Skip to main content

Contraception masculine hormonale

Hormonal male contraception

Resume

Les méthodes de contraception hormonale, qui visent toutes à la suppression des gonadotrophines, peuvent être classées en 2 catégories, selon qu’elles font appel aux dérivés des stéroïdes ou aux analogues du GnRH. L’administration de testostérone à doses supra-physiologiques a une action supressive de la spermatogenèse connue depuis longtemps. Elle a été testée dans une étude multicentrique par l’OMS sur 271 volontaires, recevant 200 mg IM par semaine d’enanthate de testostérone: 65% des hommes sont devenus azoospermiques au bout de 6 mois, la moyenne de la concentration spermatique chez les 35% restants étant de 3 millions/ml. Dans une seconde étude de l’O.M.S. parue tout récemment (1996), l’efficacité contraceptive a été testée chez 349 hommes présentant moins de 3 millions de spermatozoïdes/ml: 4 grossesses sont survenues, correspondant à un taux global de 1,4 grossesses pour 100 années-personnes, s’élevant à 8,1% si on excluait les sujets azoospermiques. Ce type de traitement présente 2 inconvénients: les androgènes doivent être obligatoirement administrés sous forme injectable, et les risques d’une hyperandrogénie prolongée, sur les plans hépatique et cardio-vasculaire, ne sont pas nuls. En dehors du traitement par les androgènes seuls, tous les autres protocoles hormonaux doivent inclure la prescription d’un androgène, à doses physiologiques cette fois, pour pallier le déficit endogène consécutif à la freination de LH. Les progestatifs associés aux androgènes (acétate de médroxy-progestérone, 19 Nor éthistérone, levonorgestre …) ont généralement une efficacité contraceptive meilleure et plus rapide que celle des androgènes seuls. En revanche, l’utilisation des agonistes du GnRH s’est révélée décevante, surtout en association avec un traitement androgénique substitutif. Des travaux récents concernant les antagonistes du GnRH (Nal-Glu en particulier) apparaissent plus prometteurs, et ont permis d’obtenir une majorité d’azoospermies, dans des séries néanmoins encore limitées.

En conclusion, les études les plus intéressantes concernent actuellement les associations d’un androgène (à doses physiologiques) avec soit un progestatif, soit un antagoniste du GnRH. Plusieurs problèmes importants demeurent non résolus, en particulier la forme d’administration de l’androgène (il faut pouvoir éviter les injections) et l’impossibilité pour un certain nombre de sujets d’atteindre l’azoospermie.

Abstract

The activities of male and female gonades depend on the same pituitary hormones FSH and LH. In the field of contraception, the situations are very different: it is rather easy to disturb maturation then rupture of the dominant follicle, whereas it is much more difficult to inhibit the daily production of more than one hundred millions spermatozoa. Therefore, even in case of efficient inhibition of gonadotrophins, azoospermia is not systematically obtained, and the problem is to appreciate the risk of pregnancy corresponding to a given value of sperm concentration.

Molecules used for hormonal male contraception can be classified in two groups: steroids and GnRH analogs. The inhibitory effect of supra-physiological doses of testosterone on sperm production has been well known for a long time. In a preliminary study conducted by World Health Organisation Task Force, 271 volunteers received 200 mg of testosterone enanthate IM once a week: 65% became azoospermic within a 6 months period; the mean sperm concentration in the non azoospermic subjects was 3 millions/ ml. Asiatic men were better responders than caucasian. In a second study recently published, the efficiency of male contraception was tested in 349 men having less than 3 millions/ml: 4 pregnancies occured, corresponding to an overall pregnancy rate of 1.4 per 100 person-years, which reached 8.1% if azoospermic subjects were excluded.

The administration during a long period of androgens at a supra-physiological level is not devoid of potential risks. The association of progestagens and androgens allows to give androgens at physiological doses as a supplementation treatment, since the main contraceptive effect is due to the progestagens. Medroxy-progesterone acetate has been widely studied, but others molecules, as Nor-ethisterone or levonorgestrel, are more powerful inhibitors or gonadotrophins and are good candidates for male contraception.

On the contrary, all the trials testing the efficiency of GnRH analogs were very disappointing, with or without androgens supplementation. Recent works using GnRH antagonists as Nalglu look promising, since almost all men became azoospermic, however several problems must be resolved (histamine-like side effects; high coast of the treatment).

Since androgens are involved in all protocols, it is very important, in order to promote hormonal male contraception, to find some gallenic forms of androgens which allow to avoid injections.

Referenences

  1. ANDERSON R.A., WU F.C.W.: Comparison between testosterone enanthate — induced azoospermia and oligozoospermia in a male contraceptive study — II Pharmacokinetics and pharmacodynamics of once weekly administration of testosterone enanthate. J. Clin. Endocrinol. Metab., 1996, 81: 896–901.

    Article  PubMed  CAS  Google Scholar 

  2. BEBB R.A., ANAWALT B.D., CHRISTENSEN B., PAULSEN C.A., BRENNER W.J., MATSUMOTO A.M.: Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraception approach. J. Clin. Endocrinol. Metab., 1996, 81: 757–762.

    Article  PubMed  CAS  Google Scholar 

  3. BEHRE H.M., NASHAN D., HUBERT W., NIESCHLAG E.: Depot gonadotropin-releasing hormone agonist blunts the androgen-induced suppression of spermatogenesis in a clinical trial of male contraception. J. Clin. Endocrinol. Metab., 1992, 74: 84–90.

    Article  PubMed  CAS  Google Scholar 

  4. BREMNER W.J., BAGATELL C.J., STEINER R.A.: Gonadotropin-releasing hormone antagonist plus testosterone: a potential male contraceptive. J. Clin. Endocrinol. Metab., 1991, 73: 465–469.

    PubMed  CAS  Google Scholar 

  5. GUERIN J.F., ROLLET J.: Inhibition of spermatogenesis in men using various combinations of oral progestagens and percutaneous or oral androgens. Int. J. Androl., 1988, 11: 187–199.

    Article  PubMed  CAS  Google Scholar 

  6. HANDELSMAN D.J., FARLEY T.M.M., PEREGOUDOV A., WAITES G.M.H., WORLD HEALTH ORGANISATION TASK FORCE: Factors in non uniform induction of azoospermia by testosterone enanthate in normal men. Fertil. Steril., 1995, 63: 125–133.

    PubMed  CAS  Google Scholar 

  7. HECKEL N.J.: Production of oligospermia in a man by the use of testosterone propionate. Proc. Soc. Exp. Biol. Med., 1939, 40: 658–659.

    Google Scholar 

  8. NIESCHLAG E., BEHRE H.M., WEINBAUER G.F.: Hormonal male contraception: a real chance? In: Spermatogenesis — fertilization — contraception — Molecular, cellular and endocrine events in male reproduction. Berlin Springer Verlag, 1992: 457–501.

    Google Scholar 

  9. PAVLOU S.N., BREWER K., FARLEY M.G., LINDNER J., BASTIAS M.C., ROGERS B.J., SWIFT L.L., RIVIER J.E., VALE W.W., CONN M., HERBERT C.M.: Combined administration of a gonadotropin-releasing hormone antagonist and testosterone in men induces reversible azoospermia without loss of libido. J. Clin. Endocrinol. Metab., 1991, 73: 1360–1369.

    PubMed  CAS  Google Scholar 

  10. PAVLOU S.N., DAHL K.D., WAKEFIELD G., RIVIER J., VALE W., HSUEH A.J.W., LINDNER J.: Maintenance of the ratio of bioactive to immunoreactive follicle-stimulating hormone in normal men during chronic luteinizing hormone-releasing-hormone agonist administration. J. Clin. Endocrinol. Metab., 1988, 66: 1005–1009.

    Article  PubMed  CAS  Google Scholar 

  11. SOUFIR J.C., JOUANNET P., MARSON J., SOUMAH A.: Reversible inhibition of sperm production and gonadotrophin secretion in men following combined oral medroxy progesterone acetate and percutaneous testosterone treatment. Acta Endocrinologica, 1983, 102: 625–632.

    PubMed  CAS  Google Scholar 

  12. WORLD HEALTH ORGANISATION TASK FORCE ON METHODS FOR THE REGULATION OF MALE FERTILITY: Contraceptive efficacy of testosterone induced azoospermia in normal men. Lancet, 1990, 336: 955–959.

    Article  Google Scholar 

  13. WORLD HEALTH ORGANISATION TASK FORCE ON METHODS FOR THE REGULATION OF MALE FERTILITY: Contraceptive efficacy of testosterone — induced azoospermia and oligozoospermia in normal men. Fertil. Steril., 1996, 65: 821–829.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Guerin, J.F. Contraception masculine hormonale. Androl. 6, 259–265 (1996). https://doi.org/10.1007/BF03035279

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03035279

Mots-clés

  • contraception masculine hormonale
  • androgènes
  • progestatifs
  • analogues du GnRH

Key words

  • hormonal male contraception
  • androgens
  • progestagens
  • GnRH analogs