An implant of a gonadotropin releasing hormone agonist (buserelin) which suppresses ovarian function in the macaque for 3–5 months

Abstract

Abstract. Four adult female stumptailed macaque monkeys with regular menstrual cycles and one with irregular cycles and dysfunctional uterine bleeding were treated with a single implant containing 2.6 mg of the GnRH agonist buserelin in a matrix of polylactide/glycolide copolymer (75:25). The implant was used as a cylindrical rod of 0.8 × 0.12 cm and implanted sc in the abdominal wall. The insertion of the implant was followed by a modest rise in serum concentrations of LH and FSH lasting 3–4 days before falling to basal values. The release profile of buserelin from the implant was measured in urine by a radioimmunoassay detecting the intact molecule and its major metabolites. Immunoreactive buserelin in urine was high between days 1–3 after implant after which there was a rapid decline to form a plateau between days 15–70 followed by a further gradual decline. This prolonged release of buserelin suppressed ovulation for a mean of 148 days (range 105–182 days) as indicated by absence of serum progesterone rises. Serum FSH concentrations were low for at least 75 days and during this time serum oestradiol concentrations were uniformly suppressed in all monkeys. Once the buserelin release from the implant declined serum FSH concentrations began to rise. There was a variable delay of 7–60 days before this rise in FSH was associated with stimulation of ovarian oestradiol secretion followed by rises in serum progesterone concentrations indicative of ovulation. Apart from the first menses after insertion of implant, 4 of the monkeys became amenorrhoeic for the period of anovulation. The remaining monkey had dysfunctional uterine bleeding prior to treatment and this gradually decreased before disappearing 7 weeks after implant. These results show that this buserelin implant can provide sustained release of peptide to suppress pituitary-ovarian function in the macaque for at least 3 months. Such an implant should provide an important addition to the currently available modes of administration for the clinical use of GnRH agonists.