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1.
Horm Behav ; 161: 105501, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38368844

RESUMO

Long-term use of anabolic androgenic steroids (AAS) in supratherapeutic doses is associated with severe adverse effects, including physical, mental, and behavioral alterations. When used for recreational purposes several AAS are often combined, and in scientific studies of the physiological impact of AAS either a single compound or a cocktail of several steroids is often used. Because of this, steroid-specific effects have been difficult to define and are not fully elucidated. The present study used male Wistar rats to evaluate potential somatic and behavioral effects of three different AAS; the decanoate esters of nandrolone, testosterone, and trenbolone. The rats were exposed to 15 mg/kg of nandrolone decanoate, testosterone decanoate, or trenbolone decanoate every third day for 24 days. Body weight gain and organ weights (thymus, liver, kidney, testis, and heart) were measured together with the corticosterone plasma levels. Behavioral effects were studied in the novel object recognition-test (NOR-test) and the multivariate concentric square field-test (MCSF-test). The results conclude that nandrolone decanoate, but neither testosterone decanoate nor trenbolone decanoate, caused impaired recognition memory in the NOR-test, indicating an altered cognitive function. The behavioral profile and stress hormone level of the rats were not affected by the AAS treatments. Furthermore, the study revealed diverse AAS-induced somatic effects i.e., reduced body weight development and changes in organ weights. Of the three AAS included in the study, nandrolone decanoate was identified to cause the most prominent impact on the male rat, as it affected body weight development, the weights of multiple organs, and caused an impaired memory function.


Assuntos
Anabolizantes , Transtornos da Memória , Nandrolona , Ratos Wistar , Testosterona , Animais , Masculino , Testosterona/sangue , Testosterona/análogos & derivados , Ratos , Nandrolona/análogos & derivados , Nandrolona/farmacologia , Anabolizantes/efeitos adversos , Anabolizantes/farmacologia , Transtornos da Memória/induzido quimicamente , Tamanho do Órgão/efeitos dos fármacos , Acetato de Trembolona/farmacologia , Decanoato de Nandrolona/farmacologia , Peso Corporal/efeitos dos fármacos , Corticosterona/sangue , Reconhecimento Psicológico/efeitos dos fármacos
2.
Int J Legal Med ; 138(5): 1791-1800, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38589641

RESUMO

Non-prescription use of anabolic androgenic steroids (AAS) is associated with an increased risk of premature death. However, these substances are seldom screened in connection with forensic cause-of-death investigation, unless the forensic pathologist specifically suspects use, often based on a positive AAS use history. Since AAS use is often concealed from others, this practice may lead to mistargeting of these analyses and significant underestimation of the true number of AAS positive cases undergoing forensic autopsy. Thus, more accurate diagnostic tools are needed to identify these cases. The main objective of this study was to determine, whether a multivariable model could predict AAS urine assay positivity in forensic autopsies. We analyzed retrospectively the autopsy reports of all cases that had been screened for AAS during forensic cause-of-death investigation between 2016-2019 at the Finnish Institute for Health and Welfare forensic units (n = 46). Binary logistic regression with penalized maximum likelihood estimation was used to generate a nine-variable model combining circumferential and macroscopic autopsy-derived variables. The multivariable model predicted AAS assay positivity significantly better than a "conventional" model with anamnestic information about AAS use only (area under the receiver operating characteristic curve [AUC] = 0.968 vs. 0.802, p = 0.005). Temporal validation was conducted in an independent sample of AAS screened cases between 2020-2022 (n = 31), where the superiority of the multivariable model was replicated (AUC = 0.856 vs. 0.644, p = 0.004). Based on the model, a calculator predicting AAS assay positivity is released as a decision-aiding tool for forensic pathologists working in the autopsy room.


Assuntos
Anabolizantes , Autopsia , Detecção do Abuso de Substâncias , Humanos , Masculino , Estudos Retrospectivos , Adulto , Anabolizantes/análise , Anabolizantes/urina , Detecção do Abuso de Substâncias/métodos , Feminino , Adulto Jovem , Modelos Logísticos , Androgênios/análise , Pessoa de Meia-Idade , Finlândia , Curva ROC , Esteróides Androgênicos Anabolizantes
3.
Clin Exp Rheumatol ; 42(7): 1311-1316, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39026507

RESUMO

Osteoporosis is a skeletal disease characterised by reduced bone mass and deterioration of bone microarchitecture, underlying a higher risk of fragility fractures. Several options are available for its treatment, including both anti-resorptive and anabolic agents. The present review discusses and summarises the most recent literature on anabolic treatment, with a focus on abaloparatide, and on the assessment of fragility fracture risk, with a focus on trabecular bone score. Finally, we provide a discussion on the effects of different antiosteoporotic medications in terms of fragility fracture risk reduction.


Assuntos
Anabolizantes , Conservadores da Densidade Óssea , Densidade Óssea , Osteoporose , Fraturas por Osteoporose , Humanos , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Anabolizantes/uso terapêutico , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Fatores de Risco , Medição de Risco , Resultado do Tratamento
4.
Anal Bioanal Chem ; 416(14): 3335-3347, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38661944

RESUMO

Stanozolol, a synthetic derivative of testosterone, is one of the common doping drugs among athletes and bodybuilders. It is metabolized to a large extent and metabolites are detected in urine for a longer duration than the parent compound. In this study, a novel dummy molecularly imprinted polymer (DMIP) is developed as a sorbent for solid-phase extraction of stanozolol metabolites from spiked human urine samples. The optimized DMIP is composed of stanozolol as the dummy template, methacrylic acid as the functional monomer, and ethylene glycol dimethacrylate as the cross-linker in a ratio of 1:10:80. The extracted analytes were quantitively determined using a newly developed and validated ultrahigh-performance liquid chromatography tandem mass spectrometry method, where the limits of detection and quantitation were 0.91 and 1.81 ng mL-1, respectively, fulfilling the minimum required performance limit decided on by the World Anti-Doping Agency. The mean percentage extraction recoveries for 3'-hydroxystanozolol, 4ß-hydroxystanozolol, and 16ß-hydroxystanozolol are 97.80% ± 13.80, 83.16% ± 7.50, and 69.98% ± 2.02, respectively. As such, the developed DMISPE can serve as an efficient cost-effective tool for doping and regulatory agencies for simultaneous clean-up of the stanozolol metabolites prior to their quantification.


Assuntos
Dopagem Esportivo , Limite de Detecção , Polímeros Molecularmente Impressos , Extração em Fase Sólida , Estanozolol , Estanozolol/urina , Extração em Fase Sólida/métodos , Humanos , Polímeros Molecularmente Impressos/química , Dopagem Esportivo/prevenção & controle , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Detecção do Abuso de Substâncias/métodos , Anabolizantes/urina , Anabolizantes/metabolismo , Impressão Molecular/métodos
5.
Anal Bioanal Chem ; 416(13): 3223-3237, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38573345

RESUMO

Over the past few decades, anabolic androgenic steroids (AASs) have been abused in and out of competition for their performance-enhancing and muscle-building properties. Traditionally, AASs were commonly detected using gas chromatography-mass spectrometry in the initial testing procedure for doping control purposes. Gas chromatography-Orbitrap high-resolution mass spectrometry (GC-Orbitrap-HRMS) is a new technology that has many advantages in comparison with GC-MS (e.g., a maximum resolving power of 240,000 (FWHM at m/z 200), excellent sub-ppm mass accuracy, and retrospective data analysis after data acquisition). Anti-doping practitioners are encouraged to take full advantage of the updated techniques of chromatography-mass spectrometry to develop sensitive, specific, and rapid screening methods for AASs. A new method for screening a wide range of AASs in human urine using GC-Orbitrap-HRMS was developed and validated. The method can qualitatively determine 70 anabolic androgenic steroids according to the minimum required performance limit of the World Anti-Doping Agency. Moreover, the validated method was successfully applied to detect six metabolites in urine after the oral administration of metandienone, and their excretion curves in vivo were studied. Metandienone M6 (17ß-hydroxymethyl-17α-methyl-18-nor-androst-1,4,13-trien-3-one) has been identified as a long-term urinary metabolite which can be detected up to 7 weeks, thus providing a longer detection window compared with previous studies. This study provides a rationale for GC-Orbitrap-HRMS in drug metabolism and non-targeted screening.


Assuntos
Anabolizantes , Esteróides Androgênicos Anabolizantes , Dopagem Esportivo , Cromatografia Gasosa-Espectrometria de Massas , Detecção do Abuso de Substâncias , Humanos , Masculino , Anabolizantes/urina , Esteróides Androgênicos Anabolizantes/urina , Androgênios/urina , Cromatografia Gasosa-Espectrometria de Massas/métodos , Limite de Detecção , Detecção do Abuso de Substâncias/métodos
6.
Arch Toxicol ; 98(3): 779-790, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38224356

RESUMO

Hair analysis is a crucial method in forensic toxicology with potential applications in revealing doping histories in sports. Despite its widespread use, knowledge about detectable substances in hair is limited. This study systematically assessed the detectability of prohibited substances in sports using a multifaceted approach. Initially, an animal model received a subset of 17 model drugs to compare dose dependencies and detection windows across different matrices. Subsequently, hair incorporation data from the animal experiment were extrapolated to all substances on the World Anti-Doping Agency's List through in-silico prediction. The detectability of substances in hair was further validated in a proof-of-concept human study involving the consumption of diuretics and masking agents. Semi-quantitative analysis of substances in specimens was performed using ultra-performance liquid chromatography-tandem mass spectrometry. Results showed plasma had optimal dose dependencies with limited detection windows, while urine, faeces, and hair exhibited a reasonable relationship with the administered dose. Notably, hair displayed the highest detection probability (14 out of 17) for compounds, including anabolic agents, hormones, and diuretics, with beta-2 agonists undetected. Diuretics such as furosemide, canrenone, and hydrochlorothiazide showed the highest hair incorporation. Authentic human hair confirmed diuretic detectability, and their use duration was determined via segmental analysis. Noteworthy is the first-time reporting of canrenone in human hair. Anabolic agents were expected in hair, whereas undetectable compounds, such as peptide hormones and beta-2 agonists, were likely due to large molecular mass or high polarity. This study enhances understanding of hair analysis in doping investigations, providing insights into substance detectability.


Assuntos
Anabolizantes , Dopagem Esportivo , Animais , Humanos , Canrenona/análise , Dopagem Esportivo/métodos , Diuréticos/análise , Fezes/química , Cabelo/química , Detecção do Abuso de Substâncias/métodos
7.
Intern Med J ; 54(6): 891-896, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38158711

RESUMO

BACKGROUND: International osteoporosis guidelines have recommended treatment approaches based on fracture risk stratification, in particular, anabolic therapy for patients with very high risk (VHR) of fragility fracture. AIM: To summarise Australian clinicians' perceptions of patients at VHR of fracture. METHODS: Australian clinicians invited to educational webinars on anabolic treatments for osteoporosis were surveyed in March and April 2021 about a typical patient they had most recently seen and identified as at VHR of fracture. RESULTS: Of the 268 clinician attendees who were invited to complete the post-webinar surveys, 67 (25%) responded and permitted the publication of aggregated data. A typical patient perceived to have a VHR of fracture was a woman in her 80's, living at home, who had been diagnosed with osteoporosis between 5 and 10 years ago, and received treatment for 1-5 years' duration, most commonly denosumab. The patient frequently had a T-score below -3.0 SD (standard deviation), multiple fragility fractures and most commonly suffered a vertebral fracture in the past 12 months, whereas on an adequate regimen of osteoporosis medication. There was a mismatch between the patient being eligible for anabolic therapy (64.2%) and actually having been prescribed an anabolic treatment in the past (20.9%). CONCLUSIONS: Australian clinicians' perceptions of patients with a VHR of fracture and the use of anabolic agents appear to be heavily influenced by local reimbursement criteria. The mismatch between patients deemed eligible for reimbursed anabolic therapy and those prescribed an anabolic agent suggests treatment inertia.


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Fraturas por Osteoporose , Humanos , Austrália , Feminino , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/epidemiologia , Osteoporose/tratamento farmacológico , Conservadores da Densidade Óssea/uso terapêutico , Masculino , Medição de Risco , Idoso de 80 Anos ou mais , Inquéritos e Questionários , Atitude do Pessoal de Saúde , Pessoa de Meia-Idade , Denosumab/uso terapêutico , Idoso , Anabolizantes/uso terapêutico
8.
BMC Public Health ; 24(1): 798, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481173

RESUMO

BACKGROUND: The COVID-19 pandemic has had a significant impact on individual health and fitness routines globally. Resistance training, in particular, has become increasingly popular among men and women looking to maintain or improve their physical fitness during the pandemic. However, using Anabolic Steroids (AS) for performance enhancement in resistance training has known adverse effects. Thus, this study aimed to explore the prevalence of AS use among men and women resistance training practitioners after the COVID-19 pandemic. METHODS: A cross-sectional survey was conducted among 3,603 resistance training practitioners (1,855 men and 1,748 women) in various geographical locations impacted by COVID-19. The participants were asked to complete self-administered questionnaires, which included questions regarding demographic information, training habits, and current or prior usage of AS. The data were analyzed using SPSS statistical software and the chi-square method, with a significance level of (P < 0.05). RESULTS: A total of 3603 men and women resistance training practitioners completed the survey. In the study, 53.05% of men and 41.99% of women used anabolic and androgenic steroids. Of those men who used steroids, 29.47% used Testosterone, while 31.20% of women used Winstrol. Additionally, 50.30% of men used steroids via injection, while 49.05% of women used them orally. According to the study, 49.99% of the participants had 6 to 12 months of experience with resistance training, and 64.25% of them underwent three training sessions per week. The analysis using the χ2 test did not reveal any significant difference between men and women in terms of duration of bodybuilding, frequency per week, and engagement in other activities. CONCLUSION: This study shows that a significant proportion of men and women resistance training practitioners used AS, particularly among young adults with limited training experience. Thus, there is a need for targeted education and awareness campaigns to address the hazards of AS use and promote healthy training habits during the COVID-19 pandemic.


Assuntos
Anabolizantes , COVID-19 , Treinamento Resistido , Masculino , Adulto Jovem , Humanos , Feminino , Esteróides Androgênicos Anabolizantes , Pandemias , Treinamento Resistido/métodos , Prevalência , Estudos Transversais , Anabolizantes/uso terapêutico , Congêneres da Testosterona , Esteroides
9.
Aging Clin Exp Res ; 36(1): 167, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39120740

RESUMO

Bone forming agents, also known as anabolic therapies, are essential in managing osteoporosis, particularly for patients at very high-risk of fractures. Identifying candidates who will benefit the most from these treatments is crucial. For example, this group might include individuals with severe osteoporosis, multiple vertebral fractures, a recent fragility fracture or those unresponsive to antiresorptive treatments. Definitions of patients with a very high fracture risk vary across nations, are often based on fracture history, bone mineral density (BMD), and/or fracture risk calculated by FRAX® or other algorithms. However, for very high-risk patients, anabolic agents such as teriparatide, abaloparatide, or romosozumab are commonly recommended as first-line therapies due to their ability to stimulate new bone formation and improve bone microarchitecture, offering significant benefits in rapid fracture reduction over antiresorptive therapies. The cost-effectiveness of these agents is a critical consideration for decision-makers. Despite their higher costs, their effectiveness in significantly reducing fracture risk and improving quality of life can justify the investment, especially when long-term savings from reduced fracture rates and associated healthcare costs are considered. Additionally, after completing a course of anabolic therapy, transitioning to antiresorptive agents like bisphosphonates or denosumab is crucial to maintain the gains in bone density and minimize subsequent fracture risks. This sequential treatment approach ensures sustained protection and optimal resource utilization. In summary, the effective use of bone forming agents in osteoporosis requires a comprehensive strategy that includes accurate patient identification, consideration of cost-effectiveness, and implementation of appropriate sequential treatments, ultimately maximizing patient outcomes and healthcare efficiency.


Assuntos
Conservadores da Densidade Óssea , Densidade Óssea , Osteoporose , Humanos , Osteoporose/tratamento farmacológico , Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Fraturas por Osteoporose/prevenção & controle , Anabolizantes/uso terapêutico , Teriparatida/uso terapêutico , Análise Custo-Benefício
10.
J Electrocardiol ; 84: 95-99, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38579637

RESUMO

BACKGROUND: The control of the cardiovascular system depends on the autonomic nerve system. Chronic anabolic andorogenic steroids (AAS) use causes sympathovagal imbalance and increases sympathetic nerve activity. OBJECTIVE: The reduction in heart rate from the peak exercise rate following the end of the exercise stress test is known as the heart rate recovery index (HRRI). Several methods have been utilized to assess myocardial repolarization, such as QT interval (QT), corrected QT interval (QTc), and T-wave peak-to-end interval (Tp-e interval). Based on a growing number of data a higher Tp-e/QT ratio is linked to malignant ventricular arrhythmias, and an increased Tp-e interval may correlate with the transmural dispersion of repolarization. Our hypothesis is that the use of chronic AAS was decrease HRRI during maximal exercise and increased risk of cardiac arrhythmias and sudden cardiac death. METHODS: This study included 44 male bodybuilders, with an average age of 29.7 ± 8.14 years, divided into AAS abuse [AAS users (n = 21) and AAS nonuser (n = 23)]. RESULTS: The first (p = 0.001) and second minute (p = 0.001) HRRI of the subjects with AAS users were significantly lower than those of the control group. Additionally, HRRI after the third (p = 0.004) and fifth minutes (p = 0.007) of the recovery period were significantly lower in AAS group compared with the control group. Who used AAS had significantly higher QT, QTc, Tp-e, Tp-e/QT, and Tp-e/QTc values than non-users (all p = 0.001). CONCLUSIONS: Chronic AAS use has been shown to cause sympathetic dominance, which may be a pro arrhythmic state.


Assuntos
Eletrocardiografia , Frequência Cardíaca , Humanos , Masculino , Frequência Cardíaca/efeitos dos fármacos , Adulto , Levantamento de Peso , Anabolizantes/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/fisiopatologia , Teste de Esforço , Androgênios/efeitos adversos , Androgênios/farmacologia , Esteróides Androgênicos Anabolizantes
11.
Subst Use Misuse ; 59(1): 10-19, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37724019

RESUMO

Background: With the online proliferation of illegal substances, the Internet offers a wide variety of information on the acquisition and intake of anabolic-androgenic steroids (AAS) and other performance and image enhancing drugs. This study focuses on investigating the characteristics of the online AAS market in Central Asia. OBJECTIVES: The primary objectives of this study were to investigate the accessibility and features of the online market for AAS in Central Asia. To achieve this, we employed a netnographic approach for a systematic exploration of websites advertising and selling AAS. The study aimed to conduct a comprehensive analysis of several key aspects, including the variety of AAS products offered, the quality of health advice provided the level of product availability, the procedures involved in making purchases, and the pricing structures within this market. RESULTS: Twenty-one websites supplying AAS in Central Asia met our inclusion criteria. Using content analysis, data were gathered on AAS offerings, quality of health advice provided, availability, purchase process, and prices. Data were synthesized using descriptive statistics. Results indicate that AAS are easily accessible for purchase without valid medical prescription in the Central Asia online market. Most websites advertised the aesthetic and ergogenic benefits of AAS use without indicating the potential complications and adverse effects. CONCLUSIONS: Public health efforts to mitigate AAS use in Central Asia should consider both the online accessibility of AAS and the lack of accompanying information on potential complications as well as adverse effects associated with their use. Efforts must be intensified to curtail the proliferation of AAS and related misleading information on the Central Asian online market.


Assuntos
Anabolizantes , Androgênios , Humanos , Androgênios/efeitos adversos , Esteróides Androgênicos Anabolizantes , Anabolizantes/efeitos adversos , Congêneres da Testosterona/efeitos adversos , Esteroides/efeitos adversos , Ásia
12.
Subst Use Misuse ; 59(10): 1488-1494, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38812099

RESUMO

BACKGROUND: Anabolic androgenic steroids (AAS) are traditionally used for the treatment/control of various diseases; however, they are being used for non-therapeutic and indiscriminate purposes to enhance sports performance and physical appearance. This study aimed to assess the prevalence and associated factors of AAS use among professional CrossFit® competitors. METHODS: We conducted an observational cross-sectional survey in which an anonymous questionnaire was applied to professional CrossFit® athletes. RESULTS: The prevalence of AAS usage was 33.3%. Most users were male (74.2%), aged between 30 and 39 years (51.6%), with completed higher education (83.9%), and had been training for more than 5 years (77.4%); the primary motivation for AAS use was performance enhancement (77.4%). Individuals who were older (p < 0.05) and more experienced in competitions (p < 0.01) are more likely to use AAS. Testosterone was the most employed AAS (71.0%); CrossFit® athletes typically used an average of 2 different AAS. The majority of users had notably sought advice from a physician (74.2%), and AAS were acquired from either drugstores (80.6%) or through illicit channels (29.0%). Moreover, 61.3% of AAS users reported experiencing adverse effects. CONCLUSIONS: Our results demonstrated a higher prevalence of AAS users among professional competitors in CrossFit® compared to the general population; older age and greater experience in official competitions were decisive factors for a greater inclination toward AAS use. A significant percentage of athletes seek drugs through illegal channels. Despite the majority of users experiencing adverse effects, athletes report satisfaction with use, believing that the benefits still outweigh the drawbacks.


Assuntos
Anabolizantes , Atletas , Dopagem Esportivo , Motivação , Humanos , Masculino , Adulto , Feminino , Estudos Transversais , Atletas/psicologia , Atletas/estatística & dados numéricos , Anabolizantes/efeitos adversos , Dopagem Esportivo/psicologia , Dopagem Esportivo/estatística & dados numéricos , Adulto Jovem , Congêneres da Testosterona/efeitos adversos , Pessoa de Meia-Idade , Inquéritos e Questionários , Prevalência , Esteróides Androgênicos Anabolizantes
13.
Int J Mol Sci ; 25(14)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39063049

RESUMO

Ostarine (enobasarm) is a selective androgen receptor modulator with great therapeutic potential. However, it is also used by athletes to promote muscle growth and enhance performances without the typical adverse effects of anabolic steroids. Ostarine popularity increased in recent years, and it is currently the most abused "other anabolic agent" (subclass S1.2. of the "anabolic agents" class S1) from the World Anti-Doping Agency's (WADA) prohibited list. Several cases of liver toxicity were recently reported in regular users. Detecting ostarine or markers of intake in biological matrices is essential to document ostarine use in doping. Therefore, we sought to investigate ostarine metabolism to identify optimal markers of consumption. The substance was incubated with human hepatocytes, and urine samples from six ostarine-positive cases were screened. Analyses were performed via liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) and software-assisted data mining, with in silico metabolite predictions. Ten metabolites were identified with hydroxylation, ether cleavage, dealkylation, O-glucuronidation, and/or sulfation. The production of cyanophenol-sulfate might participate in the mechanism of ostarine liver toxicity. We suggest ostarine-glucuronide (C25H22O9N3F3, diagnostic fragments at m/z 118, 185, and 269) and hydroxybenzonitrile-ostarine-glucuronide (C25H22O10N3F3, diagnostic fragments at m/z 134, 185, and 269) in non-hydrolyzed urine and ostarine and hydroxybenzonitrile-ostarine (C19H14O4N3F3, diagnostic fragments at m/z 134, 185, and 269) in hydrolyzed urine as markers to document ostarine intake in doping.


Assuntos
Anabolizantes , Dopagem Esportivo , Humanos , Masculino , Anabolizantes/metabolismo , Anabolizantes/urina , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Espectrometria de Massas em Tandem , Receptores Androgênicos/metabolismo , Detecção do Abuso de Substâncias/métodos , Cromatografia Líquida , Adulto , Anilidas
14.
Reumatismo ; 76(2)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38916162

RESUMO

OBJECTIVE: Fragility fractures (FF) resulting from osteoporosis pose a significant public health challenge in Italy, with considerable socio-health and economic implications. Despite the availability of safe and effective drugs, osteoporosis remains underdiagnosed and undertreated, leaving over 2 million high-risk Italian women without treatment. This paper aims to identify and propose key improvements in the management of osteoporosis, focusing particularly on the critical issues related to the use of anabolic drugs in secondary prevention, according to the current Italian Medicines Agency (AIFA) Note 79. METHODS: The Expert Panel, composed of nine recognized Italian experts in rheumatology, analyzed current practices, prescribing criteria, and the most recent literature. Three main reasons for revising the indications on pharmacological treatment of osteoporosis were identified: inadequate treatment of osteoporosis, new evidence regarding frontline placement of anabolics in high-risk conditions, and emerging sequential or combined strategies. RESULTS: The proposed improvements include the adoption of the Derived Fracture Risk Assessment algorithm for accurate fracture risk assessment, revision of AIFA Note 79 to reflect current evidence, improved prescribing appropriateness, broader access to anabolic agents, and the provision of sequential therapies with antiresorptives for teriparatide. These changes aim to enhance patient outcomes, streamline healthcare processes, and address the high percentage of undertreated individuals. CONCLUSIONS: This expert opinion emphasizes the importance of the appropriate use of anabolic drugs to reduce FF and associated costs while ensuring the sustainability of the National Health Service. The proposed recommendations are in line with the latest scientific evidence, providing a comprehensive strategy to optimize the management of osteoporosis in Italy. On behalf of the Study Group on Osteoporosis and Skeletal Metabolic Diseases of the Italian Society of Rheumatology.


Assuntos
Anabolizantes , Conservadores da Densidade Óssea , Osteoporose , Fraturas por Osteoporose , Humanos , Itália , Anabolizantes/uso terapêutico , Osteoporose/tratamento farmacológico , Conservadores da Densidade Óssea/uso terapêutico , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/epidemiologia , Feminino , Teriparatida/uso terapêutico , Medição de Risco , Prevenção Secundária , Prova Pericial
15.
Horm Behav ; 156: 105444, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38344953

RESUMO

This study examined the effect of 6 weeks of supraphysiological nandrolone decanoate (ND) administration in adult mice (7 months) on cognitive function and neuroinflammation during aging. Male C57BL/6 mice were randomized into ND (10 mg·kg-1·wk-1) or control (CTL) groups. Half of the mice were tested at a young (Y) age (ND-Y and CTL-Y), 1 week following final ND administration, while the remaining mice were tested at 16 months (O) (ND-O and CTL-O). Learning and memory were better in young mice compared to older mice, regardless of treatment. ND-O displayed decreased anxiety as compared to all other groups. TNFα and IL1ß expression were higher in older mice, regardless of treatment. ND administration in young mice appeared to attenuate the neuroinflammatory response in aging mice as evidenced by decreased COX2, IL-4 and increased IL-10 expression in ND-O compared to CTL-O. BDNF AR and ER expression increased in ND-O compared to CTL-O. Results of the study indicated that supraphysiological ND administration had no negative effect on learning and memory but may attenuate anxiety in older mice. In addition, ND administration in young adult mice may attenuate the inflammatory response during aging, which may be related to elevations in both AR and ER expression.


Assuntos
Anabolizantes , Nandrolona , Masculino , Camundongos , Animais , Decanoato de Nandrolona , Nandrolona/farmacologia , Anabolizantes/farmacologia , Fatores de Crescimento Neural , Camundongos Endogâmicos C57BL
18.
Endokrynol Pol ; 75(3): 267-278, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887114

RESUMO

Trenbolone is a synthetic analogue of testosterone, belonging to the nandrolone group. It has both a strong anabolic effect and a limited androgenic effect (i.e. an androgen and anabolic steroid - AAS). It is used illegally by professional or amateur athletes, who want to improve their athletic performance and appearance by increasing their muscle mass. Trenbolone, like other AASs, are harmful, with 90% of users experiencing injurious side effects. It acts systemically on the body, and as such, its side effects can manifest as symptoms from different systems. Nevertheless, its popularity is increasing. This paper reviews the current state of knowledge regarding the adverse effects of trenbolone on the nervous, reproductive, immune systems and breast, muscular and adipose tissues. However, various other adverse consequences of trenbolone utilization are observed, with severe acne and gynaecomastia affecting approximately one-third of all users, as well as excessive body hair, stretch marks, hypertension and cardiac arrhythmia. The drugs are also subject to contamination, with use frequently resulting in local inflammation at the injection site, muscle adhesions and fibrosis, nerve damage or, in extreme cases, necrosis of the injection site. Additionally, due to the lack of available knowledge on the subject, many of the effects of trenbolone use remain unknown. Moreover, the fact that multiple AASs may be used simultaneously presents a significant problem in their study. Therefore, further research is necessary to better understand the effects of AAS on the body, and to expand our currently incomplete knowledge of their functional pathways.


Assuntos
Anabolizantes , Acetato de Trembolona , Humanos , Anabolizantes/efeitos adversos , Acetato de Trembolona/efeitos adversos , Masculino , Feminino , Ginecomastia/induzido quimicamente
19.
Anal Methods ; 16(14): 2135-2146, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38517236

RESUMO

A new method for rapid determination of the content of selective androgenic receptor modulators (SARMs) andarine, cardarine, ligandrol, ostarine and S-23 in capsules by 1H- and 19F-high resolution nuclear magnetic resonance spectroscopy was described and validated. Specificity, linearity, accuracy, precision, detection and quantification limits were considered as validation parameters. Full 1H-, 13C- and 19F-NMR structural assignment of the SARMs is provided as a tool for self-standing identification without a reference standard. Amounts of 7-15 mg of SARMs/capsule were detected in different products with an intermediate precision of 0.8-1.7% in 4 to 20 minutes of analysis time. The validation results and rapidity of analysis confirm the applicability of the method for large-scale screening. The statistical analysis of the results from 19F- and 1H-quantitative NMR showed that both approaches were equally effective, thus expanding the potential use of the methodology to non-fluorinated SARMs. At present, no SARM has been approved for human consumption; however, SARMs are actually used by bodybuilders and recreational athletes, who purchase them even though the risk-benefit ratio of these molecules has not been definitively established.


Assuntos
Anabolizantes , Receptores Androgênicos , Humanos , Androgênios/química , Antagonistas de Androgênios , Espectroscopia de Ressonância Magnética , Anabolizantes/química
20.
Clin Chim Acta ; 557: 117871, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38467244

RESUMO

Ostarine, also known as MK-2866 or enobosarm, is a selective androgen receptor modulator (SARM). It has anabolic properties and as such is widely used in doping, accounting in 2021 for 25 % of the adverse analytical findings (AAF) among the class S1.2 "Other anabolic agents" of products banned by the World Anti-Doping Agency, to which it belongs. But in some cases, it can be responsible for an AAF following contamination. We report the case of an athlete who contaminated herself by exchanging body fluids while kissing her boyfriend, who took 25 mg per day of MK-2866 for 9 days prior to the athlete's AAF (urinary concentration evaluated at 13 ng/mL) without her knowledge. Both subjects came to our lab for hair testing. The athlete's hair was black and slightly frizzy. Six segments of 2 cm then 7 × 3 cm (33 cm) were analysed and showed increasing concentrations, from 2 pg/mg on the first segment to 17.8 pg/mg on the last segment. The boyfriend's hair, light-brown, analyzed on 4 × 2 cm, also showed increasing values, from 65 to 143 pg/mg. These gradients of concentration in the hair's athlete and in her boyfriend were compatible with external contamination of the hair, confirmed by analysis of washing baths, pillowcases (150 pg on each), and the athlete's hairbrush (250 pg). Fingernails were also contaminated, with 21 pg/mg in the athlete and 1041 pg/mg in the boyfriend, with highly contaminated washing baths, and toenails were less contaminated, with 2 pg/mg in the athlete and 17.3 pg/mg in the boyfriend. Urine samples taken 35 days after the start of MK-2866 treatment showed a value of 3690 ng/mL in the boyfriend and 5.7 ng/mL in the athlete. After 6 days off, these concentrations were 3.3 ng/mL and 0.1 ng/mL, respectively. A controlled transfer study was carried out 12 days after discontinuation (urine concentrations returned to negative level). After administration of 17 mg (the 25 mg/mL vial having been controlled at 17 mg/mL), urine samples were taken from the boyfriend and the athlete (n = 10 for each) for more than 25 h after they had been living normally with each other (regular kissing in particular). The boyfriend's urine concentrations ranged from 681 ng/mL to 12822 ng/mL (Tmax = 8:30 hrs), and the athlete's from 0.3 ng/mL to 13 ng/mL with Tmax = 8:30 hrs, i.e. at 22:30 hrs, which corresponded exactly to the time of collection of the urine that showed AAF, with a similar concentration. The dose ingested by the athlete was estimated at 15 µg. These results demonstrate the transfer of ostarine via body fluids between two subjects, with a high risk of AAF in one athlete, as observed in our case.


Assuntos
Anabolizantes , Líquidos Corporais , Dopagem Esportivo , Feminino , Humanos , Anabolizantes/urina , Anilidas , Líquidos Corporais/química , Detecção do Abuso de Substâncias/métodos , Masculino
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