THE EFFECTS OF BUSERELIN MICROPARTICLES ON OVARIAN-FUNCTION IN HEALTHY WOMEN

Objective. To investigate the tolerance, pharmacokinetics and pharmaco dynamics of the microparticle formulation of buserelin, when it was ad ministered subcutaneously. Design. A single-blind, randomised, paralle l-group design was used to investigate the duration of suppression of ovarian function associated with doses of 1,8, 3,6 and 7,2 mg busereli n administered subcutaneously as microparticles. Setting. The study wa s carried out at the Hoechst Research Centre for Clinical pharmacology , Department of Pharmacology, University of the Orange Free State, Blo emfontein. Patients. Thirty-two healthy premenopausal female volunteer s aged between 19 and 39 years and weighing between 52 and 85 kg compl eted the study. Outcome measures. Serum progesterone and oestradiol co ncentrations were measured twice weekly until normal ovarian function resumed, i.e. when serum progesterone concentrations increased to at l east 8 nmol/l (a sign of ovulation) and oestradiol concentrations incr eased to values above 300 pmol/l. Serum and urinary concentrations of buserelin were measured at the same times as those of progesterone and oestradiol. Results. Doses of 1,8, 3,6 and 7,2 mg elicited anovulatio n for mean periods of 52, 77 and 113 days and suppressed ovarian produ ction of oestrogen for 19, 38 and 69 days. Resumption of normal ovaria n function occurred when serum buserelin concentrations decreased to b etween 0,03 and 0,05 mu g/ml. The correlation coefficient between dose and duration of anovulation was 0,75; the correlation coefficient bet ween dose and duration of suppression of oestrogen production was 0,76 . Conclusion. Apart from minor side-effects such as hot flushes, vagin al spotting and acne, the compound was tolerated well. We conclude tha t a good relationship exists between dose and duration of suppression of ovarian function. Doses of 3,6 - 7,2 mg buserelin should suppress o estrogen production for approximately 6 - 9 weeks and ovulation for 11 - 16 weeks.