SAFETY & EFFICACY REPORT
Oxandrolone
Mustafa Akyurek, M.D.
Raymond M. Dunn, M.D.
Plastic Surgery Educational
Foundation DATA
Committee
Worcester, Mass.
T
here has been increasing interest in the
development of effective agents that can be
safely used to promote anabolism in pa-
tients with chronic wasting conditions. Anabolic
agents have the potential to improve body com-
position by maintaining or enhancing lean body
mass. This class includes growth hormone, insu-
lin-like growth factor 1, testosterone, dihydrotes-
tosterone, and the testosterone analog
oxandrolone.1–3
Anabolic androgenic steroids, which are syn-
thetic derivatives of testosterone, are inappropri-
ately used to enhance athletic performance or
appearance. Adverse effects include those on the
liver, serum lipids, and psyche/behavior (mani-
fested as increased levels of irritability, aggres-
sion, personality disturbance, and psychiatric di-
agnoses), cardiomyopathy, coronary artery
disease, cerebrovascular accidents, prostatic
changes, and immune function disturbance.4
Dehydroepiandrosterone is a weak androgen
used to elevate testosterone levels and is adver-
tised as an antiobesity and antiaging supplement
capable of improving libido, vitality, and immu-
nity levels. However, research demonstrates that
dehydroepiandrosterone does not increase se-
rum testosterone concentrations or increase
strength in men, and it may actually increase
testosterone levels in women, thus producing a
virilizing effect.4,5
Oxandrolone has been used for more than 30
years in such clinical situations as severe burn
injury, trauma following major surgery, human
immunodeficiency virus–related muscle wasting,
neuromuscular disorders, hereditary angio-
From the Division of Plastic Surgery, University of Massa-
chusetts Memorial Health Care.
Received for publication September 21, 2005; accepted
March 23, 2006.
Approved by the American Society of Plastic Surgeons’ Ex-
ecutive Committee on September 6, 2005.
Copyright ©2006 by the American Society of Plastic Surgeons
DOI: 10.1097/01.prs.0000233034.29726.c9
www.PRSJournal.com
edema, and alcoholic hepatitis. In the United
States, oxandrolone is the only anabolic andro-
genic steroid that is approved by the U.S. Food
and Drug Administration to treat weight loss
after severe trauma, major surgery or infections,
malnutrition due to alcoholic cirrhosis, and neu-
romuscular disorders. It has been demonstrated
that improvements in body composition, muscle
strength, and function are evident with oxan-
drolone treatment in a variety of chronic wasting
conditions.1– 8
STRUCTURE
Oxandrolone is a synthetic androgenic anabolic
steroid with the chemical name 17␤-hydroxy-17␣-
methyl-2-oxa-5␣-androstane-3-one. Structurally, ox-
androlone is a testosterone-derived substance be-
longing to the C17␣-alkylated group of anabolic
androgenic steroids. An alkyl group attached at the
C17-␣ position of the steroid nucleus allows this
agent to be formulated as an oral preparation.2
ABSORPTION, METABOLISM, AND
MECHANISM OF ACTION
Oxandrolone is well absorbed after oral ad-
ministration, with peak serum concentrations oc-
curring in approximately 1 hour.9 Oxandrolone is
95 percent protein bound. In marked contrast to
other anabolic androgenic steroids, such as tes-
tosterone, oxandrolone is relatively resistant to
liver biotransformation, thereby avoiding most
drug interactions and the liver toxicity often seen
with other steroids. Approximately 28 percent of
the drug is excreted unchanged in the urine. It is
preferentially sulfated to 17-epioxandrolone. The
lack of appreciable biotransformation and the
high degree of protein binding result in oxan-
drolone having higher plasma levels than meth-
yltestosterone. Oxandrolone has marked anabolic
and few androgenic effects, with a high anabolic-
to-androgenic ratio of 10:1. The anabolic activity
of oxandrolone in humans is approximately 6.3
times that of methyltestosterone after oral dose. It
is a schedule III controlled substance, as are all
791
 Plastic and Reconstructive Surgery • September 1, 2006
anabolic steroids, which discourages some physi-
cians from prescribing it. For treatment in rebuild-
ing tissue after a serious illness or trauma, the
recommended dosage is 2.5 g, two to four times a
day, for up to 4 weeks. The daily dose may be
increased up to 20 g. In children, the dose is based
on body weight and is 0.25 mg per kg of body
weight. The drug comes in 2.5-mg oval white tab-
lets. Tablets are stored at room temperature.9 –13
Oxandrolone can interact with other medica-
tions, such as oral anticoagulants, oral hypoglyce-
mic agents, and adrenal steroids. This possible
interaction should be considered before
treatment.14
The mechanisms by which oxandrolone pro-
duces weight gain are complex. It is known to
stimulate appetite. As a result of direct interaction
with androgen or glucocorticoid receptors in mus-
cle, anabolic steroids may promote muscle anab-
olism through both anabolic and anticatabolic
pathways.14
CLINICAL EFFICACY
Oxandrolone has been approved by U.S. Food
and Drug Administration since the early 1960s at
a dosage of 5 to 10 mg/day for conditions that
include weight loss due to extensive surgery,
chronic infection, severe trauma, failure to gain or
maintain weight without definitive pathophysio-
logic reasons, and protein catabolism due to pro-
longed steroid administration. Some physicians
have prescribed a higher dose than the Food and
Drug Administration–approved dose of 10 mg/
day, depending on the requirement of the
patient.1,2
Oxandrolone has shown to be beneficial in
patients requiring anabolic support and to pro-
mote beneficial clinical outcomes in catabolic con-
ditions, including severe burn injury, trauma after
major surgery, human immunodeficiency virus–
related muscle wasting, neuromuscular disorders,
alcoholic hepatitis, and chronic illness or muscle
wasting of unclear etiology. In a placebo-con-
trolled study encompassing a variety of clinical
conditions characterized by muscle wasting, 224
adult patients received 3 weeks of treatment with
oxandrolone 5 mg/day or placebo, followed by
the alternative treatment for another 3 weeks.
Overall, 88 percent gained or maintained weight
during oxandrolone treatment, in contrast to 57
percent during placebo treatment. Eleven percent
lost weight during oxandrolone treatment, com-
pared with 42 percent during placebo treatment.14
In a community-based study of human immuno-
deficiency virus–related muscle wasting, the pla-
792
cebo group on average continued to lose weight,
while oxandrolone-treated groups on average
maintained or gained weight. The oxandrolone
group receiving 15 mg/day showed significantly
improved weight gain and a trend toward subjec-
tive improvement of appetite, strength, and phys-
ical activity.15
Oxandrolone is also used in the treatment of
short stature due to Turner’s syndrome and con-
stitutional delay of growth and puberty. It has been
found to be reasonably safe and effective for
children.16 Murphy et al.17 reported that admin-
istration of oxandrolone in severely burned chil-
dren safely improves lean body mass, bone min-
eral content, and bone mineral density. Church18
conducted a study that indicated that oxan-
drolone has an acceptable safety profile in chil-
dren. In a randomized efficacy and safety trial of
oxandrolone, Fenichel et al.19 found no adverse
reactions attributable to oxandrolone and re-
ported that it is safe to use in children.
Severe burn injury leads to an acute catabolic
state, with marked loss of lean muscle and visceral
protein. The severity of complications correlates
with the loss of body protein. Increased catabolic
hormones (epinephrine and cortisol) and de-
creased anabolic hormones (growth hormone
and testosterone) are in large part responsible for
this situation, along with direct cell injury from
inflammatory mediators. Oxandrolone treatment
has been shown to decrease the hypermetabolic
response, significantly enhance muscle protein
synthesis, decrease weight loss and net nitrogen
loss, increase body mass and physical function,
improve healing time, decrease complications,
and improve outcome.6,8 In a prospective random-
ized study of patients with major burns, it was
demonstrated that oxandrolone given at the dose
of 20 mg/day combined with increased protein
intake (2 g/kg per day) significantly increased the
rate of restoration of weight gain after burn.6
Other studies supported the conclusion that ox-
androlone significantly decreases weight loss and
net nitrogen loss and increases donor-site healing
compared with placebo in patients with major
burns during the acute postburn period.17–23
These changes were found to be associated with
increased gene expression for functional muscle
proteins.24 In fact, it was shown not only that the
body weight and lean mass lost due to burn-in-
duced catabolism can be effectively restored in the
postburn recovery with oxandrolone but also that
the regained body weight and lean mass are main-
tained 6 months after discontinuation of the
drug.20 A recent study involving children with se-
Volume 118, Number 3 • Oxandrolone
vere burns demonstrated that long-term adminis-
tration of oxandrolone at 0.1 mg/kg orally twice
a day safely improves lean body mass, bone min-
eral density, and bone mineral content compared
with placebo.17
ADVERSE EFFECTS
Oxandrolone has the potential to exhibit
many of the adverse effects associated with andro-
genic anabolic steroids. Transient elevations of
transaminase levels, as well as reductions in high-
density lipoprotein cholesterol levels, are the most
common adverse consequences seen in clinical
trials. They appear to be readily reversible upon
discontinuation of treatment.2
Hepatic dysfunction associated with the use of
this drug range from elevated liver enzyme levels
and cholestatic jaundice to the more severe he-
patic complications of peliosis hepaticus, hyper-
plasia, adenomas, and hepatocellular carcinoma.
Adenomas and carcinomas are known to regress
after drug withdrawal. These adverse effects have
occurred mainly with high dosages, prolonged use
of more than 1 year, multiple concurrent anabolic
agents, and/or in the treatment of aplastic anemia
or Fanconi’s anemia. The rate of development of
and the severity of adverse effects are considered
to be dose dependent, and therapeutic dosages of
oxandrolone rarely lead to serious hepatic dys-
function. Most of the hepatic toxicity reported
consisted of asymptomatic and reversible eleva-
tions of transaminases during or after completion
of study, without evidence of permanent hepatic
damage.25–27
Androgenic side effects are rare. Among ap-
proximately 1000 patients, androgenic adverse ef-
fects were reported in only 14 patients and in-
cluded facial hair growth, acne, alopecia,
deepened voice, increased libido, and clitoro-
megaly. The low incidence of androgenic adverse
effects reported with oxandrolone attests to the
more favorable ratio of anabolic to androgenic
potency of the drug compared with many other
anabolic androgenic steroids that have been used
clinically.2
Cholesterol alterations may be observed with
oxandrolone treatment. The predominant effect
is to lower the high-density lipoprotein cholesterol
level. In addition, a few studies reported elevations
of total or low-density lipoprotein cholesterol.28
Oxandrolone treatment may rarely lead to psy-
chological/behavioral changes.29
CONCLUSIONS
A variety of clinical conditions are character-
ized by muscle tissue loss, leading to functional
impairment, exacerbation of underlying disease
states, and excess morbidity and mortality rates.
Oxandrolone has a role in the treatment of clin-
ical situations such as severe burn injury, major
trauma after surgery, and disease-related muscle
wasting, since it has several advantages relative to
other anabolic steroids, including oral route of
administration, high anabolic:androgenic po-
tency, absence of evidence of serious or irrevers-
ible hepatic toxicity, and less expensive cost.
Oxandrolone at therapeutic dosages has been
proven to be a safe and effective drug for treating
a variety of clinical conditions associated with wast-
ing.
Mustafa Akyurek, M.D.
Division of Plastic Surgery
University of Massachusetts Memorial Health Care
Hahnemann Campus
281 Lincoln Street
Worcester, Mass. 01605-2192
akyurekm@ummhc.org
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