In this brief clinical report, we describe 5 children with CF who received oxandrolone for at least 8–12 months. All 5 children had height z scores well below the clinic average, and 3 of the subjects had BMI z scores below the clinic average. Oxandrolone improved the height velocity and BMI z score in these patients with CF and showed a trend towards significance in weight velocity and height z score. No significant changes in pulmonary function or liver enzyme tests were appreciated.
Optimizing linear growth and weight gain is critically important in the care of children with CF. A comprehensive practice recommendation found significant evidence that weight-for-age, height-for-age, and weight-for-height percentiles are associated with improved pulmonary function and survival [7
]. It is important to emphasize that a “weight only” approach will not necessarily result in improved height and/or lung function. Lai et al. noted that poor linear growth can occur independent of weight [13
], and some children with CF have a linear height that is more adversely affected than would be suggested by the degree of malnutrition [14
]. Therefore, increasing weight alone may not fully address the short stature that is commonly seen in patients with CF. Ideally, a growth-promoting agent in patients with CF would improve both weight and height.
Multiple appetite stimulants have been studied in patients with CF, including megestrol, cyproheptadine, atypical antipsychotics, and antidepressants [15
]. Megestrol has been shown to improve weight in patients with CF, but side effects include adrenal suppression, glucose intolerance, and diabetes [16
]. More importantly, the nonanabolic glucocorticoid actions of megestrol promote accumulation of fat mass in excess of lean body mass.
In order to stimulate appetite but to also improve body composition, anabolic agents have been used in patients with CF. Growth hormone (GH) is a potent anabolic agent that has the capacity to improve the nutritional status of patients with CF. Several studies have shown that GH in children with CF leads to improved height and weight [19
], while one study found only an improvement in height [24
]. While there were theoretical concerns of glucose intolerance with the use of GH, no study of GH in patients with CF has described this complication. There are a few disadvantages of GH. A minor concern is the use of daily injections, while a major concern is cost. The mean average wholesale price for GH, based on 6 different GH preparations, is $66.60 per mg, and therefore at an expected dose of 0.30
mg/kg/week, the estimated annual cost of GH for the 5 subjects in this paper would range from $28,500 (subject #1) to $43,900 (subject #3).
Insulin is an anabolic hormone that can improve BMI in patients with CF-related diabetes, but insulin has not been studied in patients without CF-related diabetes and carries the obvious risk of hypoglycemia.
Several articles from the 1960s describe the use of older anabolic steroids (stanozolol, methandrostenolone, and norethandrolone) in patients with CF [25
]. While these studies reported some modest improvements in weight and height gain (as well as an improvement in “cheerfulness” [27
]), in general these early anabolic steroids had very high androgenic side effect profiles that limited their utility.
Oxandrolone is a weak oral androgen taken once daily that has marked anabolic properties with minimal androgenic effects [28
]. Oxandrolone is clinically efficacious across a variety of diseases associated with catabolism and wasting and is FDA-approved as adjunctive therapy for weight loss due to catabolic conditions in both adults and children [8
]. Oxandrolone has also been used as a height-promoting agent. Prior to the availability of recombinant human GH, oxandrolone was commonly used to increase growth velocity in girls with Turner Syndrome [29
]. Oxandrolone has also been shown to increase growth velocity (but not eventual adult height) in boys with constitutional delay of growth and puberty [31
]. Oxandrolone cannot be aromatized to estrogen, which minimizes advancement of the bone age. Oxandrolone is also relatively cheap. The average wholesale price of a 2.5
mg tablet of oxandrolone is $5.53, which translates to an annual cost of approximately $2,000, substantially less than the cost of GH.
While oxandrolone is generally well-tolerated, there are important potential side effects to consider. Oxandrolone can cause transient elevations in liver transaminases [8
], which could be a factor in patients with or at risk for CF-related liver disease. Importantly, however, oxandrolone does not appear to cause the severe hepatotoxic effects associated with other anabolic steroids [8
]. Secondly, while oxandrolone has a high anabolic to androgenic ratio [28
], girls in particular may experience dose-dependent androgenic side effects, such as increase in body hair, deepened voice, or clitoral hypertrophy [30
]. In a review of the efficacy and safety of oxandrolone used at modest dosages (e.g., usually 2.5–3.75
mg/day), very few studies report detectable androgenic side effects, even in studies that included women and girls [8
]. Nonetheless, it would be prudent to monitor closely for signs of excess androgen in girls treated with oxandrolone.
This retrospective, noncontrolled report of a small number of subjects has intrinsic limitations. Changes in clinical and anthropometric outcomes may be confounded by the disease itself (which waxes and wanes) or by early puberty. The duration of the study was also relatively short, which makes it difficult to determine if oxandrolone had a positive effect on pulmonary function tests or a negative effect on liver enzyme tests. A randomized controlled trial would help determine if oxandrolone, compared to an appropriate control group, improves the nutritional status and/or lung function in patients with CF.