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Hematology. American Society of... Dec 2017Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure... (Review)
Review
Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure syndromes are still not eligible for a transplant. In addition, the availability of sequencing panels has significantly improved diagnosis by identifying cryptic inherited cases. Androgens are the main nontransplant therapy for bone marrow failure in dyskeratosis congenita and Fanconi anemia, reaching responses in up to 80% of cases. Danazol and oxymetholone are more commonly used, but virilization and liver toxicity are major adverse events. Diamond-Blackfan anemia is commonly treated with corticosteroids, but most patients eventually become refractory to this treatment and toxicity is limiting. Growth factors still have a role in inherited cases, especially granulocyte colony-stimulating factor in congenital neutropenias. Novel therapies are warranted and thrombopoietin receptor agonists, leucine, quercetin, and novel gene therapy approaches may benefit inherited cases in the future.
Topics: Androgens; Bone Marrow Diseases; Chemical and Drug Induced Liver Injury; Danazol; Female; Genetic Diseases, Inborn; Genetic Therapy; Humans; Leucine; Oxymetholone; Quercetin; Stem Cell Transplantation; Syndrome; Virilism
PubMed: 29222242
DOI: 10.1182/asheducation-2017.1.96 -
Journal of Blood Medicine 2022Bone marrow transplantation, antithymocyte globulin/cyclosporine and eltrombopag are recommended as first-line therapy of severe aplastic anemia (SAA). However,...
BACKGROUND
Bone marrow transplantation, antithymocyte globulin/cyclosporine and eltrombopag are recommended as first-line therapy of severe aplastic anemia (SAA). However, androgens could be considered as front-line treatment among any patients ineligible for better methods although unsatisfactory efficacy is presented.
OBJECTIVE
This retrospective study aimed to evaluate response and survival rate of practical-based treatment with oxymetholone.
PATIENTS AND METHODS
This constituted an analysis of patients receiving a diagnosis of acquired aplastic anemia (AA) at the age of 15 or over and receiving oxymetholone between January 2004 and December 2018. Propensity Score Analysis (PSA) 1:1 matching was performed, according to sex, age and interval from first symptom to treatment. The primary outcome was one-year overall response (OR).
RESULTS
Seventy-four patients were successfully matched by PSA. The 1-year OR of oxymetholone in the nonsevere AA (nSAA) and SAA/very severe AA (vSAA) groups was 54.1 and 13.5%, respectively (P <0.001). With median follow-up 2.7 years, the overall survival was 59.5% in nSAA and 37.8% in SAA/vSAA (P = 0.051). Median survival in nSAA and SAA/vSAA were 7.0 years and 1.8 years, respectively (P = 0.045). However, the responders of SAA/vSAA had longer survival than nonresponders of the nSAA group.
CONCLUSION
These results revealed longer survival among the responders of patients with AA, even in the SAA/vSAA group. However, close monitoring of therapeutic responses is still performed. Switching therapy is necessary when remission is undetected after 6 months of oxymetholone treatment.
PubMed: 36514313
DOI: 10.2147/JBM.S383148 -
Neuroscience and Biobehavioral Reviews May 2019Supraphysiologic-dose anabolic-androgenic steroid (AAS) use is associated with physiologic, cognitive, and brain abnormalities similar to those found in people at risk... (Review)
Review
Supraphysiologic-dose anabolic-androgenic steroid (AAS) use is associated with physiologic, cognitive, and brain abnormalities similar to those found in people at risk for developing Alzheimer's Disease and its related dementias (AD/ADRD), which are associated with high brain β-amyloid (Aβ) and hyperphosphorylated tau (tau-P) protein levels. Supraphysiologic-dose AAS induces androgen abnormalities and excess oxidative stress, which have been linked to increased and decreased expression or activity of proteins that synthesize and eliminate, respectively, Aβ and tau-P. Aβ and tau-P accumulation may begin soon after initiating supraphysiologic-dose AAS use, which typically occurs in the early 20s, and their accumulation may be accelerated by other psychoactive substance use, which is common among non-medical AAS users. Accordingly, the widespread use of supraphysiologic-dose AAS may increase the numbers of people who develop dementia. Early diagnosis and correction of sex-steroid level abnormalities and excess oxidative stress could attenuate risk for developing AD/ADRD in supraphysiologic-dose AAS users, in people with other substance use disorders, and in people with low sex-steroid levels or excess oxidative stress associated with aging.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Androgens; Animals; Brain; Dementia; Humans; Hypogonadism; Oxidative Stress; Phosphorylation; Risk Factors; Testosterone Congeners; tau Proteins
PubMed: 30817935
DOI: 10.1016/j.neubiorev.2019.02.014 -
Diseases (Basel, Switzerland) Jun 2023Oxymetholone is one of the anabolic steroids that has widely been used among teenagers and athletes to increase their muscle bulk. It has undesirable effects on male...
Oxymetholone is one of the anabolic steroids that has widely been used among teenagers and athletes to increase their muscle bulk. It has undesirable effects on male health and fertility. In this study, the therapeutic effects of platelet-rich plasma (PRP) on oxymetholone-induced testicular toxicity were investigated in adult albino rats. During the experiments, 49 adult male albino rats were divided into 4 main groups: Group 0 (donor group) included 10 rats for the donation of PRP, Group I (control group) included 15 rats, Group II included 8 rats that received 10 mg/kg of oxymetholone orally, once daily, for 30 days, and Group III included 16 rats and was subdivided into 2 subgroups (IIIa and IIIb) that received oxymetholone the same as group II and then received PRP once and twice, respectively. Testicular tissues of all examined rats were obtained for processing and histological examination and sperm smears were stained and examined for sperm morphology. Oxymetholone-treated rats revealed wide spaces in between the tubules, vacuolated cytoplasm, and dark pyknotic nuclei of most cells, as well as deposition of homogenous acidophilic material between the tubules. Electron microscopic examination showed vacuolated cytoplasm of most cells, swollen mitochondria, and perinuclear dilatation. Concerning subgroup IIIa (PRP once), there was a partial improvement in the form of decreased vacuolations and regeneration of spermatogenic cells, as well as a reasonable improvement in sperm morphology. Regarding subgroup IIIb (PRP twice), histological sections revealed restoration of the normal testicular structure to a great extent, regeneration of the spermatogenic cells, and most sperms had normal morphology. Thus, it is recommended to use PRP to minimize structural changes in the testis of adult albino rats caused by oxymetholone.
PubMed: 37366872
DOI: 10.3390/diseases11020084 -
BioRxiv : the Preprint Server For... Aug 2023Fanconi Anemia (FA) is a disease caused by defective DNA repair which manifests as bone marrow failure, cancer predisposition, and developmental defects. Mice containing...
Fanconi Anemia (FA) is a disease caused by defective DNA repair which manifests as bone marrow failure, cancer predisposition, and developmental defects. Mice containing inactivating mutations in one or more genes in the FA pathway partially mimic the human disease. We previously reported that monotherapy with either metformin (MET) or oxymetholone (OXM) improved peripheral blood (PB) counts and the number and functionality of bone marrow (BM) hematopoietic stem progenitor cells (HSPCs) number in mice. To evaluate whether the combination treatment of these drugs has a synergistic effect to prevent bone marrow failure in FA, we treated cohorts of mice and wild-type controls with either MET alone, OXM alone, MET+OXM or placebo diet. Both male and female mice were treated from age 3 weeks to 18 months. The OXM treated animals showed modest improvements in blood parameters including platelet count (p=0.01) and hemoglobin levels (p<0.05). In addition, the percentage of quiescent HSC (LSK) was significantly increased (p=0.001) by long-term treatment with MET alone. However, the absolute number of progenitors, measured by LSK frequency or CFU-S, was not significantly altered by MET therapy. The combination of metformin and oxymetholone did not result in a significant synergistic effect on any parameter. Male animals on MET+OXM or MET alone were significantly leaner than controls at 18 months, regardless of genotype. Gene expression analysis of liver tissue from these animals showed that some of the expression changes caused by deletion were partially normalized by metformin treatment. Importantly, no adverse effects of the individual or combination therapies were observed, despite the long-term administration.
PubMed: 37649908
DOI: 10.1101/2023.08.16.553572 -
The Cochrane Database of Systematic... Oct 2014Anaemia occurs when blood contains fewer red blood cells and lower haemoglobin levels than normal, and is a common complication among adults with chronic kidney disease... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anaemia occurs when blood contains fewer red blood cells and lower haemoglobin levels than normal, and is a common complication among adults with chronic kidney disease (CKD). Although a number of approaches are applied to correct anaemia in adults with CKD, the use of androgen therapy is controversial.
OBJECTIVES
The aim of this review was to determine the benefits and harms of androgens for the treatment of anaemia in adult patients with CKD.
SEARCH METHODS
We searched CENTRAL, the Cochrane Renal Group's Specialised Register, the Chinese Biomedicine Database (CBM), CNKI, VIP and reference lists of articles without language restriction. The most recent search was conducted in August 2014.
SELECTION CRITERIA
All randomised controlled trials (RCTs) that assessed the use of androgens for treating anaemia of CKD in adults were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed risk of bias in the included studies. Meta-analyses were performed using relative risk (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI).
MAIN RESULTS
We included eight studies that reported data from 181 participants. Study quality was assessed as moderate in six studies, one was low quality, and one was high quality. The small number of included studies, and low participant numbers adversely influenced evidence quality overall.We found limited evidence (1 study, 24 participants) to indicate that oxymetholone can increase haemoglobin (Hb) (MD 1.90 g/dL, 95% CI 1.66 to 2.14), haematocrit (HCT) (MD 27.10%, 95% CI 26.49 to 27.71), change in albumin (MD 4.91 g/L, 95% CI 3.69 to 6.13), alanine aminotransferase (ALT) (MD 54.50 U/L, 95% CI 43.94 to 65.06), and aspartate aminotransferase (AST) (MD 47.33 U/L, 95% CI 37.69 to 56.97); and decrease high-density lipoprotein (HDL) (MD -15.66 mg/dL, 95% CI -24.84 to -6.48). We also found that compared with erythropoietin alone, nandrolone decanoate plus erythropoietin may increase HCT (3 studies, 73 participants: MD 2.54%, 95% Cl 0.96 to 4.12). Compared with erythropoietin (1 study, 27 participants), limited evidence was found to suggest that nandrolone decanoate can increase plasma total protein (MD 0.40 g/L, 95% CI 0.13 to 0.67), albumin (MD 0.20 g/L, 95% CI 0.01 to 0.39), and transferrin (MD 45.00 mg/dL, 95% CI 12.61 to 77.39) levels. Compared with no therapy (remnant kidney), evidence was found to suggest that nandrolone decanoate can increase Hb (2 studies, 33 participants: MD 1.04 g/dL, 95% Cl 0.66 to 1.41) and HCT (1 study, 24 participants: MD 3.70%, 95% Cl 0.68 to 6.72). Compared with no therapy (anephric), evidence was found (1 study, 5 participants) to suggest that nandrolone decanoate can increase Hb (MD 1.30 g/dL, 95% Cl 0.57 to 2.03), but nandrolone decanoate did not increase HCT (MD 2.00%, 95% Cl -0.85 to 4.85).However, oxymetholone was not found to reduce blood urea nitrogen (BUN), serum creatinine (SCr), cholesterol, or triglycerides; or increase plasma total protein, prealbumin, or transferrin. No evidence was found to indicate that nandrolone decanoate increased prealbumin or decreased BUN, SCr, AST, ALT, cholesterol, triglycerides, HDL or low-density lipoprotein (LDL). Adverse events associated with androgen therapy were reported infrequently.
AUTHORS' CONCLUSIONS
We found insufficient evidence to confirm that use of androgens for adults with CKD-related anaemia is beneficial.
Topics: Adult; Androgens; Anemia; Cholesterol; Erythropoietin; Hematocrit; Humans; Nandrolone; Nandrolone Decanoate; Oxymetholone; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Triglycerides
PubMed: 25300168
DOI: 10.1002/14651858.CD006881.pub2 -
Food & Nutrition Research 2023A proprietary combination of fruit rind and leaf extracts (LI80020F4, CinDura) improved the physical performance and muscle strength of resistance-trained adult males.
BACKGROUND
A proprietary combination of fruit rind and leaf extracts (LI80020F4, CinDura) improved the physical performance and muscle strength of resistance-trained adult males.
OBJECTIVE
This study assessed the underlying mechanisms of the ergogenic potential of LI80020F4 in and models.
METHODS
The individual extracts and their combination (LI80020F4) were assessed for nitrite production in EAhy926 human endothelial cells. Subsequent experiments evaluated the effect of LI80020F4 in myotube formation in C2C12 mouse myoblasts, expression of mammalian target of rapamycin (mTOR) signaling proteins, myogenic factors, and mitochondrial functions in L6 rat myoblasts.Moreover, adult male ICR mice were randomly assigned ( = 15) into vehicle control (G1), exercise alone (G2), oxymetholone-16 mg/kg body weight (bw) (G3), and 75 (G4)-, 150 (G5)-, or 300 (G6) mg/kg bw of LI80020F4, orally gavaged for 28 days. G1 and G2 mice received 0.5% carboxymethylcellulose sodium. Following completion, muscle strength and physical performance were assessed on forelimb grip strength and forced swimming test (FST), respectively. Gastrocnemius (GA), tibialis anterior (TA) muscle weights, muscle fiber cross-sectional area (CSA), levels of muscle, and serum protein markers were also determined.
RESULTS
LI80020F4 increased nitrite production in EAhy926 cells in a dose-dependent manner. LI80020F4 induced C2C12 myotube formation, increased mitochondrial biogenesis, upregulated the expressions of activated mTOR and other mitochondria and myogenic proteins, and mitigated HO-induced mitochondrial membrane depolarization in the myoblast cells. In the animal study, 75, 150, and 300 mg/kg bw LI80020F4 doses significantly ( < 0.05) increased the animals' forelimb grip strength. Mid- and high-dose groups showed increased swimming time, increased muscle weight, CSA, muscle growth-related, and mitochondrial protein expressions in the GA muscles.
CONCLUSION
LI80020F4 increases nitric oxide production in the endothelial cells, mitochondrial biogenesis and function, upregulates skeletal muscle growth-related protein expressions and reduces oxidative stress; together, it explains the basis of the ergogenic potential of LI80020F4.
PubMed: 37920678
DOI: 10.29219/fnr.v67.9750 -
Caspian Journal of Internal Medicine 2018The prevalence of using anabolic steroids such as oxymetholone is increasing. This highlights the need for closely monitoring side effects of this drug. Acute renal...
BACKGROUND
The prevalence of using anabolic steroids such as oxymetholone is increasing. This highlights the need for closely monitoring side effects of this drug. Acute renal failure (ARF) has been reported as a complication of rhabdomyolysis in anabolic steroids users.
CASE PRESENTATION
We present one 33-year-old man complaining of decreased urine volume, urine color change, and lower abdominal pain. He is engaged with a rare side effect of oxymetholone abuse. During assessments of potential medical issues associated with the intake of anabolic steroids, known side effects are known to be transient, but the need for appropriate interventions remains essential.
CONCLUSIONS
Rhabdomyolysis due to drug use and the consequent acute kidney injury are among the lethal risks associated with anabolic steroid abuse. In most cases, the symptoms are extensive and often misleading. Therefore, detailed history taking, physical scrutiny, paraclinical testing, and early diagnosis are crucial for rhabdomyolysis patients.
PubMed: 30510659
DOI: 10.22088/cjim.9.4.406