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Journal of Clinical Endocrinology & Metabolism, Vol 58, 885-888, Copyright © 1984 by Endocrine Society
ARTICLES |
G Schaison, S Brailly, P Vuagnat, P Bouchard and E Milgrom
The antigonadal effects of GnRH agonists (GnRH-A) are mediated both through pituitary and testicular inhibitory mechanisms in the rat. To investigate these effects in men, we studied patients having no gonadotropin secretion and compared their testicular response to hCG in the absence or in the presence of GnRH-A. Thirteen patients with acquired pituitary hypogonadotropism had plasma testosterone levels below 1.5 ng/ml and no gonadotropin responses to acute GnRH administration (100 micrograms iv). Testicular responsiveness was evaluated using a single im injection of hCG (5000 IU im). Plasma levels of testosterone, dihydrotestosterone, androstenedione, 17- hydroxyprogesterone (17-OHP), and progesterone were determined before and 4, 12, 24, 48, and 72 h after hCG stimulation. The same protocol was also used in the same patients on day 4 of a 6-day course of treatment with the GnRH-A, D-Ser-(TBU)6, des-Gly NH2 GnRH ethylamide (Buserelin) (3 sc injections of 250 micrograms/day). During the first 4 days of GnRH-A administration, plasma LH, FSH, and testosterone levels were measured daily in order to establish the completeness of the gonadotropin deficiency. Before treatment with hCG, plasma testosterone levels were 0.56 +/- 0.15 and 0.96 +/- 0.22 ng/ml (mean +/- SE) in the absence of GnRH-A and during GnRH-A administration, respectively. The administration of hCG elicited a significant increase in plasma testosterone in both situations; integrated testosterone concentrations were 123.7 +/- 24.9 and 155.5 +/- 27.9 ng/ml . 72 h (P greater than 0.1) in the absence of GnRH-A and during GnRH-A administration, respectively. Likewise the ratios of 17-OHP to progesterone, androstenedione to 17-OHP, and dihydrotestosterone to testosterone after hCG injection were similar in the presence or absence of GnRH-A. Since short term administration of buserelin did not inhibit hCG- induced testosterone secretion in patients with gonadotropin deficiency, we suggest that Buserelin does not grossly modify the function of testicular steroidogenesis enzymes. The antigonadal effects of GnRH-A in man appear to be mediated exclusively through the pituitary.
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