A Pilot Study of the Clinical Effectiveness of a Single Intra-Articular Injection of Stanozolol in Canines with Knee Degenerative Joint Disease and Its Correlation with Serum Interleukin-1ß Levels.

Stanozolol shows promise as an anabolic and anti-catabolic agent for treating degenerative joint disease (DJD). This study assessed the clinical efficacy of a single intra-articular stanozolol injection in canine knees with DJD and its correlation with serum IL-1ß levels. Thirty dogs (n = 30) were divided into a control group (CG, n = 10) and a study group (SG, n = 20) with DJD. Pain levels were assessed using the Brown query, and radiographs were taken at T0 and T3. IL-1ß levels were quantified via ELISA. Apart from 2 patients, all showed reduced pain intensity, with 15 patients showing improvement at T1 and 3 patients at T2. A positive correlation (r = 0.84; p < 0.01) was found between pain level and IL-1ß in 15 patients. No systemic effects were observed. Most patients (18/20) experienced reduced pain. This pilot study suggests stanozolol's potential in managing DJD in dogs. Further research is warranted to validate these findings and understand stanozolol's mechanism in DJD treatment.

Novel dummy molecularly imprinted polymer for simultaneous solid-phase extraction of stanozolol metabolites from urine.

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.

Effect of Stanozolol combined with Cyclosporine A on aplastic anemia.

OBJECTIVE: To investigate the clinical efficacy of Stanozolol combined with Cyclosporine A for treatment of aplastic anemia and its influence on cytokine levels. METHODS: This is a retrospective analysis of 90 patients with aplastic anemia treated in Department of Hematology, Shandong Provincial Third Hospital from July 2019 to July 2022. According to the different treatment methods, these patients were assigned into a control group and an observation group, with 45 cases in each group. Patients in the control group were treated with Stanozolol alone, while those in the observation group were treated with the combination of Stanozolol and Cyclosporine A. Patients in both groups were treated for six months continuously. The indicators in terms of therapeutic effect, drug onset time, cytokine levels, quality of life, and adverse reactions were recorded and compared between the two groups. RESULTS: After treatment, the total response rate in the observation group was significantly higher than in the control group (91.11% vs. 71.11%, P<0.05). The drug onset time in the observation group was shorter than that in control group (42.35±3.68 vs. 68.72±5.49, P<0.05). In contrast to the control group, the observation group exhibited significantly decreased levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin-2 (IL-2), and an increased level of vascular endothelial growth factor (VEGF) after treatment, with significant differences (all P<0.05). The QLQ-C30 scores in the observation group were significantly higher than that in the control group (P<0.05). Moreover, there was no statistical difference in the overall incidence of adverse reactions between the two groups (11.11% vs. 17.78%). CONCLUSION: Stanozolol combined with Cyclosporine A is more effective than Stanozolol alone in treatment of aplastic anemia.

QuEChERS as alternative extraction procedure in doping analyses.

QuEChERS is a dispersive solid phase extraction commonly applied in food analysis for residues, such as pesticides or mycotoxins for more than 20 years. Due to the quick and easy sample preparation procedure, a QuEChERS method based on ammonium acetate combined with formic acid in acetonitrile was tested for the preparation of urine samples for doping control purposes. Testing urine samples with different pH and specific gravity, using the combination of 10 M ammonium acetate with 3% formic acid in acetonitrile, 312 out of 342 tested compounds could be extracted at their respective minimum required performance levels according to the World Anti-Doping Agency (WADA) technical documents. For nine selected analytes representing six categories of WADA's Prohibited List, we validated the QuEChERS extraction method fulfilling WADA's requirements for a confirmation procedure of the nonthreshold substances investigated. Especially for the intact stanozolol-glucuronides analyzed by high-resolution mass spectrometry, the described extraction method might be an alternative for confirmation procedures as it is time- and cost-saving compared with the commonly applied solid phase extraction.

Liquid chromatographytandem mass spectrometry methods for determination of stanozolol and l6ß-hydroxy-stanozolol in animal urine.

Introduction: Because of the activities and effects they induce, hormones are prohibited for use for anabolic purposes in farm animals intended for slaughter, which is regulated in the European Union by relevant legal provisions. Therefore, there is an obligation to monitor residues of hormones in animals and food of animal origin to ensure consumer safety. A hormone banned but used formerly for fattening cattle, stanozolol, and its metabolite 16ß-OH-stanozolol are synthetic compounds that belong to a large group of steroid hormones. This study investigates residues of these compounds in animal urine. Material and Methods: From 2006-2022, 2,995 livestock urine samples were tested for stanozolol residues in Poland as part of the National Residue Monitoring Programme. A liquid chromatography-tandem mass spectrometry method to determine stanozolol and 16ß-OH-stanozolol in animal urine was developed and validated according to the required criteria. Urine sample analysis was based on enzymatic hydrolysis of hormones potentially present in it to the free form, extraction of them from the sample with a mixture of n-hexane and butyl alcohol, purification of an extract on an NH2 amine column and finally, instrumental detection. Results: The apparent recovery and precision parameters of the developed method were in line with the established criteria, while its decision limits CCα and detection capabilities CCß were lower than the recommended concentration for analytical purposes set at 2 µg L-1 (valid until December 15, 2022; currently set as 0.5 µg L-1). Conclusion: All examined samples were compliant with the evaluation criteria.

Fatal anabolic androgenic steroid overdose in an amateur bodybuilder: a clinical and autopsy report.

Stanozolol is a synthetic anabolic-androgenic steroid commonly used by bodybuilders to increase muscle mass. However, its use can lead to serious adverse effects on the liver, including cholestasis, hepatic necrosis, and even death. In this case report, we describe a fatal case of stanozolol overdose in an otherwise healthy 35-year-old amateur bodybuilder. The patient presented with general malaise, jaundice, and a history of hematemesis after taking stanozolol tablets orally for 3 months. Upon admission, his liver function tests were significantly abnormal, and he succumbed within 48 h despite symptomatic treatment. The autopsy revealed sub-massive hepatic necrosis, focal macro-vesicular steatosis, and a cholestatic pattern of acute liver injury, with the chemical examination confirming the presence of stanozolol in the blood, liver, and kidneys. The cause of death was determined to be hepatic necrosis as a complication of stanozolol overdose. The overuse of anabolic steroids like stanozolol can cause hepatotoxicity, resulting in reversible cholestatic hepatitis or, in rare cases, fatal liver injury. The mechanism of anabolic androgenic steroid (AAS) drug-induced liver injury is obscure, but proposed mechanisms include oxidative stress and cholestasis. In this case, the recent overuse of stanozolol, a 17 alpha-alkylated (oral) AAS led to sub-massive hepatic necrosis and subsequent liver failure, proving fatal. It is imperative that healthcare providers and the public are informed about the dangers of AAS use, especially since AAS usage has increased recently due to easy online access, to prevent potentially life-threatening consequences.

Multiresidue Determination of Growth Promoters in Bovine Serum using QuEChERS and UHPLC-Q-ORBITRAP: Validation and In Vivo Study.

A reliable method using a QuEChERS approach and liquid chromatography coupled to Q-Orbitrap mass spectrometry was optimized and validated for the quantification of 20 growth promoters in bovine serum. The recoveries ranged from 91.4-114.1%, relative standard deviations varied between 0.3-4.0%, and CCα values were between 0.023-0.350 µg L-1. The developed method was applied in an in vivo study using steers, which were intramuscularly treated with commercial injections containing stanozolol. A rapid metabolization was observed, with a detection window ranging from 3 to 10 days. The stability of incurred stanozolol was confirmed after 240 days at -20 °C and also after 5 freeze-thaw cycles. To the best of our knowledge, this is the first work in which an in vivo study was performed to support the monitoring of stanozolol in bovine serum. In addition, the use of Q-Orbitrap high-resolution mass spectrometry allows for retrospective analysis from a surveillance perspective.

Investigations into the concentration and metabolite profiles of stanozolol and LGD-4033 in blood plasma and seminal fluid using liquid chromatography high-resolution mass spectrometry.

Potential scenarios as to the origin of minute amounts of banned substances detected in doping control samples have been a much-discussed problem in anti-doping analysis in recent years. One such debated scenario has been the contamination of female athletes' urine with ejaculate containing doping agents and/or their metabolites. The aim of this work was to obtain complementary information on whether relevant concentration ranges of doping substances are excreted into the ejaculate and which metabolites can be detected in the seminal fluid (sf) and corresponding blood plasma (bp) samples. A method was established to study the concentration and metabolite profiles of stanozolol and LGD-4033-substances listed under anabolic substances (S1) on the World Anti-Doping Agency's Prohibited List-in bp and sf using liquid chromatography high-resolution mass spectrometry (LC-HRMS). For sf and bp, methods for detecting minute amounts of these substances were developed and tested for specificity, recovery, linearity, precision, and reliability. Subsequently, sf and bp samples from an animal administration study, where a boar orally received stanozolol at 0.33 mg/kg and LGD-4033 at 0.11 mg/kg, were measured. The developed assays proved appropriate for the detection of the target substances in both matrices with detection limits between 10 and 40 pg/mL for the unmetabolized drugs in sf and bp, allowing to estimate the concentration of stanozolol in bp (0.02-0.40 ng/mL) and in sf (0.01-0.25 ng/mL) as well as of LGD-4033 in bp (0.21-2.00 ng/mL) and in sf (0.03-0.68 ng/mL) post-administration. In addition, metabolites resulting from different metabolic pathways were identified in sf and bp, with sf resembling a composite of the metabolic profile of bp and urine.

What is responsible for acute myocardial infarction in combination with aplastic anemia? A case report and literature review.

BACKGROUND: Aplastic anemia (AA) complicated with myocardial infarction (MI) is rare and associated with poor prognosis. Here, we present a case of AA with recurrent acute MI (AMI) in a patient treated with cyclosporine A (CsA) and stanozolol. In this patient, we suspect the long-term use of medication linked to platelets hyperfunction. CASE SUMMARY: In 2017, a 45-year-old man was rushed to the emergency department of China-Japan Union Hospital due to precordial pain for 5 h. Based on his symptoms, medical history, blood tests, and findings from coronary angiography (CAG), the patient was diagnosed with acute anterior wall, ST-segment elevated MI, Killip II grade, AA, and dyslipidemia. In 2021, the patient was readmitted to the hospital for 2 h due to chest pain. Because the patient's platelet count was 30 × 109/L and he had severe thrombocytopenia, we performed CAG following platelet transfusion. Optical coherence tomography revealed lipid plaque and thrombus mass in his right coronary artery. The antithrombotic approach was adjusted to employ only anticoagulants (factor Xa inhibitors) and adenosine diphosphate inhibitors (clopidogrel) after assessing the risk of bleeding/thrombotic events. Long-term follow-up revealed that the patient had made a good recovery. CONCLUSION: Patients with AA should be closely monitored for the risk of thrombosis and cardiovascular events, particularly when taking stanozolol or CsA for an extended period of time.

In Vivo Administration of Stanozolol in Cattle: Depletion and Stability Studies Using UHPLC-Q-Orbitrap.

An in vivo study was performed in order to evaluate the depletion time of stanozolol and its main metabolites using naturally incurred urine sample collected after the administration of intramuscular injections in 12 steers. A stability study was also carried out to investigate the influence of the storage period and the freeze-thaw cycles. A fast parent drug metabolization was observed, because within 6 h after drug administration, the signal of the metabolite 16ß-hydroxystanozolol was predominant. After the second drug administration, a detection window of 17 days was obtained. The stability was studied using ANOVA, in which a storage condition of -20 °C proved stable during 240 days, which was also confirmed after 5 freeze-thaw cycles.

Synchronized resistance training and bioactive herbal compounds of Tribulus Terrestris reverse the disruptive influence of Stanozolol.

Androgenic-Anabolic Steroids (AAS) consumption may have irreversible effects on athletes' hearts. The beneficial effects of Tribulus Terrestris (TT) have been shown to reduce cardiovascular risks through disruption in apoptosome complex construction. Therefore, this study aimed to investigate the effect of eight weeks of resistance training (RT) with TT consumption in the heart tissue of rats exposed to Stanozolol. Thirty-five male rats were divided into seven groups, Control group, Stanozolol (ST), ST + 100 mg/kg TT, ST + 50 mg/kg TT, RT + ST, RT + ST + 100 mg/kg TT, and RT + ST + 50 mg/kg TT. Differential genes expression was measured by q-RT-PCR. Artificial intelligence highlighted apoptosis pathways as a vital process in cardiovascular risks. Hence, we estimated the binding affinity of chemical and bioactive molecules on the cut point hub gene by pharmacophore modeling and molecular docking. Moreover, ST increased IL-6, Cat, Aif-1, and Caspase-9. 100 mg/kg TT has a more favorable effect than 50 mg/kg T. Also, RT with TT had interactive effects on reducing IL-6, Cat, Aif-1, and Caspase-9. RT and TT consumption seemed to synergistically reduce the apoptotic pathway markers in the heart tissue of rats exposed to the supra-physiologic dose of ST. Moreover, TT could be added to supplements and sports drink to increase an athlete's performance.

When Bodybuilding Goes Wrong-Bilateral Renal Artery Thrombosis in a Long-Term Misuser of Anabolic Steroids Treated with AngioJet Rheolytic Thrombectomy.

Bilateral renal infarction is an extremely rare condition with only few cases reported in the literature. We present a case of bilateral renal infarction affecting an otherwise healthy 34 year old bodybuilder chronically misusing testosterone and stanozolol. The patient presented with severe flank pain mimicking renal colic and biochemical features of acute kidney injury. Diagnostic workup revealed thrombosis affecting both renal arteries. Subsequently, the patient underwent a percutaneous rheolytic thrombectomy with AngioJet catheter, along with catheter-directed thrombolysis. Right-sided retroperitoneal hematoma developed as an early complication, mandating surgical exploration and nephrectomy due to kidney rupture and the unstable condition of the patient. Intensive care and continuous renal replacement therapy were instigated until a gradual improvement of the patient status and a return of kidney function was achieved. No abnormalities were found in the cardiological and hematological evaluation. We believe this is a first report of bilateral renal infarction associated with anabolic steroid misuse in an otherwise healthy individual, and a first report of AngioJet thrombectomy in bilateral thrombosis of renal arteries. It stresses the importance of a thorough diagnostic workup of colic patients and emphasizes the need for sports medicine to reach out to amateur athletes with education on the harms of doping.

Estanozolol como anabólico: una causa de hepatotoxicidad / Estanozol as anabolic: a cause of hepatotoxicity / Estanozolol Como Anabólico: Uma Causa De Hepatotoxicidade

Los antibióticos y analgésicos han sido descritos frecuentemente como las principales causas de toxicidad hepática. Los esteroides anabólicos se han relacionado también con alteraciones en sistemas como el cardiovascular o el hepático; en este último causan colestasis, carcinoma hepatocelular, hiperplasia regenerativa nodular y sangrado de varices, secundario a hipertensión portal. Es importante entonces considerar los esteroides anabólicos como factores de riesgo para hepatotoxicidad. Se presenta el primer caso en Colombia y uno de los pocos en Latinoamérica, de colestasis asociada únicamente al uso de estanozolol. Se trata de un paciente de 21 años, en tratamiento con el medicamento para incrementar la masa muscular, que presentó compromiso hepático de tipo colestásico. Se descartaron otras posibles causas de ictericia, mediante la escala CIOMS/RUCAM se llegó a establecer causalidad entre el consumo de estanozolol y la colestasis. El objetivo de este reporte es hacer una descripción no reportada en la literatura colombiana y poco común en la literatura mundial.

Antibiotics and pain relievers have been frequently described as the main causes of liver toxicity. Anabolic steroids have also been linked to alterations in systems such as cardio-vascular or liver. In the latter, they seem to cause cholestasis, hepatocellular carcinoma, nodular regenerative hyperplasia and variceal bleeding secondary to portal hypertension. It is important to consider them as factors associated with hepatotoxicity. The first case in Colombia and one of the few in Latin America of cholestasis associated only to the use of Stanozolol is presented in a 21-year-old patient under treatment with the drug to increase muscle mass. The patient presented with cholestatic liver involvement. Other possible causes of jaundice were ruled out. From the CIOMS / RUCAM scale, causality was established between the consumption of Stanozolol and cholestasis. The objective of this case is to report a case not found in Colombian literature and little reported in world literature.

Antibióticos e analgésicos têm sido frequentemente descritos como as principais causas de toxicidade hepática. Os esteroides anabolizantes também têm sido relacionados a alterações em sistemas como cardiovasculares ou hepáticos; neste último, causam colestase, carcinoma hepatocelular, hiperplasia nodular regenerativa e sangramento varicoso, secundário à hipertensão portal. Portanto, é importante considerar os este-roides anabolizantes como fatores de risco para hepatotoxicidade. O primeiro caso é apresentado na Colômbia e um dos poucos na América Latina, de colestase associada apenas ao uso de estanozolol. Paciente de 21 anos, em tratamento com fármaco para aumento de massa muscular, apresentou acometimento hepático colestático. Outras possíveis causas de icterícia foram descartadas, a escala CIOMS / RUCAM estabeleceu causalidade entre o consumo de estanozolol e colestase. O objetivo deste relatório é fazer uma descrição não relatada na literatura colombiana e rara na literatura mundial

Stanozolol and Danazol Have Different Effects on Hematopoiesis in the Murine Model of Immune-Mediated Bone Marrow Failure.

Background: Stanozolol and danazol are widely used in the treatment of aplastic anemia; however, their mechanisms of action are unclear. Methods: Bone marrow mononuclear cells from 10 patients newly diagnosed with aplastic anemia and 10 healthy volunteers were collected and cultured together with stanozolol, danazol, or blank control separately for marrow colony assays. K562 cell lines that had been incubated with stanozolol, danazol, or blank control were tested for erythroid or megakaryocytic differentiation. Meanwhile, CB6F1/Crl mice were injected with 1 × 106 C57BL/6 donor-originated lymphocytes after irradiation with 5 Gy total body irradiation to establish a model for immune-mediated bone marrow failure (aplastic anemia mouse model). Mice with aplastic anemia were treated with cyclosporin A monotherapy, cyclosporin A in combination with stanozolol, and cyclosporin A in combination with danazol for 30 days. Peripheral blood cell counts once a week and bone marrow colony assays at the end of 1 month were performed. The proportion of T cell subsets, level of inflammatory factors, erythropoietin, and thrombopoietin were detected before and after treatment. The levels of erythropoietin receptors on bone marrow mononuclear cells after treatment were tested using western blotting. Results: In the ex vivo experiments, the number of burst-forming units-erythroid; colony-forming units-granulocyte and macrophage; and colony-forming units-granulocyte, erythrocyte, monocyte, and megakaryocyte in the patients with aplastic anemia were significantly lower than that in the normal controls (P < 0.05). However, the number of colonies and mean fluorescence intensity of CD235a or CD41 expression in the harvested cultured cells were not significantly different among the different treatment groups in the patients with aplastic anemia, normal controls, and K562 cell lines. These results show that stanozolol and danazol produce no direct hematopoiesis-stimulating effects on progenitor cells. In the in vivo experiment, the mice with aplastic anemia treated with cyclosporin A and danazol exhibited the most rapid recovery of platelet; the platelet count returned to normal levels after 3 weeks of treatment, which was at least 1 week earlier than in the other groups. In contrast, mice treated with cyclosporin A and stanozolol exhibited the highest hemoglobin level at the end of treatment (P < 0.05). Bone marrow colony assays at 30 days showed that the number of burst-forming units-erythroid was the highest in mice treated with cyclosporin A and stanozolol, while the number of colony-forming units-granulocyte and macrophage was the highest in those treated with cyclosporin A and danazol. Compared to cyclosporin A monotherapy, additional stanozolol and danazol can both increase the level of regulatory T cells and upregulate interleukin-10, inhibiting the expression of tumor necrosis factor-α (P < 0.05). However, IL-2 was more effectively reduced by danazol than by stanozolol (P < 0.05). The cyclosporin A- and stanozolol-treated mice showed higher serum erythropoietin (corrected by hemoglobin level) and higher erythropoietin receptor levels in bone marrow mononuclear cells than the other groups (P < 0.05). Conclusions: Neither stanozolol nor danazol directly stimulated hematopoiesis in vitro. However, in vivo, stanozolol may exhibit an advantage in improving erythropoiesis, while danazol may induce stronger effects on platelets. Both danazol and stanozolol exhibited immunosuppressive roles. Stanozolol could enhance the secretion of erythropoietin and expression of erythropoietin receptor in bone marrow mononuclear cells.

Anti-Apoptotic Effects of Resistance Training and Tribulus Terrestris Consumption in the Heart Tissue of Rats Exposed to Stanozolol.

OBJECTIVE: Nowadays, the use of energetic substances has become a complex problem in sports, such that the role of anabolic-androgenic steroids is undeniable. This study aimed to investigate the antiapoptotic effect of resistance training and Tribulus terrestris in the heart tissue of rats exposed to stanozolol. MATERIALS AND METHODS: 35 rats divided into 7 groups including (1) sham, (2) stanozolol-treated, (3) stanozolol+50 mg/kg Tribulus terrestris-treated, (4) stanozolol+100 mg/kg Tribulus terrestris-treated, (5) stanozolol+resistance training-treated, (6) stanozolol+resistance training+50 mg/kg Tribulus terrestris-treated, and (7) stanozolol+resistance training+100 mg/kg Tribulus terrestris-treated. During 8 weeks, groups 2-7 received 5 mg/kg stanozolol per day peritoneally; groups 5-7 performed resistance training for 3 sessions per week; and groups 3, 4, 6 and 7 received daily doses of Tribulus terrestris peritoneally. RESULTS: Stanozolol administration significantly increased the BAX, BCL-2, P53, and caspase 3 and BAX/BCL-2 ratio (P < .001). Resistance training, 100 mg/kg Tribulus terrestris administration, 50 mg/kg Tribulus terrestris administration, resistance training+100 mg/kg Tribulus terrestris administration, and resistance training+50 mg/kg Tribulus terrestris administration significantly decreased BAX, BCL-2, P53, and caspase 3 levels and BAX/BCL-2 ratio (P < .001); however, stanozolol+resistance training+100 mg/kg Tribulus terrestris administration caused more decrease than stanozolol+resistance training+50 mg/kg Tribulus terrestris administration in BAX (P < .001). CONCLUSION: Resistance training and Tribulus terrestris administration alone appear to have antiapoptotic effects; however, resistance training combined with Tribulus terrestris administration, especially at higher doses, have more desirable effects than resistance training or Tribulus terrestris administration alone on the apoptosis markers.

Stanozolol-N-glucuronide metabolites in human urine samples as suitable targets in terms of routine anti-doping analysis.

The exogenous anabolic-androgenic steroid (AAS) stanozolol stays one of the most detected substances in professional sports. Its detection is a fundamental part of doping analysis, and the analysis of this steroid has been intensively investigated for a long time. This contribution to the detection of stanozolol doping describes for the first time the unambiguous proof for the existence of 17-epistanozolol-1'N-glucuronide and 17-epistanozolol-2'N-glucuronide in stanozolol-positive human urine samples due to the access to high-quality reference standards. Examination of excretion study samples shows large detection windows for the phase-II metabolites stanozolol-1'N-glucuronide and 17-epistanozolol-1'N-glucuronide up to 12 days and respectively up to almost 28 days. In addition, we present appropriate validation parameters for the analysis of these metabolites using a fully automatic method online solid-phase extraction (SPE) method already published before. Limits of identification (LOIs) as low as 100 pg/ml and other validation parameters like accuracy, precision, sensitivity, robustness, and linearity are given.

Stanozolol for the treatment of anemic lower-risk myelodysplastic syndromes without del(5q) after failure of epoetin alfa: findings from a retrospective study.

Options for anemic lower-risk myelodysplastic syndromes (MDS) without del(5q) after failure of erythropoiesis-stimulating agents (ESAs) are very limited. The effectiveness of second-line treatments is uncertain. We retrospectively reviewed the clinical effectiveness and overall survival (OS) of lower-risk MDS without del(5q) patients exclusively treated with stanozolol (STZ) after failure of epoetin alfa. The response was defined according to the 2006 International Working Group (IWG) criteria. Fifty-six patients were included. The median follow-up time was 55 months (range: 5-156 months). Twenty-seven patients (48.2%) achieved hematologic improvement-erythroid response (HI-E). Higher response rates were observed in patients with lower IPSS-R scores (≤3.5, P = 0.008) and hypocellular bone marrow (P = 0.002). In univariate Cox analysis, HI-E was the strongest factor associated with better OS (P = 0.0003). In multivariate Cox, HI-E, age ≤ 50, and transfusion independence (TI) at the onset of STZ were factors associated with better OS. The estimated 5-year OS was 88.6% (68.7-96.2%) and 33.8% (14.9-54.0%) in responders and non-responders (P < 0.01), respectively. The most common side effects included masculinization and liver damage, but they were manageable with supportive measures and dose adjustments. STZ may be considered an alternative treatment in lower-risk MDS after failure of epoetin alfa.

Stanozolol improves the progression-free survival of patients with high-risk myelodysplastic syndrome after decitabine treatment.

It is unknown whether adding stanozolol to decitabine for maintenance can further improve progression-free survival (PFS) and overall survival (OS) after effective decitabine treatment in patients with high-risk myelodysplastic syndrome (MDS). Patients newly diagnosed with high-risk MDS who achieved at least partial remission after 4 cycles of decitabine (20 mg/m2 days 1-5) were selected. In total, 62 patients (median age 66 years) were enrolled, of whom 21 were treated with stanozolol and decitabine for maintenance, and 41 were treated with decitabine alone. The median number of cycles for maintenance treatment was 6 (2-11) and 5 (2-12) for the stanozolol and control groups, respectively (p > 0.05). PFS in the stanozolol group was significantly longer than in the control group (15.0 vs 9.0 months, hazard ratio [HR] = 0.35, 95%CI: 0.19-0.63, p = 0.0005), whereas OS was not significantly prolonged in the stanozolol group (21.0 vs 15.0 months, HR = 0.73, 95%CI: 0.39-1.37, p = 0.33). The proportion of patients with severe neutropenia during maintenance treatment in the stanozolol group was lower than in the control group (76.2% vs 95.1%, p = 0.039). In conclusion, adding stanozolol to decitabine after effective decitabine treatment can prolong PFS and reduce the severity of neutropenia for patients with high-risk MDS.

Phase II stanozolol metabolism study using the zebrafish water tank (ZWT) model.

Stanozolol (STAN) is an androgen anabolic steroid often misused in sports competitions and prohibited at all times by the World Anti-Doping Agency (WADA). It can be long term detected by the analysis of human urine for traces of intact glucuronide metabolites. The Zebrafish Water Tank (ZWT) experimental setup can produce phase I STAN metabolites. In the present study, we investigated the in vivo phase II metabolism of STAN through the ZWT model to determine whether the ZWT produces metabolites relevant for doping control. We added STAN to a 200 mL recipient containing eight fish at 32 ± 1 °C. We analyzed the noninvasive samples (recipient water) both with and without pretreatment using Liquid Chromatography coupled with High-Resolution Mass Spectrometry (LC-HRMS/MS) in positive ionization mode. Our data show that four hydroxylated-sulfate and four hydroxylated-glycoconjugate metabolites were formed, two of the last ones being 3'OH-STAN-Glucuronide and 16ß-OH-STAN-Glucuronide. Additionally, two STAN-Glucuronide derivatives were produced: one was confirmed to be 17epi-STAN-N-Glucuronide, and the other was presumed to be STAN-O-Glucuronide. After eight hours of the experiment, STAN-O-Glucuronide was the most intense phase II metabolite produced. The accumulation curves suggest that high concentrations of fish and substrate in water are required to form phase II metabolites.

High, not low-dose of stanozolol (Anabolic - androgenic steroid) impedes embryo implantation by attenuating endometrial receptivity in the mouse, Mus musculus.

The present investigation is aimed at evaluating the efficacy of one of the anabolic -androgenic steroids, stanozolol (ST), on establishment and maintenance of pregnancy in mice. A total of 40 female mice were assigned to three experimental groups. Stanozolol was dosed subcutaneously (low-dose, 0.5 mg/kg bwt; high-dose, 5.0 mg/kg bwt or 1% alcohol-baseline control) for 30 consecutive days. On the 31st day, treatment was withdrawn. The estrous cycle was disrupted in both treatment groups and its resumption was dose dependent. Following estrous resumption, mice were allowed to mate. Results reveal that the low-dose ST-treated mice maintained gestation until term with reduced litter size, while high-dose-treated mice divulged vaginal plug at frequent intervals, indicating conception failure. Because pregnancy failure was noticed in high-dose-treated mice, they were autopsied on GD1.5 and 4.5. Interestingly, neither dose of stanozolol affected early embryonic development or blastocyst hatching. A decrease in the number of corpora lutea in both treated groups suggests it affects either ovulation or recruitment of follicles that occurs in each cycle for maturation. In high-dose-treated mice, decreased serum levels of estradiol, progesterone and increased testosterone along with downregulated endometrial expression of ERα and PR suggest the deficiency of steroid hormones and their respective receptors. Decreased ovarian expression of ERα, hyperexpression of PRLR, AR and abated progesterone secretion led to luteal dysfunction, consequently attenuating endometrial receptivity. Therefore, in high-dose-treated mice, decreased maternal estradiol and progesterone levels and their receptors during implantation hindered signaling to LIF and Hoxa-10, resulting in pragmatic implantation failure.