Can conditions of skeletal muscle loss be improved by combining exercise with anabolic-androgenic steroids? A systematic review and meta-analysis of testosterone-based interventions / Hugo Falqueto, Jorge L.R. Júnior, Mauro N.O. Silvério, Juliano C.H. Farias, Brad J. Schoenfeld, Leandro H. Manfredi. - (Reviews in endocrine & metabolic disorders (2020) 30 March)

• PMID: 33783694
• DOI: 10.1007/s11154-021-09634-4

Abstract

Sarcopenia, cachexia, and atrophy due to inactivity and disease states are characterized by a loss of skeletal muscle mass, often accompanied by reduced levels of anabolic hormones (e.g. testosterone). These conditions are associated with an increase in mortality, hospitalization and worsening in quality of life. Both physical exercise (EX) and anabolic-androgenic steroid (AAS) administration can improve the prognosis of patients as they increase physical functionality. However, there is a gap in the literature as to the impact of these therapies on the gains in strength and muscle mass and their implications for patient safety. Accordingly, we performed a random-effects meta-analysis to elucidate the effects of AAS and/or EX interventions on lean body mass (LBM) and muscle strength in conditions involving muscle loss. A systematic search for relevant clinical trials was conducted in MEDLINE, EMBASE, SCOPUS, Web of Science, and SPORTDiscus. Comparisons included AAS vs. Control, EX vs. Control, AAS vs. EX, AAS + EX vs. AAS and AAS + EX vs. EX. A total of 1114 individuals were analyzed. AAS increased LBM (effect size [ES]: 0.46; 95% CI: 0.25, 0.68, P = 0.00) and muscle strength (ES: 0.31; 95% CI: 0.08, 0.53, P = 0.01) when compared to a control group. EX promoted an increase in muscular strength (ES: 0.89; 95% CI: 0.53, 1.25, P = 0.00), with no effect on LBM when compared to the control group (ES: 0.15; 95% CI: -0.07, 0.38, P = 0.17). AAS did not demonstrate statistically significant differences when compared to EX for LBM and muscle strength. The combination of EX + AAS promoted a greater increase in LBM and muscular strength when compared to AAS or EX in isolation. Qualitatively, AAS administration had relatively few side effects. Significant heterogeneity was found in some analyses, which may be explained by the use of different AAS types and EX protocols. Our findings suggest that AAS administration in cachectic and sarcopenic conditions may be a viable interventional strategy to enhance muscle function when exercise is not a possible approach. Moreover, combining AAS with exercise may enhance positive outcomes in this population.

Analysis of conjugated steroid androgens : deconjugation, derivatisation and associated issues / Rachel L. Gomes, Will Meredith, Colin E. Snape, Mark A. Sephton. - (Journal of Pharmaceutical and Biomedical Analysis 49 (2009) 5 (12 July); p. 1133-1140)

• PMID: 19304432
• PMCID: PMC2684592
• DOI: 10.1016/j.jpba.2009.01.027

Abstract

Gas chromatography/mass spectrometry (GC/MS) is the preferred technique for the detection of urinary steroid androgens for drug testing in athletics. Excreted in either the glucuronide or sulfated conjugated form, steroids must first undergo deconjugation followed by derivatisation to render them suitable for GC analysis. Discussed herein are the deconjugation and the derivatisation preparative options. The analytical challenges surrounding these preparatory approaches, in particular the inability to cleave the sulfate moiety have led to a focus on testing protocols that reply on glucuronide conjugates. Other approaches which alleviate the need for deconjugation and derivatisation are also highlighted.

Impact of the UGT2B17 polymorphism on the steroid profile. Results of a crossover clinical trial in athletes submitted to testosterone administration / Pilar Martín-Escudero, Jesús A. Muñoz-Guerra, Soledad Vargas García-Tenorio, Ester Serrano Garde, Ana B. Soldevilla-Navarro, Mercedes Galindo-Canales, Nayade Prado, Manuel E. Fuentes-Ferrer, Cristina Fernández-Pérez. - (Steroids 141 (2019) January; p. 104-113)

• PMID: 30503386
• DOI: 10.1016/j.steroids.2018.11.009

Abstract

This article studies the genetic influence of polymorphism of the UGT2B17 gen on the urinary steroid profile and its implications for the anti-doping field. The study presents the results of a triple-blind randomized placebo-controlled crossover trial with healthy athletes submitted to a single dose of 250 mg of testosterone cypionate. Forty urine samples were collected from each participant. Mass spectrometry-based techniques commonly used in Anti-Doping laboratories, were employed to measure the urinary concentration and the Δδ13C values of a selection of target compounds for testosterone (T) administration together with LH. Twelve volunteers were included in the study; the polymorphism was evenly distributed among them. After T administration, the most meaningful change affected the Testosterone/Epitestosterone ratio (T/E) and the urinary concentration of LH. In relation with T/E, the wild type homozygous (ins/ins) group there was a mean relative increase of 30 (CI 95%: 25.2 to 36.7); in the heterozygous mutant (del/ins) group it was 19.8 (CI 95%:15.9 to 24.7); and in the homozygous mutant (del/del) group it was 19.7 (CI 95% 14.9 to 26.2). In the case of LH, it́s observed how LH values decrease significantly after the administration of Testex homogeneously among the three groups. The main outcome was related to the (del/del) group (homozygous mutant), where due to the depressed basal level of the steroid profile, if the longitudinal steroid profile of the athlete was not available, the analysis by GC/MS would not produce an "atypical" result according to the WADA TD2016EAAS despite the T administration. However, the genotyping of the UGT2B17 polymorphism, the follow up of LH and the use of GC-C-IRMS makes it possible to identify most of these samples as Adverse.

Evaluation of steroidomics by liquid chromatography hyphenated to mass spectrometry as a powerful analytical strategy for measuring human steroid perturbations / Fabienne Jeanneret, David Tonoli, Michel F. Rossier, Martial Saugy, Julien Boccard, Serge Rudaz. - (Journal of Chromatography A 1430 (2016, 22 January); p. 97-112)

• PMID: 26195035
• DOI: 10.1016/j.chroma.2015.07.008

Abstract

This review presents the evolution of steroid analytical techniques, including gas chromatography coupled to mass spectrometry (GC-MS), immunoassay (IA) and targeted liquid chromatography coupled to mass spectrometry (LC-MS), and it evaluates the potential of extended steroid profiles by a metabolomics-based approach, namely steroidomics. Steroids regulate essential biological functions including growth and reproduction, and perturbations of the steroid homeostasis can generate serious physiological issues; therefore, specific and sensitive methods have been developed to measure steroid concentrations. GC-MS measuring several steroids simultaneously was considered the first historical standard method for analysis. Steroids were then quantified by immunoassay, allowing a higher throughput; however, major drawbacks included the measurement of a single compound instead of a panel and cross-reactivity reactions. Targeted LC-MS methods with selected reaction monitoring (SRM) were then introduced for quantifying a small steroid subset without the problems of cross-reactivity. The next step was the integration of metabolomic approaches in the context of steroid analyses. As metabolomics tends to identify and quantify all the metabolites (i.e., the metabolome) in a specific system, appropriate strategies were proposed for discovering new biomarkers. Steroidomics, defined as the untargeted analysis of the steroid content in a sample, was implemented in several fields, including doping analysis, clinical studies, in vivo or in vitro toxicology assays, and more. This review discusses the current analytical methods for assessing steroid changes and compares them to steroidomics. Steroids, their pathways, their implications in diseases and the biological matrices in which they are analysed will first be described. Then, the different analytical strategies will be presented with a focus on their ability to obtain relevant information on the steroid pattern. The future technical requirements for improving steroid analysis will also be presented.

Effects of androstenedione administration on epitestosterone metabolism in men / Don H. Catlin, Benjamin Z. Leder, Brian D. Ahrens, Caroline K. Hatton, Joel S. Finkelstein. - (Steroids 67 (2002) 7 (June); p. 559-564)

• PMID: 11996927
• DOI: 10.1016/s0039-128x(02)00005-3

Abstract

Androstenedione is a steroid hormone sold over-the-counter to individuals who expect that it will enhance strength and athletic performance. Endogenous androstenedione is the immediate precursor of testosterone. To evaluate the metabolism of oral androstenedione, we randomly assigned 37 healthy men to receive 0 (group 1), 100 mg (group 2), or 300 mg (group 3) of androstenedione in a single daily dose for 7 days. Eight-hour urines were collected 1 day before the start of androstenedione, and on days 1 and 7. Using gas chromatography-mass spectrometry, we measured excretion rates of glucuronide-conjugated epitestosterone, its putative precursor (E-precursor), and metabolites (EM-1 and EM-2), and we evaluated possible markers of androstenedione administration. Day 1 and 7 rates were not different: the means were averaged. The means (microg/h) for groups 1, 2, and 3, respectively were, for epitestosterone 2.27, 7.74, and 18.0; for E-precursor, 2.9, 2.0, and 1.5; for EM-1/E-precursor 0.31, 1.25, and 2.88; for EM-2/E-precursor 0.14, 0.15, and 1.15; for testosterone/epitestosterone (T/E) 1.1, 3.5, and 3.2. Epitestosterone, EM-1, and EM-2 excretion was greater in groups 2 and 3 versus group 1 (0.0001 < P < 0.03), as were EM-1/E-precursor, EM-2/E-precursor, and T/E. E-precursor excretion was lower in groups 2 (P = 0.08) and 3 (P = 0.047) versus group 1. Androstenedione increases excretion of epitestosterone and its two metabolites, while decreasing that of its precursor. Elevated ratios of EM-1- and EM-2/E-precursor, and the presence of 6alpha-hydroxyandrostenedione are androstenedione administration markers.

Long-term anabolic androgenic steroid use is associated with deviant brain aging / Astrid Bjørnebekk, Tobias Kaufmann, Lisa E. Hauger, Sandra Klonteig, Ingunn R. Hullstein, Lars T. Westlye. - (Biological Psychiatry: Cognitive Neuroscience and Neuroimaging (2021), 13 January; p. 1-11)

• DOI: 10.1016/j.bpsc.2021.01.001

Abstract

Background

High-dose long-term use of anabolic–androgenic steroids (AASs) may cause a range of adverse effects, including brain and cognitive abnormalities. We performed age prediction based on brain scans to test whether prolonged AAS use is associated with accentuated brain aging.

Methods

T1-weighted magnetic resonance imaging (3D MPRAGE [magnetization-prepared rapid acquisition gradient-echo]) scans were obtained from male weightlifters with a history of prolonged AAS use (n = 130) or no AAS use (n = 99). We trained machine learning models on combinations of regional brain volumes, cortical thickness, and surface area in an independent training set of 1838 healthy male subjects (18–92 years of age) and predicted brain age for each participant in our study. Including cross-sectional and longitudinal (mean interval = 3.5 years, n = 76) magnetic resonance imaging data, we used linear mixed-effects models to compare the gap between chronological age and predicted brain age (the brain age gap [BAG]) for the two groups and tested for group differences in the rate of change in BAG. We tested for associations between apparent brain aging and AAS use duration, pattern of administration, and dependence.

Results

AAS users had higher BAG compared with weightlifting control subjects, which was associated with dependency and longer history of use. Group differences in BAG could not be explained by other substance use, general cognitive abilities, or depression. While longitudinal analysis revealed no evidence of increased brain aging in the overall AAS group, accelerated brain aging was seen with longer AAS exposure.

Conclusions

The findings suggest that long-term high-dose AAS use may have adverse effects on brain aging, potentially linked to dependency and exaggerated use of AASs.

Disordered eating and exercise behaviour amongst young men / Suzy Veitch. - Loughborough University, 2009

Abstract

Objective: Recent research suggests a higher prevalence of body image dissatisfaction and subsequent disordered eating and exercise behaviour amongst men than was previously assumed. This project aimed to assess the prevalence of such attitudes and behaviours.

Method: 3 men were interviewed regarding their eating and exercise behaviours. They performed a somatomorphic matrix test as a means of assessing body image. Surveys were distributed and completed by 59 men to assess the prevalence of disordered behaviours. The surveys included the EAT-26, the Drive for Muscularity Scale and a selection of questions from the EDET and the EDE-Q5.

Results: 2 of the men interviewed displayed abnormal eating and exercise attitudes related to bodybuilding behaviour and similar body image, including obsession with food, strict dietary behaviour, compulsive constant over-eating, extensive use of supplements and anabolic steroid abuse. 37.3% of survey participants displayed high pathology on either the EAT-26, the DMS or both. 100% of bodybuilding participants were a part of this group. A significantly larger number of participants scored highly on the DMS than on the EAT-26.

Conclusions: Body image dissatisfaction is prevalent in men and requires much further investigation and attention. In contrast to women, much dissatisfaction in men centres on a desire to increase size and muscularity, resulting in disordered eating patterns and excessive exercise. Rather than restrict food intake, many men over-eat in order to achieve these goals.

Withdrawal from Anabolic Androgenic Steroids Does Not Affect Personality Characteristics / A.S.L. Bagge, L. Lundholm, C. Ehrnborg, B.O. Eriksson, T. Moberg, T. Rosén, C. Fahlke. - (Journal of Alcoholism & Drug Dependence 4 (2016) 4; p. 1-7)

• DOI: 10.4172/2329-6488.1000245

Abstract

Objectives: The aim of this study was to investigate the relationship between anabolic androgenic steroids (AAS) and personality characteristics with the following research questions: 1) Do personality characteristics differ between AAS-abusers and an AAS-naïve comparison group? 2) Do personality characteristics differ between active AAS abusers and former AAS-abusers? 3) Does time of withdrawal from AAS affect personality characteristics?

Design: Retrospective observational study.

Methods: Sixty men (active n=20, former n=40) seeking medical consultation for their AAS abuse were included in the study. Personality characteristics were assessed by the Karolinska Scales of Personality (KSP) inventory. Comparisons were made with an age- and gender-matched group of AAS-naïve body-builders (n=30).

Results: AAS-abusers differed significantly in their personality characteristics from the AAS-naïve control group. No major differences were found between active and former AAS-abusers. No correlations were found between personality characteristics and time of withdrawal or duration of AAS abuse.

Conclusions: Individuals with AAS abuse differ in their personality characteristics from those who have never used AAS. Withdrawal from AAS does not, however, alter personality characteristic in AAS-abusers, although the causality of this relationship is unclear, indirectly stating that AAS do not seem to alter personality characteristics in a major fashion. On the other hand, it could be argued that AAS gives a more permanent change on personality that is not affected by time of withdrawal from AAS. Thus, the present results do not explain the causality of the relationship between AAS abuse and personality characteristics and further studies are needed in order to clarify this relationship.

Does growth hormone therapy in conjunction with resistance exercise increase muscle force production and muscle mass in men and women aged 60 years or older? / J.J. Zachwieja, K.E. Yarasheski. -  (Physical Therapy & Rehabilitation Journal 79 (1999) 1 (1 January); p. 76-82)

• PMID: 9920193
• DOI: 10.1093/ptj/79.1.76

Abstract

Improved muscle protein mass and increments in maximum voluntary muscle force have rarely been observed in men and women aged 60 years and older who were treated with rhGH. Although rhGH administration has been reported to increase lean body mass in older men and women, it is doubtful that this increase is localized to skeletal muscle contractile proteins. When rhGH administration was combined with 16 weeks of resistance exercises, increases in muscle mass, muscle protein synthesis, and muscle force were not greater in the rhGH-treated group than in a weight training group that received placebo injections. Side effects of rhGH treatment in elderly people are prevalent, not trivial, and further limit its usefulness as an effective anabolic agent for promoting muscle protein accretion in men and women. In particular, the induction of insulin resistance and carpal tunnel compression reduces the efficacy of rhGH replacement therapy in elderly individuals. The evidence for a GH-induced increase in human skeletal muscle protein and maximum voluntary muscle force is weak. The optimum dose and GH-replacement paradigm (GHRH, GH-secretagogues) have not been identified. Whether rhGH therapy improves muscle protein mass and force in individuals with severe cachexia associated with major trauma, burns, surgery, or muscular dystrophy is controversial and under investigation.

In January 2017 NADO Flanders reported an anti-doping rule violation against the Dutch ice hockey player after his sample tested positive for the prohibited substance 19-norandrosterone and 19-noretiocholanolone (Nandrolone).

After notification a provisional suspension was ordered. The Athlete filed a statement in his defence and he was heard for the NADO Flanders Disciplinary Commission.

The Athlete stated that he had purchased a preworkout supplement in a drugstore, however the Disciplinary Commission deemed that the Athlete failed to demonstrate with evidence that this supplement in question contained a prohibited substance.

The Commission finds that the presence of the prohibited substance has been established in the Athlete’s sample and accordingly that he committed an anti-doping rule violation due to his intentional use of this substance.

Therefore the NADO Flanders Disciplinary Commission decides on 21 March 2017 to impose a fine and a 4 year period of ineligibility on the Athlete starting on the date of the provisional suspension, i.e. on 19 January 2017.

Fees and expenses for this Commission shall be borne partially by the Athlete.