GnRH AGONIST ADMINISTRATION IN POLYCYSTIC OVARY SYNDROME

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Abstract
SUMMARY: The study was designed to examine (1) the effects of the luteinizing hormone releasing hormone (GnRH) agonist, buserelin, on pituitary and ovarian hormone secretion, and (2) the effect that pituitary—ovarian suppression with a GnRH agonist has on subsequent ovulation induction with exogenous gonadotrophins (hMG), in polycystic ovary syndrome (PCOS). Two protocols were studied where buserelin was administered intranasally to all patients in a dose of 200 μg, six times daily. Ten patients received buserelin until an oestrogen withdrawal bleed occurred while a further 12 patients received buserelin for 4 weeks, before hMG was co‐administered. Nine of the above subjects also underwent conventional ovulation induction with hMG. Blood samples were taken daily for radioimmunoassay of LH (LH‐RIA), FSH, sex steroids and inhibin and for immunoradiometric assay of LH (LH‐IRMA). Following buserelin administration there was an initial rise in LH‐RIA, FSH, oestradiol (E2) and inhibin (P < 0.01). Fourteen days were needed for LH‐RIA to return to the normal range, with both protocols resulting in a fall in LH‐RIA and FSH (P < 0.01) before hMG was co‐administered. Twenty‐eight days of buserelin administration were needed to suppress E2 into the castrate range. Inhibin and both E2 and FSH were closely correlated throughout buserelin administration (P < 0.01). There was failure to respond to an intravenous bolus of 100 μg of GnRH from 7 days of buserelin administration onwards, despite the serum LH‐RIA still being raised at 7 days. Serum samples assayed for LH by RIA using WHO Matched Reagents and by IRMA were closely correlated (r = 0.96, P < 0.01). There was no difference in the proportion of ovulations (52%vs 66%) or pregnancies (1 vs 1) in the GnRH agonist or control group. Similar amounts of hMG were needed in both groups and there was multiple follicular development (> 3 follicles > 15 mm diameter; 41%vs 38%) following hMG administration. There was a close correlation between E2 and inhibin levels (P < 0.01). This study demonstrates that (a) 28 days of buserelin administration in a dose of 200 μg, six times daily intranasally is needed to achieve suppression of ovarian function; (b) the GnRH stimulation test is unsatisfactory as an indicator of whether inhibition of pituitary secretion has occurred; (c) following a rise in endogenous and exogenous gonadotrophin levels, E2 and inhibin are stimulated and are closely correlated; (d) there was no benefit of pituitary—ovarian suppression with a GnRH agonist on subsequent ovulation induction, and multiple follicle development was not prevented.

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