SUPPRESSIVE ACTIONS OF A GONADOTROPIN-RELEASING HORMONE ANTAGONIST ON LUTEINIZING-HORMONE, FOLLICLE-STIMULATING-HORMONE, AND PROLACTIN-RELEASE IN ESTROGEN-DEFICIENT POSTMENOPAUSAL WOMEN

We investigated time- and dose-dependent actions of a gonadotropin-releasing hormone antagonist, the "Nal-Glu" peptide [Ac-D2Nal1, 4ClDPhe2, D3Pal3, Arg5, DGlu6(AA), DAla10], in nine healthy estrogen-withdrawn postmenopausal women. Gonadotropin-releasing hormone antagonist was administered subcutaneously at doses of 10, 30, 100, and 300 μg/kg. Suppression of immunoactive luteinizing hormone concentrations was achieved with a 30 μg/kg dose of antagonist. Suppression of immunoactive follicle-stimulating hormone levels was less (40%) even at the highest antagonist dose (300 μg/kg). Bioactive luteinizing hormone concentrations also significantly decreased (60%) at the two antagonist doses tested (30 and 300 μg/kg). However, the lower antagonist dose showed an "escape" of bioactive luteinizing hormone values after 18 hours. No suppressive effects of the antagonist on prolactin secretion occurred at any dose tested. We conclude that this gonadotropin-releasing hormone antagonist can achieve effective, potent, and long-lasting suppression of pituitary secretion of biologically active luteinizing hormone at higher doses, but secretion of biologically active luteinizing hormone may escape" at lower doses. © 1990.