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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 -
Pediatric Blood & Cancer Aug 2024Fanconi anemia (FA) is a disease caused by defective deoxyribonucleic acid (DNA) repair that manifests as bone marrow failure, cancer predisposition, and developmental...
Fanconi anemia (FA) is a disease caused by defective deoxyribonucleic acid (DNA) repair that manifests as bone marrow failure, cancer predisposition, and developmental defects. 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 hematopoietic stem progenitor cells (HSPCs) number in Fancd2 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 Fancd2 mice and wildtype controls with either MET alone, OXM alone, MET+OXM, or placebo diet from age 3 weeks to 18 months. The OXM treated animals showed modest improvements in blood parameters including platelet count (p = .01) and hemoglobin levels (p < .05). In addition, the percentage of quiescent hematopoietic stem cell (HSC) (LSK [LinScac-Kit]) was significantly increased (p = .001) by long-term treatment with MET alone. The combination of metformin and oxymetholone did not result in a significant synergistic effect in any hematopoietic parameter. Gene expression analysis of liver tissue from these animals showed that some of the expression changes caused by Fancd2 deletion were partially normalized by metformin treatment. Importantly, no adverse effects of the individual or combination therapies were observed, despite the long-term administration. We conclude that androgen therapy is not a contraindication to concurrent metformin administration in clinical trials. HIGHLIGHTS: Long-term coadministration of metformin in combination with oxymetholone is well tolerated by Fancd2 mice. Hematopoietic stem cell quiescence in mutant mice was enhanced by treatment with metformin alone. Metformin treatment caused a partial normalization of gene expression in the livers of mutant mice.
Topics: Animals; Metformin; Mice; Fanconi Anemia; Oxymetholone; Disease Models, Animal; Drug Therapy, Combination; Fanconi Anemia Complementation Group D2 Protein; Mice, Knockout; Hematopoietic Stem Cells
PubMed: 38733122
DOI: 10.1002/pbc.31030 -
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 -
Steroids Oct 2019A long-term metabolite of the doping agent oxymetholone (OXM-M2, 17β-hydroxymethyl-2,17α-methyl-18-norandrost-13-en-3-one) which has been identified by GC-MS/MS was...
A long-term metabolite of the doping agent oxymetholone (OXM-M2, 17β-hydroxymethyl-2,17α-methyl-18-norandrost-13-en-3-one) which has been identified by GC-MS/MS was synthesized from commercially available materials. Two efficient synthetic routes to access both C-17 epimers of tentative metabolites were developed. The identity and molecular configuration of the in vivo metabolite: 17β-hydroxymethyl-2α,17α-methyl-18-norandrost-13-en-3-one was confirmed by single crystal X-ray diffraction.
Topics: Crystallography, X-Ray; Humans; Models, Molecular; Molecular Conformation; Oxymetholone
PubMed: 31229510
DOI: 10.1016/j.steroids.2019.108430 -
Biochemical Pharmacology Feb 2020Anabolic-androgenic steroids (AAS) are testosterone derivatives developed for steroid-replacement and treatment of debilitating conditions. They are widely used by...
Anabolic-androgenic steroids (AAS) are testosterone derivatives developed for steroid-replacement and treatment of debilitating conditions. They are widely used by athletes in elite sports and bodybuilding due to their muscle-building and performance-enhancing properties. Excessive AAS use is associated with cardiovascular diseases, mood changes, endocrine and metabolic disorders; however, the underlying mechanisms remain unknown. Selective androgen receptor modulators (SARMs) aim to reduce adverse androgenic effects, while maximizing anabolic effects. This study assessed potential steroidogenic disturbances of 19 AAS and 3 SARMs in human adrenocortical carcinoma H295R cells, comparing basal and forskolin-activated states by mass spectrometry-based quantification of nine major adrenal steroids. Mesterolone, mestanolone and methenolone increased mineralocorticoid but decreased adrenal androgen production, indicating CYP17A1 dysfunction. Cell-free activity assays failed to detect direct CYP17A1 inhibition, supported by molecular modeling. The mRNA expression levels of 3β-HSD2, CYP17A1, CYP21A2, CYP11B1 and CYP11B2 were unaffected, suggesting indirect inhibition involving post-translational modification and/or impaired protein stability. Clostebol and oxymetholone decreased corticosteroid but increased dehydroepiandrosterone biosynthesis in H295R cells, suggesting CYP21A2 inhibition, sustained by molecular modeling. These AAS did not affect the expression of key steroidogenic genes. None of the SARMs tested interfered with steroidogenesis. The chosen approach allowed the grouping of AAS according to their steroidogenic-disrupting effects and provided initial mechanistic information. Mesterolone, mestanolone and methenolone potentially promote hypertension and cardiovascular diseases via excessive mineralocorticoid biosynthesis. Clostebol and oxymetholone might cause metabolic disturbances by suppressing corticosteroid production, resulting in adrenal hyperplasia. The non-steroidal SARMs exhibit an improved safety profile and represent a preferred therapeutic option.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Anabolic Agents; Androgens; Cell Line, Tumor; Cell Survival; Cytochrome P-450 Enzyme System; Gene Expression Regulation; Humans
PubMed: 31884045
DOI: 10.1016/j.bcp.2019.113781 -
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 -
Andrologia Dec 2021This study was aimed to investigate the protective effects of Lepidium draba L. (L. draba) extract on oxymetholone (OM)-induced testicular injury in rat. Six groups of...
Protective effects of Lepidium draba L. leaves extract on testis histopathology, oxidative stress indicators, serum reproductive hormones and inflammatory signalling in oxymetholone-treated rat.
This study was aimed to investigate the protective effects of Lepidium draba L. (L. draba) extract on oxymetholone (OM)-induced testicular injury in rat. Six groups of n = 5 adult male rats were used as; 1: control, 2: OM (5 mg/kg OM orally), 3, 4 and 5: L. draba extract (100, 200 and 400 mg kg day ) +OM (5 mg kg day OM) and 6:400 mg/kg/d L. draba extract for 30 days. Serum testosterone (T), follicle-stimulating hormone (FSH) and luteinising hormone (LH), inflammatory cytokines (IL-6, IL-10, TNF-α, IL-1β), oxidative stress (OS) indicators [superoxide dismutase, catalase, glutathione peroxidase and nitric oxide (NO)], apoptotic related genes (Bcl-2, p53, caspase-3 (c3) and Bax) were investigated. OM significantly increased the serum levels of T, proinflammatory cytokines and pro-apoptotic genes expression. Also, it decreased LH and FSH, sperm viability, count and motility. L. draba extract especially could markedly normalise the serum levels of LH and FSH, and T, restore serum antioxidant enzymes and suppressed the pro-inflammatory cytokines. Also, germ cells apoptosis was inhibited against via downregulating the p53, c3, Bax and upregulating Bcl-2. It concluded that L. draba extract could protect the function and structure of testis against OM-induced testicular toxicity via its antioxidant and anti-inflammatory properties.
Topics: Animals; Lepidium; Luteinizing Hormone; Oxidative Stress; Oxymetholone; Plant Extracts; Plant Leaves; Rats; Testis
PubMed: 34520070
DOI: 10.1111/and.14239 -
Stem Cell Reports Jan 2015Androgens are widely used for treating Fanconi anemia (FA) and other human bone marrow failure syndromes, but their mode of action remains incompletely understood. Aged...
Androgens are widely used for treating Fanconi anemia (FA) and other human bone marrow failure syndromes, but their mode of action remains incompletely understood. Aged Fancd2(-/-) mice were used to assess the therapeutic efficacy of oxymetholone (OXM) and its mechanism of action. Eighteen-month-old Fancd2(-/-) mice recapitulated key human FA phenotypes, including reduced bone marrow cellularity, red cell macrocytosis, and peripheral pancytopenia. As in humans, chronic OXM treatment significantly improved these hematological parameters and stimulated the proliferation of hematopoietic stem and progenitor cells. RNA-Seq analysis implicated downregulation of osteopontin as an important potential mechanism for the drug's action. Consistent with the increased stem cell proliferation, competitive repopulation assays demonstrated that chronic OXM therapy eventually resulted in stem cell exhaustion. These results expand our knowledge of the regulation of hematopoietic stem cell proliferation and have direct clinical implications for the treatment of bone marrow failure.
Topics: Animals; Blood Cell Count; Bone Marrow; Cell Cycle; Cell Proliferation; Disease Models, Animal; Fanconi Anemia; Fanconi Anemia Complementation Group D2 Protein; Gene Expression Regulation; Hematopoiesis; Hematopoietic Stem Cells; Humans; Mice; Mice, Knockout; Osteopontin; Oxymetholone; Pancytopenia; Sequence Analysis, RNA; Time Factors; Transcription, Genetic
PubMed: 25434823
DOI: 10.1016/j.stemcr.2014.10.014 -
Andrologia Apr 2020Anabolic androgenic steroids (AAS) such as oxymetholone (OM) used for athletic enhancement, but increased free radicals damage and changes in hormonal levels, lead to...
The effects of hydroalcoholic extract of Vaccinium arctostaphylos L. on sperm parameters, oxidative injury and apoptotic changes in oxymetholone-induced testicular toxicity in mouse.
Anabolic androgenic steroids (AAS) such as oxymetholone (OM) used for athletic enhancement, but increased free radicals damage and changes in hormonal levels, lead to serious and irreversible organ damage. Vaccinium arctostaphylos(V. arctostaphylos( has been demonstrated to have antioxidant and antiinflammatory effects. The aim of present study was to investigate V. arctostaphylos effect on OM-induced oxidative injury in mouse testis and sperm parameters. In this experimental study, 30 BALB/c mice were divided into five groups, including healthy, positive control(5 mg/kg OM) and three treatment groups (100, 200 and 400 mg/kg of V. arctostaphylos extract + 5 mg/kg OM). At the end of the study, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels were measured. Testis stereological and sperm parameters were calculated. Antioxidant status was measured using nitric oxide (NO) and FRAP assay, and malondialdehyde (MDA) levels. Furthermore, the expression of p53, caspase-3, Bax and Bcl-2 was measured. V. arctostaphylos decreased the serum level of testosterone, increased the LH and FSH, and improved the stereological and sperm parameters and down-regulated the p53, caspase-3 and Bax and up-regulated Bcl-2 genes. Furthermore, this dose decreased serum levels of NO and increased testis FRAP and MDA levels in treated groups compared with OM group. V. arctostaphylos extract has protective effects against testicular toxicity caused by OM.
Topics: Animals; Apoptosis; Cell Survival; Disease Models, Animal; Ethanol; Fruit; Humans; Infertility, Male; Male; Mice; Oxidative Stress; Oxymetholone; Plant Extracts; Protective Agents; Sperm Count; Sperm Motility; Testis; Vaccinium; Water
PubMed: 32012329
DOI: 10.1111/and.13522 -
International Journal of Molecular... Sep 2020Dyskeratosis congenita (DKC) is a rare inherited disease of impaired telomere maintenance that progressively leads to multi-organ failure, including the bone marrow. By...
Comparable Effects of the Androgen Derivatives Danazol, Oxymetholone and Nandrolone on Telomerase Activity in Human Primary Hematopoietic Cells from Patients with Dyskeratosis Congenita.
Dyskeratosis congenita (DKC) is a rare inherited disease of impaired telomere maintenance that progressively leads to multi-organ failure, including the bone marrow. By enhancing telomerase activity, androgen derivatives (ADs) are a potential therapeutic option able to re-elongate previously shortened telomeres. Danazol, oxymetholone, and nandrolone are ADs most frequently used to treat DKC. However, no direct in vitro analyses comparing the efficacy of these ADs have been conducted so far. We therefore treated mononuclear cells derived from peripheral blood and bone marrow of four patients with mutations in telomerase reverse transcriptase (, = 1),in the telomerase RNA component (TERC, = 2) and in dyskerin pseudouridine synthase 1 (, = 1) and found no substantial differences in the activity of these three agents in patients with mutations. All AD studied produced comparable improvements of proliferation rates as well as degrees of telomere elongation. Increased expression levels were shown with danazol and oxymetholone. The beneficial effects of all ADs on proliferation of bone marrow progenitors could be reversed by tamoxifen, an estrogen antagonist abolishing estrogen receptor-mediated expression, thereby underscoring the involvement of in AD mechanism of action. In conclusion, no significant differences in the ability to functionally enhance telomerase activity could be observed for the three AD studied in vitro. Physicians therefore might choose treatment based on patients' individual co-morbidities, e.g., pre-existing liver disease and expected side-effects.
Topics: Androgens; Cell Cycle Proteins; Danazol; Dyskeratosis Congenita; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Mutation; Nandrolone; Nuclear Proteins; Oxymetholone; Primary Cell Culture; RNA; Telomerase; Telomere
PubMed: 33003434
DOI: 10.3390/ijms21197196