Effects of Dehydroepiandrosterone Therapy on Pubic Hair Growth ...

J Clin Endocrinol Metab, April 2009, 94(4):1182–1190 jcem.endojournals.org 1185
(7, 16). Based on an -error level <strong>of</strong> 5% and -error level <strong>of</strong> 20% (onesided
testing) to detect a change to a higher pubic stage, 12 patients were
required for each study group. To compensate for a dropout rate <strong>of</strong>
10–20%, we planned to include 30 patients. Actually, recruitment was
poorer than expected because some hospitals initially involved decided
not to take part in the study because <strong>of</strong> the inability to manage the
workload associated with this study. For partial compensation <strong>of</strong> this
event, the age range for inclusion was extended from 13–23 yr to 13–26
yr by the amendment No. 1 <strong>of</strong> the study protocol from April 2003.
Allocation sequence
To achieve balance in respect to the medical history <strong>of</strong> the patients,
randomization was stratified into a “tumor group” defined by a medical
history <strong>of</strong> a cerebral tumor <strong>of</strong> the sella region (in remission), and a “nontumor
group” defined by connatal hypopituitarism and absence <strong>of</strong> a
history <strong>of</strong> a cerebral tumor. The allocation sequence was defined by two
computer-generated randomization lists (one for each group) that were
set up by a statistician <strong>of</strong> the Department <strong>of</strong> Medical Biometry Tuebingen,
and were given to the pharmacy at the University <strong>of</strong> Ulm. These lists
ensured that members <strong>of</strong> both groups had an equal probability to get
DHEA or placebo (1:1). Independent pharmacists (University <strong>of</strong> Ulm,
Pharmacy, Ulm, Germany) dispensed either placebo or DHEA according
to these lists whose content was not available for the researchers. The
researchers were completely blinded for the content <strong>of</strong> the capsules allocated
to each patient from the time <strong>of</strong> allocation until the end <strong>of</strong> the
trial. The code <strong>of</strong> each study drug was revealed to the researchers after
the end <strong>of</strong> the trial, when the total data set was saved and blocked against
any subsequent changes by a statistician.
Statistical analysis
The primary endpoint was the change in pubic hair stage in the treatment
group compared with the placebo group. The efficacy <strong>of</strong> the therapy
was statistically evaluated using the Cochran-Mantel-Haenszel- 2
test (27), including the estimation <strong>of</strong> the relative risk, its 95% confidence
interval, and two-sided P values. Analyses <strong>of</strong> changes in the psychological
scores and changes in serum and urinary hormone levels were performed
using the two-sided Wilcoxon test. All analyses were performed
TABLE 1. Baseline characteristics <strong>of</strong> the study participants
during the 12-month controlled study phase for the changes between
pre-therapy visit and follow-up visit at 12 months. Patients with missing
values at the 12-month visit were included in the analyses with the last
observed value before the planned time point (at the 6 month visit). All
secondary endpoints were analyzed in an explorative sense.
After collection on case record forms, all data were entered twice into
the koordobas database (www.koordobas.de) by two independent study
assistants. Koordobas is a validated s<strong>of</strong>tware for support <strong>of</strong> organization
and data management <strong>of</strong> clinical studies according to common requirements
for conduction <strong>of</strong> studies (International Conference <strong>of</strong> Harmonization/Good
Clinical Practice, Food and Drug Administration). Clean
files were submitted to the Department <strong>of</strong> Medical Biometry at the University
<strong>of</strong> Tuebingen for the final analysis, which was performed using
the statistical analyzing s<strong>of</strong>tware SAS (version 9.1.3; SAS Institute Inc.,
Cary, NC), based on the intention-to-treat population, which included
all randomized patients with the exception <strong>of</strong> those who were withdrawn
from active treatment before the first assessment <strong>of</strong> efficacy (Fig. 1).
Role <strong>of</strong> the funding source
The sponsor was the Medical Faculty <strong>of</strong> the University <strong>of</strong> Tuebingen.
The study protocol was reviewed, and the revised version was finally
selected for support by a board <strong>of</strong> full pr<strong>of</strong>essors <strong>of</strong> the Medical Faculty.
There was no contribution to conduct, data collection, data analysis, or
anything else by the sponsor.
Results
The participant flow throughout the study is shown in Fig. 1: 21 <strong>of</strong>
23 patients (91%) completed the visit at 6 month treatment, and 18
<strong>of</strong> 23 patients (78%) completed the total trial lasting 12 months.
There was one case <strong>of</strong> dropout in the DHEA group because <strong>of</strong>
recurrent anxiety attacks that occurred after a frightening ride in
an amusement park carousel. Similar psychological problems
had occurred before the trial but had not been reported to the doctor
Placebo group (n 12) DHEA group (n 11)
Age (range) 19.7 4.3 yr (13.1–25.4) 18.0 1.5 yr (15.7–21.0)
Height (range) 168.1 5.6 cm (155.8–174.8) 162.2 6.1 cm (149.7–169.1)
Weight (range) 66.6 16.4 kg (42.0–99.3) 68.6 15.6 kg (51.8–93.5)
BMI (range) 23.4 4.8 kg/m 2 (17.3–33.1) 26.0 5.3 kg/m 2 (19.4–35.0)
No. <strong>of</strong> overweight (BMI P90) 2 0
No. with obesity (BMI P97) 2 5
Systolic blood pressure (mm Hg) 113 12 115 12
Diastolic blood pressure (mm Hg) 72 6 72 7
No. with cerebral tumor 8 8
No. with post-radiation 2 4
Hydrocortisone dose (mg/m 2 d) 5.1 2.2 6.0 2.1
No. with GH deficiency 12 11
RhGH dose (g/m 2 d) 0.38 0.20 0.28 0.19
No. with TSH deficiency 12 10
L-thyroxine dose (g/m 2 d) 40.4 8.2 42.7 10.9
LH/FSH deficiency 12 11
ADH deficiency 6 7
PRL deficiency 0 1
Breast stage B (range) 4.5 0.8 (3–5) 4.6 0.7 (3–5)
No. with pubic hair stage PH1 4 5
No. with pubic hair stage PH2 7 4
No. with pubic hair stage PH3 1 1
No. with pubic hair stage PH4 0 1
Drug doses are given per day and m 2 body surface. Data are means SD, if not otherwise stated. ADH, Antidiuretic hormone; BMI, body mass index; PRL, prolactin;
RhGH, recombinant human GH.