Effects of Dehydroepiandrosterone Therapy on Pubic Hair Growth ...

J Clin Endocrinol Metab, April 2009, 94(4):1182–1190 jcem.endojournals.org 1189
FIG. 3. (Continued).
Instead <strong>of</strong> DHEAS, we administered DHEA, which has been
used in all recent clinical trials in adult patients with adrenal
insufficiency. In contrast to DHEAS, the pharmacology <strong>of</strong>
DHEA has been well studied in adults (9), and it is easily available.
By using the lowest dose reported to being effective in adult
females with adrenal insufficiency (12), DHEAS serum levels
were reached that were almost identical to the healthy reference
population at this adolescent age. In comparison, when adult
females with a mean/median age between 40 and 57 yr <strong>of</strong> age
were treated with 25–50 mg DHEA, DHEAS serum levels
reached were in median around 2000 ng/ml ( 5.4 mol/liter),
which is a concentration above the median for this age (10–15).
In this context it must be noted that oral
DHEA replacement once daily does not fully
restore the diurnal rhythm <strong>of</strong> serum androgen
levels present in healthy women. Arlt et
al. (9) studied the pharmacokinetics in
healthy women (mean age 23.3 yr) with
transient suppression <strong>of</strong> adrenal androgen
secretion because <strong>of</strong> dexamethasone administration.
Using this experimental setting,
they found supraphysiological concentrations
<strong>of</strong> DHEAS during the first 12 h after
oral administration <strong>of</strong> 50 mg DHEA, which
decreased to baseline values during the
second half <strong>of</strong> the day. Similar kinetics was
found for androstenedione and testosterone;
however, these androgen serum concentrations
did not reach baseline at any
time. Therefore, the normalization <strong>of</strong>
morning serum levels in our DHEA group
observed might not have been associated
with normal serum levels during the whole
day.
In this study, adolescents and young
adults with female gender only were treated.
Therefore, results cannot be generalized to
both genders. In male adolescents, androgens
produced in testes may substitute for
the missing adrenal androgens. Whether
DHEA deficiency causes a relevant estrogen
deficiency in adult males is still a matter <strong>of</strong>
debate. In pediatrics, data are missing to
support such a hypothesis. We restricted the
inclusion to those children with adrenal insufficiency
caused by ACTH deficiency.
Therefore, the rare cases <strong>of</strong> primary adrenal
insufficiency like in Addison’s disease, congenital
adrenal hypoplasia, and familial glucocorticoid
deficiency were not investigated.
To date, there are no rational arguments that
this specific group needs a different regiment
to treat for DHEA deficiency. The group <strong>of</strong>
patients studied was small and the time <strong>of</strong>
therapy limited to 12 months. Therefore,
data on any possibly occurring rare or late
adverse effect could not be detected by this
study. However, based on the data available from studies in
adults, there is no relevant concern regarding safety <strong>of</strong> the drug
DHEA at an oral dose <strong>of</strong> 25–50 mg daily.
Here, we have shown for the first time that DHEA replacement
in female adolescents and young women with central adrenal
insufficiency causes a substantial change in sexual hair
growth indicating efficacy <strong>of</strong> this drug. For the patient with the
burden <strong>of</strong> a complex hormone deficiency disorder, normalization
<strong>of</strong> the physical appearance is very important. In addition, we
observed a clear improvement <strong>of</strong> psychological distress and depression
scores that may be beneficial in the situation <strong>of</strong> adolescence,
which is very vulnerable for any psychological crisis. In the