PITUITARY-RESPONSIVENESS TO GONADOTROPIN-RELEASING-HORMONE AGONIST STIMULATION - A DOSE-RESPONSE COMPARISON OF LUTEINIZING-HORMONE FOLLICLE-STIMULATING-HORMONE SECRETION IN WOMEN WITH POLYCYSTIC-OVARY-SYNDROMEAND NORMAL WOMEN

In polycystic ovary syndrome (PCOS), the mechanism responsible for abn ormal gonadotrophin secretion, elevated serum luteinizing hormone (LH) and normal or low follicle-stimulating hormone (FSH) concentrations h as not been elucidated, One proposed mechanism, as suggested by previo us studies, is an augmented sensitivity of pituitary LH release and a corresponding insensitivity of pituitary FSH release to gonadotrophin- releasing hormone (GnRH) agonist stimulation, This study was designed to further compare gonadotrophin responses to GnRH agonist stimulation within and between individual patients in a dose- response manner, Ea ch of six PCOS and six normal ovulatory women was administered a singl e s.c. injection of the GnRH agonist [(imBzI)D-His(6), Pro(9)-NEt]-GnR H (D-His) at a dose of 0.01, 0.1, 1 and 10 mu g/kg on four separate oc casions. Blood samples were obtained over a 72 h period following D-Hi s administration, Gonadotrophin responses were measured by (i) the max imal rise from pretreatment baseline values (Delta max); (ii) the maxi mal percentage change from baseline (%Delta max); and (iii) the integr ated response (mean of the cumulative sum of deviations from baseline) , Within-group and between-group dose-responses were compared by two-f actor analysis of variance and further characterized using the 'Flexif it' computer program, Our results showed that in both groups, progress ive increases of LH and FSH occurred following D-His at doses of 0.01 and 0.1 mu g/kg, Further increases beyond the 0.1 mu g/kg dose were no t observed. In PCOS women, Delta max and integrated response for LH we re significantly greater than those of normal subjects at each dose te sted, %Delta max of LH was significantly lower in PCOS, reflecting hig her pretreatment baseline LH concentrations in this group, FSH respons es to D-His were not significantly different between PCOS and normal w omen, In PCOS, within-group comparisons failed to reveal a uniform pat tern of LH dose- response, In contrast, LH integrated response curves were homogeneous among individual normal women, as were the correspond ing curves for FSH among both PCOS and normal women, These findings in dicate that PCOS patients exhibit greater LH responsiveness to GnRH ag onist on a per-dose basis than that of normal women, Among individual PCOS patients, inconsistent dose - response patterns of LH release und erscore the subtle variability of LH secretion amongst women with this disorder.