Inhibition of luteinizing hormone, follicle-stimulating hormone and sex-steroid levels in men and women with a potent antagonist analog of luteinizing hormone-releasing hormone, Cetrorelix (SB-75).

Cetrorelix (SB-75; [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10] luteinizing hormone-releasing hormone (LHRH)) is a new highly potent antagonist analog of LHRH containing the D-ureidoalkyl amino acid D-citrulline at position 6 and is free of allergenic effects. This study shows the inhibition of LH and follicle-stimulating hormone (FSH) release in normal men, postmenopausal women and patients with gonadal dysgenesis, using different doses and i.m., s.c. and i.v. routes of administration of SB-75. The mean serum levels of LH and FSH in normal men who received one single dose of 300 micrograms of SB-75 sc started to decline rapidly 1 h after its administration; the LH suppression was sustained for 14 h and that of FSH up to 24 h or longer as the samples were obtained only up to this time. The nadir for LH was reached at 14 h and that for FSH at 24 h or later after administration of the antagonist (p < 0.05). Serum levels of total and free testosterone decreased after the first hour and this inhibition was maintained for up to 14 h. The nadir for total testosterone was at 6 h and that for free testosterone was at 8 h (p < 0.001), corresponding to 56% and 60% of inhibition, respectively. In postmenopausal women, inhibition of the elevated basal serum LH and FSH levels occurred after a single injection of the antagonist analog SB-75 in doses of 75, 150, 300, 600 and 1200 micrograms using im, sc and iv routes of administration.(ABSTRACT TRUNCATED AT 250 WORDS)