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Cureus Aug 2022Wounds with delayed or impaired healing represent a considerable challenge in medical practice. These patients develop a sustained hypermetabolic and catabolic state,... (Review)
Review
Wounds with delayed or impaired healing represent a considerable challenge in medical practice. These patients develop a sustained hypermetabolic and catabolic state, directly impacting the wound healing process. The use of oxandrolone has been studied to control this metabolic imbalance and protect lean body mass as a beneficial resource in wound healing. This systematic review aims to analyze previously conducted randomized controlled trials to evaluate the evidence of the applicability of oxandrolone therapy. We compared its use in adult patients with burns and adult patients with pressure ulcers in terms of wound healing and healing time of the skin graft donor site in days. The digital searches were done from March 23-28, 2022, within the databases: Google Scholar, PubMed/MEDLINE, and EBSCO (Elton B. Stephens Company). Data from six studies were analyzed and included in this review. Analysis of the available data demonstrated a significant advantage in skin healing using oxandrolone in adult burn patients as an adjunct. For adult patients with pressure ulcers, the drug showed no benefit on wound healing and skin graft site healing. Importantly, we found only one study evaluating the use of oxandrolone in patients with decubitus ulcers that met our eligibility criteria, and the certainty of the evidence was low. Thus, further prospective randomized studies with larger samples and standard wound care protocols are needed to produce more solid results, allowing more definitive conclusions to be made on this theme.
PubMed: 36127967
DOI: 10.7759/cureus.28079 -
The Cochrane Database of Systematic... Jun 2017Pressure 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... (Review)
Review
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.
Topics: Female; Humans; Male; Middle Aged; Off-Label Use; Oxandrolone; Pressure Ulcer; Starch; Stearic Acids; Testosterone Congeners; Wound Healing
PubMed: 28631809
DOI: 10.1002/14651858.CD011375.pub2 -
American Journal of Men's Health 2020During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass.... (Review)
Review
During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass. Testosterone is the most abundant testicular androgen, but some effects are mediated by its conversion to the more potent androgen dihydrotestosterone (DHT) or to estradiol. Androgen deficiency, requiring replacement therapy, may occur due to a primary testicular failure or secondary to a hypothalamic-pituitary disorder. A very frequent condition characterized by a late activation of the gonadal axis that may also need androgen treatment is constitutional delay of puberty. Of the several testosterone or DHT formulations commercially available, very few are employed, and none is marketed for its use in adolescents. The most frequently used androgen therapy is based on the intramuscular administration of testosterone enanthate or cypionate every 3 to 4 weeks, with initially low doses. These are progressively increased during several months or years, in order to mimic the physiology of puberty, until adult doses are attained. Scarce experience exists with oral or transdermal formulations. Preparations containing DHT, which are not widely available, are preferred in specific conditions. Oxandrolone, a non-aromatizable drug with higher anabolic than androgenic effects, has been used in adolescents with preserved testosterone production, like Klinefelter syndrome, with positive effects on cardiometabolic health and visual, motor, and psychosocial functions. The usual protocols applied for androgen therapy in boys and adolescents are discussed.
Topics: Adolescent; Androgens; Child; Clinical Protocols; Disorders of Sex Development; Hormone Replacement Therapy; Humans; Klinefelter Syndrome; Male; Outcome Assessment, Health Care; Puberty
PubMed: 32448030
DOI: 10.1177/1557988320922443 -
Pharmacotherapy Feb 2009Severe thermal injury is associated with hypermetabolism and hypercatabolism, leading to skeletal muscle breakdown, lean body mass loss, weight loss, and negative... (Review)
Review
Severe thermal injury is associated with hypermetabolism and hypercatabolism, leading to skeletal muscle breakdown, lean body mass loss, weight loss, and negative nitrogen balance. Muscle protein catabolism in patients with severe thermal injury is the result of stress-induced increased release of cytokines and counterregulatory hormones. Coupled with decreased serum anabolic hormone concentrations such as testosterone and growth hormone along with the presence of insulin resistance, anabolism in patients with severe thermal injury is inefficient or impossible during the acute postburn period. This causes difficulty in restoring lean body mass and regaining lost body weight, as well as poor healing of the burn wound and delayed patient recovery. Oxandrolone, a synthetic derivative of testosterone, has been used in adult patients with severe thermal injury to enhance lean body mass accretion, restore body weight, and accelerate wound healing. In clinical studies, oxandrolone 10 mg orally twice/day improved wound healing, restored lean body mass, and accelerated body weight gain. During the rehabilitation period, oxandrolone therapy with adequate nutrition and exercise improved lean body mass, increased muscle strength, and restored body weight. However, most data on oxandrolone use in adult patients with severe thermal injury are derived from single-center studies, many of which enrolled a relatively small number of subjects and some of which had a poor design. Multicenter, prospective, randomized studies are needed to better define the optimal oxandrolone dosage and to confirm the efficacy and safety of this drug in adult patients with severe thermal injury.
Topics: Adult; Anabolic Agents; Body Weight; Burns; Clinical Trials as Topic; Humans; Nutritional Support; Oxandrolone; Severity of Illness Index; Wound Healing
PubMed: 19170590
DOI: 10.1592/phco.29.2.213 -
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 -
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 -
PloS One 2022Duchenne muscular dystrophy (DMD) is a rare, severely debilitating, and fatal neuromuscular disease characterized by progressive muscle degeneration. Like in many orphan... (Review)
Review
BACKGROUND
Duchenne muscular dystrophy (DMD) is a rare, severely debilitating, and fatal neuromuscular disease characterized by progressive muscle degeneration. Like in many orphan diseases, randomized controlled trials are uncommon in DMD, resulting in the need to indirectly compare treatment effects, for example by pooling individual patient-level data from multiple sources. However, to derive reliable estimates, it is necessary to ensure that the samples considered are comparable with respect to factors significantly affecting the clinical progression of the disease. To help inform such analyses, the objective of this study was to review and synthesise published evidence of prognostic indicators of disease progression in DMD. We searched MEDLINE (via Ovid), Embase (via Ovid) and the Cochrane Library (via Wiley) for records published from inception up until April 23 2021, reporting evidence of prognostic indicators of disease progression in DMD. Risk of bias was established with the grading system of the Centre for Evidence-Based Medicine (CEBM).
RESULTS
Our search included 135 studies involving 25,610 patients from 18 countries across six continents (Africa, Asia, Australia, Europe, North America and South America). We identified a total of 23 prognostic indicators of disease progression in DMD, namely age at diagnosis, age at onset of symptoms, ataluren treatment, ATL1102, BMI, cardiac medication, DMD genetic modifiers, DMD mutation type, drisapersen, edasalonexent, eteplirsen, glucocorticoid exposure, height, idebenone, lower limb surgery, orthoses, oxandrolone, spinal surgery, TAS-205, vamorolone, vitlolarsen, ventilation support, and weight. Of these, cardiac medication, DMD genetic modifiers, DMD mutation type, and glucocorticoid exposure were designated core prognostic indicators, each supported by a high level of evidence and significantly affecting a wide range of clinical outcomes.
CONCLUSION
This study provides a current summary of prognostic indicators of disease progression in DMD, which will help inform the design of comparative analyses and future data collection initiatives in this patient population.
Topics: Disease Progression; Glucocorticoids; Humans; Morpholines; Muscular Dystrophy, Duchenne; Piperidines; Prognosis; Pyrroles
PubMed: 35333888
DOI: 10.1371/journal.pone.0265879 -
Cureus Jan 2021Anabolic-androgenic steroids (AAS) are commonly used among both competitive athletes and recreational athletes in order to gain a performance edge. Unfortunately, AAS...
Anabolic-androgenic steroids (AAS) are commonly used among both competitive athletes and recreational athletes in order to gain a performance edge. Unfortunately, AAS generally carries a broad range of short term and long term adverse effects. These include endocrinological abnormalities, cardiovascular risks, psychological issues, and largely adverse effects on every organ system in the human body. While testosterone, and at times oxandrolone, are used for clinical purposes, AAS generally encompasses a very broad range of synthetic compounds that are used at high doses. In this case report, we look at a patient who has used the vast majority of common anabolic steroids over the past three decades and how these compounds may affect long-term metabolic and cardiovascular health. The purpose is to provide a primary care approach to this patient population.
PubMed: 33564503
DOI: 10.7759/cureus.12492 -
The Cochrane Database of Systematic... Jul 2015Inclusion body myositis (IBM) is a late-onset inflammatory muscle disease (myopathy) associated with progressive proximal and distal limb muscle atrophy and weakness.... (Review)
Review
BACKGROUND
Inclusion body myositis (IBM) is a late-onset inflammatory muscle disease (myopathy) associated with progressive proximal and distal limb muscle atrophy and weakness. Treatment options have attempted to target inflammatory and atrophic features of this condition (for example with immunosuppressive and immunomodulating drugs, anabolic steroids, and antioxidant treatments), although as yet there is no known effective treatment for reversing or minimising the progression of inclusion body myositis. In this review we have considered the benefits, adverse effects, and costs of treatment in targeting cardinal effects of the condition, namely muscle atrophy, weakness, and functional impairment.
OBJECTIVES
To assess the effects of treatment for IBM.
SEARCH METHODS
On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Additionally in November 2014 we searched clinical trials registries for ongoing or completed but unpublished trials.
SELECTION CRITERIA
We considered randomised or quasi-randomised trials, including cross-over trials, of treatment for IBM in adults compared to placebo or any other treatment for inclusion in the review. We specifically excluded people with familial IBM and hereditary inclusion body myopathy, but we included people who had connective tissue and autoimmune diseases associated with IBM, which may or may not be identified in trials. We did not include studies of exercise therapy or dysphagia management, which are topics of other Cochrane systematic reviews.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
The review included 10 trials (249 participants) using different treatment regimens. Seven of the 10 trials assessed single agents, and 3 assessed combined agents. Many of the studies did not present adequate data for the reporting of the primary outcome of the review, which was the percentage change in muscle strength score at six months. Pooled data from two trials of interferon beta-1a (n = 58) identified no important difference in normalised manual muscle strength sum scores from baseline to six months (mean difference (MD) -0.06, 95% CI -0.15 to 0.03) between IFN beta-1a and placebo (moderate-quality evidence). A single trial of methotrexate (MTX) (n = 44) provided moderate-quality evidence that MTX did not arrest or slow disease progression, based on reported percentage change in manual muscle strength sum scores at 12 months. None of the fully published trials were adequately powered to detect a treatment effect. We assessed six of the nine fully published trials as providing very low-quality evidence in relation to the primary outcome measure. Three trials (n = 78) compared intravenous immunoglobulin (combined in one trial with prednisone) to a placebo, but we were unable to perform meta-analysis because of variations in study analysis and presentation of trial data, with no access to the primary data for re-analysis. Other comparisons were also reported in single trials. An open trial of anti-T lymphocyte immunoglobulin (ATG) combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy, based on percentage change in quantitative muscle strength sum scores at 12 months (MD 12.50%, 95% CI 2.43 to 22.57). Data from trials of oxandrolone versus placebo, azathioprine (AZA) combined with MTX versus MTX, and arimoclomol versus placebo did not allow us to report either normalised or percentage change in muscle strength sum scores. A complete analysis of the effects of arimoclomol is pending data publication. Studies of simvastatin and bimagrumab (BYM338) are ongoing. All analysed trials reported adverse events. Only 1 of the 10 trials interpreted these for statistical significance. None of the trials included prespecified criteria for significant adverse events.
AUTHORS' CONCLUSIONS
Trials of interferon beta-1a and MTX provided moderate-quality evidence of having no effect on the progression of IBM. Overall trial design limitations including risk of bias, low numbers of participants, and short duration make it difficult to say whether or not any of the drug treatments included in this review were effective. An open trial of ATG combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy based on the percentage change data given. We were unable to draw conclusions from trials of IVIg, oxandrolone, and AZA plus MTX versus MTX. We need more randomised controlled trials that are larger, of longer duration, and that use fully validated, standardised, and responsive outcome measures.
PubMed: 35658164
DOI: 10.1002/14651858.CD001555.pub5 -
Harm Reduction Journal Apr 2023The masculinizing effects from anabolic-androgenic steroid (AAS) appear to be different between men and women, leading to calls for more gender-specific information...
BACKGROUND
The masculinizing effects from anabolic-androgenic steroid (AAS) appear to be different between men and women, leading to calls for more gender-specific information regarding women and AAS use. This study sought to gather perspectives from both men and women on the unique challenges surrounding women's use of AAS, irrespective of their personal use. Secondly, the study interrogated how women's AAS practices differ from those of men specifically.
METHODS
The data presented in this paper come from a subsample of participants who participated in a larger study investigating women and performance and image enhancing drug (PIED) use in Australia. Participants were included in the current analysis if they were: (i) males or females who competed with or coached female strength athletes using AAS and (ii) female and male strength athletes who used AAS. The final sample comprised 21 participants of which there was a proportion of males (n = 7) and females (n = 7) using AAS.
RESULTS
Women's choices in AAS selection were predominantly around oral compounds (e.g. Oxandrolone) as well as other PIEDs (e.g. Clenbuterol). Some women report the use of injectable AAS represents a change in the profile of the typical female user as it reportedly comes alongside drastic physical and psychological changes.
CONCLUSIONS
The unique challenges facing women who use AAS are largely isolation and stigma, with little evidence-based practice or education being available to them online or through peer-groups. Future work may consider piloting harm reduction strategies that may be co-designed with this group.
Topics: Humans; Male; Female; Androgens; Steroids; Anabolic Androgenic Steroids; Anabolic Agents; Testosterone Congeners; Performance-Enhancing Substances
PubMed: 37098574
DOI: 10.1186/s12954-023-00786-x