title: 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.
abstract: 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)
authors.affiliation: Department of Obstetrics and Gynecology, University of California, Davis 95616, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Cheung
authors.forename: R J
authors.initials: RJ
authors.lastname: Chang
mesh_terms: 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
chemical_list: D013256:Steroids; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C029256:histrelin