The effects of buserelin microparticles on ovarian function in healthy women.
OBJECTIVE
To investigate the tolerance, pharmacokinetics and pharmacodynamics of the microparticle formulation of buserelin, when it was administered subcutaneously.


METHODS
A single-blind, randomised, parallel-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 buserelin administered subcutaneously as microparticles.


METHODS
The study was carried out at the Hoechst Research Centre for Clinical Pharmacology, Department of Pharmacology, University of the Orange Free State, Bloemfontein.


METHODS
Thirty-two health premenopausal female volunteers aged between 19 and 39 years and weighing between 52 and 85 kg completed the study.


METHODS
Serum progesterone and oestradiol concentrations were measured twice weekly until normal ovarian function resumed, i.e. when serum progesterone concentrations increased to at least 8 nmol/l (a sign of ovulation) and oestradiol concentrations increased 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 anovulation for mean periods of 52, 77 and 113 days and suppressed ovarian production of oestrogen for 19, 38 and 69 days. Resumption of normal ovarian function occurred when serum buserelin concentrations decreased to between 0.03 and 0.05 microgram/ml. The correlation coefficient between dose and duration of anovulation was 0.75; the correlation coefficient between dose and duration of suppression of oestrogen production was 0.76.


CONCLUSIONS
Apart from minor side-effects such as hot flushes, vaginal spotting and acne, the compound was tolerated well. We conclude that a good relationship exists between dose and duration of suppression of ovarian function. Doses of 3.6 - 7.2 mg buserelin should suppress oestrogen production for approximately 6 - 9 weeks and ovulation for 11 - 16 weeks.
Meyer
B H
BH
Hoechst Research Centre for Clinical Pharmacology, Department of Pharmacology, University of the Orange Free State, Bloemfontein.
Muller
F O
FO
de la Rey
N
N
Luus
H G
HG
Rosenkranz
B
B
D000293:Adolescent; D000328:Adult; D002064:Buserelin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010053:Ovary / Q000187:drug effects* / Q000502:physiology; D010316:Particle Size; D016037:Single-Blind Method
D002064:Buserelin