Gonadotropins and testosterone escape from suppression during prolonged luteinizing hormone-releasing hormone antagonist administration in normal men

Spyros N. Pavlou, John W. Interlandi, Gail Wakefield, Donald P. Island, Jean Rivier, Wylie Vale, William J. Kovacs

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Abstract

The ability of prolonged administration of a LHRH antagonist, [Ac-Δ3Pro1, 4F-D-Phe2, D-Trp3, 6]LHRH (4F-antagonist), to suppress serum gonadotropin and testosterone levels was studied in normal men. The 4F-antagonist was given either as a continuous 13.3 μg/kg·h sc infusion for 72 h or as intermittent sc injections of 100 μg/kg every 6 h for 7 days. Serum FSH, LH, and testosterone levels decreased in the period immediatley following initiation of 4F-antagonist administration. However, an escape toward baseline levels for each of these hormones occurred during prolonged antagonist administration. When men receiving the continuous infusion were challenged with iv bolus doses of 50 μg LHRH, the response of LH after the first 12 h of 4F-antagonist administration was similar to that before its administration. This gonadotropin and testoterone escape suggests that, at the doses used, the inhibitory action of the antagonist on gonadotropin secretion is progressively lost. The initial decrease in androgen levels could serve to augment endogenous LHRH release, which, in turn, overcomes the pituitary effects of the antagonist, or to augment endogenous LH secretion directly. These results demonstrate that the pituitary can escape from the suppressive effects of prolonged LHRH antagonist administration and partially restore serum gonadotropin and testosterone levels to normal in man.

Original languageEnglish (US)
Pages (from-to)1070-1074
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume64
Issue number5
DOIs
Publication statusPublished - May 1987

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All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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