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The Journal of Pediatric Pharmacology... 2020Growth failure following surgical palliation of complex congenital heart defects (CHDs) is a prognosticator of poor outcomes. Many strategies for improving weight gain...
OBJECTIVES
Growth failure following surgical palliation of complex congenital heart defects (CHDs) is a prognosticator of poor outcomes. Many strategies for improving weight gain have been implemented in this population, with limited success. We recently described the potential of the anabolic steroid oxandrolone to improve weight gain following surgical repair of CHD when administered via a medium-chain triglyceride (MCT) oil suspension to the buccal mucosa. The current study evaluates the stability of oxandrolone in the MCT oil formulation, as well as the pharmacokinetics of oxandrolone when administered via buccal mucosa in both neonates and adults.
METHODS
Stability was assessed by long-term storage of the preparation 1) at ambient conditions and 2) under photodegradative conditions for 3 days. Neonatal pharmacokinetic parameters were determined in a cohort of neonates following surgical CHD repair, whereas adult pharmacokinetics parameters were collected as part of a prospective study to evaluate the relative bioavailability of the oxandrolone in MCT oil formulation.
RESULTS
We found that oxandrolone was stable in the MCT oil formulation for at least 1 month, although exposure to light hastened drug degradation. Both neonatal and adult oxandrolone pharmacokinetics were variable; however, oxandrolone in MCT oil was relatively well absorbed through the buccal mucosa (mean bioavailability = 62.5%).
CONCLUSIONS
These data suggest that the variability in oxandrolone exposures is inherent to the drug, and not the formulation or route of administration. Combined, these data support further study of this novel oxandrolone in MCT oil formulation and its impact on growth following complex surgical repair of CHD in neonates.
PubMed: 32265605
DOI: 10.5863/1551-6776-25.3.220 -
Archives of Disease in Childhood Jan 2021The 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... (Randomized Controlled Trial)
Randomized 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.
Topics: Anabolic Agents; Body Height; Child; Drug Administration Schedule; Female; Humans; Male; Oxandrolone; Treatment Outcome; Turner Syndrome; United Kingdom
PubMed: 31862699
DOI: 10.1136/archdischild-2019-317695 -
Burns : Journal of the International... Feb 2020Major thermal injury induces profound metabolic derangements secondary to an inflammatory "stress-induced" hormonal environment. Several pharmacological interventions... (Review)
Review
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.
Topics: Anabolic Agents; Burns; Clonidine; Growth Hormone-Releasing Hormone; Hormones; Human Growth Hormone; Humans; Hypoglycemic Agents; Inflammation; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Metformin; Oxandrolone; Propranolol; Testosterone; Thyroid Hormones
PubMed: 31852612
DOI: 10.1016/j.burns.2018.03.009 -
GMS Interdisciplinary Plastic and... 2019Severe burn injuries are associated with a rapid escalating hypermetabolic state and catabolism of muscle mass. To ameliorate this process a standardized approach using...
Severe burn injuries are associated with a rapid escalating hypermetabolic state and catabolism of muscle mass. To ameliorate this process a standardized approach using pharmacological and non-pharmacological interventions was implemented within a single burns center. Whilst individual components of this standardized package are well documented in the literature, their collective or bundled effect has not as yet been assessed. The aim of this study was to evaluate the efficacy of this standardized bundle of metabolic modulators and assess the safety of including the anabolic steroid oxandrolone within it. This retrospective observational study constituted all patients in whom the metabolic bundle including oxandrolone therapy was applied. The other elements of the metabolic bundle consisted of early surgical burn excision within seven days to completion, early active mobilization, increased ambient room temperature, expediated carbohydrate and protein rich enteral feeding with glutamine and trace element supplements (such as copper and zinc). Finally, administration of propranolol as a non-selective beta-blocker. Data collection was through review of the patient data management system focusing on the outcome criteria and hepatic blood values. The study looked at fifty consecutive patients meeting the inclusion criteria. Median patient age and burned total body surface area (TBSA) were 62 years [51.75; 73] and 33.75% [24.75; 51] respectively with an abbreviated burn severity index (ABSI) of 10 [9; 10.25]. Definitive surgical burn wound excision was completed in 44 patients [88%] within 7 days. 39 patients (78%) received propranolol over a therapeutic period of 29 days [19; 44]. Glutamine was supplemented in 45 patients (90%), while zinc and copper were applied to 42 (84%) and 31 (62%) respectively. Significant low zinc values were noted at therapeutic onset (6.5 mmol/l [4.7; 7.9]) requiring sustained substitution over 37.5 days [22; 46.75]). In respect of the inclusion criteria, all patients received oxandrolone at 20 mg/day [20; 20]. This was commenced on day 6.5 [4; 14] post burn injury and continued over 26 days [19; 31]. Despite a transitory elevation of hepatic enzyme values (ALT, GGT), these were only clinically relevant (>10 µmol/l*S) in 2.4% and 4.6% of all measurements respectively. None were sufficiently of concern to merit cessation of treatment. The application of a standardised bundle of metabolic treatment options of severe burns injured patients is reliable, repeatable and safe. Potential concerns of oxandrolone treatment regarding hepatic compromise remain unfounded.
PubMed: 31815086
DOI: 10.3205/iprs000143 -
Jornal Vascular Brasileiro Oct 2019Lipodermatosclerosis is a panniculitis characterized by hardening and hyperpigmentation of the skin involving the calves with an "inverted champagne bottle" appearance....
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.
PubMed: 31723343
DOI: 10.1590/1677-5449.190031 -
The Cochrane Database of Systematic... Oct 2019The 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... (Meta-Analysis)
Meta-Analysis
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.
Topics: Adolescent; Androgens; Body Height; Female; Human Growth Hormone; Humans; Oxandrolone; Randomized Controlled Trials as Topic; Turner Syndrome
PubMed: 31684688
DOI: 10.1002/14651858.CD010736.pub2 -
Laryngoscope Investigative... Jun 2019Cancer cachexia affects up to over 50% of advanced head and neck cancer (HNC) patients. To date, the potential utility of anabolic steroids in perioperative cachectic...
BACKGROUND
Cancer cachexia affects up to over 50% of advanced head and neck cancer (HNC) patients. To date, the potential utility of anabolic steroids in perioperative cachectic HNC patients has not been determined.
METHODS
Retrospective review of pre- and post-oxandrolone administration prealbumin levels in 18 perioperative HNC patients between October 2007 and October 2014 at a tertiary academic medical center.
RESULTS
The median pretreatment prealbumin was 88.5 mg/L. The median post-treatment prealbumin was 227 mg/L. The median interval improvement of the prealbumin level was 131.5 mg/L. The median differences between the pretreatment and post-treatment prealbumin levels were found to be statistically significant ( < .001). Subjective improvement in wound healing was also observed.
CONCLUSIONS
Perioperative administration of oxandrolone resulted in objective improvements in prealbumin levels and subjective improvements in surgical wounds. Oxandrolone administered 10 mg twice daily (BID) for 10 days may be a useful adjunct in the perioperative care of nutritionally deficient HNC patients who are at risk for or have demonstrated impaired wound healing.
LEVEL OF EVIDENCE
3.
PubMed: 31236465
DOI: 10.1002/lio2.268 -
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 -
Psychoneuroendocrinology Feb 2019Klinefelter 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,... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Adolescent; Androgens; Brain; Child; Child Development; Double-Blind Method; Hippocampus; Humans; Intelligence; Klinefelter Syndrome; Magnetic Resonance Imaging; Male; Oxandrolone; Verbal Behavior
PubMed: 30388596
DOI: 10.1016/j.psyneuen.2018.09.039 -
Allergologie Select 2018The aim of treatment of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (HAE-C1-INH) is either treating acute attacks or preventing attacks by using... (Review)
Review
The aim of treatment of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (HAE-C1-INH) is either treating acute attacks or preventing attacks by using prophylactic treatment. For treating acute attacks, plasma-derived C1 inhibitor (C1-INH) concentrates, a bradykinin B2 receptor antagonist, and a recombinant human C1-INH are available in Europe. In the United States, a plasma-derived C1-INH concentrate, a bradykinin B2 receptor antagonist, and a plasma kallikrein inhibitor were approved for the treatment of acute attacks. Fresh frozen plasma is also available for treating acute attacks. Short-term prophylactic treatment focuses on C1-INH and attenuated androgens. Long-term prophylactic treatments include attenuated androgens such as danazol, stanozolol, and oxandrolone, antifibrinolytics, and a plasma-derived C1-INH concentrate. Plasma-derived C1-INH and a bradykinin B2 receptor antagonist are admitted for self-administration and home therapy. So the number of management options increased considerably within the last few years thus helping to diminish the burden of HAE.
PubMed: 31826031
DOI: 10.5414/ALX1561E