DIFFERING RESPONSES OF PLASMA BIOACTIVE AND IMMUNOREACTIVE FOLLICLE-STIMULATING-HORMONE AND LUTEINIZING-HORMONE TO GONADOTROPIN-RELEASING-HORMONE ANTAGONIST AND AGONIST TREATMENTS IN POSTMENOPAUSAL WOMEN

Plasma bioactive (B) and immunoreactive (1) FSH and LH were measured every 10 min for 8 h in the same postmenopausal women in a three-phase study: 1) during normal pulsatile gonadotropin secretion (basal study; n = 8), 2) 8 h after a single injection of a GnRH antagonist (5 mg Nal-Glu, sc; n = 5), and 3) 21 days after a GnRH agonist injection (D-Trp6, 3.75 mg depot preparation, im; n = 7). I-FSH and I-LH were measured by monoclonal antibody immunoradiometric assays. B-FSH and B-LH were measured in selected samples with the immature rat granulosa cell and mouse interstitial cell assays, respectively. Significant pulsatility of B- and I-FSH and LH was demonstrated in the basal samples, but only the B/I ratio of LH was slightly elevated within the secretion peaks. After GnRH antagonist treatment, I-FSH decreased from a mean pretreatment level of 55.7 +/- 7.8 IU/L by 26% (P < 0.001), and B-FSH from 313.8 +/- 61.9 IU/L by 44% (P < 0.01). The B/I ratio decreased from 6.4 +/- 1.7 to 4.5 +/- 1.0 (P < 0.05). After agonist treatment, the I- and B-FSH levels decreased by 92% and 83% (P < 0.0001), respectively, but the B/I ratio increased to 17.3 +/- 4.7 (P < 0.05). The concentrations of I- and B-LH decreased by 75% and 80%, respectively (P < 0.001), after antagonist treatment. After agonist treatment, I-LH decreased by 92%, and B-LH by 93% (P < 0.0001). No changes in the B/I ratios of LH were found after either treatment. In conclusion, no changes were found in the quality of circulating LH during the treatments, whereas the antagonist treatment decreased and the agonist treatment increased the B/I ratio of FSH. These findings provide further evidence that the qualitative responses of FSH and LH to treatment with the same GnRH analog are different, and that the suppressive mechanisms of GnRH antagonist and agonist action on gonadotropin secretion are different.