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Journal of Burn Care & Research :... Jun 2019Oxandrolone, a testosterone analog, is used to counteract the catabolic effects of burn injury. Recent animal studies suggest a possible hormonal association with...
Oxandrolone, a testosterone analog, is used to counteract the catabolic effects of burn injury. Recent animal studies suggest a possible hormonal association with heterotopic ossification (HO) development postburn. This work examines oxandrolone administration and HO development by exploring historical clinical data bridging the introduction of oxandrolone into clinical practice. Additionally, we examine associations between oxandrolone administration and HO in a standardized mouse model of burn/trauma-related HO. Acutely burned adults admitted between 2000 and 2014, survived through discharge, and had a HO risk factor of 7 or higher were selected for analysis from a single burn center. Oxandrolone administration, clinical and demographic data, and elbow HO were recorded and were analyzed with logistic regression. Associations of oxandrolone with HO were examined in a mouse model. Mice were administered oxandrolone or vehicle control following burn/tenotomy to examine any potential effect of oxandrolone on HO and were analyzed by Student's t test. Subjects who received oxandrolone had a higher incidence of elbow HO than those that did not receive oxandrolone. However, when controlling for oxandrolone administration, oxandrolone duration, postburn day oxandrolone initiation, HO risk score category, age, sex, race, burn size, and year of injury, there was no significant difference between rates of elbow HO between the two populations. In agreement with the review, in the mouse model, while there was a trend toward the oxandrolone group developing a greater volume of HO, this did not reach statistical significance.
Topics: Adult; Anabolic Agents; Animals; Burns; Female; Humans; Male; Mice; Models, Animal; Ossification, Heterotopic; Oxandrolone; Risk Factors; Treatment Outcome; Wound Healing
PubMed: 31053861
DOI: 10.1093/jbcr/irz063 -
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 -
Journal of Burn Care & Research :... Jan 2020Severe burns induce a profound hypermetabolic response, leading to a prolonged state of catabolism associated with organ dysfunction and delay of wound healing.... (Meta-Analysis)
Meta-Analysis
Severe burns induce a profound hypermetabolic response, leading to a prolonged state of catabolism associated with organ dysfunction and delay of wound healing. Oxandrolone, a synthetic testosterone analog, may alleviate the hypermetabolic catabolic state thereby decreasing associated morbidity. However, current literature has reported mixed outcomes on complications following Oxandrolone use, specifically liver and lung function. We conducted an updated systematic review and meta-analysis studying the effects of Oxandrolone on mortality, length of hospital stay, progressive liver dysfunction, and nine secondary outcomes. We searched Pubmed, EMBASE, Web of Science, CINAHL, and Cochrane Databases of Systematic Reviews and Randomized Controlled Trials. Thirty-one randomized control trials and observational studies were included. Basic science and animal studies were excluded. Only studies comparing Oxandrolone to standard of care, or placebo, were included. Oxandrolone did not affect rates of mortality (relative risk [RR]: 0.72; 95% confidence interval [CI]: 0.47 to 1.08; P = .11) or progressive liver dysfunction (RR: 1.04; 95% CI: 0.59 to 1.85; P = .88), but did decrease length of stay in hospital. Oxandrolone significantly increased weight regain, bone mineral density, percent lean body mass, and decreased wound healing time for donor graft sites. Oxandrolone did not change the incidence of transient liver dysfunction or mechanical ventilation requirements. There is evidence to suggest that Oxandrolone is a beneficial adjunct to the acute care of burn patients; shortening hospital stays and improving several growth and wound healing parameters. It does not appear that Oxandrolone increases the risk of progressive or transient liver injury, although monitoring liver enzymes is recommended.
Topics: Adolescent; Adult; Aged; Anabolic Agents; Burns; Child; Child, Preschool; Humans; Incidence; Length of Stay; Liver Diseases; Middle Aged; Oxandrolone; Survival Rate; Young Adult
PubMed: 31504621
DOI: 10.1093/jbcr/irz155 -
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 -
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 -
Critical Care Medicine Jun 2016ICU-acquired weakness is a common complication of critical illness and can have significant effects upon functional status and quality of life. As part of preliminary... (Review)
Review
OBJECTIVES
ICU-acquired weakness is a common complication of critical illness and can have significant effects upon functional status and quality of life. As part of preliminary work to inform the design of a randomized trial of a complex intervention to improve recovery from critical illness, we sought to identify pharmacological interventions that may play a role in this area.
DATA SOURCES
We systematically reviewed the published literature relating to pharmacological intervention for the treatment and prevention of ICU-acquired weakness.
STUDY SELECTION
We searched MEDLINE, EMBASE, CINAHL+, Web of Science, and both U.S. and European trial registries up to July 2014 alongside reviews and reference lists from populations with no age or language restrictions. We included studies that reported a measure of muscle structure or physical function as an outcome measure.
DATA EXTRACTION
We estimated pooled odds ratios and 95% CI using data extracted from published articles or where available, original data provided by the authors. Assessment of bias was performed using the Cochrane Collaboration's risk of bias tool.
DATA SYNTHESIS
Ten studies met the inclusion criteria. The current body of evidence does not support the use of any pharmacological agent in this setting, although maintaining euglycemia may reduce the prevalence of critical illness polyneuropathy.
CONCLUSIONS
At present, no pharmacological intervention can be recommended to prevent or treat ICU-acquired weakness. Further research is required into this field to include more novel agents such as myostatin inhibitors. Challenges in the conduct of research in this area are highlighted.
Topics: Adrenergic beta-Antagonists; Anabolic Agents; Critical Illness; Glutamine; Growth Hormone; Humans; Hyperglycemia; Hypoglycemic Agents; Immunoglobulins, Intravenous; Immunologic Factors; Insulin; Muscle Weakness; Oxandrolone; Polyneuropathies; Propranolol
PubMed: 26958749
DOI: 10.1097/CCM.0000000000001652 -
Annals of Surgery Sep 2018Massive burns induce a hypermetabolic response that leads to total body wasting and impaired physical and psychosocial recovery. The administration of propranolol or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Massive burns induce a hypermetabolic response that leads to total body wasting and impaired physical and psychosocial recovery. The administration of propranolol or oxandrolone positively affects postburn metabolism and growth. The combined administration of oxandrolone and propranolol (OxProp) for 1 year restores growth in children with large burns. Here, we investigated whether the combined administration of OxProp for 1 year would reduce scarring and improve quality of life compared with control.
STUDY DESIGN
Children with large burns (n = 480) were enrolled into this institutional review board-approved study; patients were randomized to control (n = 226) or administration of OxProp (n = 126) for 1 year postburn. Assessments were conducted at discharge and 6, 12, and 24 months postburn. Scar biopsies were obtained for histology. Physical scar assessments and patient reported outcome measures of physical and psychosocial function were obtained.
RESULTS
Reductions in cellularity, vascular structures, inflammation, and abnormal collagen (P < 0.05) occurred in OxProp-treated scars. With OxProp, scar severity was attenuated and pliability increased (both P < 0.05). Analyses of patient-reported outcomes showed improved general and emotional health within the OxProp-treated group (P < 0.05).
CONCLUSIONS
Here, we have shown improvements in objective and subjective measures of scarring and an increase in overall patient-reported physical function. The combined administration of OxProp for up to a year after burn injury should be considered for the reduction of postburn scarring and improvement of long-term psychosocial outcomes in children with massive burns.
Topics: Adolescent; Anabolic Agents; Biomarkers; Biopsy; Burns; Child; Cicatrix, Hypertrophic; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Humans; Immunoenzyme Techniques; Male; Oxandrolone; Propranolol; Prospective Studies; Quality of Life; Recovery of Function; Treatment Outcome; Vasodilator Agents
PubMed: 30048322
DOI: 10.1097/SLA.0000000000002926 -
Medicine and Science in Sports and... Mar 2018Severe burns result in prolonged hypermetabolism and skeletal muscle catabolism. Rehabilitative exercise training (RET) programs improved muscle mass and strength in... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Severe burns result in prolonged hypermetabolism and skeletal muscle catabolism. Rehabilitative exercise training (RET) programs improved muscle mass and strength in severely burned children. The combination of RET with β-blockade or testosterone analogs showed improved exercise-induced benefits on body composition and muscle function. However, the effect of RET combined with multiple drug therapy on muscle mass, strength, cardiorespiratory fitness, and protein turnover are unknown. In this placebo-controlled randomized trial, we hypothesize that RET combined with oxandrolone and propranolol (Oxprop) will improve muscle mass and function and protein turnover in severely burned children compared with burned children undergoing the same RET with a placebo.
METHODS
We studied 42 severely burned children (7-17 yr) with severe burns over 30% of the total body surface area. Patients were randomized to placebo (22 control) or to Oxprop (20) and began drug administration within 96 h of admission. All patients began RET at hospital discharge as part of their standardized care. Muscle strength (N·m), power (W), V˙O2peak, body composition, and protein fractional synthetic rate and fractional breakdown rate were measured pre-RET (PRE) and post-RET (POST).
RESULTS
Muscle strength and power, lean body mass, and V˙O2peak increased with RET in both groups (P < 0.01). The increase in strength and power was significantly greater in Oxprop versus control (P < 0.01), and strength and power was greater in Oxprop over control POST (P < 0.05). Fractional synthetic rate was significantly higher in Oxprop than control POST (P < 0.01), resulting in improved protein net balance POST (P < 0.05).
CONCLUSIONS
Rehabilitative exercise training improves body composition, muscle function, and cardiorespiratory fitness in children recovering from severe burns. Oxprop therapy augments RET-mediated improvements in muscle strength, power, and protein turnover.
Topics: Adolescent; Basal Metabolism; Body Composition; Burns; Cardiorespiratory Fitness; Child; Exercise Therapy; Female; Heart Rate; Humans; Male; Muscle Strength; Muscle, Skeletal; Oxandrolone; Oxygen Consumption; Propranolol
PubMed: 29040226
DOI: 10.1249/MSS.0000000000001459 -
Current Opinion in Endocrinology,... Dec 2022This review aims to report the most recent (2020-2022) experimental scientific studies conducted on animal models, in order to highlight the relevant findings on the... (Review)
Review
PURPOSE OF REVIEW
This review aims to report the most recent (2020-2022) experimental scientific studies conducted on animal models, in order to highlight the relevant findings on the adverse effects related to androgen administration.
RECENT FINDINGS
Forty-one studies published between January 2020 and July 2022 were selected. The majority of studies investigated the effects of one androgen, whereas only four studies analyzed the effects of two drugs. Nandrolone decanoate was the most investigated drug (20 articles), boldenone was tested in 8 articles, testosterone and stanozolol were used in 7 articles each, 17b-trenbolone, metandienone, and oxandrolone were tested in 1 article each. The articles clarify the adverse effects of androgen administration on the heart, brain, kidney, liver, reproductive and musculoskeletal systems.
SUMMARY
The main findings of this review highlight that androgen administration increases inflammatory mediators, altering different biochemical parameters. The results concerning the reversibility of the adverse effects are controversial: on the one hand, several studies suggested that by stopping the androgen administration, the organs return to their initial state; on the other hand, the alteration of different biochemical parameters could generate irreversible organ damage. Moreover, this review highlights the importance of animal studies that should be better organized in order to clarify several important aspects related to androgen abuse to fill the gap in our knowledge in this research field.
Topics: Animals; Humans; Androgens; Nandrolone Decanoate; Stanozolol; Methandrostenolone; Trenbolone Acetate; Oxandrolone; Testosterone; Inflammation Mediators
PubMed: 35943186
DOI: 10.1097/MED.0000000000000768 -
The Cochrane Database of Systematic... Sep 2014Recombinant human growth hormone (rhGH) increases protein synthesis, therefore it is used in burns with a total body surface area (TBSA) greater than 40%, where there is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recombinant human growth hormone (rhGH) increases protein synthesis, therefore it is used in burns with a total body surface area (TBSA) greater than 40%, where there is frequently an increase in protein breakdown and a decrease in protein synthesis. This change in protein metabolism correlates with poor wound healing of the burn and donor sites.
OBJECTIVES
To determine the effects of rhGH on the healing rate of burn wounds and donor sites in people with burns.
SEARCH METHODS
For this first update we searched the Cochrane Wounds Group Specialised Register (searched 04 September 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 8); Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library 2014, Issue 3); Ovid MEDLINE (1950 to September Week 4 2014); Ovid MEDLINE (In-Process & Other Non-Indexed Citations September 8, 2014); Ovid EMBASE (1980 to 2014 Week 35); and EBSCO CINAHL (1982 to 8 September 2014).
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing rhGH with any comparator intervention, e.g. oxandrolone or placebo, in adults or children with burns.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed trial quality and extracted data. The primary outcomes were the healing of the burn wound and donor sites and the occurrence of wound infections. The secondary outcomes were mortality rate, length of hospital stay, scar assessment, and adverse events: hyperglycaemia and septicaemia.
MAIN RESULTS
We included 13 RCTs (701 people). Six of the RCTs included only children aged 1 to 18 years and seven involved only adults (from 18 to 65 years of age). The mean TBSA of the included participants was greater than 49%. Twelve studies compared rhGH with placebo and one study compared rhGH with oxandrolone. Two trials found that compared with placebo, burn wounds in adults treated with rhGH healed more quickly (by 9.07 days; 95% confidence interval (CI) 4.39 to 13.76, I² = 0%). The donor site healing time was significantly shorter in rhGH-treated adults compared with placebo-treated participants (by 3.15 days; 95% CI 1.54 to 4.75, I² = 0%). Two studies in children with the outcome of donor site healing time could be pooled and the donor site healing time was shorter in the rhGH-treated children (by 1.70 days; 95% CI 0.87 to 2.53, I² = 0%). No studies reporting the outcome of wound infection were found. The incidence of hyperglycaemia was higher in adults during rhGH treatment compared with placebo (risk ratio (RR) 2.43; 95% CI 1.54 to 3.85), but not in children. Pooling the studies of adults and children yielded a significantly higher incidence of hyperglycaemia in the rhGH-treated participants (RR 2.65; 95% CI 1.68 to 4.16).
AUTHORS' CONCLUSIONS
There is some evidence that using rhGH in people with large burns (more than 40% of the total body surface area) could result in more rapid healing of the burn wound and donor sites in adults and children, and in reduced length of hospital stay, without increased mortality or scarring, but with an increased risk of hyperglycaemia. This evidence is based on studies with small sample sizes and risk of bias and requires confirmation in higher quality, adequately powered trials.
Topics: Adolescent; Adult; Aged; Anabolic Agents; Body Surface Area; Burns; Child; Child, Preschool; Human Growth Hormone; Humans; Infant; Middle Aged; Oxandrolone; Randomized Controlled Trials as Topic; Recombinant Proteins; Transplant Donor Site; Wound Healing; Young Adult
PubMed: 25222766
DOI: 10.1002/14651858.CD008990.pub3