolic steroids at high doses for several months. Development of a robust test for GH has been challenging because recombinant human 22 kDa (22K) GH used in doping is indistinguishable analytically from endogenous GH and there are wide physiological fluctuations in circulating GH concentrations. One approach to GH testing is based on measurement of different circulating GH isoforms using immunoassays that differentiate between 22K and other GH isoforms. Administration of 22K GH results in a change in its abundance relative to other endogenous pituitary GH isoforms. The differential isoform method has been implemented; however, its utility is limited because of the short window of opportunity of detection. The second approach, which will extend the window of opportunity of detection, is based on the detection of increased levels of circulating GH-responsive proteins, such as insulin-like growth factor (IGF) axis and collagen peptides. Age and gender are the major determinants of variability for IGF-I and the collagen markers; therefore, a test based on these markers must take age into account for men and women. Extensive data is now available that validates the GH-responsive marker approach and implementation is now largely dependent on establishing an assured supply of standardized assays. Future directions will include more widespread implementation of both approaches by the World Anti-Doping Agency, possible use of other platforms for measurement and an athlete's passport to establish individual reference levels for biological parameters such as GH-responsive markers. Novel approaches include gene expression and proteomic profiling.

A Selective Androgen Receptor Modulator (OPK-88004) in Prostate Cancer Survivors : A Randomized Trial / Karol M. Pencina, Arthur L. Burnett, Thomas W. Storer, Wen Guo, Zhuoying Li, Adam S. Kibel, Grace Huang, Michelle Blouin, Donna L. Berry, Shehzad Basaria, Shalender Bhasin. - (Journal of Clinical Endocrinology & Metabolism 106 (2021) 8 (August); p. 2171-2186)

• PMID: 34019661
• PMCID: PMC8277210 (available on 2022-05-21)
• DOI: 10.1210/clinem/dgab361

Abstract

Background: Androgen deficiency is common among prostate cancer survivors, but many guidelines consider history of prostate cancer a contraindication for testosterone replacement. We determined the safety and efficacy of a selective androgen receptor modulator (OPK-88004) in symptomatic, testosterone-deficient men who had undergone radical prostatectomy for low-grade, organ-confined prostate cancer.

Methods: In this placebo-controlled, randomized, double-blind trial, 114 men, ≥19 years of age, who had undergone radical prostatectomy for low-grade, organ-localized prostate cancer, undetectable PSA (<0.1 ng/mL) for ≥2 years after radical prostatectomy and testosterone deficiency were randomized in stages to placebo or 1, 5, or 15 mg OPK-88004 daily for 12 weeks. Outcomes included PSA recurrence, sexual activity, sexual desire, erectile function, body composition, muscle strength and physical function measures, mood, fatigue, and bone markers.

Results: Participants were on average 67.5 years of age and had severe sexual dysfunction (mean erectile function and sexual desire domain scores 7.3 and 14.6, respectively). No participant experienced PSA recurrence or erythrocytosis. OPK-88004 was associated with a dose-related increase in whole-body (P < 0.001) and appendicular (P < 0.001) lean mass and a significantly greater decrease in percent body fat (P < 0.001) and serum alkaline phosphatase (P < 0.001) than placebo. Changes in sexual activity, sexual desire, erectile function, mood, fatigue, physical performance, and bone markers did not differ among groups (P = 0.73).

Conclusions: Administration of OPK-88004 was safe and not associated with PSA recurrence in androgen-deficient men who had undergone radical prostatectomy for organ-confined prostate cancer. OPK-88004 increased lean body mass and decreased fat mass but did not improve sexual symptoms or physical performance.

A statistical synthesis of the literature on personal and situational variables that predict doping in physical activity settings / Nikos Ntoumanis, Johan Ng, Vassilis Barkoukis, Susan Backhouse

Executive summary

Doping behaviors are not uncommon in sport or certain types of exercise settings. Over the last two decades, there has been a growing interest in understanding the psychological mechanisms associated with doping behavior. As such, there is a need to summarize the evidence in the literature and identify demographic (e.g., sex, age) and psycho-social (e.g., attitudes, perceived norms) variables that are most strongly related to doping behaviors or intentions to engage in such behaviors. To this end, this report represents the first meta- analytical (Hunter & Schmidt, 2004) review of available studies in the extant literature. The review aimed to collectively determine (i) the predictive factors of doping intentions and doping behavior, and (ii) identify moderator variables. A total of 63 studies, spanning 1990- 2013, containing 63 independent published and unpublished datasets from 18 countries were examined and included in an analysis using odds ratios, Pearson correlations, and Cohen’s d for combining study estimates. We found that factors such as the use of legal supplements, perceived social norms, and positive attitudes towards doping were the strongest positive correlates of doping intentions and behaviors. In contrast, factors such as morality and self-efficacy to refrain from doping had the strongest negative association with both intentions
and doping behaviors.

The effects of potential moderators such as sex, publication status, and study design were also tested. Although different sizes of effect were found across distinct levels of moderators, all such effects were in the expected directions. Given that the Theory of Planned Behavior (Ajzen, 1991; Fishbein & Cappella, 2006) has been the dominant framework in doping behavior research (e.g., Zelli et al. 2010; Lazuras et al. 2010; Goulet et al. 2010; Lucidi et al. 2008;), we used path analysis to test a TPB-based model of doping using the meta-analyzed correlations as input matrix. Our results suggested that attitudes and perceived norms (positively), and self-efficacy to refrain from doping negatively) predicted intentions to dope, and in turn predicted doping behaviors. A direct path from perceived norms to doping behaviors was also found, suggesting that perceptions of others’ behaviors may play a salient role in individuals’ doping behaviors. The findings of this meta-analysis provide an objective and concise synthesis of prior research on the psycho-social variables associated with doping behavior and indicate the stronger predictors of doping use. Overall, they highlight the need for a broader approach to anti-doping education. An approach which moves beyond curricula heavily skewed towards compliance and testing towards one that emphasize the social context of doping behavior via strength- and norm-based activities

A steroidomic approach for biomarkers discovery in doping control / Julien Boccard, Flavia Badoud, Elia Grata, Samia Ouertani, Mohamed Hanafi, Gérard Mazerolles, Pierre Lantéri, Jean-Luc Veuthey, Martial Saugy, Serge Rudaz. - (Forensic Science International 213 (2011) 1-3 (10 December); p. 85-94)

• PMID: 21831550
• DOI: 10.1016/j.forsciint.2011.07.023

Abstract

Anti-doping authorities have high expectations of the athlete steroidal passport (ASP) for anabolic-androgenic steroids misuse detection. However, it is still limited to the monitoring of known well-established compounds and might greatly benefit from the discovery of new relevant biomarkers candidates. In this context, steroidomics opens the way to the untargeted simultaneous evaluation of a high number of compounds. Analytical platforms associating the performance of ultra-high pressure liquid chromatography (UHPLC) and the high mass-resolving power of quadrupole time-of-flight (QTOF) mass spectrometers are particularly adapted for such purpose. An untargeted steroidomic approach was proposed to analyse urine samples from a clinical trial for the discovery of relevant biomarkers of testosterone undecanoate oral intake. Automatic peak detection was performed and a filter of reference steroid metabolites mass-to-charge ratio (m/z) values was applied to the raw data to ensure the selection of a subset of steroid-related features. Chemometric tools were applied for the filtering and the analysis of UHPLC-QTOF-MS(E) data. Time kinetics could be assessed with N-way projections to latent structures discriminant analysis (N-PLS-DA) and a detection window was confirmed. Orthogonal projections to latent structures discriminant analysis (O-PLS-DA) classification models were evaluated in a second step to assess the predictive power of both known metabolites and unknown compounds. A shared and unique structure plot (SUS-plot) analysis was performed to select the most promising unknown candidates and receiver operating characteristic (ROC) curves were computed to assess specificity criteria applied in routine doping control. This approach underlined the pertinence to monitor both glucuronide and sulphate steroid conjugates and include them in the athletes passport, while promising biomarkers were also highlighted.

A synthetic stimulant never tested in humans, 1,3-dimethylbutylamine (DMBA), is identified in multiple dietary supplements / Pieter A. Cohen, John C. Travis, Bastiaan J. Venhuis. - (Drug Testing and Analysis 7 (2015) 1 (January); p. 83-87)

• PMID: 25293509
• DOI: 10.1002/dta.1735

Erratum in

• Drug Test Anal. 2015 Jan;7(1):88
• DOI: 10.1002/dta.1762

Abstract

A synthetic stimulant never before studied in humans, 1,3-dimethylbutylamine (DMBA), was suspected of being present in dietary supplements. DMBA is an analogue of the pharmaceutical stimulant, 1,3-dimethylamylamine (DMAA), which was recently banned by the US Food and Drug Administration. We obtained all dietary supplements sold by US distributors that listed an ingredient on the label, such as AMP Citrate, that might be a marketing name for DMBA. Supplements were analyzed for the presence and quantity of DMBA. Fourteen supplements met our inclusion criteria and were analyzed by two separate laboratories using ultra high performance liquid chromatography (UHPLC) - mass spectrometry and a reference standard. The identity of DMBA was confirmed in 12 supplements in the range of 13 to 120 mg DMBA per serving. Following recommendations on the supplement label for maximum daily intake, customers would consume from 26 to 320 mg of DMBA per day. Supplements containing DMBA were marketed to improve athletic performance, increase weight loss and enhance brain function. DMBA has never before been detected in supplements. The stimulant has never been studied in humans; its efficacy and safety are entirely unknown. Regulatory agencies should act expeditiously to warn consumers and remove DMBA from all dietary supplements.

This erratum corrects DOI:10.1002/dta.1735 published online 8 October 2014 in Wiley Online Library.

The Frenzy products we tested for our study were not purchased in the USA nor were they shipped from any retailer/distributor to the USA; rather, as we said in the Short Communication, the Frenzy products were purchased from an online retailer in the UK. While we are not aware of Driven Sports (the manufacturer of Frenzy) or any of its authorized US distributors selling Frenzy in the USA, as of the relevant time period of our study (April 2014), the USA Today was reporting that on April 9, 2014, Frenzy was available for sale on ebay's U.S. site. [A. Young. FDA warns maker of controversial sports supplement Craze. USA Today, April 15, 2014.] We have since confirmed that Frenzy is still offered for sale on ebay's U.S. site and can be purchased from sellers (including those sellers based in the US) on eBay's U.S. site. The inclusion criteria, therefore, include products containing DMBA available to U.S. consumers from various on‐line sources.

A systematic review investigating the behaviour change strategies in interventions to prevent misuse of anabolic steroids / Geoff Bates, Emma Begley, David Tod, Lisa Jones, Conan Leavey, Jim McVeigh

• Journal of Health Psychology 24 (2019) 11 (September), p. 1595-1612
• PMID: 29096544
• DOI: 10.1177/1359105317737607

Abstract

We examined intervention effectiveness of strategies to prevent image- and performance-enhancing drug use. Comprehensive searches identified 14 interventions that met review inclusion criteria. Interventions were predominantly educational and delivered within school sport settings, but targeted a wide range of mediating factors. Identification of effective components was limited across studies by brief or imprecise descriptions of intervention content, lack of behavioural outcome measures and short-term follow-up times. However, studies with components in addition to information provision may be more promising. Interventions outside of sport settings are required to reflect the transition of this form of substance use to the general population.

A systematic review of research into coach perspectives and behaviours regarding doping and anti-doping / Luke T. Barnes Laurie B. Patterson Susan H. Backhouse

• Psychology of Sport and Exercise 59 (2022) 101780 (March)
• DOI: 10.1016/j.psychsport.2020.101780

AbstractObjectives

Doping threatens the integrity of sport and the health and wellbeing of athletes. Operating as both a risk and protective agent, coaches may influence athletes’ (anti-)doping thoughts, feelings and behaviours. The objective of this study was to systematically review empirical coach anti-doping literature over a 20-year period between World Anti-Doping Agency (WADA) formation (1999) and the present day (2019) to help better understand coaches’ perspectives and behaviours in relation to doping and anti-doping in sport.

Design

A systematic review was conducted using PRISMA guidelines.

Methods

Electronic searches of seven databases, twenty-four journals and citation pearl growing identified published studies between 1999 and 2019.

Results

Thirty-eight studies were included in this review. Three higher order themes were identified (individual, behavioural and contextual factors), consisting of a total of five themes (self-reported behaviour, hypothetical behaviour, coach beliefs, knowledge, and psychosocial components). Findings documented a changing research landscape, which revealed a greater frequency of total publications and emergence of qualitative study designs in conjunction with the development and induction of the 2015 World Anti-Doping Code (WADC).

Conclusion

Over the last 20 years the anti-doping literature addressing coaches has developed and diversified from narrowly focused quantitative studies of coaches’ knowledge and beliefs, to broader considerations of behavioural and contextual factors through the use of qualitative and mixed/multi-method designs. Although the existing literature sheds some light on coaches’ perspectives and behaviours relating to doping prevention, further high-quality studies investigating the wider context surrounding coach behaviours, underpinned by meta-theory, are needed to fully understand the complexity of doping in sport and guide future policy and practice.

A validated method for the quantification of IOX-2, a potent prolyl hydroxylase inhibitor in equine urine and plasma using liquid chromatography-high-resolution mass spectrometry / Ezra Mikhail, Erik Siccardi, Ali Bawazir, Ambika Rajesh, Seetharani Prathyush, Duaa Mohammad Kamal Al Wazani, Muhammed Sabeek, Thomas John. - (Drug Testing and Analysis (2021) 2 February)

• PMID: 33533201
• DOI: 10.1002/dta.3010

Abstract

IOX-2 is a potent inhibitor of enzyme prolyl hydroxylases-2 (PHD) that plays a critical role in regulating hypoxia inducible factor (HIF) abundance and oxygen homeostasis. Federation for Equestrian Sports has listed HIF activators as prohibited substances to prevent their usage in doping. Consequently, it became essential to develop adequate knowledge and testing methods to detect it in equine sports drug testing samples. The validated method utilizes ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry in order to detect extremely low concentration of the analyte present in both matrices. Confirmation for the presence of the analyte was achieved by comparing ion ratios, retention time, and accurate mass. Method linear range for plasma was between 0.25 to 100 ng/ml, and limit of detection (LOD) was 0.075 ng/ml. The linear range for urine was 0.125 to 100 ng/ml, and LOD was 0.025 ng/ml. Intraday precision at 0.5, 10, and 50 ng/ml was between 4.0% and 9.7% for plasma and 4.2% and 10.4% for urine. Accuracy at 0.5, 10, and 50 ng/ml was between 91% and 94% for plasma and 99% and 103% for urine. Elimination profile of IOX-2 in equine plasma and urine was carried out using the developed method in which two horses were intravenously administered IOX-2 and samples were collected. Metabolic profile in plasma and urine was investigated. IOX-2 was detected for a minimum of 54 and 151 h of post administration in plasma and urine, respectively, thereby providing a valuable tool for evaluating its misuse in equine racing.

Keywords: IOX-2; PHD inhibitor; equine doping; plasma; urine.

A Warning Against the Negligent Use of Cannabidiol in Professional and Amateur Athletes / Dirk W. Lachenmeier, Patrick Diel. - (Sports (Basel) 7 (2019) 12 (14 December).
- PMID: 31847307.
- DOI: 10.3390/sports7120251

Abstract

Cannabidiol (CBD) is a non-psychoactive cannabinoid, widely marketed to athletes for claimed effects such as decreased anxiety, fear memory extinction, anti-inflammatory properties, relief of pain and for post-exercise recovery. The World Anti-Doping Agency (WADA) has excluded CBD from its list of prohibited substances. Nevertheless, caution is currently advised for athletes intending to use the compound-except CBD, all other cannabinoids are still on the prohibited list. CBD products, specifically non-medicinal, so-called full-spectrum cannabis extracts, may contain significant levels of these substances, but also contaminations of tetrahydrocannabinol (THC) (>2.5 mg/day in >30% of products on the German market) potentially leading to positive doping tests. Labelled claims about CBD content and absence of THC are often false and misleading. Contaminations with the psychoactive THC can result in adverse effects on cognition and, in general, the safety profile of CBD with respect to its toxicity is a controversial topic of discussion. For these reasons, we would currently advise against the use of over-the-counter CBD products, especially those from dubious internet sources without quality control.

A ‘messenger of sex’? Making testosterone matter in motivations for anabolic-androgenic steroid injecting / Renae Fomiatti, J.R. Latham, Suzanne Fraser, David Moore, Kate Seear, Campbell Aitken

• Health Sociology 3 (2019) 3, p. 323-338
• DOI: 10.1080/14461242.2019.1678398

ABSTRACT

Anabolic-androgenic steroids are synthetic derivatives of testosterone. They are thought to be the most commonly used performance and image-enhancing drugs (PIEDs) in Australia. However, the motivations for men’s use of steroids and other PIEDs are poorly understood. Established ways of understanding these motivations highlight men’s performance and/or image-related concerns, in the context of contemporary masculinities and gender norms. Researchers have paid little attention to how the social and political features of testosterone shape and transform steroid use. Instead, testosterone tends to be taken for granted as a ‘messenger of sex’ that acts on the body in predictable and routinised ways. This article takes a different approach. Drawing on feminist science studies and interviews conducted for an Australian research project, we investigate how the cultural and symbolic meanings assigned to testosterone shape the ontological politics of men’s steroid consumption. Approaching testosterone as an emergent social and biopolitical gathering rather than as a stable sex hormone allows us to better understand how men’s PIED consumption is mediated, particularly by pervasive ideas about sexual difference and the biology of gender. In concluding, we consider ways of better engaging men who consume steroids in health initiatives, in keeping with their concerns and perspectives.