Excretion of 19-norandrosterone after consumption of boar meat / Frank Hülsemann, Gregor Fußhöller, Christine Lehn, Mario Thevis. - (Drug Testing and Analysis (2020) Special Issue (30 October); p. 1-7)

• PMID: 33125835
• DOI: 10.1002/dta.2958

Abstract

The consumption of the offal of noncastrated pigs can lead to the excretion of 19-norandrosterone (NorA) in urine of humans. In doping control, GC/C/IRMS is the method of choice to differentiate between an endogenous or exogenous origin of urinary NorA. In some cases, after the consumption of wild boar offal, the δ13 C values of urinary NorA fulfill the criteria of an adverse analytical finding due to differing food sources of boar and consumer. However, consumption of wild boar's offal is not very common in Germany, and thus, the occurrence of such an analytical finding is unlikely. In contrast, the commerce with wild boar meat has increased in Germany within the last years. Up to 20,000 tons of wild boar meat are annually consumed. In order to probe for the probability of the occurrence of urinary NorA after consumption of wild boar meat, human urine samples were tested following the ingestion of commercially available game. In approximately half of the urine samples, traces of NorA were detected postadministration of 200 to 400 g boar meat. The highest urinary concentration was 2.9 ng/ml, and significant amounts were detected up to 9 h after the meal. δ13 C values ranged from -18.5‰ to -23.5‰, which would have led to at least two adverse analytical findings if the samples were collected in an antidoping context. IRMS analysis on German boar tissue samples showed that δ13 C values for wild boar's steroids are unpredictable and may vary seasonally.

Tissue selectivity and potential clinical applications of trenbolone (17beta-hydroxyestra-4,9,11-trien-3-one) : A potent anabolic steroid with reduced androgenic and estrogenic activity / Joshua F. Yarrow, Sean C. McCoy, Stephen E. Borst. - (Steroids 75 (2010) 6 (June); p. 377-389)

• PMID: 20138077
• DOI: 10.1016/j.steroids.2010.01.019

Abstract

Recently, the development of selective androgen receptor modulators (SARMs) has been suggested as a means of combating the deleterious catabolic effects of hypogonadism, especially in skeletal muscle and bone, without inducing the undesirable androgenic effects (e.g., prostate enlargement and polycythemia) associated with testosterone administration. 17beta-Hydroxyestra-4,9,11-trien-3-one (trenbolone; 17beta-TBOH), a synthetic analog of testosterone, may be capable of inducing SARM-like effects as it binds to androgen receptors (ARs) with approximately three times the affinity of testosterone and has been shown to augment skeletal muscle mass and bone growth and reduce adiposity in a variety of mammalian species. In addition to its direct actions through ARs, 17beta-TBOH may also exert anabolic effects by altering the action of endogenous growth factors or inhibiting the action of glucocorticoids. Compared to testosterone, 17beta-TBOH appears to induce less growth in androgen-sensitive organs which highly express the 5alpha reductase enzyme (e.g., prostate tissue and accessory sex organs). The reduced androgenic effects result from the fact that 17beta-TBOH is metabolized to less potent androgens in vivo; while testosterone undergoes tissue-specific biotransformation to more potent steroids, dihydrotestosterone and 17beta-estradiol, via the 5alpha-reductase and aromatase enzymes, respectively. Thus the metabolism of 17beta-TBOH provides a basis for future research evaluating its safety and efficacy as a means of combating muscle and bone wasting conditions, obesity, and/or androgen insensitivity syndromes in humans, similar to that of other SARMs which are currently in development.

Acute pancreatitis secondary to the use of the anabolic steroid trenbolone acetate / Vidhya Kumar, Danny Issa, George Smallfield, Doumit Bouhaidar. - (Clinical Toxicology 57 (2019) 1 (12 August); p. 60-62)

• PMID: 30101635
• DOI: 10.1080/15563650.2018.1491983

Abstract

Background: The use of performance-enhancing drugs has increased dramatically in the last decade with high prevalence reported among the young athlete population. Many of these drugs contain anabolic steroids and may carry potential significant side effects and health risks. We report a case of anabolic steroid-induced acute pancreatitis (AP) that recurred after the reuse of the same drug by the patient, confirming the causative relationship.

Case report: A 24 year-old male presented with severe epigastric pain. His past medical history was significant for two hospitalizations during the last year with AP. During his hospital admissions, extensive workup was performed ruling out the common and uncommon causes of AP. Upon further pressing, the patient admitted to a history of past and current anabolic steroid use for athletic performance enhancement. He began this use four years ago and most recently started using trenbolone acetate (TA). The correlation between the timing of the anabolic steroids administration and the attacks of AP, along with ruling out other causes, confirmed TA as the cause of pancreatitis.

Discussion: The side effects associated with the use of these increasingly prevalent drugs are difficult to study in clinical trials due to the unethical nature of their consumption. In addition, these medications are difficult to study due to the varied usage cycles and patterns, unknown origin and source, as well as often high dose ingestion. Physicians and body builders need to be aware of the possible serious consequences of their use.

Death after misuse of anabolic substances (clenbuterol, stanozolol and metandienone) / Sabrina Lehmann, Andreas Thomas, Karl-Heinz Schiwy-Bochat, Hans Geyer, Mario Thevis, Frank Glenewinkel, Markus Alexander Rothschild, Hilke Andresen-Streichert, Martin Juebner. - (Forensic Science International 303 (2019) 109925 (October))

• PMID: 31499423
• DOI: 10.1016/j.forsciint.2019.109925

Abstract

A 34-year old male was found breathless and panting at home by his girlfriend three hours after a gym workout. Minutes later, he collapsed and died. Autopsy, histological and chemical analyses were conducted. The examination of the heart showed left ventricular hypertrophy, while the right coronary artery showed only a small vascular lumen (3 mm in diameter), due to its anatomical structure. In femoral blood concentrations of approx. 1 μg/L clenbuterol, approx. 56 μg/L stanozolol and approx. 8 μg/L metandienone, with trenbolone (<limit of quantification (LOQ)) were detected. Additionally, there were positive results in urine for boldenone, clomiphene, trenbolone, metandienone, stanozolol, clenbuterol and drostanolone, along with indications of testosterone and/or testosterone prohormones having been taken. In consideration of all aspects of this case, in can be assumed that the long-term consumption of anabolic androgen steroids (AAS) caused apparently pathological changes of the heart. Over and above, the combination of anatomical (small lumed coronary artery, ventricular hypertrophy) and substance-induced risk factors led to the fatal cardiovascular failure.

Identification of Trenbolone Metabolites Using Hydrogen Isotope Ratio Mass Spectrometry and Liquid Chromatography/High Accuracy/High Resolution Mass Spectrometry for Doping Control Analysis / Marlen Putz, Thomas Piper, Mario Thevis. - (Frontiers in Chemistry (2020) 435 (20 May); p. 1-15)

• PMID: 32509736
• PMCID: PMC7251174
• DOI: 10.3389/fchem.2020.00435

Abstract

Trenbolone is a synthetic anabolic-androgenic steroid, which has been misused for performance enhancement in sports. The detection of trenbolone doping in routine sports drug testing programs is complex as methods utilizing gas chromatography/mass spectrometry are complicated by unspecific derivatization products and artifacts, and liquid chromatography/mass spectrometry-based assays have shown to allow for comparably high limits-of-detection only. The number of previously reported metabolites in human urine is limited, and most analytical methods rely on targeting epitrenbolone, trenbolone glucuronide, and epitrenbolone glucuronide. In order to probe for the presence of additional trenbolone metabolites and to re-investigate the metabolism, an elimination study was conducted. One single dose of 10 mg of 5-fold deuterated trenbolone was administered to a healthy male volunteer and urine samples were collected for 30 days. For sample processing, published protocols were combined considering unconjugated, glucuronic acid-, sulfo- and alkaline-labile conjugated steroid metabolites. The sample preparation strategy consisted of solid-phase extractions, liquid-liquid extractions, metabolite de-conjugation, HPLC fractionation, and derivatization. Analytical methods included gas chromatography/thermal conversion/hydrogen isotope ratio mass spectrometry combined with single quadrupole mass spectrometry as well as liquid chromatography/high accuracy/high resolution mass spectrometry of the hydrolyzed and non-hydrolyzed samples. Twenty deuterium-labeled metabolites were identified including glucuronic acid-, sulfo- and potential cysteine-conjugates, and characterized by parallel reaction monitoring experiments yielding corresponding product ion mass spectra. Main metabolites were attributed to trenbolone-diol and potential trenbolone-diketone derivatives excreted as glucuronic acid and sulfo-conjugated analytes with detection windows of 5, respectively 6 days. Further characterization was conducted with pseudo MS3 experiments of the intact conjugates and by comparison of resulting product ion mass spectra with reference material.

Cholestasis induced by parabolan successfully treated with the molecular adsorbent recirculating system / Jacek Sein Anand, Zygmunt Chodorowski, Adam Hajduk, Wojciech Waldman. -  (ASAIO Journal 52 (2006) 1 (January-February); p. 117-118)

• PMID: 16436902
• DOI: 10.1097/01.mat.0000196712.32953.21

Abstract

We describe a case of a 21-year-old male bodybuilder who overdosed on Parabolan (trenbolone acetate) because of its anabolic activity. The patient, with no previous medical history, experienced pruritus and yellow discoloration of the skin and sclerae. Basic biochemical laboratory examination revealed signs of cholestasis with a serum bilirubin level of up to 65.5 mg/dl. Because supportive medical treatment was ineffective, the patient was treated with the molecular adsorbent recirculating system (MARS). Five MARS cycles lasting from 8 to 12 hours were performed every second day. The procedure was well tolerated by the patient and resulted in a sustained relief of pruritus. At the 2-month follow-up visit the plasma bilirubin level had decreased to 2 mg/dl.

Androgenic anabolic steroid-induced liver injury: two case reports assessed for causality by the updated Roussel Uclaf Causality Assessment Method (RUCAM) score and a comprehensive review of the literature / Robin Daniel Abeles, Matthew Foxton, Shahid Khan, Robert Goldin, Belinda Smith, Mark R. Thursz, Suman Verma. - (BMJ Open Gastroenterology 7 (2020) 1 (19 November); p. 1-6)

• PMID: 33214235
• PMCID: PMC7678230
• DOI: 10.1136/bmjgast-2020-000549

Abstract

Background: Anabolic androgenic steroids (AAS) usage is widespread and increasing. AAS drug-induced liver injury (DILI) is recognised but its clinical course and management is poorly described. We report 2 cases of AAS DILI with associated renal dysfunction, managed successfully with oral corticosteroids.

Methods: A comprehensive review identified 50 further cases to characterise the clinical and biochemical course. Causality grading was calculated using the updated Roussel Uclaf Causality Assessment Method (RUCAM) score. Data are presented as median values.

Results: The most common AAS taken was methyldrostanolone. Patients commonly present with jaundice and pruritus but may exhibit other constitutional symptoms. Patients presented 56 days after starting, and bilirubin peaked 28 days after stopping, AAS. Causality assessment was 'unlikely' in 1 (2%), 'possible' in 31 (60%) and 'probable' in 20 (38%). Peak values were: bilirubin 705 μmol/L, alanine transaminase 125 U/L, aspartate transaminase 71 U/L, alkaline phosphatase 262 U/L, gamma-glutamyl transferase 52 U/L, international normalised ratio 1.1. Liver biopsies showed 'bland' canalicular cholestasis. 43% of patients developed kidney injury (peak creatinine 225 μmol/L). Therapies included antipruritics, ursodeoxycholic acid and corticosteroids. No patients died or required liver transplantation.

Conclusions: Physicians are likely to encounter AAS DILI. Causality assessment using the updated RUCAM should be performed but defining indications and proving efficacy for therapies remains challenging.

Thyrotoxic periodic paralysis in a competitive bodybuilder with thyrotoxicosis factitia / Amy J. Patel, Stephanie Tejera, Stanislaw P. Klek, Gary D. Rothberger. - (AACE Clinical Case Reports 6 (2020) 5 (September/October); e252-e256)

• PMID: 32984532
• PMCID: PMC7511107
• DOI: 10.4158/ACCR-2020-0154

Abstract

Objective: We report a case of thyrotoxic periodic paralysis (TPP) in a bodybuilder who developed paralysis secondary to thyrotoxicosis factitia after taking a supplement containing thyroid hormone. Interestingly, the patient had no intrinsic thyroid disease. Prompt recognition of thyrotoxicosis is critical to avoid progression of paralysis and subsequent complications.

Methods: We discuss a 27-year-old body builder who presented after a 3-day bodybuilding competition with sudden upper and lower extremity paralysis. He admitted to taking anabolic steroids, a supplement containing an unknown amount of thyroid hormone for 2 weeks, and furosemide 40 mg twice daily with near-complete fluid restriction for 3 days.

Results: Laboratory results showed a thyroid-stimulating hormone (TSH) level of <0.010 μIU/mL (normal, 0.3 to 5.8 μIU/mL), normal total triiodothyronine level, elevated free thyroxine level of 3.6 ng/dL (normal, 0.8 to 1.9 ng/dL), and potassium level of 1.9 mEq/L (normal, 3.7 to 5.2 mEq/L). Thyroid peroxidase antibody, thyroid-stimulating immunoglobulin, and thyroglobulin antibody levels were normal. Thyroid uptake was 1% (normal, 8 to 25%) after administration of I-123 and thyroglobulin level was 9 ng/mL (normal, 1.4 to 29.2 ng/mL). The patient was treated with normal saline infusion, magnesium supplementation and a total of 230 mEq of potassium within 12 hours of hospitalization. Muscle weakness resolved within this time period and potassium level normalized. By the third day of hospitalization free thyroxine level also normalized and TSH improved to 0.1 mIU/L.

Conclusion: TPP is a rare complication of thyrotoxicosis that should be considered in bodybuilders who are presenting with acute muscle weakness.

Sudden Cardiac Death in Anabolic-Androgenic Steroid Users : A Literature Review / Marco Torrisi, Giuliana Pennisi, Ilenia Russo, Francesco Amico, Massimiliano Esposito, Aldo Liberto, Giuseppe Cocimano, Monica Salerno, Giuseppe Li Rosi, Nunzio Di Nunno, Angelo Montana. - (Medicina 56 (2020) 11 (4 November); p. 1-19)

• PMID: 33158202
• PMCID: PMC7694262
• DOI: 10.3390/medicina56110587

Abstract

Background and objectives: Anabolic-androgenic steroids (AASs) are a group of synthetic molecules derived from testosterone and its related precursors. AASs are widely used illicitly by adolescents and athletes, especially by bodybuilders, both for aesthetic uses and as performance enhancers to increase muscle growth and lean body mass. When used illicitly they can damage health and cause disorders affecting several functions. Sudden cardiac death (SCD) is the most common medical cause of death in athletes. SCD in athletes has also been associated with the use of performance-enhancing drugs. This review aimed to focus on deaths related to AAS abuse to investigate the cardiac pathophysiological mechanism that underlies this type of death, which still needs to be fully investigated. Materials and Methods: This review was conducted using PubMed Central and Google Scholar databases, until 21 July 2020, using the following key terms: "((Sudden cardiac death) OR (Sudden death)) AND ((androgenic anabolic steroid) OR (androgenic anabolic steroids) OR (anabolic-androgenic steroids) OR (anabolic-androgenic steroid))". Thirteen articles met the inclusion and exclusion criteria, for a total of 33 reported cases. Results: Of the 33 cases, 31 (93.9%) were males while only 2 (61%) were females. Mean age was 29.79 and, among sportsmen, the most represented sports activity was bodybuilding. In all cases there was a history of AAS abuse or a physical phenotype suggesting AAS use; the total usage period was unspecified in most cases. In 24 cases the results of the toxicological analysis were reported. The most detected AASs were nandrolone, testosterone, and stanozolol. The most frequently reported macroscopic alterations were cardiomegaly and left ventricular hypertrophy, while the histological alterations were foci of fibrosis and necrosis of the myocardial tissue. Conclusions: Four principal mechanisms responsible for SCD have been proposed in AAS abusers: the atherogenic model, the thrombosis model, the model of vasospasm induced by the release of nitric oxide, and the direct myocardial injury model. Hypertrophy, fibrosis, and necrosis represent a substrate for arrhythmias, especially when combined with exercise. Indeed, AAS use has been shown to change physiological cardiac remodeling of athletes to pathophysiological cardiac hypertrophy with an increased risk of life-threatening arrhythmias.

Effects of oral administration of androstenedione on plasma androgens in young women using hormonal contraception / Thomas Bassindale, David A. Cowan, Sian Dale, Andrew J. Hutt, Anthony R. Leeds, Michael J. Wheeler, Andrew T. Kicman. - (Journal of Clinical Endocrinology & Metabolism 89 (2004) 12 (1 December); p. 6030-6038)

• PMID: 15579755
• DOI: 10.1210/jc.2004-0790

Abstract

Androstenedione as a dietary supplement has been targeted at the sporting community, but there are limited data regarding its effects on plasma androgens in young women. A double-blind, cross-over study was undertaken involving 10 women (20-32 yr) using hormonal contraception. Because contamination of supplements has been reported, an in-house oral formulation was prepared containing purified androstenedione, the control being lactose only. After oral administration of a single dose of androstenedione (100 mg), blood was collected frequently up to 8 h and at 24 h. Maximum plasma androgen concentrations observed between volunteers were well above the upper limit of reference ranges for women, being 121-346 nmol/liter for androstenedione, 14-54 nmol/liter for testosterone (T), 11-32 nmol/liter for 5alpha-dihydrotestosterone, and 23-90 nmol/liter for 3alpha-androstanediol glucuronide. The free androgen index and T concentration changed in a similar manner. The mean change in area under the plasma concentration-time curve (0-24 h), compared with control data were: androstenedione approximately 7-fold, T approximately 16-fold, 5alpha-dihydrotestosterone approximately 9-fold, and 3alpha-androstanediol glucuronide approximately 5-fold; the mean conversion ratio of androstenedione to T was 12.5% (range 7.8-21.6%). Increases in T area under the plasma concentration-time curve were correlated with SHBG concentration (r = 0.80; P = 0.005). Formulation characteristics and SHBG levels appear to be important factors when considering plasma androgen increases after acute androstenedione administration.