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 respon ses in patients suffering from polycystic ovary syndrome (PCOS) with t he GnRH agonist nafarelin, a 1.2-mg dose of nafarelin was given intran asally to 19 women with PCOS and 15 healthy premenopausal women. The s ubsequent 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 o f 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 pat ient group, but there was no significant change during the test in eit her 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 24h, 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 level s were significantly higher in PCOS than in controls. The PCOS patient s displayed a significant increase in androgen and gestagen metabolite s as well as in glucocorticoid metabolites excreted in the urine durin g the 24 h. In the control subjects, except for 17 alpha-hydroxypregna nolone, which rose significantly, none of the urinary steroids investi gated showed relevant changes during the nafarelin test. The posttest excretion of allo-tetrahydrocortisol (1.4 +/- 0.2 vs. 0.3 +/- 0.1 mu m ol/g creatinine; P < 0.001) and the increase in 17 alpha-hydroxypregna nolone excretion (1.4 +/- 0.2 vs. 0.3 +/- 0.1 mu mol/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 8 9% at a 93% specificity. Thus, measurements of 17 alpha-hydroxyprogest erone levels in serum and of urinary allo-tetrahydrocortisol and 17 al pha-hydroxypregnanolone after nafarelin treatment make this stimulatio n test a valuable diagnostic tool for identifying PCOS patients. The s ignificant changes in the excretion of urinary androgen and gestagen m etabolites, unmasked by GnRH agonist stimulation, suggest a functional alteration of the pituitary-ovarian axis. The reason for the increase d excretion of glucocorticoid metabolites after nafarelin stimulation remains to be clarified.