GnRH Analogues in the Development of a Male Contraceptive: Importance of Testosterone Substitution and Reversibility of Pituitary and Testicular Suppression
GnRH agonists and antagonists are potent and selective inhibitors of gonadotropin synthesis and release resulting in suppression of spermatogenesis. For these reasons, GnRH analogues have received considerable attention as potential male contraceptives. The GnRH analogue-mediated suppression of LH is also associated with a reduction of androgen levels comparable to that seen after orchidectomy. Since androgens are indispensable for normal male physiology, their substitution is thus mandatory in clinical trials with GnRH analogues for male contraception. The evidence available so far, however, suggests that androgen therapy may decrease the antispermatogenic activity of GnRH analogues and careful attention needs to be given to androgen substitution. The present contribution deals with the antispermatogenic potency of GnRH analogues and the crucial role of androgen substitution. Emphasis is placed on preclinical studies in non-human primates and reference is given to relevant clinical trials.
KeywordsGnRH Agonist GnRH Antagonist GnRH Analogue LHRH Agonist Testicular Function
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- 3.Mann, DR, Gould, KG and Collins, DC (1984). Influence of continuous gonadotropin-releasing hormone (GnRH) agonist treatment on luteinizing hormone and testosterone secretion, the response to GnRH and the testicular response to human chorionic gonadotropin in the male rhesus monkey. J Clin Endocrinol Metab, 58, 262PubMedCrossRefGoogle Scholar
- 4.Schaison, G, Brailly, S, Vuagnat, P, Bouchard, P and Milgram, E. (1984). Absence of a direct inhibitory effect of gonadotropin- releasing hormone (GnRH) agonist D-Ser (TBU)6, des-Glu NH<Stack><Subscript>2</Subscript><Superscript>10</Superscript></Stack>-ethylamide (Buserelin) on testicular steroidogenesis in men. J Clin Endocrinol Metab, 58, 885PubMedCrossRefGoogle Scholar
- 5.Sundaram, K, Thau, R, Goldstein, M, Philips, DM, Rivier, J and Bardin, CW (1983). Effects of an LHRH agonist on pituitary and testicular function in rhesus monkeys. J Reprod Fertil, 72, 365Google Scholar
- 16.Akhtar, FB, Wickings, EJ, Jaidi, P and Nieschlag, E (1982). Pituitary and testicular functions in sexually mature rhesus monkeys under high-dose LHRH-agonist treatment. Acta Endocrinol, 101, 1013Google Scholar
- 17.Pineda, JL, Lee, BC, Spiliotis, BE, Vale, W, Rivier, J, Brown TJ and Bereu. BB (1980). Effect of GnRH antagonist [Ac- 3Pro1, pFDPhe2, DTrp3,6]-GnRH on pulsatile gonadotropin secretion in the castrate male primate. Endocrinology, 56, 420Google Scholar
- 24.Bouchard, P, Blondet, C, Spitz, I, Brailly, S, Jouannet, P and Schaison, G (1986). Sperm suppression by long-acting GnRH agonist therapy in men: Critical effect of testosterone substitution and duration of therapy. 68th Meeting Endocr. Soc, Anaheim, USA, Abstr, No 498Google Scholar
- 31.Pavlou, SN, Wakefield, GB, Kamilaris, TC, Lindner, J, Island, DP and Kovacs, WJ (1987). Clinical studies using “Nal-Glu”, a new LHRH antagonist. 69th Annual Meeting Endocr Soc, Indianapolis, USA, Abstr, No 914Google Scholar
- 41.Rajfer, J, Swerdloff, RS and Heber, DM (2984): Testicular histology following chronic gonadotropin-releasing hormone agonist treatment. Fertil Steril, 42, 765Google Scholar