Sensitivity of pituitary and corpus luteum responses to single intranasal administration of (D-ser[TBU]6-des-gly-NH2(10)) luteinizing hormone-releasing hormone ethylamide (Buserelin) in normal women

Abstract

We have previously shown that intranasal administration of Buserelin (Hoechst AG, Frankfurt, Germany) at mid-luteal phase inhibits progesterone secretion and shortens the luteal phase. In order to determine the best possible use of this medication, we studied the effect of increasing doses (50 to 1500 microgram) of the luteinizing hormone-releasing hormone (LH-RH) agonist administered between days 6 and 12 after the luteinizing hormone (LH) peak on the pituitary response and corpus luteum function. A near-maximal gonadotropin response was obtained at a dose of 200 microgram. Maximal LH stimulation was observed at 4 hours, and serum levels of the hormone remained elevated for at least 14 hours at the two highest doses. Maximal serum follicle-stimulating hormone (FSH) levels were usually observed 2 hours later than for LH, and the response was longer lasting. A 2- to 2.5-fold stimulating of serum progesterone levels was observed at 8 hours for all doses studied. There was a tendency for a dose effect on serum estradiol levels, a 2-fold stimulation being obtained at 14 hours at the highest dose of LH-RH analog. Up to 200 microgram, there was no apparent change in the luteal phase. At the 500-microgram dose, there was a clear tendency for decreased estradiol and progesterone concentrations during the treatment cycle, while at 1000 and 1500-microgram doses steroid levels were clearly inhibited and the luteal phase was shortened by 2.5 days. Posttreatment cycles were normal. Thus the corpus luteum is sensitive to a single high intranasal dose of Buserelin, the luteolytic effect being related to the prolonged gonadotropin response.