Variations of Steroid Hormone Metabolites in Serum and Urine in Polycystic Ovary Syndrome after Nafarelin Stimulation: Evidence for an Altered Corticoid Excretion.

To evaluate the clinical relevance of testing pituitary-ovarian
responses in patients suffering from polycystic ovary syndrome
(PCOS) with the GnRH agonist nafarelin, a 1.2-mg dose of nafarelin
was given intranasally to 19 women with PCOS and 15 healthy
premenopausal women. The subsequent analysis of steroids in both
serum and urine during the test was carried out at several time
points for up to 24 h. Serum levels of 17 alpha-hydroxyprogesterone
were elevated at all time points of the test in PCOS patients vs.
controls [at baseline, 3.5 +/- 0.2 vs. 1.8 +/- 0.1 nmol/L (P <
0.001); at 24 h, 9.9 +/- 0.9 vs. 4.9 +/- 0.3 nmol/L (P <
0.001)]. Basal levels of androstenedione were higher in the patient
group, but there was no significant change during the test in
either group. Serum testosterone levels were also found to differ
in PCOS patients compared with the control values at baseline (2.2
+/- 0.2 vs. 1.5 +/- 0.1 nmol/L; P < 0.05) and after nafarelin
treatment (at 24 h, 3.2 +/- 0.4 vs. 1.8 +/- 0.2 nmol/L; P <
0.05). Serum estradiol levels rose significantly in both groups
during the test; the posttest levels were significantly higher in
PCOS than in controls. The PCOS patients displayed a significant
increase in androgen and gestagen metabolites as well as in
glucocorticoid metabolites excreted in the urine during the 24 h.
In the control subjects, except for 17 alpha-hydroxypregnanolone,
which rose significantly, none of the urinary steroids investigated
showed relevant changes during the nafarelin test. The posttest
excretion of allo-tetrahydrocortisol (1.4 +/- 0.2 vs. 0.3 +/- 0.1
mumol/g creatinine; P < 0.001) and the increase in 17
alpha-hydroxypregnanolone excretion (1.4 +/- 0.2 vs. 0.3 +/- 0.1
mumol/g creatinine; P < 0.001) were distinctly higher in PCOS
patients than in the controls; the diagnostic sensitivity of the
combination of both parameters was 89% at a 93% specificity. Thus,
measurements of 17 alpha-hydroxyprogesterone levels in serum and of
urinary allo-tetrahydrocortisol and 17 alpha-hydroxypregnanolone
after nafarelin treatment make this stimulation test a valuable
diagnostic tool for identifying PCOS patients. The significant
changes in the excretion of urinary androgen and gestagen
metabolites, unmasked by GnRH agonist stimulation, suggest a
functional alteration of the pituitary-ovarian axis. The reason for
the increased excretion of glucocorticoid metabolites after
nafarelin stimulation remains to be clarified.