Escape from the down-regulation of the pituitary-ovarian axis following decreased infusion of luteinizing hormone-releasing hormone agonist.

In order to suppress the pituitary-ovarian axis for treatment of endometriosis, the luteinizing hormone-releasing hormone (LH-RH) agonist buserelin (Hoechst Canada Inc., Montreal, Quebec, Canada) was administered by continuous subcutaneous (SC) infusion using an osmotic minipump system. The down-regulation of gonadotropin release was confirmed by the absence of LH and follicle-stimulating hormone (FSH) stimulation at pump change every 2 weeks. Between week 3 and week 8 of treatment, a marked decrease in the urinary excretion of buserelin coincided with an increase in serum gonadotropins and estradiol (E2) in four patients. Following pump change, gonadotropins were stimulated and follicular cysts were observed at ultrasound examination. Serum progesterone (P) was in the luteal phase range in two cases. The suppression was re-established when the buserelin/creatinine ratio in the urine had re-increased. Otherwise, the pumping rate was doubled. Menopausal symptoms temporarily disappeared during the ovarian stimulation. A moderate uterine bleeding occurred when E2 suppression was reestablished. These observations show a rapid recovery of the pituitary-ovarian response to LH-RH agonist following a short period of a reduced infusion rate. In a slow release system, the constant delivery of an effective dose is required for the maintenance of suppression and for the avoidance of a possible hyperstimulation.