Evaluation and significance of the degree of pituitary-gonadal inhibition during intranasal administration of buserelin

In 12 patients (11 girls, 1 boy) with central precocious puberty and 4 patients (3 girls, 1 boy) with idiopathic short stature treated for 1 year with a GnRH superagonist, buserelin (0.3 mg intranasally, 4 times a day), a variable degree of inhibition of sex steroid secretion and pubertal development was observed. Regression of breast or genital development required a daily dosage of buserelin ≥ 34 μg/kg. After 3, 6, 9 and 12 months of treatment, the serum oestradiol level in the girls was positively related (r = 0.69) to basal serum LH measured at the same time and to change in breast development during the previous 3 months. In contrast, LH response to GnRH was very low in all the patients and not related to the degree of oestradiol inhibition. Height velocity and bone age velocity during the year of treatment showed no significant correlation with mean oestradiol level. Bone age velocity during treatment was inversely related to bone age at onset of buserelin. These data show that 1) the pituitary gonadal suppression during intranasal administration of buserelin is variable and dose-dependent; 2) gonadotropin response to GnRH is not a sensitive indicator of incomplete pituitary suppression during buserelin treatment; and 3) bone age velocity during treatment is more reduced the more advanced bone age is at onset of treatment.