madman
Super Moderator
A Reappraisal of Oxandrolone in Burn Management (2022)
Jonathan Kopel, Ph.D., Grant Sorensen, MD, and John Griswold, MD
Abstract
Objective: Burn injuries remain among the most severe traumatic injuries globally. With the discovery of cortisol, the use of steroids has become an essential therapy for the management of inflammatory and metabolic conditions. Several studies have shown the steroid oxandrolone improves burn injuries by stimulating anabolic and reducing catabolic processes. In this review, we examine the efficacy and applications of oxandrolone with regard to burn management and treatment.
Data Sources: A literature search was performed using the PubMed database from January 1990 to May 2020 to identify articles on oxandrolone and burn management. A total of 18 studies were included in our review. Study.
Selection and Criteria: The keywords used in our search strategy for PubMed included “oxandrolone” and “burns.”
Data Synthesis: The main benefit of oxandrolone is the improved long-term lean body, protein, and bone mineral mass of burn patients. In addition, 3 separate meta-analyses showed oxandrolone shortened length of hospital stay, donor-site healing time, reduced weight loss, and net protein loss. However, oxandrolone therapy did not affect mortality, infection, or liver function.
Conclusion: Oxandrolone remains an effective therapy for reducing the hypermetabolic response and comorbidities from burn injuries. Future clinical trials are needed using larger sample sizes and long-term follow-up to determine whether oxandrolone in the context of rehabilitation programs can reduce mortality, lower treatment costs, and improve functional outcomes among burn patients.
Introduction-Oxandrolone History
With the discovery of cortisol, steroids have become an essential therapy for the management of inflammatory and metabolic conditions.1 The synthesis of steroids was originally directed toward the treatment of rheumatoid arthritis; subsequently, it was expanded to improve metabolic function in hospitalized patients and athletes.1 The success of cortisol also increased the use of other anabolic steroids, including oxandrolone.1 Oxandrolone was first synthesized in the 1960s by Fox and Gherondache et al for women and children to promote lean tissue growth after surgery, trauma, and infection.2-5 Subsequent studies later showed oxandrolone had 6 times greater anabolic activity compared with testosterone.4,5 Given its potent anabolic activities, bodybuilders and competitive athletes abused oxandrolone to increase muscle gain without fat or water accumulation; as a result, oxandrolone was discontinued in 1989.4,5 However, oxandrolone was reintroduced in 1995 for preserving lean mass, particularly among patients with AIDS wasting, alcoholic hepatitis, and Turner syndrome.4,5 Since then, oxandrolone has shown clinical outcomes in several catabolic conditions, such as neuromuscular disorders, alcoholic hepatitis, and chronic inflammatory illnesses. In recent years, oxandrolone has shown several beneficial effects in the treatment and management of burn injuries.
Oxandrolone Pharmacology and Guidelines
Oxandrolone is a nonreducible, nonaromatizable synthetic chemical. Oxandrolone is structurally similar to testosterone but has a unique chemical arrangement in which an oxygen atom replaces the methylene group.5 Oxandrolone is rapidly absorbed, with peak serum concentrations occurring in about 1 hour. With a distribution half-life of 30 minutes and an elimination half-life of approximately 9 hours, plasma oxandrolone concentrations drop in a biphasic manner. In addition, 95% of oxandrolone is bound to proteins.5
Currently, oxandrolone can be given at 10 mg orally twice daily in adults and 0.1 mg/kg twice daily in children with burns greater than 20%. For elderly patients (>65 years of age), oxandrolone is given at 5 mg twice daily. Despite minimal adverse effects, oxandrolone has many of the adverse effects of steroids, such as fluid retention, high blood pressure, mood swing, and hyperglycemia.5 Steroids, such as oxandrolone, with an alkyl group linked to the steroid nucleus, are known to have hepatotoxic effects. The more serious hepatic consequences from increased liver enzymes and cholestatic jaundice include peliosis hepatis, hyperplasia, adenomas, and hepatocellular carcinoma. High doses, long-term usage (>1 year), and several concurrent anabolic drugs like oxandrolone have all been linked to these adverse effects.5
Administration of oxandrolone has been linked to elevated liver enzymes, most notably aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, and alkaline phosphatase. Specifically, patients who are younger and have concurrent amiodarone or vasopressor use have the highest risk of developing oxandrolone-induced transaminitis.6 These adverse effects have been shown to develop following large doses and/or chronic use of oxandrolone. However, the elevation of transaminases returns to normal once oxandrolone is discontinued. With relatively low dosages (0.1-0.2 mg/kg/d), slight increases in liver function enzyme levels have been observed with the administration of oxandrolone.5 However, most hepatic toxicity observed is asymptomatic and leaves no persistent liver damage.
In addition, virilizing signs in female patients taking oxandrolone are monitored on a regular basis.5 The most common symptoms of female virilization from oxandrolone include facial hair growth, acne, alopecia, deepened voice, increased libido, and clitoromegaly. In 2 studies of oxandrolone, female patients were withdrawn due to virilizing effects of oxandrolone.5 In 27 studies examining female virilization using oxandrolone, only 14 female patients among the total 1000 patients developed symptoms of virilization.5 Although the rate of virilization is low, only 15% of patients in the clinical trials examining oxandrolone were female. As such, further investigation is warranted to examine the incidence of female virilization among patients taking oxandrolone.5
The general contraindications for using oxandrolone include suspected carcinoma of the prostate or the male breast, carcinoma of the breast in females with hypercalcemia, pregnancy, nephrosis, and hypercalcemia. Current guidelines suggest discontinuation of oxandrolone if hypercalcemia develops. In addition, the use of adrenal cortical steroids or adrenocorticotropic hormone (ACTH) with oxandrolone may also exacerbate edema. Furthermore, patients with preexisting cardiac, renal, or hepatic illness and edema with or without congestive heart failure should be monitored closely when given oxandrolone. At relatively modest doses, oxandrolone can also cause cholestatic hepatitis and jaundice.5 If this occurs, oxandrolone should be discontinued and the cause assessed before restarting the medication. Furthermore, androgen treatment in children may hasten bone maturation without a compensating increase in linear growth. Specifically, the younger the child, the greater the chance of the child having a lower final mature height. Therefore, current guidelines suggest oxandrolone should be examined every 6 months by measuring the bone age of the left wrist and hand.5
For childhood burn injuries, the National Health Services (NHS) recommends that oxandrolone be initiated at 3 to 5 days postburn injury using a dose of 0.1 mg/kg once to twice daily for burns with a greater total body surface area (TBSA) of 40%.7 Depending on the severity of the burns and the severity of the hypermetabolic reaction, oxandrolone can be continued for at least 1 to 2 years.7 Once a collaborative decision is reached by the appointed pediatrician and burn specialist, oxandrolone can be discontinued immediately. Follow-up appointments for children prescribed oxandrolone should also occur at 1-, 3-, 6-, 9-, and 12 months postburn and then continued for at least 6 months after discontinuing oxandrolone. At each visit, the height, weight, sexual maturation, and signs of virilization (acne, deep voice, clitoromegaly, pubic hair) and liver function tests should be assessed.7 If oxandrolone is started in prepubertal children, bone aging may be accelerated. In these children, bone age analysis at 1 year and 2 years after starting oxandrolone are indicated. Similar guidelines by the American Burn Association suggest using 10 mg of oxandrolone immediately after burn injuries for adult patient populations with similar follow-up intervals to assess the liver injury and virilization in female patients.8
Oxandrolone and Burn Management
Burn injuries remain among the most severe traumatic injuries globally.9 As the amount of body surface burned increases, there is a corresponding increase in hypermetabolism.10,11 hypermetabolism results from increased stress and inflammatory mediators in response to toxic chemicals released from damaged collagen and fat.12-14 The physiological demands to maintain this energy production requires large amounts of glucose, which are maintained through gluconeogenesis through catabolism of proteins in the liver. If left untreated, the hypermetabolic response increases liver and cardiac work, impairs muscle function, increases the risk of sepsis, and alters hormone levels. These combined influences lead to a greater increase in morbidity and mortality among burn patients.12-14 In response, several pharmacological agents have been investigated in their efficacy to reduce the hypermetabolic response and improving outcomes in burn patients.15-19 Oxandrolone was one of the first anabolic steroids to be administered for acute burn injury and rehabilitation given the drug’s effect on increasing weight gain and urinary nitrogen balance without significant virilization or hepatotoxicity.20,21
Limitations
Oxandrolone remains an effective therapy for reducing the hypermetabolic response and comorbidities from burn injuries. However, these studies would also benefit from stratifying pediatric and adult patients based on gender to determine whether the efficacy of oxandrolone differs in male or female patients. Furthermore, additional research is required to assess whether combining other pharmaceuticals with oxandrolone may further reduce hypermetabolism and other postburn outcomes. Specifically, studies usingβ-blockers, such as propranolol, have shown effectiveness in reducing hypermetabolism responses after burn injuries.43 Only a few studies have examined the combined effect of β-blockers with oxandrolone to improve hypermetabolism responses in children and adults. Additional studies with these agents could provide greater efficacy and long-term outcomes for burn patients. Lastly, many of the studies did not assess the long-term effects of oxandrolone after burn injuries in adults and children. Longitudinal studies assessing the long-term efficacy and effects of steroids after burn injuries may provide insight into any other potential benefits or complications associated with the use of these pharmacological agents.
Conclusion
We have presented a summary of the literature that provides quality data showing the benefit of the use of oxandrolone in burn patients. Oxandrolone remains one of the first-line drugs administered for the treatment and recovery of severe burns by reducing hypermetabolism.44,45 Without treatment, hypermetabolism leads to insulin resistance, lipolysis, bone loss, and proteolysis, which can increase morbidity and mortality among burn patients.45 The main benefit of oxandrolone is the improved long-term lean body, protein, and bone mineral mass of patients after sustaining a severe burn injury. Three meta-analyses showed oxandrolone shortened length of hospital stay, donor-site healing time, reduced weight loss, and net protein loss.23-25 Furthermore, oxandrolone therapy did not affect mortality, infection, or liver dysfunction compared with the control groups.23-25 Over 6 to 12 months, oxandrolone also reduces weight loss and increases lean body mass.23-25 The improved metabolism and cardiopulmonary outcomes for years after discontinuing oxandrolone suggest the drug may attenuate inflammatory response and transcription factors increasing in the catabolic process among burn patients. The recent studies showing improved outcomes with rehabilitation exercises and oxandrolone suggest combination therapies with rehabilitation programs may provide further long-term functional and physical recovery in burn patients. Therefore, future RCT may examine whether combinations of pharmaceutical agents and rehabilitation strategies may improve the overall quality of life for burn patients.
Jonathan Kopel, Ph.D., Grant Sorensen, MD, and John Griswold, MD
Abstract
Objective: Burn injuries remain among the most severe traumatic injuries globally. With the discovery of cortisol, the use of steroids has become an essential therapy for the management of inflammatory and metabolic conditions. Several studies have shown the steroid oxandrolone improves burn injuries by stimulating anabolic and reducing catabolic processes. In this review, we examine the efficacy and applications of oxandrolone with regard to burn management and treatment.
Data Sources: A literature search was performed using the PubMed database from January 1990 to May 2020 to identify articles on oxandrolone and burn management. A total of 18 studies were included in our review. Study.
Selection and Criteria: The keywords used in our search strategy for PubMed included “oxandrolone” and “burns.”
Data Synthesis: The main benefit of oxandrolone is the improved long-term lean body, protein, and bone mineral mass of burn patients. In addition, 3 separate meta-analyses showed oxandrolone shortened length of hospital stay, donor-site healing time, reduced weight loss, and net protein loss. However, oxandrolone therapy did not affect mortality, infection, or liver function.
Conclusion: Oxandrolone remains an effective therapy for reducing the hypermetabolic response and comorbidities from burn injuries. Future clinical trials are needed using larger sample sizes and long-term follow-up to determine whether oxandrolone in the context of rehabilitation programs can reduce mortality, lower treatment costs, and improve functional outcomes among burn patients.
Introduction-Oxandrolone History
With the discovery of cortisol, steroids have become an essential therapy for the management of inflammatory and metabolic conditions.1 The synthesis of steroids was originally directed toward the treatment of rheumatoid arthritis; subsequently, it was expanded to improve metabolic function in hospitalized patients and athletes.1 The success of cortisol also increased the use of other anabolic steroids, including oxandrolone.1 Oxandrolone was first synthesized in the 1960s by Fox and Gherondache et al for women and children to promote lean tissue growth after surgery, trauma, and infection.2-5 Subsequent studies later showed oxandrolone had 6 times greater anabolic activity compared with testosterone.4,5 Given its potent anabolic activities, bodybuilders and competitive athletes abused oxandrolone to increase muscle gain without fat or water accumulation; as a result, oxandrolone was discontinued in 1989.4,5 However, oxandrolone was reintroduced in 1995 for preserving lean mass, particularly among patients with AIDS wasting, alcoholic hepatitis, and Turner syndrome.4,5 Since then, oxandrolone has shown clinical outcomes in several catabolic conditions, such as neuromuscular disorders, alcoholic hepatitis, and chronic inflammatory illnesses. In recent years, oxandrolone has shown several beneficial effects in the treatment and management of burn injuries.
Oxandrolone Pharmacology and Guidelines
Oxandrolone is a nonreducible, nonaromatizable synthetic chemical. Oxandrolone is structurally similar to testosterone but has a unique chemical arrangement in which an oxygen atom replaces the methylene group.5 Oxandrolone is rapidly absorbed, with peak serum concentrations occurring in about 1 hour. With a distribution half-life of 30 minutes and an elimination half-life of approximately 9 hours, plasma oxandrolone concentrations drop in a biphasic manner. In addition, 95% of oxandrolone is bound to proteins.5
Currently, oxandrolone can be given at 10 mg orally twice daily in adults and 0.1 mg/kg twice daily in children with burns greater than 20%. For elderly patients (>65 years of age), oxandrolone is given at 5 mg twice daily. Despite minimal adverse effects, oxandrolone has many of the adverse effects of steroids, such as fluid retention, high blood pressure, mood swing, and hyperglycemia.5 Steroids, such as oxandrolone, with an alkyl group linked to the steroid nucleus, are known to have hepatotoxic effects. The more serious hepatic consequences from increased liver enzymes and cholestatic jaundice include peliosis hepatis, hyperplasia, adenomas, and hepatocellular carcinoma. High doses, long-term usage (>1 year), and several concurrent anabolic drugs like oxandrolone have all been linked to these adverse effects.5
Administration of oxandrolone has been linked to elevated liver enzymes, most notably aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, and alkaline phosphatase. Specifically, patients who are younger and have concurrent amiodarone or vasopressor use have the highest risk of developing oxandrolone-induced transaminitis.6 These adverse effects have been shown to develop following large doses and/or chronic use of oxandrolone. However, the elevation of transaminases returns to normal once oxandrolone is discontinued. With relatively low dosages (0.1-0.2 mg/kg/d), slight increases in liver function enzyme levels have been observed with the administration of oxandrolone.5 However, most hepatic toxicity observed is asymptomatic and leaves no persistent liver damage.
In addition, virilizing signs in female patients taking oxandrolone are monitored on a regular basis.5 The most common symptoms of female virilization from oxandrolone include facial hair growth, acne, alopecia, deepened voice, increased libido, and clitoromegaly. In 2 studies of oxandrolone, female patients were withdrawn due to virilizing effects of oxandrolone.5 In 27 studies examining female virilization using oxandrolone, only 14 female patients among the total 1000 patients developed symptoms of virilization.5 Although the rate of virilization is low, only 15% of patients in the clinical trials examining oxandrolone were female. As such, further investigation is warranted to examine the incidence of female virilization among patients taking oxandrolone.5
The general contraindications for using oxandrolone include suspected carcinoma of the prostate or the male breast, carcinoma of the breast in females with hypercalcemia, pregnancy, nephrosis, and hypercalcemia. Current guidelines suggest discontinuation of oxandrolone if hypercalcemia develops. In addition, the use of adrenal cortical steroids or adrenocorticotropic hormone (ACTH) with oxandrolone may also exacerbate edema. Furthermore, patients with preexisting cardiac, renal, or hepatic illness and edema with or without congestive heart failure should be monitored closely when given oxandrolone. At relatively modest doses, oxandrolone can also cause cholestatic hepatitis and jaundice.5 If this occurs, oxandrolone should be discontinued and the cause assessed before restarting the medication. Furthermore, androgen treatment in children may hasten bone maturation without a compensating increase in linear growth. Specifically, the younger the child, the greater the chance of the child having a lower final mature height. Therefore, current guidelines suggest oxandrolone should be examined every 6 months by measuring the bone age of the left wrist and hand.5
For childhood burn injuries, the National Health Services (NHS) recommends that oxandrolone be initiated at 3 to 5 days postburn injury using a dose of 0.1 mg/kg once to twice daily for burns with a greater total body surface area (TBSA) of 40%.7 Depending on the severity of the burns and the severity of the hypermetabolic reaction, oxandrolone can be continued for at least 1 to 2 years.7 Once a collaborative decision is reached by the appointed pediatrician and burn specialist, oxandrolone can be discontinued immediately. Follow-up appointments for children prescribed oxandrolone should also occur at 1-, 3-, 6-, 9-, and 12 months postburn and then continued for at least 6 months after discontinuing oxandrolone. At each visit, the height, weight, sexual maturation, and signs of virilization (acne, deep voice, clitoromegaly, pubic hair) and liver function tests should be assessed.7 If oxandrolone is started in prepubertal children, bone aging may be accelerated. In these children, bone age analysis at 1 year and 2 years after starting oxandrolone are indicated. Similar guidelines by the American Burn Association suggest using 10 mg of oxandrolone immediately after burn injuries for adult patient populations with similar follow-up intervals to assess the liver injury and virilization in female patients.8
Oxandrolone and Burn Management
Burn injuries remain among the most severe traumatic injuries globally.9 As the amount of body surface burned increases, there is a corresponding increase in hypermetabolism.10,11 hypermetabolism results from increased stress and inflammatory mediators in response to toxic chemicals released from damaged collagen and fat.12-14 The physiological demands to maintain this energy production requires large amounts of glucose, which are maintained through gluconeogenesis through catabolism of proteins in the liver. If left untreated, the hypermetabolic response increases liver and cardiac work, impairs muscle function, increases the risk of sepsis, and alters hormone levels. These combined influences lead to a greater increase in morbidity and mortality among burn patients.12-14 In response, several pharmacological agents have been investigated in their efficacy to reduce the hypermetabolic response and improving outcomes in burn patients.15-19 Oxandrolone was one of the first anabolic steroids to be administered for acute burn injury and rehabilitation given the drug’s effect on increasing weight gain and urinary nitrogen balance without significant virilization or hepatotoxicity.20,21
Limitations
Oxandrolone remains an effective therapy for reducing the hypermetabolic response and comorbidities from burn injuries. However, these studies would also benefit from stratifying pediatric and adult patients based on gender to determine whether the efficacy of oxandrolone differs in male or female patients. Furthermore, additional research is required to assess whether combining other pharmaceuticals with oxandrolone may further reduce hypermetabolism and other postburn outcomes. Specifically, studies usingβ-blockers, such as propranolol, have shown effectiveness in reducing hypermetabolism responses after burn injuries.43 Only a few studies have examined the combined effect of β-blockers with oxandrolone to improve hypermetabolism responses in children and adults. Additional studies with these agents could provide greater efficacy and long-term outcomes for burn patients. Lastly, many of the studies did not assess the long-term effects of oxandrolone after burn injuries in adults and children. Longitudinal studies assessing the long-term efficacy and effects of steroids after burn injuries may provide insight into any other potential benefits or complications associated with the use of these pharmacological agents.
Conclusion
We have presented a summary of the literature that provides quality data showing the benefit of the use of oxandrolone in burn patients. Oxandrolone remains one of the first-line drugs administered for the treatment and recovery of severe burns by reducing hypermetabolism.44,45 Without treatment, hypermetabolism leads to insulin resistance, lipolysis, bone loss, and proteolysis, which can increase morbidity and mortality among burn patients.45 The main benefit of oxandrolone is the improved long-term lean body, protein, and bone mineral mass of patients after sustaining a severe burn injury. Three meta-analyses showed oxandrolone shortened length of hospital stay, donor-site healing time, reduced weight loss, and net protein loss.23-25 Furthermore, oxandrolone therapy did not affect mortality, infection, or liver dysfunction compared with the control groups.23-25 Over 6 to 12 months, oxandrolone also reduces weight loss and increases lean body mass.23-25 The improved metabolism and cardiopulmonary outcomes for years after discontinuing oxandrolone suggest the drug may attenuate inflammatory response and transcription factors increasing in the catabolic process among burn patients. The recent studies showing improved outcomes with rehabilitation exercises and oxandrolone suggest combination therapies with rehabilitation programs may provide further long-term functional and physical recovery in burn patients. Therefore, future RCT may examine whether combinations of pharmaceutical agents and rehabilitation strategies may improve the overall quality of life for burn patients.
