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Hormonal Effects of Single Gonadotropin-Releasing Hormone Antagonist Doses in Men^*

F. JOCKENHÖVEL, S. BHASIN, B. S. STEINER, J. E. RIVIER, W. W. VALE and R. S. SWERDLOFF

Division of Endocrinology, Harbor-UCLA Medical Center Torrance, California 90509
The Clayton Foundation Laboratories for Peptide Biology, (J.E.R, W.W.V.) La Jolla, California 92138

Address requests for reprints to: Dr. Shalender Bhasin, Division of Endocrinology, Harbor-UCLA Medical Center, 1000 Carson Street, Torrance, California 90509.

To assess its gonadotropin-inhibiting potency in man, three different doses of a GnRH antagonist ([Ac-D²-Nal¹,D⁴-Cl-Phe², D³-Pal³, Arg⁵,D⁴-p-methoxybenzoyl-2-amino butyric acid⁶,D-Ala¹⁰]GnRH; Nal-Glu GnRH antagonist) were given to six normal men. Single sc doses of 0.5, 1.5, and 5.0 mg Nal-Glu GnRH decreased mean serum immunoactive LH (iLH) to 45.0 ± 5.7% (±SE), 37.0 ± 4.9%, and 31.3 ± 4.2% of baseline, respectively. Maximal suppression occurred between 4 and 8 h after drug injection. Serum bioassayable LH concentrations significantly diminished 8 h after injection of 1.5 and 5.0 mg GnRH antagonist, but not after the 0.5-mg dose. Mean serum testosterone (T) fell to 39.8 ± 5.0%, 32.1 ± 4.9%, and 20.7 ± 4.4% of baseline, respectively, after the 0.5-, 1.5-, and 5.0-mg doses. The decreases in serum iLH and testosterone (T) were more sustained after the higher doses; serum iLH and T were significantly suppressed 24 h after administration of the 5.0-mg dose. Twenty-four-hour integrated serum iLH and T concentrations decreased in a dose-dependent manner. However, basal and 24-h integrated serum FSH concentrations were not significantly affected by the drug. No adverse systemic side-effects occurred. Thus, the Nal-Glu GnRH antagonist effectively decreases serum LH and T concentrations in a dose- and timedependent manner, and it, therefore, has potential as a male contraceptive.

^* This work was supported by NICHHD Contract N01-D-6-2935.

Supported by a Research Training Grant of the Deutsche Forchungsgemeinschaft (Jo 148/1).

Received August 7, 1987.

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