Dose-related changes in LH bioactivity with intranasal GnRH agonist administration

In order to evaluate changes in bioactive (bio) and immunoreactive (i) LH and in FSH after intranasal administration of a GnRH agonist, two doses (125 micrograms and 250 micrograms) of nafarelin acetate were administered for 14 weeks to 7 normal women. Maximum changes in gonadotropins were observed 2-4 hours after both the first and last doses. However, the maximum acute responses of iLH, bioLH and FSH were significantly reduced after 14 weeks of treatment while no changes occurred in the bio: iLH ratio. The decrease in these acute responses were not dose-related. Serum iLH and FSH levels obtained prior to each dose (baseline) were not significantly altered by 14 weeks with either dose. However, baseline serum bioLH was significantly reduced compared to pretreatment by 14 weeks but only with the 250 micrograms dose (p less than 0.05). This level was also significantly different from the level of bioLH achieved with 125 micrograms (p less than 0.05). The bio: iLH ratio was also significantly decreased with the 250 micrograms dose. Although serum estradiol and progesterone levels suggested ovarian follicular activity and luteinization with the 125 micrograms dose, this did not occur with 250 micrograms of intranasal nafarelin. These data support a dose response effect of intranasal agonist treatment on the bioactivity of LH and also suggest the relevance of measurements of bioLH in assessing the effectiveness of agonist therapy.