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.

Oxandrolone Use in Trans-Masculine Youth Appears to Increase Adult Height: Preliminary Evidence.

Purpose: Early use of oxandrolone and gonadotropin-releasing hormone analogs has been shown to increase adult height in patients at risk for short stature, but use in trans-masculine (TM) youth to augment height has not been explored. The purpose of this study was to identify the impact of oxandrolone on adult height in TM youth. Methods: This was a single-center, retrospective chart review of TM patients seen between 2013 and 2018. Hormone regimens, heights, mid-parental height, and bone ages were recorded. We examined correlations between adult height and age at the initiation of treatment or with the age of referral (in untreated patients). Results: Of TM patients, 154 had achieved adult height, including 34 who received oxandrolone, 42 who reached adult height before starting gender-affirming hormone therapy (GAHT), and 14 who received no treatment. Adult height correlated inversely with age at hormone initiation in oxandrolone-treated patients only (p = 0.001). Each earlier year of treatment yielded a 2.3 cm increase in adult height. Those who started oxandrolone younger than the median age achieved an adult height of 169.6 ± 6.4 cm compared to 162.1 ± 6.0 cm in those starting later than the median age (p < 0.001), 164.6 ± 4.8 cm in those receiving no treatment (p = 0.02), and 163.9 ± 6.5 cm in those receiving all other regimens (p < 0.001). Conclusions: Early use of oxandrolone may augment adult height in TM youth. Height discussions should be part of comprehensive GAHT counseling.

Burn-induced hypermetabolism and skeletal muscle dysfunction.

Critical illnesses, including sepsis, cancer cachexia, and burn injury, invoke a milieu of systemic metabolic and inflammatory derangements that ultimately results in increased energy expenditure leading to fat and lean mass catabolism. Burn injuries present a unique clinical challenge given the magnitude and duration of the hypermetabolic response compared with other forms of critical illness, which drastically increase the risk of morbidity and mortality. Skeletal muscle metabolism is particularly altered as a consequence of burn-induced hypermetabolism, as it primarily provides a main source of fuel in support of wound healing. Interestingly, muscle catabolism is sustained long after the wound has healed, indicating that additional mechanisms beyond wound healing are involved. In this review, we discuss the distinctive pathophysiological response to burn injury with a focus on skeletal muscle function and metabolism. We first examine the diverse consequences on skeletal muscle dysfunction between thermal, electrical, and chemical burns. We then provide a comprehensive overview of the known mechanisms underlying skeletal muscle dysfunction that may be attributed to hypermetabolism. Finally, we review the most promising current treatment options to mitigate muscle catabolism, and by extension improve morbidity and mortality, and end with future directions that have the potential to significantly improve patient care.

Effect of oxandrolone and timing of pubertal induction on final height in Turner syndrome: final analysis of the UK randomised placebo-controlled trial.

The UK Turner syndrome (TS) study examined the effect on final height of oxandrolone 0.05 mg/kg/day (maximum dose 2.5 mg) versus placebo from 9 years of age; and delaying ethinylestradiol induction of puberty by 2 years from 12 (E12) to 14 (E14) years in growth hormone-treated girls with TS. The study ran from 1999 to 2013. By 2011, eighty-two of 92 participants had reached final height and an interim analysis using the Super-Imposition by Translation And Rotation model showed significant increases in final height with both oxandrolone and E14. The analysis has been repeated now that all 92 patients have reached final height. Oxandrolone still significantly increased final height by 4.1 cm (95% CI 1.6 to 6.6, n=92) compared with 4.6 cm previously. However, the E14 effect was no longer significant at 2.7 cm (95% CI -0.8 to 6.1, n=56) compared with 3.8 cm previously.

Oxandrolone in Patients on Venovenous Extracorporeal Membrane Oxygenation: A Case Series.

Venovenous extracorporeal membrane oxygenation (VV ECMO) induces a systemic inflammatory response, which may progress to persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The anabolic steroid oxandrolone may improve the metabolic aberrations of PICS. We report our experience with 3 patients on VV ECMO who received oxandrolone after demonstrating refractory catabolism on serial nitrogen balance (NB) studies or persistent weakness. Patients in cases 1 and 3 were started on oxandrolone on VV ECMO days 45 and 29, respectively, for negative NB despite nutrition optimization. The case 2 patient started oxandrolone for persistent weakness 68 days after cannulation. All patients demonstrated improvements in NB results. One patient developed mild transaminitis while on oxandrolone, which did not alter his medication course and resolved after the medication was discontinued. The impact of oxandrolone on functional capacity varied between patients. Oxandrolone may be beneficial in persistently catabolic VV ECMO patients to improve NB results. In some patients, this may support functional recovery. Additional research is needed to identify optimal patients for therapy and to investigate the impact of oxandrolone in this population.

Oxandrolone in the Treatment of Burn Injuries: A Systematic Review and 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.

Anabolic and anticatabolic agents used in burn care: What is known and what is yet to be learned.

Major thermal injury induces profound metabolic derangements secondary to an inflammatory "stress-induced" hormonal environment. Several pharmacological interventions have been tested in an effort to halt the hypermetabolic response to severe burns. Insulin, insulin growth factor 1, insulin growth factor binding protein 3, metformin, human growth hormone, thyroid hormones, testosterone, oxandrolone, and propranolol, among others, have been proposed to have anabolic or anticatabolic effects. The aim of this broad analysis of pharmacological interventions was to raise awareness of treatment options and to help establishing directions for future clinical research efforts. A PubMed search was conducted on the anabolic and anticatabolic agents used in burn care. One hundred and thirty-five human studies published between 1999 and 2017 were included in this review. The pharmacological properties, rationale for the treatments, efficacy considerations and side effect profiles are summarized in the article. Many of the drugs tested for investigational purposes in the severely thermally injured are not yet gold-standard therapies in spite of their potential benefit. Propranolol and oxandrolone have shown great promise but further evidence is still needed to clarify their potential use for anabolic and anticatabolic purposes.

Oxandrolone for growth hormone-treated girls aged up to 18 years with Turner syndrome.

BACKGROUND: The final adult height of untreated girls aged up to 18 years with Turner syndrome (TS) is approximately 20 cm shorter compared with healthy females. Treatment with growth hormone (GH) increases the adult height of people with TS. The effects of adding the androgen, oxandrolone, in addition to GH are unclear. Therefore, we conducted this systematic review to investigate the benefits and harms of oxandrolone as an adjuvant therapy for people with TS treated with GH. OBJECTIVES: To assess the effects of oxandrolone on growth hormone-treated girls aged up to 18 years with Turner syndrome. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was October 2018. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled clinical trials (RCTs) that enrolled girls aged up to 18 years with TS who were treated with GH and oxandrolone compared with GH only treatment. DATA COLLECTION AND ANALYSIS: Three review authors independently screened titles and abstracts for relevance, selected trials, extracted data and assessed risk of bias. We resolved disagreements by consensus, or by consultation with a fourth review author. We assessed trials for overall certainty of the evidence using the GRADE instrument. MAIN RESULTS: We included six trials with 498 participants with TS, 267 participants were randomised to oxandrolone plus GH treatment and 231 participants were randomised to GH only treatment. The individual trial sample size ranged between 22 and 133 participants. The included trials were conducted in 65 different paediatric endocrinology healthcare facilities including clinics, centres, hospitals and academia in the USA and Europe. The duration of interventions ranged between 3 and 7.6 years. The mean age of participants at start of therapy ranged from 9 to 12 years. Overall, we judged only one trial at low risk of bias in all domains and another trial at high risk of bias in most domains. We downgraded the level of evidence mainly because of imprecision (low number of trials, low number of participants or both). Comparing oxandrolone plus GH with GH only for final adult height showed a mean difference (MD) of 2.7 cm in favour of oxandrolone plus GH treatment (95% confidence interval (CI) 1.3 to 4.1; P < 0.001; 5 trials, 270 participants; moderate-quality evidence). The 95% prediction interval ranged between 0.3 cm and 5.1 cm. For adverse events, we based our main analysis on reliable date from two trials with overall low risk of bias. There was no evidence of a difference between oxandrolone plus GH and GH for adverse events (RR 1.81, 95% CI 0.83 to 3.96; P = 0.14; 2 trials, 170 participants; low-quality evidence). Six out of 86 (18.6%) participants receiving oxandrolone plus GH compared with 8/84 (9.5%) participants receiving GH only reported adverse events, mainly signs of virilisation (e.g. deepening of the voice). One trial each investigated the effects of treatments on speech (voice frequency; 88 participants), cognition (51 participants) and psychological status (106 participants). The overall results for these comparisons were inconclusive (very low-quality evidence). No trial reported on health-related quality of life or all-cause mortality. AUTHORS' CONCLUSIONS: Addition of oxandrolone to the GH therapy led to a modest increase in the final adult height of girls aged up to 18 years with TS. Adverse effects identified included virilising effects such as deepening of the voice, but reporting was inadequate in some trials.

Risk Factors Associated with the Development of Transaminitis in Oxandrolone-Treated Adult Burn Patients.

Oxandrolone has proven benefits in thermal burn injury and has become a standard of care. Transaminitis is the most frequent side effect of oxandrolone use, although no risk factors have been identified that increase the risk of transaminitis. The objective was to evaluate the frequency of transaminitis while on oxandrolone and to identify risk factors leading to an increased risk of transaminitis in adult burn patients. This multicenter retrospective risk factor analysis compared two patient groups with and without occurrence of transaminitis, which was detected by an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >100 mg/dL. Secondary outcomes included percentage increase from baseline for AST/ALT, length of stay, and mortality. After univariable analysis, a multivariable logistic regression analysis was performed to detect possible risk factors leading to transaminitis. A total of 309 patients were included, with transaminitis occurring in 128 patients (41.4%) after 13 (interquartile range [IQR] 8-23) days on oxandrolone. After multivariable analysis, age (odds ratio [OR] 0.91; 95% confidence interval [CI] 0.84-0.99 for a 5-year increase in age), intravenous vasopressor use (OR 1.85; 95% CI 1.05-3.27), and amiodarone use (OR 2.51; 95% CI 1.09-5.77) were independent predictors of transaminitis, controlling for TBSA%. Transaminitis was not significantly associated with length of stay or mortality after adjusting for age and TBSA%. We conclude that patients who are younger and have concurrent amiodarone or vasopressor use have the highest risk of developing oxandrolone induced transaminitis and should be monitored closely.

Investigation into Possible Association of Oxandrolone and Heterotopic Ossification Following Burn Injury.

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.

Hormone Therapy in Trauma Patients.

Low-dose hydrocortisone reduces the dose of vasopressors and hospital length of stay; it may also decrease the rate of hospital-acquired pneumonia and time on ventilator. No major side effect was reported, but glycemia and natremia should be monitored. Progesterone did not enhance outcome of trauma patients. A meta-analysis suggested that oxandrolone was associated with shorter length of stay and reduced weight loss. Erythropoietin did not enhance neurologic outcome of traumatic brain-injured patients; such treatment, however, could reduce the mortality in subgroups of patients. This review focuses mainly on glucocorticoids, which are the most extensively investigated treatments in hormone therapy.

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.

Assessment of the impact of oxandrolone on outcomes in burn injured patients.

The purpose of this study is to use a retrospective cohort of burn patients to evaluate the contribution of oxandrolone on burn care outcomes. Longitudinal clinical data is used to analyze outcomes from a new perspective. Our random-effects longitudinal regression analysis model used temporal clinical data to evaluate oxandrolone's impact on outcomes (oxandrolone/non-oxandrolone n=50/11, median length of stay [LOS]=42.2/39.3, mean weight (kg)=192.2/207.6, mean initial prealbumin (mg/dL) 10.1/7.5). The resultant predictive models (p<0.001) described how certain factors influence clinically significant outcomes via a robust data analysis method. LOS was predicted and extended by a greater magnitude of 3rd-degree versus 2nd-degree burns (1.01 versus 0.85 additional days for each %TBSA, p<0.001). Weight was decreased by LOS (145.2g lost per day, p<0.001). Oxandrolone improved prealbumin (3.503mg/dL increase, p<0.001) but instead did not influence patient weight (p>0.05) nor LOS (5.27days shortening, p=0.361). Prealbumin over time was also influenced by initial value (0.293mg/dL, p=0.003), LOS (0.072mg/dL increase per additional day, p<0.001), and the presence of inhalation injury (2.652mg/dL decrease if present, p=0.009). Oxandrolone appears to benefit anabolic protein production. It is difficult to isolate the role of oxandrolone on major outcomes due to the concomitant influence of other variables.

Oxandrolona no tratamento da lipodermatoesclerose: relato de caso / Oxandrolone for treatment of lipodermatosclerosis: case report

A lipodermatoesclerose é uma paniculite que se caracteriza por endurecimento e hiperpigmentação da pele envolvendo as panturrilhas, com a aparência de "garrafa de champanhe invertida". Muitas abordagens terapêuticas têm sido recomendadas, mas o uso de oxandrolona para essa finalidade foi pouco estudado até o momento. Relatamos um caso de lipodermatoesclerose aguda em uma mulher de 61 anos, com história prévia de tratamento cirúrgico para insuficiência venosa de membros inferiores. A paciente apresentava edema e lesões dolorosas e eritematosas com infiltração difusa, que acometiam principalmente a face posterior da panturrilha esquerda. Foi tratada inicialmente com estanozolol e pentoxifilina, com boa resposta. Devido à indisponibilidade do estanozolol, iniciou-se o uso de oxandrolona. Esse tratamento foi bem tolerado, resultando em redução significativa do edema, do eritema e da infiltração presentes nos membros inferiores, além de alívio da dor. A oxandrolona pode representar uma opção útil e segura no tratamento da lipodermatoesclerose aguda

Lipodermatosclerosis is a panniculitis characterized by hardening and hyperpigmentation of the skin involving the calves with an "inverted champagne bottle" appearance. Many therapeutic approaches have been recommended, but the use of oxandrolone for this purpose has been studied very little to date. We report a case of acute lipodermatosclerosis in a 61-year-old woman with a previous history of surgical treatment for venous insufficiency of the lower limbs. The patient presented with edema and painful, erythematous lesions with diffuse infiltration, mainly affecting the posterior aspect of the left calf. She was initially treated with stanozolol and pentoxifylline, with good response. Due to unavailability of stanozolol, she was put on oxandrolone. This treatment was well tolerated, reduced the intensity of edema, erythema, and infiltration in the lower limbs, effectively leading to pain relief. Oxandrolone may be a useful and safe treatment for patients with acute lipodermatosclerosis

Reduced Postburn Hypertrophic Scarring and Improved Physical Recovery With Yearlong Administration of Oxandrolone and Propranolol.

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.

Propranolol and Oxandrolone Therapy Accelerated Muscle Recovery in Burned Children.

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 ß-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.

Anabolic steroids for treating pressure ulcers.

BACKGROUND: Pressure ulcers, also known as bed sores, pressure sores or decubitus ulcers develop as a result of a localised injury to the skin or underlying tissue, or both. The ulcers usually arise over a bony prominence, and are recognised as a common medical problem affecting people confined to a bed or wheelchair for long periods of time. Anabolic steroids are used as off-label drugs (drugs which are used without regulatory approval) and have been used as adjuvants to usual treatment with dressings, debridement, nutritional supplements, systemic antibiotics and antiseptics, which are considered to be supportive in healing of pressure ulcers. Anabolic steroids are considered because of their ability to stimulate protein synthesis and build muscle mass. Comprehensive evidence is required to facilitate decision making, regarding the benefits and harms of using anabolic steroids. OBJECTIVES: To assess the effects of anabolic steroids for treating pressure ulcers. SEARCH METHODS: In March 2017 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: Published or unpublished randomised controlled trials (RCTs) comparing the effects of anabolic steroids with alternative treatments or different types of anabolic steroids in the treatment of pressure ulcers. DATA COLLECTION AND ANALYSIS: Two review authors independently carried out study selection, data extraction and risk of bias assessment. MAIN RESULTS: The review contains only one trial with a total of 212 participants, all with spinal cord injury and open pressure ulcers classed as stage III and IV. The participants were mainly male (98.2%, 106/108) with a mean age of 58.4 (standard deviation 10.4) years in the oxandrolone group and were all male (100%, 104/104) with a mean age of 57.3 (standard deviation 11.6) years in the placebo group. This trial compared oxandrolone (20 mg/day, administered orally) with a dose of placebo (an inactive substance consisting of 98% starch and 2% magnesium stearate) and reported data on complete healing of ulcers and adverse events. There was very low-certainty evidence on the relative effect of oxandrolone on complete ulcer healing at the end of a 24-week treatment period (risk ratio RR) 0.81, 95% confidence interval (CI) 0.52 to 1.26) (downgraded twice for imprecision due to an extremely wide 95% CI, which spanned both benefit and harm, and once for indirectness, as the participants were mostly male spinal cord injury patients). Thus, we are uncertain whether oxandrolone improves or reduces the complete healing of pressure ulcers, as we assessed the certainty of the evidence as very low.There was low-certainty evidence on the risk of non-serious adverse events reported in participants treated with oxandrolone compared with placebo (RR 3.85, 95% CI 1.12 to 13.26) (downgraded once for imprecision and once for indirectness, as the participants were mostly male spinal cord injury patients). Thus, the treatment with oxandrolone may increase the risk of non-serious adverse events reported in participants.There was very low-certainty evidence on the risk of serious adverse events reported in participants treated with oxandrolone compared with placebo (RR 0.54, 95% CI 0.25 to 1.17) (downgraded twice for imprecision due to an extremely wide 95% CI, which spanned both benefit and harm, and once for indirectness, as the participants were mostly male spinal cord injury patients). Of the five serious adverse events reported in the oxandrolone-treated group, none were classed by the trial teams as being related to treatment. We are uncertain whether oxandrolone increases or decreases the risk of serious adverse events as we assessed the certainty of the evidence as very low.Secondary outcomes such as pain, length of hospital stay, change in wound size or wound surface area, incidence of different type of infection, cost of treatment and quality of life were not reported in the included trial.Overall the evidence in this study was of very low quality (downgraded for imprecision and indirectness). This trial stopped early when the futility analysis (interim analysis) in the opinion of the study authors showed that oxandrolone had no benefit over placebo for improving ulcer healing. AUTHORS' CONCLUSIONS: There is no high quality evidence to support the use of anabolic steroids in treating pressure ulcers.Further well-designed, multicenter trials, at low risk of bias, are necessary to assess the effect of anabolic steroids on treating pressure ulcers, but careful consideration of the current trial and its early termination are required when planning future research.

Androgen Treatment Effects on Motor Function, Cognition, and Behavior in Boys with Klinefelter Syndrome.

OBJECTIVES: To examine the effects of early low-dose androgen on motor, cognitive, and behavioral function in prepubertal boys with Klinefelter syndrome (47,XXY). STUDY DESIGN: Double-blind trial of 84 boys, ages 4-12 years, randomized to oxandrolone (Ox; 0.06?mg/kg daily; n?=?43) or placebo (Pl; n?=?41) for 24 months. Standardized assessments were performed at baseline and every 12 months for 24 months evaluating motor, cognitive, and behavioral function. RESULTS: The 24-month outcomes were better in the Ox vs. Pl group on 1 of 5 primary endpoints (motor function/strength): Bruininks Visual-Motor scale (P?=?.005), without significant differences between the 2 groups for the other 4 components. Secondary analyses suggested improvement in the Ox vs. Pl group in the anxiety/depression (P?=?.03) and social problems (P?=?.01) scales on the Child Behavior Checklist, anxiety (P?=?.04) on the Piers Harris Self Concept Scale, and interpersonal problems (P?=?.02) on the Children's Depression Inventory, without significant differences in hyperactive or aggressive behaviors. CONCLUSIONS: This double-blind, randomized trial demonstrates that 24 months of childhood low-dose androgen treatment in boys with Klinefelter syndrome benefited 1 of 5 primary endpoints (visual-motor function). Secondary analyses demonstrated positive effects of androgen on aspects of psychosocial function (anxiety, depression, social problems), without significant effects on cognitive function, or hyperactive or aggressive behaviors. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00348946.

Oxandrolone Coadministration Does Not Alter Plasma Propranolol Concentrations in Severely Burned Pediatric Patients.

The systemic impact of severe burn injury results in a variety of disorders that require therapeutic intervention. Propranolol, a nonselective ß1, ß2-adrenergic receptor antagonist, reduces resting heart rate and cardiac work caused by elevated circulating catecholamines. Oxandrolone, a testosterone mimetic, promotes protein synthesis and anabolism to counter muscle wasting. Coadministration of these drugs is expected to synergistically improve patient outcomes. Testosterone administration is known to alter ß-adrenergic receptor-mediated signaling. Here, we determined whether the coadministration of oxandrolone alters plasma propranolol concentrations. Ninety-two pediatric patients with burns covering ≥30% of the TBSA were enrolled in this institutional review board-approved study and randomized to receive propranolol (n = 49) or oxandrolone + propranolol (n = 43). Plasma propranolol concentrations were determined following two dosing strategies: Q6 (liquid formulation; n = 86) and Q24 (extended-release capsule; n = 22). Samples were drawn before drug administration and at regular intervals throughout the next two dosing periods. Heart rate and blood pressure were recorded throughout the study. Propranolol half-life was 3.3 hours for the Q6 drug dosing frequency (P < .0001) and 11.2 hours for the Q24 strategy (P < .0001). Percentage of predicted heart rate declined by 2.8% for each doubling of the propranolol concentration in the Q6 dosing schedule (P < .0001). Percentage of predicted heart rate declined by 2.5% for each doubling of propranolol concentration on the Q24 dosing schedule (P < .0001). Maximum and minimum propranolol plasma concentrations were similar with either dosing regimen. The addition of oxandrolone did not affect any of the measured parameters. Oxandrolone coadministration does not alter propranolol's plasma concentration, half-life, or effect on heart rate. This study is registered at clincialtrials.gov: NCT00675714.

Effects of Oxandrolone on Cardiometabolic Health in Boys With Klinefelter Syndrome: A Randomized Controlled Trial.

Context: Klinefelter syndrome (KS) is a common condition in males, resulting in androgen deficiency and cardiometabolic diseases. These interrelated conditions may be present in prepubertal boys with KS. Objective: To determine whether supplemental low-dose androgen has a beneficial effect on body composition in prepubertal boys with KS. Design, Setting, and Participants: We conducted a secondary analysis of a randomized, double-blind, placebo-controlled clinical trial in 93 boys with KS aged 4 to 12 years. Interventions: Oral oxandrolone (Ox) 0.06 mg/kg/d or placebo for 2 years. Outcome Measures: The primary outcome was percent body fat standard deviation score (%BF SDS) at 2 years. Secondary outcomes included additional measures of cardiometabolic health and safety. Results: The %BF SDS at 2 years was significantly lower in the treatment (0.29 ± 0.76 SDS) compared with placebo group (0.81 ± 0.72 SDS) after adjusting for age and baseline %BF SDS (95% confidence interval for the difference between means -0.86 to -0.19 SDS, P = 0.009). Ox resulted in lower triglycerides (P = 0.043), but also lower high-density lipoprotein (HDL) cholesterol (P < 0.001) and a more rapid advancement in bone age (P = 0.011). Conclusions: Ox has positive effects on measures of cardiometabolic health in prepubertal boys with KS; however, it does lower HDL cholesterol and advance bone age.