Pituitary responsiveness to gonadotrophin-releasing hormone agonist stimulation: a dose-response comparison of luteinizing hormone/follicle-stimulating hormone secretion in women with polycystic ovary syndrome and normal women.
In polycystic ovary syndrome (PCOS), the mechanism responsible for abnormal gonadotrophin secretion, elevated serum luteinizing hormone (LH) and normal or low follicle-stimulating hormone (FSH) concentrations has not been elucidated. One proposed mechanism, as suggested by previous 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. Each of six PCOS and six normal ovulatory women was administered a single s.c. injection of the GnRH agonist [(imBzl)D-His6, Pro9-NEt]-GnRH (D-His) at a dose of 0.01, 0.1, 1 and 10 micrograms/kg on four separate occasions. Blood samples were obtained over a 72 h period following D-His administration. Gonadotrophin responses were measured by (i) the maximal rise from pretreatment baseline values (delta max); (ii) the maximal percentage change from baseline (%delta max); and (iii) the integrated response (mean of the cumulative sum of deviations from baseline). Within-group and between-group dose-responses were compared by two-factor analysis of variance and further characterized using the 'Flexifit' computer program. Our results showed that in both groups, progressive increases of LH and FSH occurred following D-His at doses of 0.01 and 0.1 microgram/kg. Further increases beyond the 0.1 microgram/kg dose were not observed. In PCOS women, delta max and integrated response for LH were significantly greater than those of normal subjects at each dose tested. %delta max of LH was significantly lower in PCOS, reflecting higher pretreatment baseline LH concentrations in this group.(ABSTRACT TRUNCATED AT 250 WORDS)
Cheung
A P
AP
Department of Obstetrics and Gynecology, University of California, Davis 95616, USA.
Chang
R J
RJ
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007700:Kinetics; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000503:physiopathology*; D013256:Steroids / Q000097:blood
D013256:Steroids; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C029256:histrelin