Oxandrolone (Anavar)

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

Porro LJ, Herndon DN, Rodriguez NA, Jennings K, Klein GL, Mlcak RP, Meyer WJ, Lee JO, Suman OE, Finnerty CC.

Source
Shriners Hospitals for Children-Galveston, Galveston, TX 77550, USA.

Abstract

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.

Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
PMID: 22463890 PMCID: PMC3412530 [Available on 2013/4/1]

Oxandrolone enhances hepatic ketogenesis in adult men.

Vega GL, Clarenbach JJ, Dunn F, Grundy SM.

Source
Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Gloria.Vega@utsouthwestern.edu

Abstract

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.

PMID: 18797410

Androgen therapy induces muscle protein anabolism in older women.

Sheffield-Moore M, Paddon-Jones D, Casperson SL, Gilkison C, Volpi E, Wolf SE, Jiang J, Rosenblatt JI, Urban RJ.

Source
University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0569, USA.

Abstract

CONTEXT:
Normal healthy men and women undergo a gradual loss of skeletal muscle mass and strength with advancing age. While androgens are protein anabolic in older men, the metabolic effects in older women are poorly understood.

OBJECTIVE AND DESIGN:
The objective of this study was to determine whether oral administration of a synthetic derivative of testosterone [oxandrolone, Oxandrin (OX)] (7.5 mg orally twice daily for 14 d) to five older women (age, 65 +/- 2 yr) would enhance skeletal muscle anabolic biomarkers including mixed muscle fractional synthetic rate (FSR), net phenylalanine balance, androgen receptor, and IGF-I protein expression at d 0, 5, and 14 of treatment. As a positive control, seven older men were examined after 14 d of OX (10 mg orally twice daily).

SETTING:
The study was performed at the General Clinical Research Center.

RESULTS:
Fourteen days of OX significantly increased skeletal muscle FSR in older women (d 0, 0.073 +/- 0.006 vs. d 5, 0.092 +/- 0.006 vs. d 14, 0.115 +/- 0.007%/h) (P < 0.05, d 0 vs. d 14). Conversely, OX stimulated FSR in older men after only 5 d (d 0, 0.061 +/- 0.003 vs. d 5, 0.101 +/- 0.01 vs. d 14, 0.084 +/- 0.01%/h) (P < 0.05, d 0 vs. d 5). Androgen receptor expression was significantly increased in older men by d 14, but had not increased in older women. No change was noted in IGF-I expression in either group. We conclude that the skeletal muscle of older women and men responds to androgen administration, although the time course of anabolism appears to be gender specific.

PMID: 16895962

Full article: Androgen Therapy Induces Muscle Protein Anabolism in Older Women

Six-week improvements in muscle mass and strength during androgen therapy in older men.

Schroeder ET, Vallejo AF, Zheng L, Stewart Y, Flores C, Nakao S, Martinez C, Sattler FR.

Source
Department of Biokinesiology & Physical Therapy, University of Southern California, Los Angeles, CA 90089, USA. eschroed@usc.edu

Abstract

BACKGROUND:
The purpose of our study was to assess the early effects of a potent anabolic androgen on muscle mass and strength, lower extremity power, and functional performance in older men.

METHODS:
Thirty-two men 72 +/- 6 years of age were randomized to receive oxandrolone (10 mg twice daily) or matching placebo in a 2:1 manner for 12 weeks. Total and appendicular lean body mass (LBM) were assessed by dual-energy x-ray absorptiometry (DEXA). Lower extremity muscle volume was determined by magnetic resonance imaging to validate DEXA changes.

RESULTS:
Total LBM increased by 2.7 +/- 1.6 kg after 6 weeks with oxandrolone (p <.001), which was greater (p <.001) than the decline in LBM (-0.5 +/- 0.9 kg) with placebo. Appendicular LBM increased by 1.2 +/- 0.9 kg after just 6 weeks with oxandrolone (p <.001), which was greater (p <.001) than the decline in LBM (-0.4 +/- 0.5 kg) with placebo. These changes were >90% of the gains in total and appendicular LBM (3.0 +/- 1.5 kg and 1.3 +/- 0.9 kg, respectively) after 12 weeks. Total thigh and hamstring muscle volume increased by 111 +/- 29 mm(3) (p =.001) and 75 +/- 18 mm(3) (p =.001), respectively, after 12 weeks. Maximal strength increased for the leg press 6.3 +/- 5.6% (p =.003), leg curl 6.7 +/- 8.6% (p =.01), chest press 6.9 +/- 6.5% (p =.001), and latissimus pull-down 4.8 +/- 6.3% (p =.009) with oxandrolone after 6 weeks; these increases were different than those with placebo (p <.001) and were 93%, 96%, 74%, and 94% of the respective gains at week 12. There were no improvements in functional measures.

CONCLUSION:
Treatment with a potent anabolic androgen may produce significant increases in muscle mass and strength after only 6 weeks in healthy older men. However, such treatment did not improve leg muscle power or walking speed.

PMID: 16424293

Oxandrolone induced lean mass gain during recovery from severe burns is maintained after discontinuation of the anabolic steroid.

Demling RH, DeSanti L.

Source
Department of Surgery, Trauma and Burn Center, Brigham & Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. rhdemling@partners.org

Abstract

Weight loss and lean mass loss from burn induced catabolism can be more rapidly restored when the anabolic steroid oxandrolone is added to optimum nutrition compared to nutrition alone. Our purpose in this study was to determine whether the regained lean body mass (LBM) is retained 6 months after stopping oxandrolone. Forty-five severe burn patients, entering the recovery phase were randomized into a nutrition group alone or with the addition of oxandrolone, 20mg per day upon admission to the acute burn rehabilitation (RH) unit. Oxandrolone was discontinued after at least 80% of the involuntary weight loss occurring in the acute burn period, was restored. Body composition was measured using bioelectric impedence analysis (BIA). We found that patients receiving oxandrolone, in the rehabilitation unit, regained weight and lean mass two to three times faster than with nutrition alone. The difference was statistically significant (P<0.05). All patients were discharged from RH on a nutrition and exercise program and monitored in the outpatient burn center. After 6 months, body weight and body composition were again measured. We found that the body weight and lean mass which was restored during RH, was maintained 6 months after discontinuation of oxandrolone. Lost lean mass was not yet restored in the nutrition alone group. We can conclude that body weight and lean mass which is lost, due to burn induced catabolism, can be effectively restored in the post-burn recovery period with oxandrolone. The body weight and lost lean mass which is regained, is maintained 6 months after stopping the drug.

PMID: 14636753

Oxandrolone therapy in constitutionally delayed growth and puberty. Bio-Technology General Corporation Cooperative Study Group

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Oxandrolone therapy in constitutionally delayed growth and puberty. Bio-Technology General Corporation Cooperative Study Group.
Wilson DM, McCauley E, Brown DR, Dudley R.
Source

Department of Pediatrics, Stanford University, California, USA.
Abstract
BACKGROUND:

Male adolescents with constitutional delay of growth and puberty may have significant psychosocial difficulties related to their sexual immaturity and short stature. The purpose of this study was to test the hypothesis that 1 year of oxandrolone therapy would increase growth velocity and thereby improve psychosocial functioning in boys with constitutional delay of growth and pubertal development.
METHODS:

Forty boys (ages 11 to 14.7 years) with delayed pubertal development and short stature were recruited from the pediatric endocrine clinics of 14 medical centers. The boys were randomized using a block design stratified for age to receive either oxandrolone (0.1 mg/kg daily for 1 year) or an identical-appearing placebo tablet, using a double-masked design.
RESULTS:

Growth velocity in the oxandrolone-treated boys was significantly greater than in the control boys (9.5 vs 6.8 cm/y). Likewise, the mean height SD score increased 0.41 in the oxandrolone group, whereas it decreased 0.03 in the control group. Those in the oxandrolone group gained 2.4 kg more than those in the placebo group. Mean predicted adult heights did not change in either group. The mean rates of pubertal progression were equivalent in both groups. Self-image (Piers-Harris Self Concept Scale) and social competence (Child Behavior Profile) were normal at baseline in both groups and did not change significantly over the course of the study in either group. No complications of oxandrolone therapy were identified.
CONCLUSIONS:

This randomized, placebo-controlled trial demonstrates that low-dose oxandrolone can increase both height and weight velocity in boys with delayed puberty safely. Under the conditions of this study, however, the increased growth velocity in the oxandrolone-treated boys was not associated with a greater improvement in psychosocial status compared with the control boys.

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Oxandrolone therapy in constitutionally delayed g... [Pediatrics. 1995] - PubMed - NCBI

Oxandrolone in AIDS-wasting myopathy

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Oxandrolone in AIDS-wasting myopathy.
Berger JR, Pall L, Hall CD, Simpson DM, Berry PS, Dudley R.
Source

Department of Neurology, University of Miami School of Medicine, Florida, USA.
Abstract
OBJECTIVE:

To evaluate oxandrolone, an oral anabolic steroid with potent anabolic activity and minimal androgenic effects, for the treatment of AIDS-associated myopathy and wasting.
METHODS:

In a multicenter, double-blind study, 63 HIV-seropositive men with > 10% loss of body weight were randomized to receive either placebo, 5 mg/day oxandrolone, or 15 mg/day oxandrolone for 16 weeks. Body weight, neuromuscular evaluation, and measures of well-being were repeatedly assessed.
RESULTS:

Patients who received 15 mg/day oxandrolone showed weight gain throughout the 16-week treatment period. Overall, the 5 mg/day oxandrolone group maintained their weight gain over the 16-week period, whereas the placebo group showed continual weight loss. At week 16, significantly more patients in the 15 mg/day dose group reported increases in appetite and activity than those receiving placebo. There were no consistent, dose-related, statistically significant differences from baseline in laboratory values or adverse events.
CONCLUSION:

Oxandrolone, at a dose of either 5 mg/day or 15 mg/day, in contrast to placebo, had a positive impact on the weight and well-being of HIV-seropositive patients suffering from wasting and weakness. Measurable improvement in muscle strength was not noted at the doses employed in this study. Oxandrolone was well tolerated in all the patients who were enrolled in the study. Based on the results reported here, additional studies using higher doses of oxandrolone seem warranted.

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Oxandrolone in AIDS-wasting myopathy. [AIDS. 1996] - PubMed - NCBI

Short-term oxandrolone administration stimulates net muscle protein synthesis in young men

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Abstract

Short term administration of testosterone stimulates net protein synthesis in healthy men. We investigated whether oxandrolone [Oxandrin (OX)], a synthetic analog of testosterone, would improve net muscle protein synthesis and transport of amino acids across the leg. Six healthy men [22+/-1 (+/-SE) yr] were studied in the postabsorptive state before and after 5 days of oral OX (15 mg/day). Muscle protein synthesis and breakdown were determined by a three-compartment model using stable isotopic data obtained from femoral arterio-venous sampling and muscle biopsy. The precursor-product method was used to determine muscle protein fractional synthetic rates. Fractional breakdown rates were also directly calculated. Total messenger ribonucleic acid (mRNA) concentrations of skeletal muscle insulin-like growth factor I and androgen receptor (AR) were determined using RT-PCR. Model-derived muscle protein synthesis increased from 53.5+/-3 to 68.3+/-5 (mean+/-SE) nmol/min.100 mL/leg (P < 0.05), whereas protein breakdown was unchanged. Inward transport of amino acids remained unchanged with OX, whereas outward transport decreased (P < 0.05). The fractional synthetic rate increased 44% (P < 0.05) after OX administration, with no change in fractional breakdown rate. Therefore, the net balance between synthesis and breakdown became more positive with both methodologies (P < 0.05) and was not different from zero. Further, RT-PCR showed that OX administration significantly increased mRNA concentrations of skeletal muscle AR without changing insulin-like growth factor I mRNA concentrations. We conclude that short term OX administration stimulated an increase in skeletal muscle protein synthesis and improved intracellular reutilization of amino acids. The mechanism for this stimulation may be related to an OX-induced increase in AR expression in skeletal muscle.

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Short-term oxandrolone administratio... [J Clin Endocrinol Metab. 1999] - PubMed - NCBI

Oxandrolone, an anabolic steroid, enhances the healing of a cutaneous wound in the rat

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Abstract

The effect of the anabolic steroid oxandrolone on the healing rate of a standardized full thickness linear wound on the back of the rat was studied. Oxandrolone was given orally by gavage in peanut oil at a dose of 0.1 mg/kg/day. A placebo powder in peanut oil was given at the same dose to a control group. Parameters monitored were time to complete wound closure, wound hydroxyproline content and tensile strength, as well as histology. We found that wounds closed completely in 12+/-3 days with oxandrolone, compared to 18+/-3 days for a placebo, a statistically significant difference. The rate of body weight gain was identical in both groups. Hydroxyproline content of the healed incision site was 23+/-4 mg/g tissue vs. 17+/-3 mg/g tissue, while the tensile strength increased to 185+/-13 g/mm2 vs. 102+/-18 g/mm2 in the oxandrolone and placebo groups, respectively. Both parameters were significantly increased with the anabolic steroid. Histologic examination showed a wound that contained more mature and densely packed collagen and was also hypercellular with oxandrolone treatment. We conclude that the anabolic steroid oxandrolone significantly enhanced wound healing unrelated to any generalized increase in protein mass as would be reflected in body weight.

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Oxandrolone, an anabolic steroid,... [Wound Repair Regen. 2000 Mar-Apr] - PubMed - NCBI

Oxandrolone blocks glucocorticoid signaling in an androgen receptor-dependent manner

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Oxandrolone blocks glucocorticoid signaling in an androgen receptor-dependent manner.
Zhao J, Bauman WA, Huang R, Caplan AJ, Cardozo C.
Source

Rehabilitation and Research Development Center of Excellence for the Medical Consequences of Spinal Cord Injury, VA Medical Center, Bronx, NY, USA.
Abstract

The anabolic steroid oxandrolone is increasingly used to preserve or restore muscle mass in those with HIV infection or serious burns. These effects are mediated, in part, by the androgen receptor (AR). Anti-glucocorticoid effects have also been reported for some anabolic steroids, and the goal of our studies was to determine whether oxandrolone had a similar mechanism of action. Studies with in vitro translated glucocorticoid receptor (GR), however, showed no inhibition of cortisol binding by oxandrolone. Conversely, experiments in cell culture systems demonstrated significant antagonism of cortisol-induced transcriptional activation by oxandrolone in cells expressing both the AR and GR. Inhibition was not overcome by increased cortisol concentration, and no inhibition by oxandrolone was observed in cells expressing GR alone, confirming that non-competitive mechanisms were involved. AR-dependent repression of transcriptional activation by oxandrolone was also observed with the synthetic glucocorticoids dexamethasone and methylprednisolone. Furthermore, the AR antagonists 2-hydroxyflutamide and DDE also repressed GR transactivation in an AR-dependent manner. A mutant AR lacking a functional nuclear localization signal (AR(4RKM)) was active in oxandrolone-mediated repression of GR even though oxandrolone-bound AR(4RKM) failed to enter the nucleus and did not affect nuclear import of GR. These data indicate a novel action of oxandrolone to suppress glucocorticoid action via crosstalk between AR and GR.

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Oxandrolone blocks glucocorticoid signaling in an a... [Steroids. 2004] - PubMed - NCBI