Effects of Dehydroepiandrosterone Therapy on Pubic Hair Growth ...

1186 Binder et al. DHEA Replacement in Young Females J Clin Endocrinol Metab, April 2009, 94(4):1182–1190
at inclusion. In the placebo group, one withdrawal was caused
by relapse <strong>of</strong> craniopharyngioma, another due to the manifestation
<strong>of</strong> type 1 diabetes mellitus. Two patients with placebo
were lost at follow-up because <strong>of</strong> change in residence
after 6 month therapy. The remaining 18 patients completed
the trial.
Recruitment was started in January 2004 and ended in March
2006. All 23 patients attended the clinic at baseline after recruitment
and randomization. There were 21 patients seen at the 6
month visit, and 18 completed the trial at the 12 month visit. The
last patient had her 12-month visit in April 2007.
Study population
Baseline characteristics <strong>of</strong> the randomized study participants
are shown in Table 1. The groups were well balanced
with respect to age, weight, tumor and radiation history, presence
<strong>of</strong> additional pituitary hormone deficiencies, doses <strong>of</strong>
hormones substituted, and pubic hair stage. All 23 patients
had hypogonadotropic hypogonadism and were substituted
with sex steroids. The only clinical characteristic that was
different between the two groups was height (the placebo
group was taller), which was presumably <strong>of</strong> no clinical relevance
for this study.
The analyses <strong>of</strong> the primary and secondary outcome measures
involved all patients who took part in the 6-month visit and
FIG. 2. Chronological changes <strong>of</strong> the pubic hair stage according to Tanner. Each filled circle represents
one individual patient. Pubic hair stage V (PH5) is normal in females with an age above 13 yr.
excluded the two patients who were withdrawn from active
treatment before the first assessment <strong>of</strong> efficacy. Treatment compliance
was good; the counts <strong>of</strong> unused capsules were in good
agreement to the expected numbers. In addition, no relevant
violation <strong>of</strong> the study protocol was noted.
Primary efficacy outcome
The chronological change <strong>of</strong> the pubic hair stage in each individual
treated is shown in Fig. 2. The DHEA group exhibited
a significant progress in pubic hair growth from Tanner stage
I–III to II–V (mean: 1 1 ⁄2 stages), whereas the placebo group
did not (mean: 0stages) (P0.0046). Progress in pubic hair stage
was observed in nine <strong>of</strong> 10 patients in the DHEA group, but only
in three <strong>of</strong> 11 patients in the placebo group (relative risk: 0.138;
95% confidence interval 0.021–0.914; P 0.0046). In the
DHEA group, five adolescents reached the mature pubic hair
stages IV and V, whereas only one individual did in the placebo
group.
Secondary efficacy outcomes
The psychometric measurement <strong>of</strong> psychological distress using
the SCL-90-R at baseline and after 12 month therapy gave
different results in the DHEA group when compared with the
placebo group. We evaluated the psychological distress at baseline
and after 12 month therapy, and calculated the differences
<strong>of</strong> the scores observed. The values are
shown in Table 2. At the start, the DHEA
group scored higher than the placebo
group in all scales, but differences were not
significant. In all 10 scores, the DHEA
group improved during therapy, whereas
the placebo group worsened. These
changes were significantly different in
eight <strong>of</strong> 10 scores, including the global severity
index, which is the central integrating
score <strong>of</strong> this psychometric test. Baseline
and outcome scores <strong>of</strong> both groups
were within the normal range observed in
the reference population (19).
We used an additional psychometric instrument,
the German version <strong>of</strong> the CES-D,
to observe the presence <strong>of</strong> depressive symptoms
in each patient treated. The effects <strong>of</strong>
the treatment were evaluated by comparison
<strong>of</strong> changes in the CES-D sum score. The
treatment group improved by 2.1 points
(6.8; range 11 to 13) between baseline
and the 12-month visit (P 0.316; n 10).
In the control group, the scores decreased
[mean: 7.9, (12.0; range 38 to 5; P
0.027; n 9]. The comparison <strong>of</strong> the score
changes with the Wilcoxon test resulted in a
P value <strong>of</strong> 0.018.
The changes in serum and urinary androgens
that were additional secondary out-
come measures are shown in Fig. 3. DHEA
substitution resulted in normalization <strong>of</strong>