Hindawi Publishing Corporation
International Journal of Pediatric Endocrinology
Volume 2009, Article ID 826895, 5 pages
OxandroloneImproves Height VelocityandBMI in
Patients withCystic Fibrosis
Todd Varness,1ErinE.Seffrood,2EllenL.Connor,1Michael J. Rock,1andDavidB.Allen1
1Department of Pediatrics, University of Wisconsin School of Medicine and Public Health,
H4/4 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792-4108, USA
2Department of Clinical Nutrition, American Family Children’s Hospital, 600 Highland Avenue,
Madison, WI 53792, USA
Correspondence should be addressed to Todd Varness, email@example.com
Received 4 September 2009; Accepted 3 November 2009
Recommended by Fergus Cameron
Objective. To evaluate the effectiveness of oxandrolone in improving the nutritional status and linear growth of pediatric patients
with cystic fibrosis (CF). Methods. Medical records of patients with CF treated with oxandrolone were reviewed for height z score,
height velocity (HV), BMI z score, weight velocity (WV), Tanner stage, pulmonary function, liver enzyme levels, and any reported
adverse events. Data were compared before (pre-Ox) and after (Ox) oxandrolone using a paired t-test. Results. 5 subjects (ages 8.5–
14.5 years) were treated with oxandrolone 2.5mg daily for 8–38 months. After 8–12 months of treatment, there was a statistically
significantimprovementinHV(pre-Ox = 5.3±1.4cm/yr,Ox = 8.3±1.2cm/yr,P < .01)andBMIzscore(pre-Ox = −0.61±1.04,
Ox = −0.30 ± 0.86, P = .02). Both height z score (pre-Ox = −1.64 ± 0.63, Ox = −1.30 ± 0.49, P = .057) and WV (pre-Ox =
4.2±3.7kg/yr, Ox = 6.8±1.0kg/yr, P = .072) showed beneficial trends thatdid notreach statisticalsignificance. No adverse events
were reported. Conclusions. In this brief clinical report, oxandrolone improved the HV and BMI z score in patients with CF. Larger
studies are needed to determine if oxandrolone is an effective, safe, and affordable option to stimulate appetite, improve weight
gain, and promote linear growth in patients with CF.
Copyright © 2009 Todd Varness et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cystic fibrosis (CF) is an autosomal recessive disorder that
features chronic pulmonary disease, pancreatic insufficiency,
and other organ involvement. Patients with CF often have
malnutrition and short stature. According to the Cystic
Fibrosis Foundation Patient Registry 2007 Annual Data
Report, 21% of patients with CF had weight less than
the 10th percentile, while 13% had height below the 5th
percentile . Malnutrition and poor growth velocity are
associated with declining pulmonary function, morbidity,
tus are associated with greater pulmonary function , and
evidence-based practice recommendations strongly advise
close monitoring of growth and nutritional status as well
as aggressive nutritional intervention for patients with CF
Multiple agents have been used to stimulate appetite
and growth in patients with CF, but their utility has been
limited due to side effects (such as adrenal suppression with
megestrol) or cost (such as growth hormone). Oxandrolone
is a relatively weak androgen that stimulates appetite and
promotes linear growth and has been safely used to treat a
variety of conditions associated with wasting, poor weight
gain, or short stature . Furthermore, oxandrolone is an
attractive option in growing children because it cannot be
aromatized to estrogen, and therefore estrogen-dependent
advancement of the bone age is minimized. To our knowl-
edge, there are no reports in the literature of the use of
oxandrolone in patients with CF.
For the past 4 years, children with CF referred to
our endocrine clinic for persistent growth concerns in
spite of other nutrition-augmentation strategies have occa-
sionally been treated with oxandrolone. This retrospec-
tive analysis evaluates the effectiveness of oxandrolone in
improving the weight gain and linear growth of these
2International Journal of Pediatric Endocrinology
Table 1: Patient characteristics at the initiation of oxandrolone treatment.
We reviewed the medical records of all patients in our
endocrine clinic with CF who were treated with oxandrolone
for at least 8 months between January of 2005 and October
of 2008. Medical records were reviewed to determine height
z score, height velocity (HV), body mass index (BMI) z
score, and weight velocity (WV). Additional information
obtained included age, Tanner stage, pulmonary function,
liver enzyme levels, and any reported adverse events. This
retrospective chart review was approved by the University of
Wisconsin Human Subjects Committee.
Patients from the University of Wisconsin CF Clinic are
and/or poor height gain, particularly when the growth is
well below the clinic reference population (see data in results
below). There were no predetermined nutritional cutoffs or
pubertal stage for the initiation of oxandrolone. All subjects
were treated with 2.5mg of oxandrolone.
Height was measured on a wall-mounted stadiometer
to the nearest 0.1cm. Weight was measured on a calibrated
beam balance platform scale to the nearest 0.1kg. Weight
and height measurements were used to calculate the BMI
z score, which is the preferred method (as opposed to
percentage of ideal body weight) for monitoring nutri-
tional status in patients with cystic fibrosis [7, 9, 10].
Pretreatment height/weight velocities were calculated using
the measurement at initiation of oxandrolone and the
measurement 4–8 months prior to initiation of oxandrolone.
Posttreatment height/weight velocities were calculated using
the measurement at initiation of oxandrolone and the
measurement 8–12 months after initiation of oxandrolone.
Lung function parameters were measured with a Jaeger
Masterscreen spirometer in accordance with the American
Thoracic Society guidelines . Forced vital capacity (FVC)
and forced expiratory volume in one second (FEV1) were
determined and the results expressed as percentages of the
reference values of Wang et al. .
Descriptive statistics are expressed as mean ± SD or
frequency with a percentage. Data were compared before
(pre-Ox) and after (Ox) initiation of oxandrolone using a
Five subjects (3 boys and 2 girls) were identified. The
Table 1 lists the baseline characteristics for each subject. The
subjects ranged from 8.5 to 14.5 years in age and were
treated with oxandrolone for 8–38 months. All subjects were
prescribed oral oxandrolone 2.5mg daily. All subjects had
pancreatic insufficiency. At the start of oxandrolone therapy,
four subjects had Tanner 1 genitalia or breasts, and one male
patient had Tanner 4 genitalia.
The five subjects had a mean height z score of −1.64 and
a mean BMI z score of −0.61. As a comparison, we obtained
data for patients between the ages of 11 and 14 seen between
January 1, 2004 and December 31, 2008 in our CF Clinic.
For females (n = 21), the average height z score was −0.14
and the average BMI z score was 0.04. For males (n = 37),
the average height z score was −0.28 and the average BMI z
score was −0.19. Therefore, the subjects’ poor weight and/or
height gain was validated by a comparison to other patients
in the CF clinic.
oxandrolone. After 8–12 months of treatment, there was a
statistically significant improvement in HV (pre-Ox = 5.3 ±
1.4cm/yr, Ox = 8.3 ± 1.2cm/yr, P < .01) and BMI z score
(pre-Ox = −0.61 ± 1.04, Ox = −0.30 ± 0.86, P = .02). Both
height z score (pre-Ox = −1.64 ± 0.63, Ox = −1.30 ± 0.49,
P = .057) and WV (pre-Ox = 4.2 ± 3.7kg/yr, Ox=6.8 ±
1.0kg/yr, P = .072) showed beneficial trends that did not
reach statistical significance. When the subject with Tanner 4
genitalia (#3) was removed from the analysis, there was still a
significant improvement in HV and BMI z score.
There was no significant change in pulmonary function
or liver enzyme levels, and no adverse events were reported.
Neither female subject experienced hirsutism, clitoromegaly,
or any evidence of hyperandrogenism. One female subject
(#2) remained on oxandrolone for a total of 38 months
data shown above) and had normal pubertal progression
and menarche. One subject (#4) had CF-related liver disease
with mildly elevated liver enzyme tests at the initiation of
oxandrolone, and his liver enzyme tests improved slightly
while on oxandrolone. Two subjects (#4 and #5) had
previously been on mirtazapine to stimulate appetite.
International Journal of Pediatric Endocrinology3
Height z score
Height z score
P = .057
Height velocity (cm/yr)
P < .01
BMI z score
P = .018
BMI z score
P = .072
Weight velocity (kg/yr)
Figure 1: Anthropometric data for subjects (n = 5) before and after initiation of oxandrolone.
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
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 per-
centiles are associated with improved pulmonary function
and survival . 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 , and some children
with CF have a linear height that is more adversely affected
than would be suggested by the degree of malnutrition .
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.
4International Journal of Pediatric Endocrinology
Multiple appetite stimulants have been studied in
patients with CF, including megestrol, cyproheptadine, atyp-
ical antipsychotics, and antidepressants . Megestrol has
been shown to improve weight in patients with CF, but
side effects include adrenal suppression, glucose intolerance,
and diabetes [16–18]. 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
CF. Growth hormone (GH) is a potent anabolic agent that
has the capacity to improve the nutritional status of patients
CF leads to improved height and weight [19–23], while one
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 0.30mg/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 [25–27]. While
these studies reported some modest improvements in weight
and height gain (as well as an improvement in “cheerfulness”
), 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 andro-
genic effects . 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
. 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
been shown to increase growth velocity (but not eventual
adult height) in boys with constitutional delay of growth
and puberty . Oxandrolone cannot be aromatized to
estrogen, which minimizes advancement of the bone age.
Oxandrolone is also relatively cheap. The average wholesale
price of a 2.5mg tablet of oxandrolone is $5.53, which trans-
lates to an annual cost of approximately $2,000, substantially
less than the cost of GH.
While oxandrolone is generally well-tolerated, there are
cause transient elevations in liver transaminases , which
disease. Importantly, however, oxandrolone does not appear
to cause the severe hepatotoxic effects associated with other
anabolic steroids . Secondly, while oxandrolone has a high
anabolic to androgenic ratio , girls in particular may
experience dose-dependent androgenic side effects, such as
. In a review of the efficacy and safety of oxandrolone
used at modest dosages (e.g., usually 2.5–3.75mg/day), very
few studies report detectable androgenic side effects, even
in studies that included women and girls . 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 num-
ber 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.
In this small retrospective exploratory study, oxandrolone
safely and effectively improved the height velocity and BMI
z score in patients with CF. Larger prospective studies are
should be considered an effective, safe, and affordable option
to stimulate appetite and promote growth in patients with
 Cystic Fibrosis Foundation, “Patient Registry 2007,” Annual
Data Report to the Center Directors, Cystic Fibrosis Founda-
tion, Bethesda, Md, USA, 2008.
 R. Sharma, V. G. Florea, A. P. Bolger, et al., “Wasting as an
independent predictor of mortality in patients with cystic
fibrosis,” Thorax, vol. 56, no. 10, pp. 746–750, 2001.
 M. Corey, F. J. McLaughlin, M. Williams, and H. Levison, “A
comparison of survival, growth, and pulmonary function in
patients with cystic fibrosis in Boston and Toronto,” Journal of
Clinical Epidemiology, vol. 41, no. 6, pp. 583–591, 1988.
 L. T. Beker, E. Russek-Cohen, and R. J. Fink, “Stature as a
prognostic factor in cystic fibrosis survival,” Journal of the
American Dietetic Association, vol. 101, no. 4, pp. 438–442,
 B. S. Zemel, A. F. Jawad, S. FitzSimmons, and V. A. Stallings,
“Longitudinal relationship among growth, nutritional status,
and pulmonary function in children with cystic fibrosis:
analysis of the Cystic Fibrosis Foundation National CF Patient
Registry,” Journal of Pediatrics, vol. 137, no. 3, pp. 374–380,
 M. L. Peterson, D. R. Jacobs Jr., and C. E. Milla, “Longitudinal
changes in growth parameters are correlated with changes
in pulmonary function in children with cystic fibrosis,”
Pediatrics, vol. 112, no. 3, pp. 588–592, 2003.
 V. A. Stallings, L. J. Stark, K. A. Robinson, A. P. Feranchak,
and H. Quinton, “Evidence-based practice recommendations
International Journal of Pediatric Endocrinology5 Download full-text
for nutrition-related management of children and adults with
cystic fibrosis and pancreatic insufficiency: results of a system-
atic review,” Journal of the American Dietetic Association, vol.
108, no. 5, pp. 832–839, 2008.
 R. Orr and M. Fiatarone Singh, “The anabolic androgenic
steroid oxandrolone in the treatment of wasting and catabolic
disorders: review of efficacy and safety,” Drugs, vol. 64, no. 7,
pp. 725–750, 2004.
 H. J. Lai, “Classification of nutritional status in cystic fibrosis,”
Current Opinion in Pulmonary Medicine, vol. 12, no. 6, pp.
 Z. Zhang and H. J. Lai, “Comparison of the use of body mass
for malnutrition in children with cystic fibrosis,” American
Journal of Clinical Nutrition, vol. 80, no. 4, pp. 982–991, 2004.
 R. O. Crapo, J. L. Hankinson, C. Irvin, et al., “Standardization
of spirometry: 1994 update,” American Journal of Respiratory
and Critical Care Medicine, vol. 152, no. 3, pp. 1107–1136,
 X. Wang, D. W. Dockery, D. Wypij, M. E. Fay, and B. G.
Pediatric Pulmonology, vol. 15, no. 2, pp. 75–88, 1993.
 H.-C. Lai, M. R. Kosorok, S. A. Sondel, et al., “Growth status
in children with cystic fibrosis based on the National Cystic
Fibrosis Patient Registry data: evaluation of various criteria
used to identify malnutrition,” Journal of Pediatrics, vol. 132,
no. 3, pp. 478–485, 1998.
 D. S. Hardin, “Growth problems and growth hormone
treatment in children with cystic fibrosis,” Journal of Pediatric
 S. Z. Nasr and D. Drury, “Appetite stimulants use in cystic
fibrosis,” Pediatric Pulmonology, vol. 43, no. 3, pp. 209–219,
 V. Eubanks, N. Koppersmith, N. Wooldridge, et al., “Effects
of megestrol acetate on weight gain, body composition, and
pulmonary function in patients with cystic fibrosis,” Journal of
Pediatrics, vol. 140, no. 4, pp. 439–444, 2002.
 V. Marchand, S. S. Baker, T. J. Stark, and R. D. Baker,
“Randomized, double-blind, placebo-controlled pilot trial
of megestrol acetate in malnourished children with cystic
fibrosis,” Journal of Pediatric Gastroenterology and Nutrition,
vol. 31, no. 3, pp. 264–269, 2000.
Rosen, “Treatment of anorexia and weight loss with megestrol
acetate in patients with cystic fibrosis,” Pediatric Pulmonology,
vol. 28, no. 5, pp. 380–387, 1999.
in children with cystic fibrosis: the National Cooperative
Growth Study experience,” Journal of Pediatrics, vol. 131, no.
1, supplement 1, pp. S65–S69, 1997.
 D. S. Hardin, R. Stratton, J. C. Kramer, S. Reyes de la Rocha,
K. Govaerts, and D. P. Wilson, “Growth hormone improves
weight velocity and height velocity in prepubertal children
cystic fibrosis,” Hormone and Metabolic Research, vol. 30, no.
10, pp. 636–641, 1998.
 D. S. Hardin, T. Ferkol, C. Ahn, et al., “A retrospective study
of growth hormone use in adolescents with cystic fibrosis,”
Clinical Endocrinology, vol. 62, no. 5, pp. 560–566, 2005.
 D. S. Hardin, K. J. Ellis, M. Dyson, J. Rice, R. McConnell,
and D. K. Seilheimer, “Growth hormone improves clinical
status in prepubertal children with cystic fibrosis: results of a
5, pp. 636–642, 2001.
 D. S. Hardin, B. Adams-Huet, D. Brown, et al., “Growth
hormone treatment improves growth and clinical status
in prepubertal children with cystic fibrosis: results of a
multicenter randomized controlled trial,” Journal of Clinical
Endocrinology and Metabolism, vol. 91, no. 12, pp. 4925–4929,
 D. Schnabel, C. Grasemann, D. Staab, H. Wollmann, and F.
Ratjen, “A multicenter, randomized, double-blind, placebo-
controlled trial to evaluate the metabolic and respiratory
effects of growth hormone in children with cystic fibrosis,”
Pediatrics, vol. 119, no. 6, pp. e1230–e1238, 2007.
 R. R. Dooley, A. J. Moss, P. M. Wright, and P. C. Hassakis,
“Norethandrolone in cystic fibrosis of the pancreas,” Journal
of Pediatrics, vol. 74, no. 1, pp. 95–102, 1969.
 T. A. Good and S. P. Bessman, “Anabolic steroids in cystic
fibrosis of the pancreas,” American Journal of Diseases of
Children, vol. 111, no. 3, pp. 272–277, 1966.
 J. L. Dennis and T. C. Panos, “Growth and bone-age retarda-
of the American Medical Association, vol. 194, no. 8, pp. 855–
anabolic steroid of novel chemical configuration,” Journal of
Clinical Endocrinology & Metabolism, vol. 22, pp. 921–924,
 R. W. Naeraa, J. Nielsen, I. L. Pedersen, and K. Sorensen,
“Effect of oxandrolone on growth and final height in Turner’s
syndrome,” Acta Paediatrica Scandinavica, vol. 79, no. 8-9, pp.
 P. Crock, G. A. Werther, and H. N. B. Wettenhall, “Oxan-
drolone increases final height in Turner syndrome,” Journal of
Paediatrics and Child Health, vol. 26, no. 4, pp. 221–224, 1990.
 D. M. Wilson, E. McCauley, D. R. Brown, et al., “Oxandrolone
therapy in constitutionally delayed growth and puberty. Bio-
Technology General Corporation Cooperative Study Group,”
Pediatrics, vol. 96, no. 6, pp. 1095–1100, 1995.