Differential benefits of steroid therapies in adults following major burn injury.

BACKGROUND: Major thermal injury induces a complex pathophysiological state characterized by burn shock and hypercatabolism. Steroids are used to modulate these post-injury responses. However, the effects of steroids on acute post-burn outcomes remain unclear. METHODS: In this study of 52 thermally injured adult patients (median total burn surface area 42%, 33 males and 19 females), the effects of corticosteroid and oxandrolone on mortality, multi-organ failure (MOF), and sepsis were assessed individually. Clinical data were collected at days 1, 3, 7, and 14 post-injury. RESULTS: Twenty-two (42%) and 34 (65%) burns patients received corticosteroids and oxandrolone within the same cohort, respectively. Following separate analysis for each steroid, corticosteroid use was associated with increased odds of in-hospital mortality (OR 3.25, 95% CI: 1.32-8•00), MOF (OR 2.36, 95% CI: 1.00-1.55), and sepsis (OR 5.95, 95% CI: 2.53-14.00). Days alive (HR 0.32, 95% CI: 0.18-0.60) and sepsis-free days (HR 0.54, 95% CI: 0.37-0.80) were lower among corticosteroid-treated patients. Oxandrolone use was associated with reduced odds of 28-day mortality (OR 0.11, 95% CI: 0.04-0.30), in-hospital mortality (OR 0.19, 95% CI: 0.08-0.43), and sepsis (OR 0.24, 95% CI: 0.08-0.69). Days alive, at 28 days (HR 6.42, 95% CI: 2.77-14.9) and in-hospital (HR 3.30, 95% CI: 1.93-5.63), were higher among the oxandrolone-treated group. However, oxandrolone was associated with increased MOF odds (OR 7.90, 95% CI: 2.89-21.60) and reduced MOF-free days (HR 0.23, 95% CI: 0.11-0.50). CONCLUSION: Steroid therapies following major thermal injury may significantly affect patient prognosis. Oxandrolone was associated with better outcomes except for MOF. Adverse effects of corticosteroids and oxandrolone should be considered when managing burn patients.

The Protective Effect of Metformin against Oxandrolone-Induced Infertility in Male Rats.

BACKGROUND: Oxandrolone is a synthetic testosterone analog that is widely used among bodybuilders and athletes. However, oxandrolone causes male infertility. Recently, it was found that metformin reduces the risk of infertility associated with diabetes mellitus. AIM: This study aimed to investigate the protective effects of metformin against oxandrolone-induced infertility in male rats. METHODS: Rats continuously received one of four treatments (n=7) over 14 days: control DMSO administration, oxandrolone administration, metformin administration, or co-administration of oxandrolone and metformin. Doses were equivalent to those used for human treatment. Subsequently, testicular and blood samples were collected for morphological, biochemical, and histological examination. In addition, gene expression of the testosterone synthesizing enzyme CYP11A1 was analyzed in the testes using RT-PCR. RESULTS: Oxandrolone administration induced male infertility by significantly reducing relative weights of testes by 48%, sperm count by 82%, and serum testosterone levels by 96% (ANOVA, P value < 0.05). In addition, histological examination determined that oxandrolone caused spermatogenic arrest, which was associated with 2-fold downregulation of testicular CYP11A1 gene expression. However, co-administration of metformin with oxandrolone significantly ameliorated toxicological alterations induced by oxandrolone exposure (ANOVA, P-value < 0.05). CONCLUSION: Metformin administration provided protection against oxandrolone-induced infertility in male rats. Further clinical studies are needed to confirm the protective effect of metformin against oxandrolone-induced infertility among athletes.

Metabolism of oral turinabol by the human brain cholesterol 24-hydroxylase CYP46A1.

The human microsomal cytochrome P450 enzyme CYP46A1 plays a crucial role in cholesterol elimination from the brain. It performs a 24-hydroxylation of cholesterol and is of outstanding significance for memory and cognition. This study demonstrates the catalytic activity of human CYP46A1 towards an anabolic androgenic steroid, oral turinabol (dehydrochloromethyltestosterone, 4-chloro-17ß-dihydroxy,17α-methylandrosta-1,4-dien-3-one), which is a doping substance. CYP46A1 is the first human microsomal steroid-converting P450 showing activity towards this xenobiotic compound. Furthermore, the inhibitory effect of oral turinabol on the cholesterol conversion has been investigated in vitro demonstrating competition of the two substrates on the active site of CYP46A1 which might be of importance for potential pathogenic effects of oral turinabol. The conversion of oral turinabol was found to be selective resulting in the formation of only one product, as shown by HPLC analysis. To produce sufficient amounts of this product for NMR analysis, a system expressing human full-length CYP46A1 and CPR on a bicistronic vector was successfully developed realizing the selective cholesterol 24-hydroxylation in E. coli in mg amounts. Using this novel whole-cell system, the conversion of oral turinabol was performed and the product of this conversion by CYP46A1 was isolated and identified as 16ß-hydroxy oral turinabol by NMR.

Oxandrolone protects against the development of multiorgan failure, modulates the systemic inflammatory response and promotes wound healing during burn injury.

Oxandrolone is a synthetic oral non-aromatizable testosterone derivative. This drug has been used successfully for several decades to safely treat growth delays in various diseases including Turner's syndrome. Currently the use of oxandrolone is under clinical testing in children with burn injury; the available data indicate that the anabolic steroid increases net muscle protein balance, maintains lean body mass, and reduces intensive care unit stay. Although oxandrolone is already in clinical trials in burn patients, preclinical burn-related studies with oxandrolone - especially those that go beyond muscle-related parameters and focus on burn-associated organ dysfunction, inflammatory response and wound healing - remain to be conducted. In the current project, using a well-characterized murine model of third-degree burn, we have tested the effect of oxandrolone on indices of organ injury, clinical chemistry parameters and plasma levels of inflammatory mediators. In oxandrolone-treated mice (1mg/kg/day for up to 21 days) there was a significant amelioration of burn-induced accumulation of myeloperoxidase levels in heart and lung (but not the liver and kidney) and significantly lower degree of malon dialdehyde accumulation in the liver (but not the heart, lung and kidney). Oxandrolone-treated mice showed a significant attenuation of the burn-induced elevation in circulating alkaline aminotransferase and amylase levels, while blood urea nitrogen and creatinine levels remained unaffected, indicative of protective effects of the anabolic hormone against burn-induced hepatic and pancreatic (but not renal) functional impairment. Multiple burn-induced inflammatory mediators (TNF-α, IL-1α, IL-1ß, IL-4, IL-6, IL-10, IL-12, IP-10, G-CSF, GM-CSF and interferon-γ) were significantly lower in the plasma of oxandrolone-treated animals after burn injury than in the plasma of controls subjected to burns. Finally, oxandrolone significantly accelerated burn wound healing. We conclude that oxandrolone improves organ function, modulates the systemic inflammatory response and accelerates wound healing in a murine model of burn injury.

Androgen treatment effects on hippocampus structure in boys with Klinefelter syndrome.

Klinefelter syndrome (KS, 47,XXY) is the most common sex chromosome aneuploidy in males. A variety of complex clinical needs is associated with KS, including physical, cognitive and psychosocial impairments. Standard treatment for KS consists of androgen replacement therapy in adolescence to offset testosterone deficiency. Such treatment has a beneficial effect on the physical and behavioral manifestations of this syndrome. Whether androgen supplementation has a significant influence on the brain, however, is unknown. In the current study, we examined regional gray matter volume in boys with KS to assess whether treatment with oxandrolone, a synthetic hormone analog of testosterone, was associated with structural changes in the brain. Specifically, we focused our investigation on the hippocampus, given (1) its involvement in KS, and (2) the high concentration of androgen receptors found in this region. Structural magnetic resonance imaging data was acquired from a subsample of boys who completed a 2-year double-blind clinical trial in which patients were randomized to treatment with oxandrolone or to placebo, as well as from a sample of typically developing (TD) boys. Group differences in hippocampal volume were examined. A significant main effect of group was observed. Pairwise comparisons indicated smaller hippocampal volume in the placebo group relative to the oxandrolone group, as well as smaller volume in the placebo group relative to the TD control group. No difference in volume was observed between the treatment and TD groups. Moreover, across KS subgroups, a significant positive association was observed between hippocampus volume and performance on a spatial memory task, indicating treatment-based changes in brain structure may underlie cognitive change. These findings confirm prior reports implicating a role of the hippocampus in KS and are important in extending previous research by demonstrating a significant effect of androgens on brain structure.

Novel Uses for the Anabolic Androgenic Steroids Nandrolone and Oxandrolone in the Management of Male Health.

There has recently been renewed interest in novel clinical applications of the anabolic-androgenic steroid (AAS) testosterone and its synthetic derivatives, particularly given with the rising popularity of testosterone supplementation therapy (TST) for the treatment of male hypogonadism. In this manuscript, we provide a brief review of the history of AAS and discuss clinical applications of two of the more well-known AAS: nandrolone and oxandrolone. Both agents exhibit favorable myotrophic/androgenic ratios and have been investigated for effectiveness in numerous disease states. We also provide a brief synopsis of selective androgen receptor modulators (SARMs) and postulate how these orally active, non-aromatizing, tissue-selective agents might be used in contemporary andrology. Currently, the applications of testosterone alternatives in hypogonadism are limited. However, it is tempting to speculate that these agents may one day become accepted as alternatives, or adjuncts, to the treatment of male hypogonadism.

Long-term effects of oxandrolone treatment in childhood on neurocognition, quality of life and social-emotional functioning in young adults with Turner syndrome.

Turner syndrome (TS) is the result of (partial) absence of one X-chromosome. Besides short stature, gonadal dysgenesis and other physical aspects, TS women have typical psychological features. Since psychological effects of androgen exposure in childhood probably are long-lasting, we explored long-term psychological functioning after oxandrolone (Ox) therapy during childhood in adults with TS in terms of neurocognition, quality of life and social-emotional functioning. During the initial study, girls were treated with growth hormone (GH) combined with placebo (Pl), Ox 0.03 mg/kg/day, or Ox 0.06 mg/kg/day from the age of eight, and estrogen from the age of twelve. Sixty-eight women participated in the current double-blinded follow-up study (mean age 24.0 years, mean time since stopping GH/Ox 8.7 years). We found no effects on neurocognition. Concerning quality of life women treated with Ox had higher anxiety levels (STAI 37.4 ± 8.4 vs 31.8 ± 5.0, p=0.002) and higher scores on the depression subscale of the SCL-90-R (25.7 ± 10.7 vs 20.5 ± 4.7, p=0.01). Regarding social-emotional functioning, emotion perception for fearful faces was lower in the Ox-treated patients, without effect on interpersonal behavior. Our exploratory study is the first to suggest that androgen treatment in adolescence possibly has long-term effects on adult quality of life and social-emotional functioning. However, differences are small and clinical implications of our results seem limited. Therefore we would not recommend against the use of Ox in light of psychological consequences.

Five-year outcomes after oxandrolone administration in severely burned children: a randomized clinical trial of safety and efficacy.

BACKGROUND: Oxandrolone, an anabolic agent, has been administered for 1 year post burn with beneficial effects in pediatric patients. However, the long-lasting effects of this treatment have not been studied. This single-center prospective trial determined the long-term effects of 1 year of oxandrolone administration in severely burned children; assessments were continued for up to 4 years post therapy. STUDY DESIGN: Patients 0 to 18 years old with burns covering >30% of the total body surface area were randomized to receive placebo (n = 152) or oxandrolone, 0.1 mg/kg twice daily for 12 months (n = 70). At hospital discharge, patients were randomized to a 12-week exercise program or to standard of care. Resting energy expenditure, standing height, weight, lean body mass, muscle strength, bone mineral content (BMC), cardiac work, rate pressure product, sexual maturation, and concentrations of serum inflammatory cytokines, hormones, and liver enzymes were monitored. RESULTS: Oxandrolone substantially decreased resting energy expenditure and rate pressure product, increased insulin-like growth factor-1 secretion during the first year after burn injury, and, in combination with exercise, increased lean body mass and muscle strength considerably. Oxandrolone-treated children exhibited improved height percentile and BMC content compared with controls. The maximal effect of oxandrolone was found in children aged 7 to 18 years. No deleterious side effects were attributed to long-term administration. CONCLUSIONS: Administration of oxandrolone improves long-term recovery of severely burned children in height, BMC, cardiac work, and muscle strength; the increase in BMC is likely to occur by means of insulin-like growth factor-1. These benefits persist for up to 5 years post burn.

Long-term oxandrolone treatment increases muscle protein net deposition via improving amino acid utilization in pediatric patients 6 months after burn injury.

BACKGROUND: We recently showed that mechanisms of protein turnover in skeletal muscle are unresponsive to amino acid (AA) infusion in severely burned pediatric patients at 6 months postinjury. In the current study, we evaluated whether oxandrolone treatment affects mechanisms of protein turnover in skeletal muscle and whole-body protein breakdown in pediatric burn patients 6 months postinjury. METHODS: At the time of admission, patients were randomized to control or oxandrolone treatments. The treatment regimens were continued until 6 months postinjury, at which time patients (n = 26) underwent study with a stable isotope tracer infusion to measure muscle and whole-body protein turnover. RESULTS: Protein kinetics in leg muscle were expressed in nmol/min per 100 mL leg volume (mean ± SE). During AA infusion, rates of protein synthesis in leg muscle were increased (P < .05) in both groups (basal vs AA: control, 51 ± 8 vs 86 ± 21; oxandrolone, 56 ± 7 vs 96 ± 12). In the control group, there was also a simultaneous increase in breakdown (basal vs AA: 65 ± 10 vs 89 ± 25), which resulted in no change in the net balance of leg muscle protein (basal vs AA: -15 ± 4 vs -2 ± 10). In the oxandrolone group, protein breakdown did not change (basal vs AA: 80 ± 12 vs 77 ± 9), leading to increased net balance (basal vs AA: -24 ± 7 vs 19 ± 7; P < .05). Protein breakdown at the whole-body level was not different between the groups. CONCLUSION: Long-term oxandrolone treatment increased net deposition of leg muscle protein during AA infusion by attenuating protein breakdown, but did not affect whole-body protein breakdown.

The effect of oxandrolone on body proportions and body composition in growth hormone-treated girls with Turner syndrome.

OBJECTIVE: Untreated girls with Turner syndrome (TS) have short stature, relatively broad shoulders, a broad pelvis, short legs, a high fat mass and low muscle mass. Our objective was to assess the effect of the weak androgen oxandrolone (Ox) on body proportions and composition in growth hormone (GH)-treated girls with TS. DESIGN/PATIENTS: 133 patients were included in a randomized, placebo-controlled, double-blind study. METHODS: Patients were treated with GH (1.33 mg/m(2) per day) from baseline, combined with placebo (Pl) or Ox in a low (0.03 mg/kg per day) or previously conventional (0.06 mg/kg per day) dose from the age of eight, and oestrogens from the age of twelve. Sitting height, biacromial and biiliacal distances compared with height (i.e. shape values), BMI, waist circumference, sum of 4 skinfolds (sum4skin) and upper arm muscle area (UAMA) SD scores (SDS) were assessed half-yearly. RESULTS: Compared with GH + Pl, adult shape values on GH + Ox tended to be higher for sitting height (Ox 0.03, P = 0.2; Ox 0.06, P = 0.02) and biacromial distance (Ox 0.03, P = 0.2; Ox 0.06, P = 0.07) and lower for biiliacal distance (Ox 0.03, P = 0.004; Ox 0.06, P = 0.08). Sum4skin SDS tended to decrease more (Ox 0.03, P = 0.2; Ox 0.06, P = 0.005) while UAMA SDS increased more (Ox 0.03, P < 0.001; Ox 0.06, P < 0.001) than on GH + Pl. The increase in BMI and waist circumference SDS was comparable between the dosage groups. CONCLUSIONS: In GH-treated girls with TS, Ox 0.06 increases sitting height and tends to increase biacromial distance and decrease biiliacal distance, while Ox 0.03 significantly decreases biiliacal distance compared with height. Furthermore, Ox 0.06 reduces subcutaneous fat mass, and both Ox dosages increase muscle mass.

The effects of an anabolic agent on body composition and pulmonary function in tetraplegia: a pilot study.

STUDY DESIGN: Prospective repeated-measures longitudinal study. OBJECTIVES: To determine if an 8-week course of an oral anabolic steroid can positively effect body composition or pulmonary function in healthy individuals with chronic tetraplegia. SETTING: United States. METHODS: Oxandrolone (20 mg per day) was administered for 8 weeks to 10 men with motor complete tetraplegia. Dual X-ray absorptiometry scans, pulmonary function tests (PFTs), serum lipids and liver function tests (LFTs) were obtained at baseline, 4, 8, 12 and 20 weeks. To analyze change over time, a repeated measures General Linear Model and nonparametric tests were utilized. RESULTS: Following treatment, total lean body mass (LBM) increased 1.9% and LBM of the arms increased 5.4%. Total body fat decreased 1.5%, and increased 3.9% in the arms and, on average, combined measures of PFTs improved 2.2%. High-density lipoprotein cholesterol decreased 31.8%, low density lipoprotein cholesterol increased 41.2%, and LFTs increased 9.7-65.6% while on therapy but all trended to baseline at 20 weeks. CONCLUSION: Baseline body composition was characterized by a high proportion of fat and a body mass index that underestimated chronic disease risk. Treatment with oxandrolone was associated with modest improvements in PFTs and in arm and total body LBM. Unfavorable changes in serum lipids and LFTs indicate that reported benefits of using oxandrolone in this population must be carefully weighed against potential adverse effects.

New oxandrolone derivatives by biotransformation using Rhizopus stolonifer.

Structural transformation of the steroidal lactone, oxandrolone (1), by suspended-cell cultures of the plant pathogen fungus Rhizopus stolonifer, resulted in the production of three new metabolites. These metabolites were identified as 11alpha-hydroxyoxandrolone (2), 6alpha-hydroxyoxandrolone (3) and 9alpha-hydroxyoxandrolone (4), by different spectroscopic methods and single-crystal X-ray diffraction analysis for metabolite 2. Compounds 1 and 3 showed a significant beta-glucuronidase inhibitory activity.

Improved functional recovery with oxandrolone after spinal cord injury in rats.

At present, only the corticosteroid, methylprednisolone, is used for acute spinal cord injury to improve function. However, improvements are modest, and are associated with myopathy and immunosuppression so that alternative treatments are needed. Oxandrolone is an androgenic steroid with potential neuroprotective properties that is used to prevent muscle loss and is not immunosuppressive. Oxandrolone increased locomotor recovery concomitant with reduced loss of cord tissue in a standard weight drop model of spinal cord contusion injury indicating oxandrolone as a possible alternative to methylprednisolone. Oxandrolone also increased axonal sprouting within the ventral horns distal to the injury consistent with formation of relay circuits mediating locomotor recovery.

Androgen receptor modulation does not affect longitudinal growth of cultured fetal rat metatarsal bones.

BACKGROUND: Systemic administration of the nonaromatizable androgen oxandrolone stimulates growth in girls with Turner syndrome and boys with a constitutional delay of growth and puberty. It is unknown if oxandrolone acts locally at the growth plate level to stimulate longitudinal bone growth. METHODS: Metatarsal bones from female and male rat fetuses (day E20) were cultured for 14 days in the presence of oxandrolone, testosterone or the androgen receptor (AR) antagonist flutamide with/without insulin-like growth-factor-I (IGF-I) or charcoal-treated serum. RESULTS: The AR was found to be expressed in both male and female fetal rat metatarsal bones. Neither oxandrolone nor testosterone had any effect on metatarsal bone growth when tested at a wide concentration range (1 nM to 10 microM), not even in the presence of IGF-I (100 ng/ml) or charcoal-treated serum (10%). Bone growth was also unaffected when the AR was blocked by flutamide. Control experiments confirmed that metatarsal bone growth was significantly stimulated by IGF-I (p < 0.001). CONCLUSION: Modulation of AR activity in the fetal rat growth plate does not affect linear bone growth. Extrapolating from these in vitro data, it could be speculated that oxandrolone stimulates longitudinal bone growth in treated children by acting indirectly rather than directly through AR activation in growth plate chondrocytes.

Oxandrolone treatment in adults with severe thermal injury.

Severe thermal injury is associated with hypermetabolism and hypercatabolism, leading to skeletal muscle breakdown, lean body mass loss, weight loss, and negative nitrogen balance. Muscle protein catabolism in patients with severe thermal injury is the result of stress-induced increased release of cytokines and counterregulatory hormones. Coupled with decreased serum anabolic hormone concentrations such as testosterone and growth hormone along with the presence of insulin resistance, anabolism in patients with severe thermal injury is inefficient or impossible during the acute postburn period. This causes difficulty in restoring lean body mass and regaining lost body weight, as well as poor healing of the burn wound and delayed patient recovery. Oxandrolone, a synthetic derivative of testosterone, has been used in adult patients with severe thermal injury to enhance lean body mass accretion, restore body weight, and accelerate wound healing. In clinical studies, oxandrolone 10 mg orally twice/day improved wound healing, restored lean body mass, and accelerated body weight gain. During the rehabilitation period, oxandrolone therapy with adequate nutrition and exercise improved lean body mass, increased muscle strength, and restored body weight. However, most data on oxandrolone use in adult patients with severe thermal injury are derived from single-center studies, many of which enrolled a relatively small number of subjects and some of which had a poor design. Multicenter, prospective, randomized studies are needed to better define the optimal oxandrolone dosage and to confirm the efficacy and safety of this drug in adult patients with severe thermal injury.

Oxandrolone enhances hepatic ketogenesis in adult men.

BACKGROUND: Immediate administration of oxandrolone markedly increases hepatic lipase activity and reduces levels of plasma high-density lipoprotein. RATIONALE FOR THE STUDY: We postulated that oxandrolone should increase hepatic lipase and that the nonesterified fatty acids generated would enhance hepatic ketogenesis during an extended fat tolerance test. MAIN RESULTS: Eighteen men participated in the study using short-term administration of oxandrolone (10 mg/d) over a week. Subjects had evaluation of hepatic ketogenesis at baseline and after 7 days of administration of oxandrolone. Ketogenesis was assessed by measuring plasma levels of 3-hydroxybutyrate during a fat tolerance test. Oxandrolone increased fasting levels of 3-hydroxybutyrate by 70%, and increased the area under the curve during an FFT by 53% above pretreatment levels without affecting the areas under the curve for nonesterified fatty acids, glycerol, or triglycerides. Fasting 3-hydroxybutyrate levels correlated with nonesterified fatty acids and with triglycerides; however, there were no significant correlations with any other parameter. CONCLUSIONS: This study shows that short-term administration of oxandrolone results in marked increases in hepatic ketogenesis. This finding is consistent with an increased influx of fatty acids into the liver secondary to lipoprotein lipolysis by increased hepatic lipase. However, the possibility cannot be ruled out that oxandrolone acts directly in the liver to stimulate fatty acid oxidation. Therefore, the observation of increased ketogenesis will require further studies to determine the molecular basis of the response.

Oxandrolone in pediatric patients with severe thermal burn injury.

OBJECTIVE: To review the role of oxandrolone in pediatric patients with severe thermal burn injury. DATA SOURCES: MEDLINE (1950-April 2008) and Science Citation Index (1900-April 2008) searches were performed using the key terms oxandrolone, burn, and children. STUDY SELECTION AND DATA EXTRACTION: All English-language articles that evaluated the efficacy and safety of oxandrolone in pediatric patients with severe thermal burn injury were included in this review. DATA SYNTHESIS: Oxandrolone stimulates protein synthesis by binding to androgen receptors. The efficacy and safety of adjunct oxandrolone therapy in pediatric patients (20%) were evaluated in 8 clinical studies. Oral oxandrolone 0.1 mg/kg twice daily increased protein synthesis, lean body mass accretion, and muscle strength; improved serum visceral protein concentrations; promoted weight gain; and increased bone mineral content. During the postburn rehabilitation period, oxandrolone 0.1 mg/kg/day improved muscle strength, especially when combined with exercise. Based on clinical studies, oxandrolone 0.1 mg/kg twice daily is safe when given for up to 12 months. However, mild increases in serum liver transaminase concentrations and reversible sexual changes were observed during therapy. Although data on the efficacy and safety of oxandrolone in severely burned children are supported by prospective, randomized, controlled studies, limitations of available data are that they originated from a single study center and that wound healing measurement is lacking in children with severe thermal burns. CONCLUSIONS: The benefits of adjunct oxandrolone therapy in severely burned pediatric patients have been demonstrated in the acute postburn injury and long-term postburn rehabilitation periods. Close monitoring of liver function, sexual development, and growth pattern is recommended during oxandrolone treatment.

The effect of oxandrolone on the endocrinologic, inflammatory, and hypermetabolic responses during the acute phase postburn.

OBJECTIVE AND SUMMARY BACKGROUND DATA: Postburn long-term oxandrolone treatment improves hypermetabolism and body composition. The effects of oxandrolone on clinical outcome, body composition, endocrine system, and inflammation during the acute phase postburn in a large prospective randomized single-center trial have not been studied. METHODS: Burned children (n = 235) with >40% total body surface area burn were randomized (block randomization 4:1) to receive standard burn care (control, n = 190) or standard burn care plus oxandrolone for at least 7 days (oxandrolone 0.1 mg/kg body weight q.12 hours p.o, n = 45). Clinical parameters, body composition, serum hormones, and cytokine expression profiles were measured throughout acute hospitalization. Statistical analysis was performed by Student t test, or ANOVA followed by Bonferroni correction with significance accepted at P < 0.05. RESULTS: Demographics and clinical data were similar in both groups. Length of intensive care unit stay was significantly decreased in oxandrolone-treated patients (0.48 +/- 0.02 days/% burn) compared with controls (0.56 +/- 0.02 days/% burn), (P < 0.05). Control patients lost 8 +/- 1% of their lean body mass (LBM), whereas oxandrolone-treated patients had preserved LBM (+9 +/- 4%), P < 0.05. Oxandrolone significantly increased serum prealbumin, total protein, testosterone, and AST/ALT, whereas it significantly decreased alpha2-macroglobulin and complement C3, P < 0.05. Oxandrolone did not adversely affect the endocrine and inflammatory response as we found no significant differences in the hormone panels and cytokine expression profiles. CONCLUSIONS: In this large prospective, double-blinded, randomized single-center study, oxandrolone shortened length of acute hospital stay, maintained LBM, improved body composition and hepatic protein synthesis while having no adverse effects on the endocrine axis postburn, but was associated with an increase in AST and ALT.

Effects of oxandrolone, an anabolic steroid, on hemostasis.

This study evaluated the short-term effects of oxandrolone, an anabolic androgenic synthetic steroid, on blood coagulation and the hemostatic/fibrinolytic system in healthy individuals. Subjects (n = 14) were administered oxandrolone (10 mg twice daily) for 14 days. Blood was obtained on days 0, 1, 3, 7, 9, 14, and then at day 42 (28 days after discontinuation of the drug). Samples were analyzed for the plasma plasminogen, plasminogen activator inhibitor (PAI-1), fibrinogen, and coagulation factors (II, V, VII, VIII, and X). After 7 days of administration of oxandrolone, the plasma plasminogen level significantly increased [100% +/- 21% to 174% +/- 21% (P < 0.0001)]. PAI-1 was significantly decreased at day 3 [16 +/- 9 to 7 +/- 4 mg/dL (P < 0.01)]. Coagulation factors II and V significantly increased at day 14 [88 +/- 15 to 122 +/- 11 (P < 0.005) and 105 +/- 21 to 179 +/- 36% (P < 0.0001)], respectively. Factor VII level decreased by day 3 [91% +/- 26% to 83% +/- 18%, NS], but after 14 days factor VII level returned to baseline (91% +/- 26% to 93% +/- 19%, NS). The increase of factor VIII level was not significant (111% +/- 64% to 125% +/- 55%, NS). Factor X increased steadily over 14 days of drug treatment [96% +/- 11% to 107% +/- 25%, NS] and after discontinuation, decreased and returned to baseline by day 42 [107% +/- 25% to 89% +/- 25%, NS]. Fibrinogen decreased by 22% +/- 12%, (NS). Administration of oxandrolone, to healthy young men was associated with a significant increase in select blood coagulation factors and plasminogen. These changes create a state of potential hypercoagulability that appears to be counterbalanced by increased fibrinolytic activity to maintain homeostasis.