Misuse Of Anabolic Androgenic Steroids Research Articles

Cutaneous manifestations of misuse of androgenic anabolic steroids: A retrospective cohort study

Cutaneous manifestations of misuse of androgenic anabolic steroids: A retrospective cohort study

Anabolic-Androgenic Steroid Misuse: Mechanisms, Patterns of Misuse, User Typology, and Adverse Effects.

Anabolic-androgenic steroids (AAS) encompass a broad group of natural and synthetic androgens. AAS misuse is highly prevalent on a global scale, with the lifetime prevalence of AAS misuse in males being estimated to be around 6%, with 15 to 25% of male gym attendees using it at any one time. AAS are associated with sudden cardiac death, neuropsychiatric manifestations, and infertility. The average AAS user is unlikely to voluntarily declare their usage to a physician, with around 1 in 10 actively engaging in unsafe injection techniques. The aim of this paper is to review the current evidence base on AAS with emphasis on mechanisms of action, adverse effects, and user profiles that are most likely to engage in AAS misuse. This paper also reviews terminologies and uses methods specific to the AAS user community.

The Tragedy of a Strong Muscle and a Weak Heart: Complications of Anabolic-Androgenic Steroid Misuse

Misuse of anabolic-androgenic steroids (AAS) to boost performance and appearance is rising in the United States (US) with approximately one million people experiencing dependence. Long-term AAS misuse can lead to cardiovascular pathology but rarely cardiogenic shock. We report the case of an acute ischemic stroke secondary to an intracardiac thrombus in a patient with biventricular failure and cardiogenic shock associated with AAS misuse. Discontinuation of AAS and institution of guideline-directed medical therapy might reverse AAS-related heart failure.

Withania somnifera ameliorates nandrolone-decanoate-induced brain damage in rats by inhibiting cell death, prodynorphin mRNA expression and acetylcholinesterase activity

The misuse of anabolic-androgenic steroids by athletes and non-athletes causes harmful effects on the central nervous system. In Ayurvedic medicine, Withania somnifera (WS) as an herbal drug has been reported for several functions including adaptogenic, anticonvulsant, cytoprotective and antioxidant. The present study investigated the neuroprotective functions of WS (100, 200 and 400 mg/kg body weight) in nandrolone decanoate (ND)-induced (16 mg/kg body weight) brain injury in male Wistar rats. ND was injected intramuscularly twice weekly for 4 weeks. The water emulsion of WS root powder was administered orally once daily for 30 days to ND-treated rats. At the end of the experiment, anxiety-like behaviour was assessed in rats using the elevated plus maze. Haematoxylin-and-eosin-stained coronal sections of the parietal cortex and hippocampus of ND rats showed severe alterations in brain histology compared with control rats. Acetylcholinesterase (AChE) activity in the striatum and prodynorphin gene expression in the hippocampus was significantly elevated in the ND group compared with the control group. Treating ND induced rats with various doses of WS significantly reversed the brain damage, anxiety behaviour, increased striatal AChE activity and reduced prodynorphin gene expression in the hippocampus. In conclusion, WS extract can be used as a neuroprotective agent to reduce the effects of anabolic steroids.

Anabolic Steroid-Induced Myocardial Infarction in a Young Male

Misuse of androgenic-anabolic steroids (AAS) has been well known to increase the risk for a cardiac problem, including acute myocardial infarction (MI). Steroids once thought a magic drug providing immediate relief to patients, also have a darker aspect of its severe side effects. AAS are widely used these days, especially in teenagers, bodybuilders, and athletes. MI is thought to be a disease of old age, but young patients with MI without risk factors draw attention to the possibility of drugs such as cocaine, AAS abuse, and amphetamine. In this article, we report the case of a 38-year-old African-American male, with a history of AAS abuse, who arrived at the emergency department with complaints of severe chest pain radiating to the left arm. An electrocardiogram (ECG) revealed ST-elevation MI (STEMI) and elevated troponin. The patient was transferred to the cardiac catheterization lab for an emergent catheterization which showed 100% stenosis of the left anterior descending artery and a drug-eluting stent was placed. An echocardiogram showed an ejection fraction of 35%. All blood workup was negative. The patient was discharged on aspirin, ticagrelor, statin, ACE inhibitor, and B-blocker after three days.Chest pain in a young patient population secondary to MI is not uncommon these days and the most important thing to evaluate is drug history, including AAS use. Athletes, bodybuilders, and others who use steroids or other drugs that are responsible for MI should be under the supervision of physicians so that the complications of steroids are ascertained, and if steroids are needed for any medical illness, proper dosage and follow-up should be emphasized. Therefore, while taking history from a patient, it is essential for physicians to be aware of this association of steroids with coronary artery disease.

Adverse Effects of Anabolic-Androgenic Steroids: A Literature Review.

Anabolic-androgenic steroids (AASs) are a large group of molecules including endogenously produced androgens, such as testosterone, as well as synthetically manufactured derivatives. AAS use is widespread due to their ability to improve muscle growth for aesthetic purposes and athletes’ performance, minimizing androgenic effects. AAS use is very popular and 1–3% of US inhabitants have been estimated to be AAS users. However, AASs have side effects, involving all organs, tissues and body functions, especially long-term toxicity involving the cardiovascular system and the reproductive system, thereby, their abuse is considered a public health issue. The aim of the proposed review is to highlight the most recent evidence regarding the mechanisms of action of AASs and their unwanted effects on organs and lifestyle, as well as suggesting that AAS misuse and abuse lead to adverse effects in all body tissues and organs. Oxidative stress, apoptosis, and protein synthesis alteration are common mechanisms involved in AAS-related damage in the whole body. The cardiovascular system and the reproductive system are the most frequently involved apparatuses. Epidemiology as well as the molecular and pathological mechanisms involved in the neuropsychiatric side-effects of AAS abuse are still unclear, further research is needed in this field. In addition, diagnostically reliable tests for AAS abuse should be standardized. In this regard, to prevent the use of AASs, public health measures in all settings are crucial. These measures consist of improved knowledge among healthcare workers, proper doping screening tests, educational interventions, and updated legislation.

Improved Method for Differentiation of Synthetic and Natural Endogenous Anabolic Steroids using Gas Chromatography Isotope Ratio Mass Spectrometry (GC/C/IRMS) followed by Two-Fold High Performance Liquid Chromatography (HPLC) Cleanup Method: A Perspective

Abstract: Background: Androgenic Anabolic Steroids (AAS) are also synthetic derivatives of testosterone, modified to improve its anabolic actions. The misuse of AAS is of particular concern in sports and society. Gas chromatography-mass spectrometry had some limitations and allows identification and characterization of steroids and their metabolites in the urine but may not be able to distinguish between pharmaceutical (Exogenous) and endogenous origin. Thus, it is of great importance to discriminate endogenous steroids such as testosterone or testosterone prohormones from their chemically identical synthetic copies. The abuse of Androgenic Anabolic Steroids (AAS) by sports person is banned by World Anti-doping Agency (WADA) as per the WADA Prohibited list 2019. Methodology: The gas chromatography-combustion/isotope ratio mass spectrometry (GC/C/IRMS) technique differentiates between natural and synthetic endogenous steroids by comparing compounds specific 13C/12C ratio. However, the analytes have to be efficiently isolated and purified prior to GC/C/IRMS analysis. Results and Discussion: HPLC Cleanup method prior to analysis by GC−C/IRMS needs to be developed and validated for discriminating the origin of anabolic androgenic steroids. These methods involves the solid-phase extraction, enzymatic hydrolysis with β-glucuronidase, HPLC-fractionation for the cleanup and analysis by GC−C/IRMS. The difference (Δ13C) of urinary δ13C values between synthetic analogues and Endogenous Reference Compounds (ERC) by GC-C/IRMS would be used to elucidate the origin of steroids. The present perspective gives an overview of the use of anabolic-androgenic steroids in sport and methods used in anti-doping laboratories for their detection in urine, with special emphasis on GC−C/ IRMS technique after two-fold HPLC cleanup. Key words: Endogenous Steroids, Exogenous Steroids, HPLC Cleanup, Doping, GC/C/ IRMS.

Machismo and anabolic steroid misuse among young Latino sexual minority men

Latino sexual minority men (SMM) have elevated anabolic-androgenic steroid (AAS) misuse in comparison to their heterosexual and non-Latino peers. Within a gender role framework, desire to present as masculine through heightened muscularity may be related to increased AAS misuse. To assess the association between AAS misuse and a culturally-distinct masculinity, this study examined the relationship of two aspects of machismo, traditional machismo and caballerismo, with AAS misuse in the past month. Participants were 141 young adult Latino SMM recruited from the San Diego area. Participants completed a self-report questionnaire online in English or Spanish, which included measures of machismo and AAS misuse. Out of 141 participants, 27 reported AAS misuse (19.1%). Traditional machismo was positively associated with AAS misuse and caballerismo was negatively associated with AAS misuse. Traditional machismo, which emphasizes dominance, may be positively associated with AAS misuse due to its facilitation of muscle development, which could enable physical intimidation; greater musculature may also counteract assumptions about femininity and sexual orientation. Caballerismo may be negatively associated with AAS by providing a flexible masculinity model that emphasizes social cohesion over dominance. Future AAS misuse interventions could include values-based work and cognitive restructuring of masculinity schemas.

Effects of Anabolic Steroids on the Histological Structure of Renal Cortex of Adult Male Albino Rats and the Possible Protective Role of Taurine

Introduction: Misuse of anabolic androgenic steroids (AAS) has become a widespread health problem with subsequent multisystem adverse effects. However, among their adverse effects, renal toxicity remains one of the least discussed.Aim of work: To study the histopathological effects of Nandrolone Decanoate (ND) abuse on renal cortex and examine the possible protective role of taurine. Materials and methods: Thirty-six adult male albino rats, aging 4-6 months and weighing 200 - 250 gms, were used in this study. Animals were divided equally into three groups; Group I (control group): subdivided into Subgroup IA: negative control and Subgroup IB: rats received intramuscular 0.5ml sesame oil twice weekly for six weeks and Subgroup IC: received 100 mg/kg/day Taurine by gavage, for six weeks. Group II (ND Group): received intramuscular 5 mg/kg ND, dissolved in sesame oil, twice weekly for six weeks. Group III (Taurine and ND Group): given both Taurine and ND in the same dose and duration as subgroup IC and group II respectively. At the end of the experiment, venous blood samples were collected from the tail vein for biochemical assays. Kidneys were dissected out and processed for light and electron microscopic examination. Results: Examination of group II revealed marked congestion, obliteration of Bowman’s space and lumina of both proximal and distal tubules. Ultrastructural distortion was evident in glomerular filtration barrier and tubular lining cells. Statistically significant biochemical changes were also observed. However, group III showed almost preserved glomerular and tubular architecture with few persistent changes. Biochemical results also revealed marked improvement. Conclusion: Marked renal cortical affection with renal functional deterioration were noted following ND. Taurine exerted marked reno-protection thus, it would be also of great help to protect AAS users against possible renal hazards in case their AAS use was inevitable.

Nandrolone administration with or without strenuous exercise increases cardiac fatal genes overexpression, calcium/calmodulin-dependent protein kinaseiiδ, and monoamine oxidase activities and enhances blood pressure in adult wistar rats

Misuse of anabolic androgenic steroids (AAS) increases prevalence of cardiovascular abnormalities in athletes, and the underlying molecular mechanism involved in those abnormalities continues to be investigated. The aim of this study was to investigate the effect of chronic nandrolone exposure on alpha and beta–myosin heavy chain (MHC) isoforms gene expression transition, blood pressure related parameters, calcium/calmodulin-dependent protein kinaseIIδ (CaMKIIδ), and monoamine oxidase (MAO) activities in rats' hearts. It was also planned to evaluate the effect of strenuous exercise on cardiac abnormalities induced by nandrolone. Thirty-two male wistar rats were assigned into four groups, namely control, nandrolone, nandrolone with strenuous exercise, and strenuous exercise groups. Nandrolone consumption significantly increased systolic, diastolic, pulse and dicrotic pressure, mean arterial pressure, as well as the amplitude of first peak (H1). Moreover, exercise combined with nandrolone completely masked this effect. The mRNA expression of β-MHC and the ratio of β -MHC/α -MHC showed a significant increase in the nandrolone and nandrolone with strenuous exercise groups compared to those in the control group. The values of heart tissue calcium/calmoldulin-dependent protein kinase IIδ (CaMKIIδ), and monoamine oxidase (MAO) in the nandrolone, nandrolone with strenuous exercise and exercise groups were significantly higher than those values in the control group.These findings indicate that nandrolone-induced heart and hemodynamic abnormalities may in part be associated with MHC isoform changes and Ca2+ homeostasis changes mediated by increased CaMKIIδ and MAO activities and that these effects can be provoked via strenuous exercise.

PO-246 Nandrolone affects cell growth and differentiation in hepatoma cells

IntroductionHepatocellular carcinoma (HCC) represents the sixth leading cancer and the third most common cause of death from cancer. Many different aetiological factors are involved in the development of HCC, which may be modulated by both estrogens and androgens hormones during its initiation, progression and metastasis. The misuse of anabolic androgenic steroids (AAS) is associated with serious adverse effects to the liver, including cellular adenomas and adenocarcinomas, and is considered a factor risk of developing hepatic sex hormone related tumours. The purpose of this study was to investigate the role of Nandrolone, one of the most commonly used AAS, in regulating proliferation and differentiation of HCC.Material and methodsHuman HCC cell line HepG2 was treated with Nandrolone, a synthetic androgen ligand, for 48 hs and its viability and proliferation was assessed by MTS and cell cycle analysis, respectively. The expression of protein involved in cell cycle regulation and differentiation markers were analysed by western blot and real time PCR. Measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were performed using Seahorse XF96 extracellular flux analyzer. Respiratory chain complex activities were assayed spectrophotometrically. Stemness surface markers expression was detected by FACSCalibur flow cytometer.Results and discussionsNandrolone treatment caused cell growth inhibition associated to a downregulation of cyclin D1 and an upregulation of the cyclin-dependent kinase inhibitors p21Waf1/Cip1 leading to cell cycle arrest in the G2 phase. Moreover, a significant overall impairment of mitochondrial functions, resulting in a reduced OCR and impairment of OXPHOS complexes activities were also observed, thus suggesting a role in the control of the metabolic reprogramming. Finally, a significant increase of the stemness markers was detected following Nandrolone treatment, also confirmed in additional human stem cell types and in an in vivo mouse model.ConclusionNandrolone shows a strong anti-proliferative effect in differentiated tumour cells, promoting cancer cells stemness through cellular metabolic reprogramming. These results could have important public health implications in order to improve the primary prevention such as revising altered lifestyles, like AAS abuse.

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

OBJECTIVES:Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels.METHODS:Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device.RESULTS:Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity.CONCLUSIONS:Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population.

Applications of Isotope Ratio Mass Spectrometry in Sports Drug Testing Accounting for Isotope Fractionation in Analysis of Biological Samples.

The misuse of anabolic-androgenic steroids (AAS) in sports aiming at enhancing athletic performance has been a challenging matter for doping control laboratories for decades. While the presence of a xenobiotic AAS or its metabolite(s) in human urine immediately represents an antidoping rule violation, the detection of the misuse of endogenous steroids such as testosterone necessitates comparably complex procedures. Concentration thresholds and diagnostic analyte ratios computed from urinary steroid concentrations of, e.g., testosterone and epitestosterone have aided identifying suspicious doping control samples in the past. These ratios can however also be affected by confounding factors and are therefore not sufficient to prove illicit steroid administrations. Here, carbon and, in rare cases, hydrogen isotope ratio mass spectrometry (IRMS) has become an indispensable tool. Importantly, the isotopic signatures of pharmaceutical steroid preparations commonly differ slightly but significantly from those found with endogenously produced steroids. By comparing the isotope ratios of endogenous reference compounds like pregnanediol to that of testosterone and its metabolites, the unambiguous identification of the urinary steroids' origin is accomplished. Due to the complex urinary matrix, several steps in sample preparation are inevitable as pure analyte peaks are a prerequisite for valid IRMS determinations. The sample cleanup encompasses steps such as solid phase or liquid-liquid extraction that are presumably not accompanied by isotopic fractionation processes, as well as more critical steps like enzymatic hydrolysis, high-performance liquid chromatography fractionation, and derivatization of analytes. In order to exclude any bias of the analytical results, each step of the analytical procedure is optimized and validated to exclude, or at least result in constant, isotopic fractionation. These efforts are explained in detail.

Characteristics and Behaviors of Older Male Anabolic Steroid Users

Objective: To compare and contrast the characteristics of 2 groups of men ≥40 years old: reported anabolic–androgenic steroid (AAS) users and nonusers. Design: Cross-sectional survey. Setting: Thirty-eight online fitness, weight lifting, bodybuilding, and steroid Web sites. Participants: A total of 67 male AAS users and 76 male nonusers ≥40 years old. Main Outcomes Measured: Demographics, utilization of AAS and other performance-enhancing agents (PEAs), exercise patterns, history of illicit drugs and alcohol use, and psychiatric traits/diagnoses. Results: The majority of AAS users ≥40 years old were caucasian (92.5%), heterosexual (97.0%), and classified themselves as recreational exercisers (79.1%). AAS users took more PEAs (11.5 ± 5.6 vs 4.6 ± 2.7; P < .001), were more likely to binge drink (47.8% vs 29.0%; P = .025), report heavy alcohol use (21.0% vs 7.9%; P = .031), meet criteria for substance dependence disorder (27.4% vs 4.0%; P < .001), and report an anxiety disorder diagnosis (12.0% vs 2.6%; P = .046) than nonusers. Conclusions: AAS misuse is prevalent among older men and is associated with polypharmacy, more aggressive alcohol use, and a higher incidence of substance dependence and anxiety disorders compared to nonusers. This information may help clinicians and researchers identify and develop appropriate intervention strategies for AAS abuse among older men.

Validation and Applications of Gas Chromatography-Combustion/isotope Ratio Mass Spectrometric Method to Control Misuse of Androgens in Human

The misuse of anabolic androgenic steroids is of particular concern in sports and society. Thus, it is of great importance to discriminate endogenous steroids such as testosterone or testosterone prohormones from their chemically identical synthetic copies. In this study, gas chromatography-combustion/isotope ratio mass spectrometric (GC−C/IRMS) method has been developed and validated for discriminating the origin of anabolic androgenic steroids. The method involves the solid-phase extraction, enzymatic hydrolysis with β-glucuronidase, HPLC-fractionation for the cleanup and analysis by GC−C/IRMS. The difference (∆13C) of urinary δ13C values between synthetic analogues and endogenous reference compounds (ERC) by GC−C/IRMS was used to elucidate the origin of steroids, and intraand inter-day precision, specificity and isotope fractionation were evaluated. The present GC−C/IRMS method combined with HPLC cleanup was accurate and reproducible enough to be successfully applied to the test of urine sample from suspected anabolic steroid abusers.

Nandrolone decanoate administration elevates hippocampal prodynorphin mRNA expression and impairs Morris water maze performance in male rats

The misuse of anabolic androgenic steroids has in several reports been associated with effects resulting in altered behavior. This study used the Morris water maze task to investigate the effect of high doses of the anabolic androgenic steroid nandrolone on spatial learning and memory in male rats. During the experiment, we observed a significantly impaired Morris water maze performance in the nandrolone-treated rats compared with controls. The hippocampus, a brain region associated with cognitive function, was analyzed for mRNA expression of prodynorphin, the precursor of dynorphinergic peptides. The results indicated that the transcription levels of prodynorphin were significantly elevated in the animals treated with nandrolone compared with controls. Thus, the findings suggest that administration of nandrolone to male rats impairs memory function, possibly via dynorphinergic actions.

Sub-chronic nandrolone treatment modifies neurochemical and behavioral effects of amphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in rats

Misuse of anabolic-androgenic steroids (AASs) is increasing, and appears to have much in common with the use of substances known to induce drug dependence. Moreover, persons who abuse AASs also tend to abuse other psychotropic drugs such as amphetamine or 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). The aim of this study was to investigate whether nandrolone (5 × 5 or 5 × 20 mg/kg) pre-exposure modulates the acute neurochemical and behavioral effects of amphetamine (1 mg/kg) and MDMA (5 mg/kg) in rats. Dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites were measured from samples collected from the nucleus accumbens (NAc) by in vivo microdialysis. The behavior of the animals was recorded on videotapes, from which it was later rated. Our results demonstrate that sub-chronic treatments with supraphysiological doses of nandrolone attenuate dose-dependently the increase in extracellular DA concentration evoked by amphetamine or MDMA. The lower dose of nandrolone attenuated MDMA-induced increase in 5-HT-levels, while the higher dose potentiated it. Analysis of the behavioral data suggests that effects of the amphetamine and MDMA are dose-dependently attenuated by AAS-treatment, paralleling DA results. In conclusion, the results of this study show that AAS-pre-treatment is able to modulate the reward-related neurochemical and behavioral effects of amphetamine and MDMA.

Nandrolone-induced hippocampal phosphorylation of NMDA receptor subunits and ERKs

The age-related decline in gonadal steroids is associated with changes in mood and memory function. It appears that normal physiological concentrations of the steroids are required for adequate synaptic plasticity. However, the effects of high levels of androgens subsequent to misuse of anabolic androgenic steroids (AAS) are largely unknown. In this study, rats were given i.m. nandrolone as a single dose or daily for 14 days and the effects on synaptic components in hippocampal synaptoneurosomes were measured 24 h after the last injection. Western blot analysis revealed that a single injection of AAS increased phosphorylation of the NMDA receptor subunits NR2A and NR2B and ERK1/2, while the levels of phosphorylated CaMKIIα were unaltered. No changes were seen in other synaptic proteins tested, i.e., BDNF, Arc, TUC-4, and β-tubulin III. Daily administration of nandrolone for 2 weeks did not affect the content of any of the proteins tested. From this in vivo study, it is concluded that important synaptic components respond to a single high dose of nandrolone, an effect that may influence synapse function.

Enzymatic conversion of dynorphin A in the rat brain is affected by administration of nandrolone decanoate

The misuse of anabolic androgenic steroids (AAS) seems to produce profound effects on the central nervous system, leading to aggressive behavior and increased sensitivity to other drugs of abuse. The present study addresses the effect on the enzymatic transformation, here called dynorphin converting enzyme-like activity. The formation of the mu/delta opioid peptide receptor-preferring Leu-enkephalin-Arg 6 from the kappa opioid peptide receptor-preferring dynorphin A was measured in rats treated with nandrolone decanoate. Significant variations in enzymatic transformation were observed in several brain regions. An altered receptor activation profile in these regions may be one contributory factor behind AAS-induced personality changes.

Left ventricular early myocardial dysfunction after chronic misuse of anabolic androgenic steroids: a Doppler myocardial and strain imaging analysis

Background: Anabolic androgenic steroids (AAS) are sometimes used by power athletes to improve performance by increasing muscle mass and strength. Recent bioptical data have shown that in athletes under the...