Suppressive actions of a gonadotropin-releasing hormone antagonist on luteinizing hormone, follicle-stimulating hormone, and prolactin release in estrogen-deficient postmenopausal women

Urban, R.J.; Pavlou, S.N.; Rivier, J.E.; Vale, W.W.; Dufau, M.L.; Veldhuis, J.D.

American Journal of Obstetrics and Gynecology 162(5): 1255-1260


ISSN/ISBN: 0002-9378
PMID: 2111095
DOI: 10.1016/0002-9378(90)90030-b
Accession: 041492579

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We investigated time- and dose-dependent actions of a gonadotropin-releasing hormone antagonist, the "Nal-Glu" peptide [Ac-D2Nal1, 4CIDPhe2, D3Pal3, Arg5, DGlu6(AA), DAla10], in nine healthy estrogen-withdrawn postmenopausal women.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 micrograms/kg. Suppression of immunoactive luteinizing hormone concentrations was achieved with a 30 micrograms/kg dose of antagonist. Suppression of immunoactive follicle-stimulating hormone levels was less (40%) even at the highest antagonist dose (300 micrograms/kg). Bioactive luteinizing hormone concentrations also significantly decreased (greater than 60%) at the two antagonist doses tested (30 and 300 micrograms/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.