Gonadotrophin and gonadal steroid response to a single dose of a long-acting agonist of gonadotrophin-releasing hormone in ovulatory and anovulatory women with polycystic ovary syndrome.
OBJECTIVE
A previously published study has identified that anovulatory women with PCOS have an increased response of 17 alpha-hydroxyprogesterone (17OHP) and androstenedione to a GnRH analogue suggesting dysregulation of cytochrome P450c17 alpha. The object of this study was to compare the responses of the pituitary-ovarian axis to a single dose of a long-acting GnRH agonist (GnRHa) in both ovulatory and anovulatory women with PCOS with those in normal subjects.


METHODS
Comparative study of responses of LH, FSH and ovarian steroids to buserelin and the adrenal steroid response to synthetic ACTH in two groups of women with hyperandrogenaemia and polycystic ovaries: those with anovulatory menses or amenorrhoea and those with equally elevated serum testosterone concentrations but regular menses. Results in both groups of women with PCO were compared with those in normal subjects.


METHODS
Twenty-four women with hyperandrogenism and PCO (14 had oligo or amenorrhoea, 10 regular cycles) and 12 weight matched controls with normal ovaries, regular cycles and neither clinical nor biochemical evidence of hyperandrogenism. Subjects were given synthetic ACTH (Synacthen) 250 micrograms i.v. on day 1 of the study and blood collected at 30 and 60 minutes thereafter. On the evening of day 1, dexamethasone treatment was commenced to suppress adrenal androgens. GnRHa 100 micrograms s.c. was given on day 2 and blood samples collected at 30-minute intervals for 4 hours and once more at 24 hours after the injection.


RESULTS
The acute responses of both immunoactive and bioactive LH to GnRHa were significantly greater in the ovulatory PCO group (ovPCO) than controls but the response was greater in anovulatory women with polycystic ovaries (anovPCO) than in either ovPCO or controls, throughout the 24-hour study period. Despite the discrepancy in LH concentrations, basal serum concentrations of androstenedione were equally elevated in anovulatory and ovulatory women with PCO, compared with controls. There was a small but significant increase in androstenedione following GnRHa in both PCO groups at 24 hours but not in controls. A similar pattern was observed in the response of 17OHP to GnRHa although the response was significantly higher than controls in anovPCO women only. By contrast, the responses of both androstenedione and 17OHP to 250 micrograms synthetic ACTH were similar in PCO women to those in controls.


CONCLUSIONS
These data provide evidence for ovarian hypersecretion of androgens in ovulatory, as well as anovulatory women with PCO, supporting the concept of abnormal regulation of 17-hydroxylase and (17,20-lyase activity in the ovary. The finding of an equal degree of hyperandrogenaemia in ovPCO and anovPCO groups, even though LH levels were much higher in the latter, suggests that hypersecretion of LH is not the primary cause of ovarian hyperandrogenism. Hyperandrogenism in PCOs may therefore represent an intrinsic abnormality of ovarian theca-interstitial cell function.
White
D
D
Department of Obstetrics and Gynaecology, St Mary's Hospital Medical School, London, UK.
Leigh
A
A
Wilson
C
C
Donaldson
A
A
Franks
S
S
D019326:17-alpha-Hydroxyprogesterone; D000311:Adrenal Glands / Q000187:drug effects; D000324:Adrenocorticotropic Hormone; D000328:Adult; D000735:Androstenedione / Q000378:metabolism; D000858:Anovulation / Q000503:physiopathology; D002064:Buserelin; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006065:Gonadotropins, Pituitary / Q000378:metabolism*; D006801:Humans; D006908:Hydroxyprogesterones / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D010053:Ovary / Q000378:metabolism* / Q000503:physiopathology; D010902:Pituitary Gland / Q000378:metabolism* / Q000503:physiopathology; D011085:Polycystic Ovary Syndrome / Q000378:metabolism* / Q000503:physiopathology; D013739:Testosterone / Q000378:metabolism
D012739:Gonadal Steroid Hormones; D006065:Gonadotropins, Pituitary; D006908:Hydroxyprogesterones; D013739:Testosterone; D000735:Androstenedione; D019326:17-alpha-Hydroxyprogesterone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D002064:Buserelin