Androgen abuse epidemiology / Dominic Sagoe, Ståle Pallesen. - (Current opinion in endocrinology, diabetes, and obesity 25 (2018) 3 (June); p. 185-194)

• PMID: 29369917
• DOI: 10.1097/MED.0000000000000403

Abstract

Purpose of review: To systematically review current epidemiological literature on androgen abuse. Estimates from 32 empirical epidemiological articles were reviewed.

Recent findings: Generally, androgen abuse epidemiology and prevalence is higher in Europe, the Middle East, North America (the USA), Oceania (Australia and New Zealand), and South America (Brazil) and lower in Africa and Asia. In contrast to the general population, androgen abuse epidemiology and prevalence is higher among athletes, injection drug users, recreational sportspeople, and sexual and gender minorities.

Summary: From the 1970s, androgen abuse spread from athletes into the general population. Consistent with previous evidence, reviewed studies suggest that androgen abuse epidemiology and prevalence is higher in Western cultural contexts, the Middle East, and South America (Brazil) and lower in Africa and Asia. Evidence also corroborates indications that androgen abuse is less prevalent among women (vs. men), and in the general population in contrast to particular subpopulations consisting of athletes, injection drug users, recreational sportspeople, and sexual and gender minorities. Adolescents' androgen abuse should be of special concern. Androgen abuse in some nonsports occupations (e.g. security workers) requires further exploration. Polypharmacy and the Internet proliferation of androgens and other PIEDs require surveillance for prevention and harm reduction.

Effects of Long Term Supplementation of Anabolic Androgen Steroids on Human Skeletal Muscle / Ji-Guo Yu, Patrik Bonnerud, Anders Eriksson, Per S. Stål, Yelverton Tegner, Christer Malm. - (PLoS One 9 (2014) 9 (10 September); p. 1-11)

• DOI: 10.1371/journal.pone.0105330
• PMCID: PMC4160183
• PMID: 25207812

Abstract

The effects of long-term (over several years) anabolic androgen steroids (AAS) administration on human skeletal muscle are still unclear. In this study, seventeen strength training athletes were recruited and individually interviewed regarding selfadministration of banned substances. Ten subjects admitted having taken AAS or AAS derivatives for the past 5 to 15 years (Doped) and the dosage and type of banned substances were recorded. The remaining seven subjects testified to having never used any banned substances (Clean). For all subjects, maximal muscle strength and body composition were tested, and biopsies from the vastus lateralis muscle were obtained. Using histochemistry and immunohistochemistry (IHC), muscle biopsies were evaluated for morphology including fiber type composition, fiber size, capillary variables and myonuclei.
Compared with the Clean athletes, the Doped athletes had significantly higher lean leg mass, capillary per fibre and
myonuclei per fiber. In contrast, the Doped athletes had significantly lower absolute value in maximal squat force and
relative values in maximal squat force (relative to lean body mass, to lean leg mass and to muscle fiber area). Using
multivariate statistics, an orthogonal projection of latent structure discriminant analysis (OPLS-DA) model was established, in which the maximal squat force relative to muscle mass and the maximal squat force relative to fiber area, together with capillary density and nuclei density were the most important variables for separating Doped from the Clean athletes (regression = 0.93 and prediction = 0.92, p,0.0001). In Doped athletes, AAS dose-dependent increases were observed in lean body mass, muscle fiber area, capillary density and myonuclei density. In conclusion, long term AAS supplementation led to increases in lean leg mass, muscle fiber size and a parallel improvement in muscle strength, and all were dosedependent. Administration of AAS may induce sustained morphological changes in human skeletal muscle, leading to physical performance enhancement.

Enhanced UHPLC-MS/MS screening of selective androgen receptor modulators following urine hydrolysis / Anna Gadaj, Emiliano Ventura, Jim Healy, Francesco Botrè, Saskia S. Sterk, Tom Buckley, Mark H. Mooney. - (MethodsX 7 (2020) 100926 (21 May); p. 1-12)

• PMID: 32547930
• PMCID:
• PMC7286957
• DOI: 10.1016/j.mex.2020.100926 

Abstract

Selective androgen receptor modulators (SARMs) represent non-steroidal agents commonly abused in human and animal (i.e. equine, canine) sports, with potential for further misuse as growth promoting agents in livestock-based farming. As a direct response to the real and possible implications of illicit application in both sport as well as food production systems, this study incorporated enzymatic hydrolysis (β-glucuronidase/arylsulfatase) into a previously established protocol while maintaining the minimal volume (200 µL) of urine sample required to detect SARMs encompassing various pharmacophores in urine from a range of species (i.e. equine, bovine, human, canine and rodent). The newly presented semi-quantitative UHPLC-MS/MS-based assay is shown to be fit-for-purpose, being rapid and offering high-throughput, with validation findings fulfilling criteria stipulated within relevant doping and food control legislation.•CCβ values determined at 1 ng mL-1 for majority of analytes.•Deconjugation step included in the method led to significantly increased relative abundance of ostarine in analysed incurred urine samples demonstrating the requirement for hydrolysis to detect a total form of emerging SARMs.•Assay amenable for use within routine testing to ensure fair play in animal and human sports and that animal-derived food is free from contamination with SARM residues.

Management of Anabolic Steroid-Induced Infertility: Novel Strategies for Fertility Maintenance and Recovery / Alexander J. Tatem, Jonathan Beilan, Jason R. Kovac, Larry I. Lipshultz. - (World Journal of Men's Health 38 (2020) 2 (April); p. 141-150)

• DOI: 10.5534/wjmh.190002
• PMCID: PMC7076311
• PMID: 30929329

Abstract

There is often inherent conflict in the overlapping fields of male fertility and andrology. While the goal of all male fertility specialists is to facilitate and preserve biologic paternity, many practitioners also care for a significant number of patients suffering from hypogonadism. Exogenous testosterone administration, the gold standard for the management of these patients, almost universally impairs spermatogenesis and can even completely eradicate it in some men. With steady increases in both the incidence of hypogonadism and average paternal age, practitioners are now encountering hypogonadal men who desire future fertility or men suffering the effects of earlier androgenic anabolic steroid use with increasing frequency. In this manuscript, we review management strategies for these complex patients and explore novel medications that may be of use in this population.

Risk of false positive results to SARM S-4 in case of therapeutic use of antineoplastic/antiandrogen drug containing flutamide : a case study / L. Perrenoud, C. Schweizer Grundisch, N. Baume, Martial Saugy, Raul Nicoli. - (Drug Testing and Analysis 8 (2016) 11-12 (November-December); p. 1109-1113)

• PMID: 27511110
• DOI: 10.1002/dta.2051

Glucocorticoid administration in athletes: Performance, metabolism and detection / Katia Collomp, Alexandre Arlettaz, Corinne Buisson, Anne-Marie Lecoq, Cynthia Mongongu. - (Steroids 115 (2016) November; p. 193-202)

• PMID: 27643452
• DOI: 10.1016/j.steroids.2016.09.008

Abstract

It is generally acknowledged in the sporting world that glucocorticoid (GC) use enhances physical performance. This pharmacological class is therefore banned by the World Anti-Doping Agency (WADA) in in-competition samples after systemic but not local (defined as any route other than oral, intravenous, intramuscular or rectal) administration, which thus allows athletes to use GCs for therapeutic purposes. According to the 2016 WADA list, the urine reporting level for all GCs is set at 30ng/ml to distinguish between the authorized and banned routes of administration. The actual data on the ergogenic effects of GC intake are nevertheless fairly recent, with the first study showing improved physical performance with systemic GC administration dating back only to 2007. Moreover, the studies over the last decade coupling ergogenic and metabolic investigations in humans during and after GC intake have shown discrepant results. Similarly, urine discrimination between banned and authorized GC use remains complex, but it seems likely to be improved thanks to new analytical studies and the inclusion of the authorized GC uses (local routes of administration and out-of-competition samples) in the WADA monitoring program. In this review, we first summarize the current knowledge on the ergogenic and metabolic GC effects in humans during various types of exercise. We then present the antidoping legislation and methods of analysis currently used to detect GC abuse and conclude with some practical considerations and perspectives.

Analysis of new growth promoting black market products / Oliver Krug, Andreas Thomas, Helle Malerød-Fjeld, Yvette Dehnes, Tim Laussmann, Ingo Feldmann, Albert Sickmann, Mario Thevis. - (Growth Hormone & IGF Research 41 (2018) August; p. 1-6)

• PMID: 29864719
• DOI: 10.1016/j.ghir.2018.05.001

Abstract

Detecting agents allegedly or evidently promoting growth such as human growth hormone (GH) or growth hormone releasing peptides (GHRP) in doping controls has represented a pressing issue for sports drug testing laboratories. While GH is a recombinant protein with a molecular weight of 22 kDa, the GHRPs are short (3-6 amino acids long) peptides with GH releasing properties. The endogenously produced GH (22 kDa isoform) consists of 191 amino acids and has a monoisotopic molecular mass of 22,124 Da. Within this study, a slightly modified form of GH was discovered consisting of 192 amino acids carrying an additional alanine at the N-terminus, leading to a monoisotopic mass of 22,195 Da. This was confirmed by top-down and bottom-up experiments using liquid chromatography coupled to high resolution/high accuracy mass spectrometry. Additionally, three analogues of GHRPs were identified as Gly-GHRP-6, Gly-GHRP-2 and Gly-Ipamorelin, representing the corresponding GHRP extended by a N-terminal glycine residue. The structure of these peptides was characterised by means of high resolution (tandem) mass spectrometry, and for Gly-Ipamorelin and Gly-GHRP-2 their identity was additionally confirmed by custom synthesis. Further, established in-vitro experiments provided preliminary information considering the potential metabolism after administration.

Identification of a novel growth hormone releasing peptide (a glycine analogue of GHRP-2) in a seized injection vial / Magdalena Popławska, Agata Błażewicz. - (Drug Testing and Analysis 11 (2019) 1 (January); p. 162-167)

• PMID: 30051972
• DOI: 10.1002/dta.2467

Abstract

Growth hormone releasing peptides (GHRPs) are synthetic peptides with the ability to stimulate human growth hormone (hGH) secretion. Several GHRPs have been developed as drug candidates; however, only one of them, GHRP-2 (Pralmorelin), has received a clinical approval. Nevertheless, they are distributed on the black market and misused by cheating athletes, due to their performance-enhancing effects. Hence, GHRPs have been included in the World-Anti-Doping-Agency's Prohibited List as forbidden substances in sport. Predominantly, analytical methods for detection and unequivocal identification of doping substances are based on mass spectrometry. Therefore, in the present work, a qualitative analysis by liquid chromatography coupled to high-resolution tandem mass spectrometry with a quadrupole time-of-flight analyzer was performed to identify a new heptapeptide (MW = 874.02 Da) - a glycine analogue of GHRP-2. Structure determination using de novo sequencing is described here in detail. The results of this study may indicate a new approach to circumvent a detection of doping practices.

Glycine-modified growth hormone secretagogues identified in seized doping material / Paulina Marta Gajda, Niels Bjerre Holm, Lars Jakobsen Hoej, Brian Schou Rasmussen, Petur Weihe Dalsgaard, Lotte Ask Reitzel, Kristian Linnet. - (Drug Testing and Analysis 11 (2019) 2 (February); p. 350-354)

• PMID: 30136411
• DOI: 10.1002/dta.2489

Abstract

A number of unknown pharmaceutical preparations seized by Danish customs authorities were submitted for liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis. Comparison with reference standards unequivocally identified the content of the powders as analogs of the growth hormone secretagogues GHRP-2 (Pralmorelin), GHRP-6, Ipamorelin, and modified growth hormone releasing factor (modified GRF 1-29), which can be used as performance-enhancing substances in sports. In all cases, the detected modification involved the addition of an extra glycine amino acid at the N-terminus, and analytical methods targeting growth hormone secretagogues should hence be updated accordingly.

Use of anabolic-androgenic steroids and other substances prior to and during imprisonment - Results from the Norwegian Offender Mental Health and Addiction (NorMA) study / Ingrid Amalia Havnes, Anne Bukten, Eline Borger Rognli, Ashley Elizabeth Muller. - (Drug and Alcohol Dependence 217 (2020) 108255 (1 December); p. 1-7)

• PMID: 32949884
• DOI: 10.1016/j.drugalcdep.2020.108255

Abstract:

Background: Anabolic-androgenic steroid (AAS) use is associated with health problems and substance use.
Substance use is common among inmates. This study aims to estimate lifetime and prison use of AAS and other
substances, compare characteristics of groups of inmates, and describe factors associated with AAS use in a
national prison population.
Methods: Data from the Norwegian Offender Mental Health and Addiction (NorMA) Study, a cross-sectional
survey of people in prisons, included sociodemographic variables and lifetime and prison use of AAS and other
substances. Altogether 1,499 inmates, including 96 (6.4%) women, were divided into three mutually exclusive
groups according to lifetime AAS use, non-AAS substance use and no substance use.
Results: Lifetime AAS use was reported by 427 (28.5%) inmates; 6 women and 421 men. Non-AAS substance use
was reported by 593 (39.6%) and 479 (31.9%) had never used AAS or non-AAS substances.
Compared to the non-AAS substance group, the AAS group reported younger debut ages for nearly all non-AAS
substances, higher mean number of non-AAS substances used in their lifetime (8.9, 6.6, p < 0.001), during the six
months prior to incarceration (5.2, 3.1, p < 0.001), and during (2.3, 1.3, p < 0.001) imprisonment. Although 120
(8.0%) inmates used AAS during the six months prior to incarceration, only ten continued during imprisonment.
Conclusions: Lifetime AAS use is common among inmates and may be an indicator of more severe substance use
problems. Screening for previous and present AAS use at incarceration and increased staff awareness are needed
to tailor treatment approaches appropriately.