R. Rossi, L. Tauchmanovà, A. Luciano, et al.
cotropin stimulation test (1, 11, 12) together with the
recent diagnostic use of GnRH-analogues (13-16) al-
low clinicians to understand whether androgen ex-
cess is also present in patients with apparently idio-
pathic hirsutism, and whether the origin of this dis-
order is ovarian, adrenal, or both. To this aim, several
authors have evaluated the ovarian production of an-
drogens after both acute and prolonged GnRH-ana-
logue administration, the first to stimulate (13-16),
and the second to suppress ovarian hormonal se-
cretion (11, 17). Abnormal response to either acute
or chronic GnRH-analogue administration was found
predictive of ovarian origin of androgen excess (11,
13-16). The acute stimulation test has the advantage
of being a short, direct, and specific test of pituitary-
ovarian-function, capable to disclose the nature of
ovarian steroidogenesis (13, 14, 16).
In order to better understand the etiology of idio-
pathic hirsutism, the present study evaluated ovar-
ian and adrenal function using the GnRH-analogue
triptorelin acute stimulation test (GnRHa) and the
corticotropin long stimulation test, in 48 women
with apparently idiopathic hirsutism. The combina-
tion of these tests was able to reveal mild to mod-
erate abnormalities in the steroidogenesis of ova-
ries, adrenals, or both, in most hirsute women with
normal baseline androgen concentrations.
syndrome or severe insulin resistance, which were
excluded by anamnestic data and standard en-
docrine tests.
Seventy-eight normal women without signs of hy-
perandrogenism or a family history of endocrine dis-
ease, not taking any medication, whose ages were
between 20 and 31 years, entered the study as con-
trols for 1,24-ACTH and dexamethasone (DXM) tests,
while 36 of them also underwent GnRHa testing.
Both patients and controls were evaluated during
the early follicular phase of their menstrual cycle
(days 3 to 6) and at least 6 months after discontinu-
ing estrogen and progestin therapy.
Informed consent was obtained from all subjects and
the study was conducted in accordance with the
guidelines laid down in the Declaration of Helsinki.
Design of the study
BMI, expressed as weight divided by height square,
fasting glucose and C-peptide concentrations were
determined the first day of hospitalization. Transpa-
rietal pelvic ultrasonography was performed in all pa-
tients, using a 3.5-MHz transducer. The diagnosis of
polycystic ovary was considered on the basis of crite-
ria previously published (19).
ACTH test: Two-hundred and fifty micrograms of
1,24-ACTH (Synacthen, Ciba-Geigy, Balsel, Swit-
zerland) were administrated as a continuous 250 ml
saline iv infusion for 5 h, beginning at 08:00 h of
the first day, and plasma F, 17-OHP, ꢀ4, DHEAS,
total T, 11-deoxycortisol (S) were measured at time
0, 300 and 360 min.
SUBJECTS AND METHODS
The study population was composed of 48 women
with peripuberal or adult-onset hirsutism with a
Ferriman-Galwey score ꢀ12 (4), normal values of the
main androgens – i.e. T, DHEAS and ꢀ4-androste-
nedione (ꢀ4A) – normal levels of 17-hydroxypro-
gesterone (17-OHP) and SHBG concentrations, and
regular menstrual cycles (every 25-35 days). Ovu-
lation was assumed to be regular in all women on
the basis of regular cycles, reported symptoms of
ovulation, such as mid-cycle pain, pre-menstrual
discomfort and breast tenderness. Moreover, serum
progesterone was determined in a random subset
of 12 women in days 20-22 of their menstrual cy-
cle and resulted always >6 ng/ml (range, 7.4-16.7),
thus confirming previous ovulation (18). The wom-
en included in the study were 16 to 34 years old
and were a part of a group of 123 hirsute women
referred to our department for the evaluation of
their androgen pattern. Seventy-five women were
excluded after the initial evaluation because of ab-
normal baseline concentrations of one or more an-
drogens or 17-OHP, considering the mean of 3 dif-
ferent determinations. None of the 48 women in-
cluded in this study had drug-induced hirsutism,
thyroid dysfunction, hyperprolactinemia, Cushing's
DXM test: A low-dose 2-mg suppression test was
carried out by an oral administration of 0.5 mg DXM
from the second day, four times a day for 2 days;
serum steroids were measured at 08:00 h the fol-
lowing morning (fourth day).
GnRHa test: A dose of 0.5 mg DXM was continued
four times a day for 2 more days, which means that
DXM was administered 2 days before and during
the whole sampling period following the adminis-
tration of GnRHa. On the fourth day, from 07:00 h,
2 blood samples were collected every 30 min for
baseline measurements of serum gonadotropins
and steroid hormones (17-OHP, ꢀ4, 17β-estradiol
and total T). Then, at 08:00 h a single 100-μg dose
of GnRHa triptorelin (D-Trp6-GnRH, Decapaptyl,
Ipsen, Italy) was injected sc, and blood samples
were collected after 0.5, 1, 2, 3, 4, 20 and 24 h.
Gonadotropin levels were measured in all samples
and, after 20 and 24 h, steroid hormones were also
determined.
The response to GnRHa was considered abnormal
if the plasma 17-OHP peak was greater than 6.2
nmol/l, the ꢀ4 peak greater than 5.7 nmol/l and
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