Search Results (95)

Selective androgen receptor modulators (SARMs) are commonly described as tissue-selective anabolic agents, yet the extent to which this selectivity is reflected at the level of receptor-binding energetics remains uncertain. This study evaluated the receptor interaction profiles of the steroidal SARM YK11 and the nonsteroidal SARM ostarine across five steroid hormone nuclear receptors. Flexible molecular docking was performed with AutoDock 4.2 against the androgen (AR), estrogen (ER), progesterone (PR), glucocorticoid (GR), and mineralocorticoid (MR) receptors, using testosterone, estradiol, progesterone, cortisol, and aldosterone as endogenous reference ligands. Binding free energy, docking-derived inhibition constants, intermolecular interaction energies, conformational sampling, and two-dimensional interaction maps were analyzed. Ostarine showed favorable binding across all receptor systems, with binding energies ranging from −10.42 to −12.05 kcal/mol and no pronounced energetic preference for the androgen receptor. YK11 displayed stronger predicted binding, particularly toward the glucocorticoid, progesterone, and androgen receptors, with a docking energy trend of GR > PR > AR > MR > ER. Interaction analysis revealed conserved polar anchoring residues across receptor pockets, together with scaffold-specific contacts that may explain cross-receptor compatibility. These findings indicate that, within the AutoDock 4.2 flexible docking framework applied in this study, docking-derived binding energies primarily describe thermodynamic compatibility with nuclear receptor ligand-binding domains and should not be interpreted as direct predictors of functional SARM tissue selectivity. The observed discordance between predicted receptor affinity and the established tissue-selective pharmacology of ostarine highlights the need for caution when using single-method docking workflows to infer selectivity among closely related steroid hormone receptors. The novelty of this study lies in demonstrating, using a defined AutoDock 4.2-based comparative protocol, that receptor-binding energetics alone do not recapitulate the functional tissue-selective behavior attributed to SARMs. Full article

This study aimed to identify environmental and hormonal determinants of steroid receptor expression in the bone tissue of men with osteoarthritis. Twenty-six men undergoing total hip arthroplasty were included. Serum hormones, bone turnover markers, and elemental concentrations were assessed, and bone samples were analyzed using immunohistochemistry and multivariate regression models. Results: Estrogen receptor alpha (ERα) expression was a significant positive predictor of the bone formation marker procollagen type I N-terminal propeptide (PINP) (p = 0.0386), indicating its key role in anabolic processes. Androgen receptor (AR) expression showed a positive trend with the resorption marker CTX-I (p = 0.0956). A strong negative association was observed between Body Mass Index (BMI) and ERα expression (β = −0.50; p = 0.0018), suggesting reduced estrogen sensitivity in individuals with higher adiposity. Local accumulation of metals significantly influenced receptor expression. Lead in bone was strongly associated with increased AR expression (β = +1.457; p = 0.0009), whereas manganese was positively associated with ERα expression (β = +2.112; p = 0.0409). These findings indicate that local bone tissue analysis provides more accurate insight into hormonal regulation than serum measurements and highlight the role of environmental factors in modulating bone metabolism in men. Full article

Ecdysterone is a natural compound proposed as an alternative to anabolic-androgenic steroids (AAS) due to its comparable ergogenic potential and more favorable safety profile. This narrative review summarizes current evidence using a standardized search protocol. Although many plants synthesize ecdysteroids, only a few cultivated species—emphasizing quinoa and spinach—contribute meaningfully to dietary intake, while wild species such as those from the Ajuga genus contain substantially higher concentrations. Experimental studies indicate that ecdysterone enhances protein synthesis and physical performance through estrogen receptor-beta activation, avoiding the adverse effects typically associated with AAS. Additional pharmacological effects, including potential roles in breast cancer therapy and Alzheimer’s disease, have also been described. Ecdysteroids are generally considered non-toxic in humans; however, analysis of commercial supplements frequently reveals poor quality control and discrepancies between labeled and actual ecdysterone content. Although prevalence of use among athletes appears low, establishing urinary reference ranges to differentiate dietary exposure from supplement-derived intake is essential. Ecdysterone and its metabolites, 14-deoxy-ecdisterone and 14-deoxy-poststerone, are detectable in urine for more than two days depending on dosage. Given its ergogenic potential and detectability, ecdysterone may pose risks for unethical use and should be considered for inclusion in initial anti-doping testing procedures. Further research on ecdysteroids is required to elucidate their mechanisms of action, confirm the absence of adverse effects, and establish reference urinary concentration ranges that allow differentiation between diet-related metabolites and those derived from drug use. Full article

Androgens regulate skeletal muscle, bone, erythropoiesis, and male reproductive function via the androgen receptor (AR), a ligand-dependent transcription factor. Pharmacologic modulation of AR has been pursued for clinical and non-medical purposes. Anabolic androgenic steroids (AAS), synthetic testosterone derivatives, act as full AR agonists, broadly activating multiple tissues. While effective in promoting muscle growth and strength, AAS cause well-known adverse effects, including hypothalamic–pituitary–gonadal (HPG) axis suppression, dyslipidemia, hepatotoxicity, cardiovascular disease, tendon injury, and neuropsychiatric disturbances. Selective androgen receptor modulators (SARMs) aim to stimulate AR in muscle and bone while minimizing androgenic effects in prostate and skin. They induce ligand-specific AR conformations, altering coactivator and corepressor recruitment, and avoiding metabolism by 5α-reductase or aromatase. Preclinical studies show favorable anabolic-to-androgenic ratios, but clinical translation is limited. Early human trials report modest lean mass gains, variable functional outcomes, and dose-dependent testosterone suppression. Emerging evidence also suggests cardiotoxicity, tendon injury, and liver toxicity, though long-term effects are unclear. Pharmacokinetically, SARMs have predictable oral absorption and moderate half-lives, enabling once-daily dosing, unlike AAS. This review compares AAS and SARMs in molecular mechanisms, pharmacokinetics, and safety. While SARMs offer partial tissue selectivity and reduced adverse effects, risks remain, and long-term safety is uncertain. Regulatory oversight is limited, and non-medical use is rising. Preclinical and clinical studies are needed to clarify whether SARMs can separate anabolic benefits from androgenic toxicity and inform safe clinical application. Full article

Synthetic derivatives of testosterone known as 17α-alkylated anabolic–androgenic steroids have been developed to retain anabolic effects while enabling oral administration. Here, we present newly identified hydrated solid forms of three agents: oxandrolone hemihydrate (C₁₉H₃₀O₃·0.5H₂O), fluoxymesterone hydrate (C₂₀H₂₉FO₃·H₂O), and methandienone hemihydrate (C₂₀H₂₈O₂·0.5H₂O). Their crystal structures were determined using single-crystal X-ray diffraction, supplemented by powder X-ray diffraction and thermal analyses. Computational methods were employed to investigate molecular interactions and crystal packing. Lattice energy evaluations revealed that the hydrated forms are energetically less stable than their anhydrous counterparts, with significantly less negative values (e.g., −113.4 kJ/mol for oxandrolone hemihydrate vs. −164.4 kJ/mol for the anhydrous form). Energy decomposition analysis indicates that while water molecules participate mostly in electrostatic-driven hydrogen bonding, they disrupt the dispersive packing efficiency found in the anhydrous phases. Specifically, intermolecular interaction energies show that host–host hydrogen bonds (up to −62.2 kJ/mol in oxandrolone) dominate over weaker host–water couplings (−8.9 to −34.9 kJ/mol). The newly reported crystal structures contribute to the expanding catalog of solid-state forms for 17α-alkylated steroids and provide important details regarding their metastable nature and the dehydration-driven phase transformations observed under climatic stress conditions. Full article

Steroid hormones exert diverse and tissue-specific biological effects despite sharing a conserved tetracyclic scaffold. Among these, anabolic–androgenic steroids (AAS) present a longstanding paradox: structurally related compounds can elicit markedly different anabolic, androgenic, and cardiovascular outcomes. This narrative review integrates advances in steroid structural chemistry, androgen receptor (AR) biology, and intracellular signaling to elucidate the molecular mechanisms underlying anabolic–androgenic dissociation. We summarize classical genomic and emerging non-genomic modes of steroid action, emphasizing how receptor conformation, ligand-binding domain architecture, co-regulator recruitment, and signaling bias shape downstream biological responses. Particular focus is placed on the structure–activity relationships of endogenous and synthetic androgens, with C17-substitution chemistry highlighted as a central determinant of receptor affinity, metabolic stability, pharmacokinetics, and tissue selectivity. By linking molecular structure to receptor-level mechanisms, we contextualize the physiological and pathophysiological effects of major AAS classes used clinically and non-medically, including testosterone esters, 19-nor derivatives, 17α-alkylated steroids, heterocyclic compounds, and halogenated compounds. While much of the mechanistic evidence derives from preclinical models, the integrated framework presented here provides a coherent basis for interpreting divergent anabolic, androgenic, and cardiovascular effects observed in humans. Collectively, this review bridges fundamental steroid biology with applied physiology and sports medicine, offering mechanistic insight relevant to therapeutic development, anti-doping science, and risk assessment of supraphysiological androgen exposure. Full article

Inorganic nitrate (NO₃⁻) has demonstrated therapeutic efficacy in several populations characterised by cardiovascular risk. However, it is unknown whether increasing nitric oxide (NO) bioavailability affects vascular and cardiovascular responses in men with androgenic–anabolic steroid (AAS) abuse. Objective: To investigate the effects of dietary NO₃⁻ on cardiovascular, autonomic, and strength performance in men with AAS abuse. Methods: In this double-blind, randomised, placebo-controlled crossover trial, participants consumed beetroot juice (12.8 mmol [800 mg] NO₃⁻) or a placebo (0.3 mmol NO₃⁻). After two hours, assessments included saliva collection, endothelial function, heart rate, and systolic (SBP) and diastolic (DBP) blood pressure at rest, during, and after an isometric handgrip test. Results: Thirteen resistance-trained males [mean (standard deviation) age: 31 (9) y; body mass index (BMI): 30 (4) kg/m²; SBP: 132 (3) mmHg; DBP: 70 (2) mmHg] completed the protocol. NO₃⁻-rich juice significantly increased salivary NO₃⁻ (40.6 μM, p < 0.001) and nitrite (NO₂⁻) (3.1 μM, p = 0.002) versus placebo. Flow-mediated dilation was greater with NO₃⁻ both at pre-exercise (2.37%, p = 0.02) and post-exercise (2.57%, p = 0.01). No between-group differences were observed in isometric strength (0.02 kgf, p = 0.99) or systolic/diastolic blood pressure across conditions. Conclusions: Dietary NO₃⁻ enhanced salivary NO₂⁻ and NO₃⁻ concentrations and modestly improved endothelial function but did not reduce the elevated blood pressure or alter cardiac autonomic responses associated with AAS abuse. Full article

Background/Objectives: Thyroid hormones, considered safe in therapeutic doses, are used to treat hypothyroidism, a common condition. Due to a combination of factors, including their mechanism of action, availability, and low price, these drugs are used illegally, mainly to improve performance, to assist in weight loss, or for attempting suicide. Their overuse can lead to serious health consequences, including death. Although thyroid hormones are abused, there are no studies assessing the scale, characteristics, and consequences of their illegal use. The aim of this study was to evaluate case reports of thyroid hormone poisoning from the last 30 years, assessing their dynamics and characteristics. Methods: Full-text clinical case studies were obtained by searching PubMed, Google Scholar, MEDLINE, Embase, Web of Science, and Scopus for the following terms: “thyroid hormones”, “thyroxine”, “levothyroxine”, “triiodothyronine”, and “liothyronine”, as well as “intoxication”, “overdose”, and “poisoning”. This study adhered to Preferred Reporting for Systematic Reviews and Meta-analyses (PRISMA) guidelines for systematic reviews. Results: Thyroid hormones are abused particularly by athletes, persons trying to lose weight, or those attempting suicide. There has been an upward trend in thyroid hormone poisoning over the past 30 years, particularly since 2015. The same trend has been observed in cases of thyroid hormone use for doping, among other performance-enhancing drugs. Thyroid hormone use for doping was the most common cause of poisoning with these drugs, with other clinical manifestations from poisonings due to other causes. No upward trend has been observed in the use of thyroid hormones in suicide attempts since 2017, as this number remains stable. Conclusions: Although exploratory in nature, our work indicates that thyroid hormone poisoning, associated mostly with the illegal use of anabolic–androgenic steroids, exhibits an increasing tendency. Moreover, thyroid hormone abuse is an important issue in suicidology. Full article

Anabolic–androgenic steroids (AAS) are synthetic derivatives of testosterone that are used therapeutically but are frequently abused by athletes and individuals seeking to increase muscle mass. Their anabolic (promoting muscle growth) and androgenic (inducing masculine characteristics) effects result from androgen receptor activation in target tissues. However, chronic supraphysiological AAS exposure is associated with serious cardiovascular consequences, ranging from hypertension and lipid disorders to cardiomyopathy, atherosclerosis, and sudden cardiac death. This review provides an updated and integrative perspective on both the molecular and clinical aspects of AAS-induced cardiovascular toxicity, highlighting recent advances in understanding endothelial injury, oxidative stress, fibrosis, and arrhythmogenesis. Importantly, it emphasizes the emerging recognition of AAS abuse as a modifiable cardiovascular risk factor and discusses potential preventive and therapeutic strategies, including early cardiovascular screening and risk stratification. Understanding these mechanisms is essential for recognizing the clinical manifestations of AAS misuse and for improving cardiovascular risk assessment in affected individuals. These insights underscore the clinical significance of AAS abuse as a cardiovascular risk factor and the need for vigilant cardiac monitoring and early intervention in this population. Full article

Anabolic–androgenic steroids (AASs) are synthetic derivatives of testosterone and are increasingly misused to enhance muscle growth and physical performance, particularly among athletes and recreational bodybuilders. Although AASs affect multiple organ systems, their severe and potentially life-threatening complications involve the cardiovascular system. This review summarizes current knowledge on the pathophysiological mechanisms and clinical manifestations of AAS-induced cardiomyopathy. Chronic supraphysiologic AAS use promotes cardiac injury and adverse cardiac remodeling via oxidative stress, androgen receptor overactivation, RAAS dysregulation, and pro-apoptotic signaling. These changes could lead to hypertension, dyslipidemia and atherosclerosis, myocardial fibrosis and hypertrophy, arrhythmias, heart failure, and kidney injury. Vascular dysfunction, increased arterial stiffness, and a prothrombotic state further compound the cardiovascular risks. Diagnostic approaches involve biomarker evaluation, echocardiography, and cardiac magnetic resonance imaging, revealing structural and functional cardiac abnormalities such as reduced ejection fraction, concentric hypertrophy, myocardial fibrosis, and impaired diastolic function. Although cessation of AAS use may lead to partial or complete reversal of cardiac dysfunction in some individuals, others may experience irreversible myocardial damage. The reversibility appears to depend on dosage, duration of exposure, and early intervention. This review explores the cardiovascular consequences of AAS use, with a focus on the mechanisms, diagnosis, and management of AAS-induced cardiomyopathy, and underlines the importance of education and early detection. Full article

Muscle dysmorphia (MD) is a body image disorder characterized by an obsessive preoccupation with muscularity and compulsive behaviors such as excessive exercise, rigid dieting, and frequent body checking. MD has been linked to obsessive–compulsive traits and the use of anabolic–androgenic steroids (AASs), yet these associations have not been comprehensively synthesized. This systematic review and meta-analysis examined the relationships between MD, obsessive–compulsive symptomatology, and AASs or performance-enhancing drug use. Following PRISMA 2020 guidelines and PROSPERO preregistration (CRD42025640206), we searched four major databases for peer-reviewed studies published between 2015 and 2025. Ten studies (five quantitative, five qualitative) met the inclusion criteria. Meta-analytic findings revealed a moderate positive correlation between MD symptom severity and obsessive–compulsive traits (r ≈ 0.24), and significantly higher MD symptoms among AAS users compared to non-users (Cohen’s d ≈ 0.45). Odds of MD were markedly higher in steroid-using populations. Thematic synthesis of qualitative studies highlighted compulsive training routines, identity conflicts, motivations for AAS use, and limited engagement with healthcare services. These findings suggest that MD exists at the intersection of obsessive–compulsive psychopathology and substance-related behavior, warranting integrated interventions targeting both dimensions. The study contributes to understanding MD as a complex, multi-faceted disorder with significant clinical and public health relevance. Full article

Background: Anabolic–androgenic steroids (AASs) are commonly used for performance enhancement but have been linked to significant neurobiological consequences. This review explores the impact of AASs on neurochemical pathways, cognitive function, and psychiatric disorders, highlighting their potential neurotoxicity. Methods: A narrative review of current literature was conducted to examine AASs-induced alterations in neurotransmitter systems, structural and functional brain changes, and associated psychiatric conditions. The interplay between AASs use and other substances was also considered. Results: Chronic AASs exposure affects serotonin and dopamine systems, contributing to mood disorders, aggression, and cognitive deficits. Structural and functional changes in the prefrontal cortex and limbic regions suggest long-term neurotoxicity. AASs use is associated with increased risks of depression, anxiety, and psychosis, potentially driven by hormonal dysregulation and neuroinflammation. Co-occurring substance use exacerbates neurocognitive impairments and behavioral disturbances. Discussion: While evidence supports the link between AASs use and neurotoxicity, gaps remain in understanding the precise mechanisms and long-term effects. Identifying biomarkers of brain damage and developing targeted interventions are crucial for mitigating risks. Increased awareness among medical professionals and policymakers is essential to address AASs-related neuropsychiatric consequences. Conclusions: AASs abuse poses significant risks to brain health, necessitating further research and prevention efforts. Evidence-based strategies are needed to educate the public, enhance early detection, and develop effective interventions to reduce the neuropsychiatric burden of AASs use. Full article

Background/Objectives: Muscle dysmorphia (MD), a subtype of body dysmorphic disorder, is prevalent among males who engage in the non-medical use of anabolic–androgenic steroids (AASs) and performance-enhancing drugs (PEDs). These individuals often experience severe psychopathology, including mood instability, compulsivity, and a distorted body image. Despite its clinical severity, no randomized controlled trials (RCTs) have evaluated structured psychological treatments in this subgroup. This study aimed to assess the efficacy of a manualized cognitive behavioral therapy (CBT) protocol in reducing MD symptoms and associated psychological distress among male steroid users. Results: Participants in the CBT group showed significant reductions in MD symptoms from the baseline to post-treatment (MDDI: p < 0.001, d = 1.12), with gains sustained at follow-up. Large effect sizes were also observed in secondary outcomes including depressive symptoms (PHQ-9: d = 0.98), psychological distress (K10: d = 0.93), disordered eating (EDE-Q: d = 0.74), and exercise addiction (EAI: d = 1.07). No significant changes were observed in the control group. Significant group × time interactions were found for all outcomes (all p < 0.01), indicating CBT’s specific efficacy. Discussion: This study provides the first RCT evidence that CBT significantly reduces both core MD symptoms and steroid-related psychopathology in men engaged in AAS/PED misuse. Improvements extended to mood, body image perception, and compulsive exercise behaviors. These findings support CBT’s transdiagnostic applicability in addressing both the cognitive–behavioral and affective dimensions of MD. Materials and Methods: In this parallel-group, open-label RCT, 59 male gym-goers with DSM-5-TR diagnoses of MD and a history of AAS/PED use were randomized to either a 12-week CBT intervention (n = 30) or a waitlist control group (n = 29). CBT sessions were delivered weekly online and targeted distorted muscularity beliefs, compulsive behaviors, and emotional dysregulation. Primary and secondary outcomes—Muscle Dysmorphic Disorder Inventory (MDDI), PHQ-9, K10, EDE-Q, EAI, and BIG—were assessed at the baseline, post-treatment, and 3-month follow-up. A repeated-measures ANOVA and paired t-tests were used to analyze time × group interactions. Conclusions: CBT offers an effective, scalable intervention for individuals with muscle dysmorphia complicated by anabolic steroid use. It promotes broad psychological improvement and may serve as a first-line treatment option in high-risk male fitness populations. Future studies should examine long-term outcomes and investigate implementation in diverse clinical and cultural contexts. Full article

This study investigates the potential of ¹H and ¹³C NMR for the characterization and classification of anabolic androgenic steroids (AASs) in various formulations. First, twenty AAS formulations, including tablets, capsules, and injectable solutions, were analyzed using ¹H NMR for the qualitative identification and quantification of active compounds. The results revealed discrepancies between the labeled and detected substances in several samples, highlighting issues related to product mislabeling and potential health risks. Then, twelve oil-based injectable formulations were examined using ¹³C NMR, demonstrating its effectiveness in differentiating and quantifying closely related steroid structures that cannot be discriminated with ¹H NMR. A chemometric approach from ¹³C NMR data, based on a principal component analysis (PCA) and hierarchical cluster analysis (HCA), enabled the classification of samples and the identification of key active ingredients. Full article

SPS is characterized by progressive spasmodic muscular rigidity. SPS is thought to be an autoimmune disease with a prominent feature of antibodies against glutamic acid decarboxylase (GAD). GAD is responsible for the enzymatic conversion of glutamic acid (glutamate) into the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Reduced GABA activity leads to increased excitability in the central nervous system, resulting in muscle rigidity and spasms characteristic of SPS. While SPS is rare, anti-GAD antibodies seen in SPS are also seen in the much more common autoimmune disease, type 1 diabetes (T1D). There is evolving research showing that the anti-GAD antibodies of T1D are produced in response to the presence of mycobacterial heat shock protein 65 (mHSP65), and the mHSP65 is produced in response to an occult infection by a bacterium, Mycobacterium avium subspecies Paratuberculosis (MAP). Humans are broadly exposed to MAP in food, water, and air. There are linear and conformational similarities between the epitopes of GAD and mHSP65. This article proposes that MAP is also an infectious trigger for SPS. Dehydroepiandrosterone (DHEA) is a principal component of the steroid metabolome; it plateaus in young adults and then steadily declines. Bromo-epi-androsterone (BEA) is a potent synthetic analog of DHEA; unlike DHEA, it is non-androgenic, non-anabolic, and an effective modulator of immune dysregulation. BEA is also an anti-infective agent and has been shown to benefit mycobacterial infections, including tuberculosis and leprosy. With the immune stabilizing capacity of BEA as well as its anti-mycobacterial properties, there is reason to believe that a randomized clinical trial with BEA may be beneficial for SPS. Full article