The Influence of 6 Months of Oral Anabolic Steroids

on Body Mass and Respiratory Muscles in

Undernourished COPD Patients*
Ivane Martins Ferreira, MD, PhD; Ieda T. Verreschi, MD, PhD;
Luiz E. Nery, MD, PhD; Roger S. Goldstein, MD, FCCP;
Noe Zamel, MD, FCCP; Dina Brooks, BSc (PT), PhD; and
Jose R. Jardim , MD, PhD

Study objective: To evaluate the influence of oral anabolic steroids on body mass index (BMI),
lean body mass, anthropometric measures, respiratory muscle strength, and functional exercise
capacity among subjects with COPD.
Design: Prospective, randomized, controlled, double-blind study.
Setting: Pulmonary rehabilitation program.
Participants: Twenty-three undernourished male COPD patients in whom BMI was below 20
kglm 2 and the maximal inspiratory pressure (Pimax) was below 60% of the predicted value.
Intervention: The study group received 250 mg of testosterone IM at baseline and 12 mg of oral
stanozolol a day for 27 weeks, during which time the control group received placebo. Both groups
participated in inspiratory muscle exercises during weeks 9 to 27 and cycle ergometer exercises
during weeks 18 to 27.
Measurements and results: Seventeen of 23 subjects completed the study. Weight increased in
nine of 10 subjects who received anabolic steroids (mean, + 1.8±0.5 kg; p<0.05), whereas the
control group lost weight ( -0.4±0.2 kg). The study group's increase in BMI differed significantly
from that of the control group from weeks 3 to 27 (p<0.05). Lean body mass increased in the
study group at weeks 9 and 18 (p<0.05). Arm muscle circumference and thigh circumference also
differed between groups (p<0.05). Changes in Plmax (study group, 41 %; control group, 20%)
were not statistically significant. No changes in the 6-min walk distance or in maximal exercise
capacity were identified in either group.
Conclusion: The administration of oral anabolic steroids for 27 weeks to malnourished male
subjects with COPD was free of clinical or biochemical side effects. It was associated with
increases in BMI, lean body mass, and anthropometric measures of arm and thigh circumference,
with no significant changes in endurance exercise capacity. (CHEST 1998; 114:19-28)

Key words: anabolic steroids; body mass index; chronic obstructive pulmonary disease; nutrition; respiratory muscle
function

Abbreviations: BMI=body mass index; DEXA = dual energy x-ray absortiometry; IMT = inspiratory muscle
t_raining; LH=Iuteinizing hormone; PEmax=maximal expiratory pressure; Pimax=maximal inspiratory pressure;
Vo 2 max=maximal oxygen consumption

Malnutrition is associated with severe COPD,
having been observed in 10 to 26% of outpa-
tients with COPD and in up to 47% of patients
*From the Respiratmy Division of Federal University of Sao
Paulo, Brazil (Drs. Ferreira, Ne1y, and Jardim ); Endocrinology
Division of Federal University of Sao Paulo, Brazil (Dr. VeJTe-
schi); and Division of Respiratory Medicine, University of
Toronto, Canada (Drs. Goldstein, Brooks, and Zamel).
Manuscript received June 25, 1997; revision accepted February
11, 1998.
Supported by Fundar;:ao de Amparo a Pesquisa de Sao Paulo
(FAPESP ) and Conselho Nacional de Pesquisa do Brazil (CNPq).
Reprint requests: Ivane Martins Ferreira, MD, c/o Roger S.
Goldstein, MD, West Park Hospital, 82 Buttonwood Ave,
Toronto, Ontario M6M 2]5, Canada
hospitalized with acute respiratory failure. 1 Although
the underlying mechanisms and pathophysiology re-
main unclear, at least one report has noted that
individuals who lost weight had a higher morbidity
and mortality compared with those whose weight
was within predicted values for their age, height, and
sex. 2 When compared with normal-weight patients
with similar airflow limitation, low-weight COPD
patients had more hyperinflation, more gas trapping,
a lower diffusing capacity,3 more dyspnea, and re-
duced exercise capacity. 4
Malnutrition affects the composition5 and the
function 6 of the respiratory muscles. As in other

CHEST/114/1 /JULY, 1998 19

 skeletal muscles, protein is degraded to produce
energy and to assist with the synthesis of visceral
protein. In subjects with COPD whose weight was
reduced to 70% of predicted values, diaphragmatic
mass was reduced to 60%. R eductions in the thick-
ness of the sternocleidomastoid muscles also have
been reported.7 This reduction in respiratory muscle
mass reduces the capacity of the ventilatory system
to respond to the increases in elastic and resistive
loads, such as those present during exercise or with
respiratory exacerbations.
Over the past 20 years, a variety of reports have
claimed that anabolic steroids improved the perfor-
mance of high-level athletes consequent to improve-
ments in skeletal muscle mass and strength.8 - 11
Although in some individuals the gains in muscle
strength associated with good nutrition and exercise
appear to be further enhanced by the addition of
anabolic androgenic steroids, errors in design, anal-
ysis, and reporting have limited the credibility of
many studies. A recent meta-analysis on the effects
of anabolic steroids in healthy volunteers concluded
that there were slight improvements in strength
among previously trained athletes. However, the
authors were unable to reach a conclusion regarding
the influence of anabolic steroids on overall athletic
performance. 12
In a well-designed, randomized, controlled trial,
testosterone combined with strength training was
found to increase fat-free mass as well as muscle size
and strength among healthy male volunteers. 13 The
authors suggested that by extension, androgens may
be beneficial when administered for a limited period
in those vvith cachexia associated with chronic con-
ditions. Schols and colleagues 14 reported that sub-
jects with COPD sustained greater improvements in
fat-free muscle mass and in maximal inspiratory
pressure (PI max) when anabolic steroids were added
to nutritional supplementation than when they re-
ceived only nutritional support. The subjects were
given anabolic steroids IM at baseline and at 2, 4,
and 6 weeks, and their primary outcomes (body
composition and respiratory muscle function) were
measured after 8 weeks.
We were interested in learning whether oral ana-
bolic steroids improve respiratory muscle function
and exercise capacity if administered over a more
protracted p eriod of 6 months. Therefore, we under-
took a randomized, controlled trial in which an
anabolic steroid (stanozolol) was administered orally
for 27 weeks to ambulatory undernomished individ-
uals with COPD. During the period of steroid
administration, study subjects participated in respi-
ratory rehabilitation, including cycle ergometry and
inspiratory muscle training. Our primary outcome
20
measures were body mass index (BMI), muscle mass,
respiratory muscle strength, and functional exercise
capacity.
MATERIALS AND METHODS
Population
Twenty-three ambulatory male patients with stable COPD (no
respiratmy exacerbation for at least 6 weeks ) were selected for
the study. Inclusion crite ria included a BMI below 20 kglm 2 and
a PI max below 60% of the predicted value. Subjects did not have
any other associated medical conditions that might have influ-
enced their weight or respiratory muscle fun ction. Patients with
prostate or known cardiac disease were excluded because of the
potential side effects of anabolic steroid admin istration. The
protocol was approved by th e Human Ethics Committee of the
Federal University of Sao Paulo.
Protocol
After th eir informed consent was obtained, th e subjects were
randomized in a double-blind fashion to receive either placebo
(control group ) or anabolic steroids (study group). Patients in the
anabolic steroid group received 250 mg of testosterone IM
(Durateston, a preparation containing phenpropionate, isocap-
roate, propionate, and caproate of testosterone) at baseline as an
"attack" dose; the study group also took oral stanozolol (12
mglday) for 27 weeks.
The study was divided into three 9-week periods. For the first
9 weeks, the study group received stanozolol and th e control
group a placebo. Between weeks 9 and 18, both groups received
daily inspiratory muscle training (IMT) in addition to stanozolol
or placebo. During weeks 18 to 27, exercise training at approxi-
mately 80% of maximal work, as determined b y asymptom-
limited incre mental exercise test, was added to this regimen. A
cycle e rgometer was used for training (Model II; Funbec; Sao
Paulo, Brazil). This was calibrated regularly (physically and
electronically) by the manufacturer.
Between weeks 9 and 27, IMT was pe rformed for 20 min,
t:vvice a day, at 20 breaths/min using a pressure-loaded d evice
(Resp-Trein ; Imebras; Sao Paulo, Brazil). Training was targeted
to be a t apressure equal to 50% of Plmax. PI max was measured
every 3 weeks using a n analogue pressure gauge, and the target
pressure was adjusted as necessary. Although most of th e IMT
sessions were unsupervised, to promote subject compliance
patients had one session of supervised IMT every 3 weeks.
During these sessions, subjects were provided with feedback on
their technique as well as encou ragement. Family members were
encouraged to assist the subjects with their home rehabilitation
program .
Between weeks 18 and 27, patients performed cycle training a t
th e hospital for 30 min three times a week, at a workload equal
to 80% of the maximal workload derived from the incremental
exercise test; sessions were supervised by a physical therapist. If
the patient was unable to perform at that workload, he started
v.<ith a ol wer load and increased the load after 1 week. One
subject whocould not reach this workload trained at the maximal
level that he could achieve.
Measurements
At baseline and at 9-week intervals (9, 18, and 27 weeks), dual
energy x-ray absortiometry (DEXA) was performed to determine
Clinical Investigations
body composition (total lean body mass and percentage of fat
mass) . Tests of respiratory muscle strength and endurance, the
6-min walk test, and the incremental exercise test also were
performed at each of those times. Anthropometric measures and
respiratory muscle strength (PI max and maximal expiratory pres-
sure [PEmax]) were measured every 3 weeks.
Nutriti onal Assessment
Weight was measured in the morning using a beam scale, with
the patient clothed but not wearing shoes. Ideal body weight was
determined from the patient's weight range and fram e size based
on the tables from Metropolitan Life Insurance. 15
BMI was calculated b ydividing the patient's weight in kg by his
height squared (m2 ). We considered subjects with a BMI of less
than 20 kglm2 to be undernourished. 16
To measure midarm circumference, the nondominant arm was
positioned parallel to the trunk and a nondistensible tape was
placed around the midpoint of the arm without compressing the
arm tissue, halfway between the tip of the shoulder (acromial
process) and the tip of the elbow (olecranon process). Three
consecutive measurements we re made. If there was agreement
between them (within 0.5 em), the intermediate measurem ent
was accepted as the actual value.
Triceps skinfold thickness was used as an indirect estimate of
body fat. It was derived b y gathering skin at the midarm point
between the thumb and the index finger and measuring its
thickness with a skinfold caliper. Three consecutive measure-
ments were made. If there was agreement between them (within
4 mm ), the intermediate measurement was accepted as the actual
value.
The arm muscle circumference index reflects the amount of
muscle or lean tissue in the body. This measure ment was derived
from the following equation: arm muscle circumference=
midarm circumference-(3.14Xtriceps skinfold thickness) 17
With the patien t standing and his weight evenly distributed,
the thigh circumference was determined on the nondominant
side at h alf the distance between the inguinal crease and a point
midway along the patella. Three consecutive measurements were
made. If there was agreement between them (within 0.5 em), the
intermediate measurement was accepted as the actual value.
Total body and soft-tissue composition were measured with
dl!al energy X-ray absortiometry (DEXA). DEXA measurements
were made with a total body scanner (Model DPX; Lunar
Radiation Corp; Madison, Wise).
Total serum protein and albumin were obtained from venous
blood at baseline and every 9 weeks.
Respiratory Muscle Assessment
Respiratory muscle strength was assessed b y measuring Pimax
and PEmax (Pimax at residual volume and PEmax at total lung
capacity) with an analogue pressure gauge using standard meth-
odology.1" Patients were seated and asked to make maximal
efforts against an obstructed mouthpiece that had a small leak to
prevent patients from closing their glottis during the respiratory
maneuver. Patients had to sustain maximal effort for 1 s. The best
of five consecutive atte mpts was used, provided the variability
betwee n the best two efforts did not exceed 5%. w
To measure respiratmy muscle endurance, subjects breath ed
through a pressure-dependent inspiratmy device set to generate
mouth pressures close to 80% of their PI max until they could no
longer maintain this pressure target. Endurance time and breath-
ing frequency were reco rded. After the subj ects practiced at
home daily for aweek, the baseline endurance was measured. As
an approximate measurement of the total work, we calculated the
product of press ure, inspiratory time, and number of breaths
during the endurance run. Inspiratory time was considered to be
50% of total respiratory time.20
Exercise Capacity
Maximal exercise capacity was assessed with a graded, symp-
tom-limited exercise test. The test was performed using the CPX
Diagnostic System (Medical Graphics Corp; St. Paul, Minn)
linked to a cycle ergometer (CPE 2000; Medical Graphics Corp)
with 10-W increments each minute. Maximal oxygen consump-
tion (Vo 2 max) was calculated as a percentage of the predicted
value.
Three 6-min walk tests were perform ed. During the first two
tests, patients were encouraged every 2 min. In the third test,
they were encouraged and accompanied in order to achieve the
best performance.2 l The value used was the greatest distance a
patient walked in 6 min in any of the three tests.
Side Effects
We measured several indices that might reflect toxic effects of
anabolic s teroids. Venous blood concentrations of testosterone
and luteinizing hormone (LH) were measured at baseline and at
9, 18, and 27 weeks. Screening for possible side effects associated
\vith anabolic steroids was carded out according to World Health
Organization guidelines. 22 Live r fun ction was assessed b y mea-
suring levels of serum aspartate aminotransferase, alanine ami-
notransferase, gamma-glutamyltransferase, total bilirubin, conju-
gated bilirubin, and alkaline phosphatase. Every 9 weeks, we
recorded the international normalized r atio, partial thromboplas-
tin time, fibrinogen level, platelet count, and platelet aggregation
to monitor coagulation. Evaluation also included a complete
blood count and measurement of prostatic acid phosphatase,
triglycerides, total cholesterol, and lipoproteins. In addition, we
performed transrectal clinical evaluation of the prostate and
transrectal prostatic ultrasound. We also monitored cardiac func-
tion by means of ECGs, chest radiographs, and two-dimensional
echocardiograms.
Other Measures
Calcium, phosphorus, magnesium , sodium, potassium, and
glucose levels were measured at baseline and at 9, 18, and 27
weeks.
Statistical Analysis
Data are presented as mean ±SE. Nonparametric analysis of
variance was used to determine the significance of differences
between th e two groups (Mann-Whitney) and between periods
(Friedman) . Results were considered statistically significant at
p<O.OS.
RESULTS
The baseline features of the patients are shown in
Table l. There were no significant differences be-
tween groups at baseline. Both groups had a mean
BMI of 17.3 (below predicted values for their age
and sex), severe or moderate airway obstruc-
tion ,23·24·25 and reduced respiratory muscle strength.
Data from six patients were excluded from analysis:
CHEST I 114 I 1 I JULY, 1998 21
 Table }-Anthropometric and Pulmonary Function group). All subjects with tracheobronchitis received
Data at Baseline * antibiotics. Corticosteroids were administered for 5
Control Group Study Group to 7 days in 11 subjects (five control and six study
(n= 7) (n=lO ) subjects ). During exacerbations, subjects missed 1
Age, yr 66.1 (2.6) 70.3 (1.5) week of exercise. They then restarted at a lower
Weight, kg 45.8 (2. 1) 46.1 (14.7) workload, gradually returning to their previous level
BMI, kglm 2 17.3 (0.6 ) 17.3 (0.5) over 1 week. Measures of exercise tolerance were
% o f ideal weight 79.1 (3. 1) 78.4 (2.3)
postponed for 1 week and measures of respiratory
FEV ,,% pred 49.4 (5.9) 41.2 (4.5)
FEV/FVC,% 41.6 (3. 0) 39.7 (2.7) muscle strength and endurance were postponed for
PI max, -em H 2 0 47.7 (3. 7) 43.2 (3. 1) 2 weeks. One control subject and two patients from
PEmax, em H 2 0 114.0 (8.8) 113.4 (8. 1) the treatment group missed the last test because of
Pa0 2 , mm Hg 66.0 (3.7) 71.2 (3.0)
40.5 (13)
respiratory exacerbations; their data for that test was
PaC0 2 , mm Hg 42.0 (2.9 )
excluded from analysis.
*Data presented as mean (SEM ). There were no significant differ-
The changes in anthropometric measurements in
ences between the control and study groups.
study and control subjects during the 27 -week period
are summarized in Figure 1. For changes in BMI,
differences between groups were statistically signif-
two patients in the control group died of respiratory icant at 3 weeks and were sustained throughout the
failure before the study's end; one patient in each 27 weeks (p < 0.05; Fig 1, left ). The arm muscle
group was unable to attend regularly for exercise circumference increased consistently among the
measures; one member of the study group developed study subjects; at 21 weeks, the increase was signif-
atelectasis associated with a non-small cell lung icantly greater in the study group compared with the
cancer; and one study patient was withdrawn be- control group (p< 0.05; Fig 1, center). Between-
cause of depression. Thus, 17 patients completed the group differences in thigh circumference were de-
protocol, 10 in the study group and seven in the tectable at 3 weeks and increased progressively
control group. during the study (p < 0.05; Fig 1, right).
There were numerous respiratory exacerbations, Weight increased in 9 out of 10 subjects who
including flulike illnesses (two control and five study received anabolic steroids (mean, + 1.8±0.5 kg;
subjects), tracheobronchitis (12 control and 11 study p < 0.05), whereas the control group lost weight
subjects), and pneumonia (one subject in each (mean, -0.4±0.2 kg) after 6 months. At baseline,

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0 3 6 9 12 15 18 21 24 27 1-
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weeks weeks weeks

- anabolic steroid-- control

FIGURE l. Changes in anthropometric measurements in study subjects who received anabolic steroids
(squares) and control subjects (circles). Left: percentage change in BMI. The study group's changes in
BMI were significantly greater than the control group's throughout most of the study. Cente·r:
percentage change in arm muscle circumference (AMC ). At 21 weeks, AMC had increased significantly
more in the study group than in the control group. Right: percentage change in thigh circumference.
Significant between-group differences were de tectable at 3 weeks and increased steadily throughout
the study. *=p< 0.05 (study group vs control group ). #= p < 0.05 (vs baseline).

22 Clinical Investigations
lean body mass as measured by DEXA was similar in
both groups. In subjects who received anabolic
steroids, lean body mass increased significantly at 9
weeks compared with baseline (p < 0.05; Fig 2, left),
whereas control subjects showed no increase. The
increase in the study group was sustained at 18
weeks . There were no statistically significant changes
in fat mass over time or differences between groups
(Fig 2, right).
All subjects reported compliance with the training
regimen. Both groups demonstrated increased respi-
ratory muscle strength at 27 weeks (20.0± 11.0% in
the control group, 41.0±9.4% in the study group),
although the increases were not significant; between-
group differences were also not significant (Fig 3,
left ). There were no changes in PEmax (Fig 3, right).
Changes in functional exercise capacity (6 MW)
and Vo 2 max were not significant in either group
(Table 2) .
There were no significant differences in biochem-
ical measures (electrolytes, glucose, calcium, phos-
phorus, magnesium), total protein, albumin, blood
cell count, prostatic acid phosphatase, or prostate
size within groups, between groups, or across time.
Baseline levels of prostatic acid phosphatase were
2.7 IU/L and 2.5 IU/L in the control and study
groups, respectively, compared with 2.3 IU/L (con-
trol group) and 2.2 IU/L (study group) after 27
weeks. The baseline prostate size was 25.8 and 28.0
cm3 in the control and study groups, respectively,
compared with 24.2 and 29.4 cm 3 after 27 weeks .
Levels of LH and testosterone were similar in both
groups at baseline but showed significant decreases
in those receiving anabolic steroids (Table 3). The
between-group differences for LH were evident at 9
weeks and through 27 weeks. Testosterone levels
were significantly lower in the study group compared
with the control group at 9 and 18 weeks. The results
of all other screening tests for side effects of anabolic
steroids did not change.
DISCUSSION
We undertook this randomized controlled trial in
order to evaluate the potential benefits of anabolic
steroids in malnourished individuals with COPD
whose BMI was less than 20 kglm 2 and whose Plmax
was below 60% of the predicted value. Such individ-
uals have been noted to have a reduced body fat
content, skinfold thickness, and arm circumfer-
ence.16 At the end of the 6-month study, the control
and treatment groups' weights differed, with subjects
who received anabolic steroids weighing an average
of 2 kg more than control subjects. This weight gain
was associated with significant increases in arm
muscle and thigh circumference and in lean body
mass as measured by DEXA.
The improved nutritional status that we observed
was confined to those who received anabolic s te-
roids. Although the absolute weight gain among
those receiving anabolic steroids in the study by
Schols et al 14 was not influenced by the nutritional
supplement, the fat-free mass was significantly

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weeks weeks

------ control - - - anabolic steroid

FIGURE 2. Changes in lean body mass (left ) and percent f at mass (right), as measured by DEXA, in
study subjects who received anabolic steroids (squares) and control subjects (circles ). Left: at weeks 9
and 18, the study group experienced a significant increase in lean body mass compared with baseline;
no significant change was noted in control subjects. Right: no significant differences were noted
between groups or over time. #= p< 0.05 (vs baseline) .

CHEST I 11 4 I 1 I JULY, 1998 23

 60 40

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3 6 9 12 15 18 21 24 27 3 6 9 12 15 18 21 24 27

weeks weeks

---+- control ------ anabolic steroid

FIGURE 3. Changes in PI max and PEmax in study subjects who received anabolic steroids (squares) and
con trol subjects (circles). Left: both groups experi enced an improvement in Plmax (20.0% in the
control group, 41.0% in the study group), but the differences between the groups were not statistically
significant. Right: there were no significant changes in PEmax ove r time or differences between groups.

greater in those receiving both steroids and nutri-
tional supplements. Their placebo group lost 0.4 kg,
as did our control subjects . The increase in lean body
mass that we obseiVed without a nutritional supple-
ment (2.5 kg at 9 weeks and 1.9 kg at 27 weeks) was
similar in magnitude to that reported by Schols et
aP 4 (1.4 kg at 8 weeks in nondepleted subjects and
1.9 kg in depleted subjects), despite th e use of
different measurement techniques; Schols et aJl 4
used bioelechical resistance. 26 In our study, lean
body mass did not change in control subjects, but
increased in treatment subjects . Although statistical
significance was not reached at 27 weeks, the trend
for the increase was still evident (Figure 2). Fat mass
did not change in either group.
Although Schols et al 14 also measured body com-
position and respiratory muscle strength in subjects
with COPD , our study differed in several ways . First,
because we wanted to separate the influence of the
anabolic steroid from that of nutritional supplemen-
tation, we did not modify subjects' nutritional intake.
Second, we included IMT, which was not patt of the
study by Schols et al. 14 Third, we chose to study an
oral anabolic steroid rather than a parenterally ad-
ministered steroid and administered it for 27 weeks
in order to approximate an outpatient clinical ap-
proach to those with COPD; Schols et aP 4 gave
subjects a parenteral steroid for 8 weeks. Fourth, we
were concerned about side effects and performed
detailed monitoring of biochemical, hormonal, and
hematologic measures, as well as both clinical and
ultrasound assessment of prostatic function.
Although our subjects did undergo cycle training,
this training was not associated with increases in
measurements of maximal or functional exercise
capacity. We selected malnourished, severely im-
paired individuals with COPD who had high target
exercise levels. Whereas a less impaired cohort may
have improved more than our study subjects, the
literature suggests that improvements in exercise
tolerance can be achieved among severely impaired
individuals. 27 In their well-designed study, Schols et
al 14 succeeded in obtaining reliable measures of
functional exercise (12-min walk distances ) in only
62% of nutritionally depleted individuals. These

Table 2-Distance Walked in 6 Min and Vo 2 max in Control and Study Groups*

Control Study
Baseline Week 9 Week 18 Week 27 Baseline Week 9 Wee k 18 Week 27
Six-min walk, m 540 (24) 545 (29) 561 (35) 573 (26) 523 (19) 540 (23) 516 (27) 510 (33)
Vo 2 m~tx, % pred 54.6 (6) 57.5 (7) 57.8 (5) 64.2(8) 56.8 (3) 54.2 (7) 55.0 (6) 51.8 (6)
*Data presented as mean (SEM ). % pred=percentage of predicted value.

24 Clinical Investigations
 Table 3-LH and Testosterone Levels in Control and Study Groups*
Baseline
LH, IU/L
Control group 5.7 (1. 7)
Study group 3.3 (0.6)
Testosterone, ngldL
Control group 496 (J 17)
Study group 415 (34)
*Data presented as mean (SE M).
1
p<0.05 compared with baseline.
1p<0. 05 compared with control group.
authors did not identifY any increase in 12-min walk
distances in their subjects.
We observed clear trends in the measures of
respiratmy muscle strength (increases of 20.0% and
41.0% in the control and treatment groups, respec-
tively) . However, the differences b etween the two
groups did not reach statistical significance. In the
Schols et all 4 study, nutritionally depleted individu-
als who received both anabolic s teroids and nutri-
tional supplementation achieved a significant in-
crease in Plmax at 8 weeks. Conceivably, a larger
sample size might have allowed u s to detect a
statistically significant change . Alternatively, the sub-
jects in our study may have been too impaired to
experience a significant response to the training
regimen. Another factor contributing to the lack of
change in respiratory muscle fun ction may have been
the a bsence of supervision during IMT sessions. This
is consistent with rehabilitation literature suggesting
that unsupervised training interventions are less
effective than supervised interventions.28 Finally, the
role of IMT in this population is questionable; even
among well-nourished individuals with COPD who
underwent training at highly controlled and super-
vised centers , the evidence of improvement in dys-
pnea or exercise capacity is equivocal.29
Malnutrition impairs skeletal muscle function
among healthy individuals and those with respiratory
conditions. By affecting both ventilatory6·30.31 and
peripheral muscles,32 malnutrition increases impair-
ment and likely adds to the disability of individuals
vvith COPD . Malnourished subjects have been
shown in at least one report33 to have worse scores
for the impact and activity domains of a specific
respiratory quality-of-life questionnaire. R eductions
in muscle mass, especially in the lower limbs, are
common in elderly men,34 ·35 this has been linked to
deconditioning as well as decreased production of
growth hormone and testosterone levels.36 ·37 In
some men, the levels of testosterone, dehydroepi-
androste rone, and dehydroepiandrosterone sulphate
decrease slowly, but in others , these hormones r e-
main within the normal range. 38 In a study of 36
\Veek 9 Week 18 Week 27
7.2 (2.3) 7.1 (1.8) 7.4 (2.0)
0 66 11 (0 2) 1.8 1 (0 7) 2.1 1 (0 8)
452 (43) 463 (3 1) 402 (89)
157 11 (28) 135 1I (1 4) 220 1 (61 )
individuals with COPD , Roth et aP 9 noted that in
those who had experienced a weigh t loss of more
than 4.5 kg in the preceding 6 months or those in
whom weight was below 90% of the predicted value,
the incidence of hypogonadism was higher than in
those with normal weights. Although both an animal
study4° and an uncontrolled clinical study'11 have
suggested that growth hormone may be of benefit,
growth hormone is expensive and has side effects; in
elderly men, growth hormone was no better than a
placebo when evaluated in conjunction with physical
training. 42 When administered to 12 subjects with
COPD, growth hormone plus exercise training re-
sulted in greater increases in lean body mass and
muscle cross-sectional area than either placebo plus
training (12 subjects) or placebo alone (five sub-
jects), with no measurable between-group differ-
ences in exercise tolerance. 43
A wide range of responses to anabolic steroids has
been r eported. Anabolic steroids have been claimed
to increase muscle mass and performance among
athletes b y inducing an anabolic effect on proteins
via androgenic receptors as well as by inhibiting
protein catabolism via glucocorticoid receptors. 11
Testosterone stimulates muscle growth via its effects
on somatomedin ,8 influences actin and myosin to
increase strength,44·46 and might even act centrally to
stimulate athletes to strive for higher training inten-
sities.9·47·48 Unfmtunately, accurate reports on the
effects of anabolic steroids have been difficult to
obtain; there have been wide variations in dosages
and methods of administration, as well as a relative
paucity of w ell-designed outcome studies. In a w ell-
designed study by Bhasin et al,13 supraphysiologic
doses of testosterone were administered to healthy
male volunteers, some of whom also received super-
vised w eight training three times p er week. The
authors reported significant improvements in muscle
size and strength between placebo and testosterone
in nonexercising groups and greater increases in
fat-free mass, muscle size, and strength among those
receiving testosterone in the exercising groups.
CHEST I 114 I 1 I JULY, 1998 25
There were no side effects in mood or behavior
attributable to testosterone.l.3
The effects of anabolic steroids on the athlete and
athletic performance remain controversial. There
appears to be a consensus, however, regarding the
effects of anabolic steroids on aerobic metabolism:
no beneficial effect of anabolic steroids has ever
been shown on aerobic metabolism or an individual's
Vo 2max. 10
The clinical applications of anabolic steroids have
been acknowledged for some time. They have been
administered as adjuvants in the management of
protein deficiency states, after major surgery or
severe trauma, for malabsorption during radiother-
apy, and in conjunction with cytotoxic chemothera-
py.49 Anabolic steroids have also been included with
parenteral nutrition and have been shown to have a
markedly beneficial effect. 50 The response to ana-
bolic steroids has been most favorable among those
in negative nitrogen balance. Undernourished el-
derly people respond to steroids with marked nitro-
gen retention and significant weight gain:SI
Justification of Methods
Testosterone cannot be effectively administered
by mouth, as it is rapidly absorbed into the portal
blood stream for degradation by the liver. Thus, only
a small amount reaches the systemic circulation.
When administered parenterally, effective levels are
not sustained in the plasma because anabolic steroids
are promptly degraded.l 1 We chose to use stanozolol
(a synthetic substance derived from testosterone) ,
which can be orally administered. Synthetic deriva-
tives have the added advantage of having more
anabolic and less androgenic effects than natural
testosterone. The dosage we selected, 12 mg per day,
is twice the replacement dosage 10 and is the dosage
conventionally used by athletes.l 1 We used one dose
of IM testosterone at the start of the study as an
"attack" dose, in keeping with the approach pre-
ferred by athletes. Generally, athletes use either a
pyramidal administration schedule, starting with low
daily dosage and building to higher dosages, or they
use a "stacking" schedule in which several different
preparations are taken simultaneously (oral and par-
enteral) .38·47
During the administration of stanozolol, testoster-
one levels decreased significantly at weeks 9, 18, and
27. At week 27, the differences between groups were
not statistically significant even though the levels of
testosterone in the anabolic steroid group were
comparable to prepubertallevels.52
We used DEXA to measure body composition.
This method has been shown to be accurate to within
1.5% for measurements of total body mass as well as
26
fat and lean mass percentages.53 The advantage of
DEXA for composition studies is that it requires only
10 to 20 min to complete, involves minimal exposure
to radiation, and gives regional values as well as total
body values. The reproducibility is such that serial
measurements are routinely used in estimates of
calcium balance and are accurate to within 0.8%.53
We used Lunar DPX, which is a precise and accurate
tool for the assessment of whole body composition.54
Since there is no method available to measure body
cell mass in clinical practice, it is generally acknowl-
edged that in absence of fluid shifts, the fat-free mass
provides an acceptable estimate. 55 In our study, the
increase in lean body weight cannot be equated
unequivocally to an increase in muscle or tissue mass
because fluid retention could not be absolutely ruled
out. However, regular clinical evaluation by the same
physician did not reveal clinical evidence of fluid
retention nor any change in BP. In addition, DEXA
scanning was standardized to be performed at the
same time of the day (late morning, before lunch)
and by the same technician.
In our study, the dietary intake of our subjects
remained open, without any attempt at standardiza-
tion or supplementation. Supplementation has been
shown to be useful when provided to patients with
COPD in conjunction with anabolic steroids.l4 Many
of our study subjects spontaneously reported an
increase in tl1eir appetite, consistent with reports on
the influence of anabolic steroids on appetite.38
However, even in the absence of supplementation,
BMI and muscle circumference increased among
those who received anabolic steroids.
Our relatively small sample size may have influ-
enced the power of our measurements. For example,
there appeared to be a clinical effect of anabolic
steroids on Pimax but this did not reach statistical
significance, possibly because of the lack of power in
a small sample. Further studies on the influence of
anabolic steroids should examine a larger sample and
should also evaluate their influence on health-related
quality of life.
In summary, anabolic steroids administered to
severely impaired, malnourished men with COPD
were associated with a greater increase in weight,
fat-free mass, and arm and thigh muscle circumfer-
ence than was placebo. There was a trend for an
increase in inspiratory muscle strength in both
groups. These changes occurred in the absence of
clinical or biochemical side effects.
ACKNOWLEDGMENTS: The authors acknowledge the assis-
tance of Drs. Agnaldo P. Cedegno (Urology), N. Ferreira Novo
and Y. Juliano (Statistics), J.G.H. Vieira (Endocrinology), Jose
Lazaro de A~drade (Echocardiography), Celso Guerra (Haema-
tology), Serg10 Ayzen (RadiOlogy), and Braulio Luna Filho (Car-
diology).
Clinical Investigations
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28 Clinical Investigations