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Pediatrics Jan 2007Severe burns are associated with a significant loss of muscle and strength. Studies have reported that oxandrolone improves lean body mass in muscle-wasting conditions.... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Severe burns are associated with a significant loss of muscle and strength. Studies have reported that oxandrolone improves lean body mass in muscle-wasting conditions. Also shown previously in burned children is that an exercise program increases lean body mass and muscle strength. We hypothesized that oxandrolone, in combination with exercise, would increase lean body mass and muscle strength in severely burned children more than oxandrolone alone or exercise alone.
METHODS AND PATIENTS
Fifty-one burned children (> or = 40% total body surface area burned) were randomly assigned to receive oxandrolone alone (0.1 mg/kg per day orally; n = 9), oxandrolone and exercise (n = 14), placebo and no exercise (n = 11), or placebo and exercise (n = 17). Administration of oxandrolone was started at discharge and continued until 1 year after burn. The 12-week exercise training program was started 6 months after burn. Serum hormones, lean body mass, muscle strength, and peak cardiopulmonary capacity were assessed at 6 (baseline) and 9 months after burn. Data were analyzed using a 1-way analysis of variance, and significance was set at P < .05.
RESULTS
The mean percentage of change or increase in weight and lean body mass in the oxandrolone and exercise group was significant compared with placebo and exercise, as well as with the oxandrolone alone group or placebo and no exercise group. Furthermore, lean body mass was significantly improved in the oxandrolone and exercise, oxandrolone alone, and placebo and exercise group compared with the group only receiving placebo. Muscle strength significantly increased in oxandrolone and exercise, placebo and exercise, and the oxandrolone alone group when compared with the placebo and no exercise group. The peak cardiopulmonary capacity was significantly higher in both exercise groups. Insulin-like growth factor 1 was significantly increased in the oxandrolone alone group compared with placebo and exercise and placebo and no exercise. Both exercise groups showed significant changes in insulin-like binding-protein-3 when compared with groups without exercise.
CONCLUSIONS
Oxandrolone, in combination with exercise, is beneficial in severely burned children, thus improving their rehabilitation.
Topics: Adolescent; Anabolic Agents; Body Mass Index; Body Weight; Burns; Child; Exercise Test; Exercise Therapy; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Muscle Strength; Muscle, Skeletal; Oxandrolone; Oxygen Consumption
PubMed: 17130281
DOI: 10.1542/peds.2006-1548 -
Biosensors Dec 2017We have studied the Fourier Transform Infrared (FT-IR) and the Fourier transform Raman (FT-Raman) spectra of stanozolol and oxandrolone, and we have performed quantum...
We have studied the Fourier Transform Infrared (FT-IR) and the Fourier transform Raman (FT-Raman) spectra of stanozolol and oxandrolone, and we have performed quantum chemical calculations based on the density functional theory (DFT) with a B3LYP/6-31G (d, p) level of theory. The FT-IR and FT-Raman spectra were collected in a solid phase. The consistency between the calculated and experimental FT-IR and FT-Raman data indicates that the B3LYP/6-31G (d, p) can generate reliable geometry and related properties of the title compounds. Selected experimental bands were assigned and characterized on the basis of the scaled theoretical wavenumbers by their total energy distribution. The good agreement between the experimental and theoretical spectra allowed positive assignment of the observed vibrational absorption bands. Finally, the calculation results were applied to simulate the Raman and IR spectra of the title compounds, which show agreement with the observed spectra.
Topics: Anabolic Agents; Oxandrolone; Quantum Theory; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Stanozolol
PubMed: 29278383
DOI: 10.3390/bios8010002 -
Frontiers in Endocrinology 2023To study the impact of GH dose and age at GH start in girls with Turner syndrome (TS), aiming for normal height and age at pubertal onset (PO) and at adult height (AH)....
OBJECTIVE
To study the impact of GH dose and age at GH start in girls with Turner syndrome (TS), aiming for normal height and age at pubertal onset (PO) and at adult height (AH). However, age at diagnosis will limit treatment possibilities.
METHODS
National multicenter investigator-initiated studies (TNR 87-052-01 and TNR 88-072) in girls with TS, age 3-16 years at GH start during year 1987-1998, with AH in 2003-2011. Of the 144 prepubertal girls with TS, 132 girls were followed to AH (intention to treat), while 43 girls reduced dose or stopped treatment prematurely, making n=89 for Per Protocol population. Age at GH start was 3-9 years (young; n=79) or 9-16 years (old; n=53). Treatment given were recombinant human (rh)GH (Genotropin Kabi Peptide Hormones, Sweden) 33 or 67 µg/kg/day, oral ethinyl-estradiol (2/3) or transdermal 17β-estradiol (1/3), and, after age 11 years, mostly oxandrolone. Gain in height, AH, and age at PO and at AH were evaluated.
RESULTS
At GH start, height was -2.8 (versus non-TS girls) for all subgroups and mean age for young was 5.7 years and that of old was 11.6 years. There was a clear dose-response in both young and old TS girls; the mean difference was (95%CI) 0.66 (-0.91 to -0.26) and 0.57 (-1.0 to -0.13), respectively. The prepubertal gain (1.3-2.1) was partly lost during puberty (-0.4 to -2.1). Age/height at PO ranged from 13 years/-0.42 for GH to 15.2 years/-1.47 for GH. At AH, GH group became tallest (17.2 years; 159.9 cm; -1.27 SDS; total gain, 1.55) compared to GH group being least delayed (16.1 years; 157.1 cm; -1.73 SDS; total, 1.08). The shortest was the GH group (17.3 years; 153.7 cm: -2.28 SDS; total gain, 0.53), and the most delayed was the GH group, (18.5 years; 156.5 cm; -1.82 SDS; total gain, 0.98).
CONCLUSION
For both young and old TS girls, there was a GH-dose growth response, and for the young, there was less delayed age at PO and at AH. All four groups reached an AH within normal range, despite partly losing the prepubertal gain during puberty. Depending on age at diagnosis, low age at start with higher GH dose resulted in greater prepubertal height gain, permitting estrogen to start earlier at normal age and attaining normal AH at normal age, favoring physiological treatment and possibly also bone health, hearing, uterine growth and fertility, psychosocial wellbeing during adolescence, and the transition to adulthood.
Topics: Female; Adolescent; Humans; Adult; Child, Preschool; Child; Human Growth Hormone; Growth Hormone; Turner Syndrome; Sweden; Body Height; Puberty; Estradiol
PubMed: 37529614
DOI: 10.3389/fendo.2023.1197897 -
Hormone Research in Paediatrics 2014There has been no consensus regarding the efficacy and safety of oxandrolone (Ox) in addition to growth hormone (GH) in girls with Turner syndrome (TS), the optimal age... (Review)
Review
There has been no consensus regarding the efficacy and safety of oxandrolone (Ox) in addition to growth hormone (GH) in girls with Turner syndrome (TS), the optimal age of starting this treatment, or the optimal dose. This collaborative venture between Dutch, UK and US centers is intended to give a summary of the data from three recently published randomized, placebo-controlled, double-blind studies on the effects of Ox. The published papers from these studies were reviewed within the group of authors to reach consensus about the recommendations. The addition of Ox to GH treatment leads to an increase in adult height, on average 2.3–4.6 cm. If Ox dosages<0.06 mg/kg/day are used, side effects are modest. The most relevant safety concerns are virilization(including clitoromegaly and voice deepening) and a transient delay of breast development. We advise monitoring signs of virilization breast development and possibly blood lipids during Ox treatment, in addition to regular follow-up assessments for TS. In girls with TS who are severely short for age, in whom very short adult stature is anticipated,or in whom the growth rate is modest despite good compliance with GH, adjunctive treatment with Ox at a dosage of 0.03–0.05 mg/kg/day starting from the age of 8–10 years onward scan be considered.
Topics: Adolescent; Adult; Age Factors; Androgens; Child; Child, Preschool; Double-Blind Method; Female; Human Growth Hormone; Humans; Oxandrolone; Randomized Controlled Trials as Topic; Turner Syndrome
PubMed: 24776783
DOI: 10.1159/000358195 -
Annals of Burns and Fire Disasters Mar 2022In severe burns, hyper-metabolic conditions due to elevation of pro-inflammatory cytokines and stress hormones usually occur. Unregulated hypermetabolism can lead to...
In severe burns, hyper-metabolic conditions due to elevation of pro-inflammatory cytokines and stress hormones usually occur. Unregulated hypermetabolism can lead to muscle protein catabolism, inducing weakness, infection, and delayed wound healing. Oxandrolone is known as an anabolic agent with minor side effects. This study aims to determine the effect of oxandrolone on lean body mass (LBM) in severe burn patients. A randomized, double blind and placebo controlled trial was conducted in the burn centre of the Dr. Soetomo Hospital. Severe burn patients who met the inclusion criteria were randomized into two groups, oxandrolone and placebo group. Oxandrolone was given with a dose 0.1 mg/kg twice a day for 14 consecutive days. Estimated lean body mass (eLBM) for each group was measured on admission (day 0) and day 14. Fourteen burn patients were enrolled in this study. Lean body mass reduced significantly from 48.69±7.71 to 46.70±7.96 in the placebo group (p-value 0.008) by independent t-test. There was no significant decrease of LBM in the oxandrolone group. Delta LBM (Δ eLBM) before and after treatment was 0.38±1.64 in the oxandrolone group, and -1.32±1.23 in the placebo group (p-value = 0.049). There were no adverse effects during the administration to the oxandrolone group. In severe burn patients, oxandrolone could prevent reduction of LBM compared to placebo and is relatively safe. These findings suggest the efficacy of oxandrolone in preventing muscle catabolism as a part of hypermetabolism in burn patients.
PubMed: 35582088
DOI: No ID Found -
The Journal of Pediatric Pharmacology... 2020Growth failure following surgical palliation of complex congenital heart defects (CHDs) is a prognosticator of poor outcomes. Many strategies for improving weight gain...
OBJECTIVES
Growth failure following surgical palliation of complex congenital heart defects (CHDs) is a prognosticator of poor outcomes. Many strategies for improving weight gain have been implemented in this population, with limited success. We recently described the potential of the anabolic steroid oxandrolone to improve weight gain following surgical repair of CHD when administered via a medium-chain triglyceride (MCT) oil suspension to the buccal mucosa. The current study evaluates the stability of oxandrolone in the MCT oil formulation, as well as the pharmacokinetics of oxandrolone when administered via buccal mucosa in both neonates and adults.
METHODS
Stability was assessed by long-term storage of the preparation 1) at ambient conditions and 2) under photodegradative conditions for 3 days. Neonatal pharmacokinetic parameters were determined in a cohort of neonates following surgical CHD repair, whereas adult pharmacokinetics parameters were collected as part of a prospective study to evaluate the relative bioavailability of the oxandrolone in MCT oil formulation.
RESULTS
We found that oxandrolone was stable in the MCT oil formulation for at least 1 month, although exposure to light hastened drug degradation. Both neonatal and adult oxandrolone pharmacokinetics were variable; however, oxandrolone in MCT oil was relatively well absorbed through the buccal mucosa (mean bioavailability = 62.5%).
CONCLUSIONS
These data suggest that the variability in oxandrolone exposures is inherent to the drug, and not the formulation or route of administration. Combined, these data support further study of this novel oxandrolone in MCT oil formulation and its impact on growth following complex surgical repair of CHD in neonates.
PubMed: 32265605
DOI: 10.5863/1551-6776-25.3.220 -
Burns & Trauma Jan 2021Wound healing is a complex process involving four overlapping phases: haemostasis, inflammation, cell recruitment and matrix remodeling. In mouse models, surgical,... (Review)
Review
Wound healing is a complex process involving four overlapping phases: haemostasis, inflammation, cell recruitment and matrix remodeling. In mouse models, surgical, pharmacological and genetic approaches targeting androgen actions in skin have shown that androgens increase interleukin-6 and tumor necrosis factor-α production and reduce wound re-epithelization and matrix deposition, retarding cutaneous wound healing. Similarly, clinical studies have shown that cutaneous wound healing is slower in men compared to women. However, in major burn injury, which triggers not only local wound-healing processes but also systemic hypermetabolism, the role of androgens is poorly understood. Recent studies have claimed that a synthetic androgen, oxandrolone, increases protein synthesis, improves lean body mass and shortens length of hospital stay. However, the possible mechanisms by which oxandrolone regulates major burn injury have not been reported. In this review, we summarize the current findings on the roles of androgens in cutaneous and major burn wound healing, as well as androgens as a potential therapeutic treatment option for patients with major burn injuries.
PubMed: 33928173
DOI: 10.1093/burnst/tkaa046 -
Burns & Trauma 2024Prospective randomized trials in severely burned children have shown the positive effects of oxandrolone (OX), beta blockers (BB) and a combination of the two (BBOX) on...
BACKGROUND
Prospective randomized trials in severely burned children have shown the positive effects of oxandrolone (OX), beta blockers (BB) and a combination of the two (BBOX) on hypermetabolism, catabolism and hyperinflammation short- and long-term post-burn. Although data on severely burned adults are lacking in comparison, BB, OX and BBOX appear to be commonly employed in this patient population. In this study, we perform a secondary analysis of an international prospective randomized trial dataset to provide descriptive evidence regarding the current utilization patterns and potential treatment effects of OX, BB and BBOX.
METHODS
The RE-ENERGIZE (RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury, NCT00985205) trial included 1200 adult patients with severe burns. We stratified patients according to their receipt of OX, BB, BBOX or none of these drugs (None) during acute hospitalization. Descriptive statistics describe the details of drug therapy and unadjusted analyses identify predisposing factors for drug use per group. Association between OX, BB and BBOX and clinical outcomes such as time to discharge alive and 6-month mortality were modeled using adjusted multivariable Cox regressions.
RESULTS
More than half of all patients in the trial received either OX (n = 138), BB (n = 293) or BBOX (n = 282), as opposed to None (n = 487, 40.6%). Per study site and geographical region, use of OX, BB and BBOX was highly variable. Predisposing factors for the use of OX, BB and BBOX included larger total body surface area (TBSA) burned, higher acute physiology and chronic health evaluation (APACHE) II scores on admission and younger patient age. After adjustment for multiple covariates, the use of OX was associated with a longer time to discharge alive [hazard ratio (HR) 0.62, confidence interval (CI) (0.47-0.82) per 100% increase, = 0.001]. A higher proportion of days on BB was associated with lower in-hospital-mortality (HR: 0.5, CI 0.28-0.87, = 0.015) and 6-month mortality (HR: 0.44, CI 0.24-0.82, = 0.01).
CONCLUSIONS
The use of OX, BB and BBOX is common within the adult burn patient population, with its use varying considerably across sites worldwide. Our findings found mixed associations between outcomes and the use of BB and OX in adult burn patients, with lower acute and 6-month-mortality with BB and longer times to discharge with OX. Further research into these pharmacological modulators of the pathophysiological response to severe burn injury is indicated.
PubMed: 38650969
DOI: 10.1093/burnst/tkad063 -
Current Opinion in Clinical Nutrition... Mar 2011The hypermetabolic response in critically ill patients is characterized by hyperdynamic circulatory, physiologic, catabolic and immune system responses. Failure to... (Review)
Review
PURPOSE OF REVIEW
The hypermetabolic response in critically ill patients is characterized by hyperdynamic circulatory, physiologic, catabolic and immune system responses. Failure to satisfy overwhelming energy and protein requirements after, and during critical illness, results in multiorgan dysfunction, increased susceptibility to infection, and death. Attenuation of the hypermetabolic response by various pharmacologic modalities is emerging as an essential component of the management of severe burn patients. This review focuses on the more recent advances in therapeutic strategies to attenuate the hypermetabolic response and its associated insulin resistance postburn.
RECENT FINDINGS
At present, beta-adrenergic blockade with propranolol represents probably the most efficacious anticatabolic therapy in the treatment of burns. Other pharmacological strategies include growth hormone, insulin-like growth factor, oxandrolone and intensive insulin therapy.
SUMMARY
Novel approaches to the management of critical illness by judicious glucose control and the use of pharmacologic modulators to the hypercatabolic response to critical illness have emerged. Investigation of alternative strategies, including the use of metformin, glucagon-like-peptide-1 and the PPAR-γ agonists are under current investigation.
Topics: Anabolic Agents; Blood Glucose; Burns; Growth Hormone; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Oxandrolone; Propranolol
PubMed: 21157309
DOI: 10.1097/MCO.0b013e3283428df1 -
Burns & Trauma 2017Trauma and related sequelae result in disturbance of homeostatic mechanisms frequently leading to cellular dysfunction and ultimately organ and system failure.... (Review)
Review
Trauma and related sequelae result in disturbance of homeostatic mechanisms frequently leading to cellular dysfunction and ultimately organ and system failure. Regardless of the type and severity of injury, gender dimorphism in outcomes following trauma have been reported, with females having lower mortality than males, suggesting that sex steroid hormones (SSH) play an important role in the response of body systems to trauma. In addition, several clinical and experimental studies have demonstrated the effects of SSH on the clinical course and outcomes following injury. Animal studies have reported the ability of SSH to modulate immune, inflammatory, metabolic and organ responses following traumatic injury. This indicates that homeostatic mechanisms, via direct and indirect pathways, can be maintained by SSH at local and systemic levels and hence result in more favourable prognosis. Here, we discuss the role and mechanisms by which SSH modulates the response of the body to injury by maintaining various processes and organ functions. Such properties of sex hormones represent potential novel therapeutic strategies and further our understanding of current therapies used following injury such as oxandrolone in burn-injured patients.
PubMed: 28920065
DOI: 10.1186/s41038-017-0093-9