Male Contraception in the 21st Century

  • C. Wang
  • R. S. Swerdloff
Part of the Mineralogical Society Series book series (ENDO, volume 5)


World population growth is a major problem of modern civilization. At present there are 6 billion people in the world and most of them live in developing countries. The rate of population growth is about 1 billion per decade. Studies have shown that about 50% of couples in the reproductive age do not have access or choose not to use modern contraceptive methods. In the female, the available methods include the oral contraceptive pills, injectables, implants, intrauterine devices, cervical caps, diaphragm, female condom and tubal ligation. In the male, the paucity of methods persists. International agencies, national governments, women’s health groups and communities recognize the need and are supporting research and development in contraceptive methods for men (World Health Organization, 1998). We believe that a variety of methods of male contraception will be available in the twenty-first century.


GnRH Agonist Sperm Concentration GnRH Antagonist Cyproterone Acetate Testosterone Enanthate 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anawalt BD, Bebb RA, Bremner WJ, Matsumoto A. Lower dosage of levonorgestrel (LNG) and testosterone enanthate (TE) equally effective spermatogenic suppression and fewer metabolic effects. 79th Annual Meeting Endo Soc 1997; OR 21-6, p 95.Google Scholar
  2. Anderson RA, Wallace AM, Wu FCW. Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. I. Higher 5α reductase activity in oligozoospermic men administered supraphysiological doses of testosterone. J Clin Endocrinol Metab 1996; 81:902–908.PubMedCrossRefGoogle Scholar
  3. Bagatell CJ, Matsumoto AM, Christensen RB, Rivier JE, Bremner WJ. Comparison of a gonadotropin releasing-hormone antagonist plus testosterone (T) versus T alone as potential male contraceptive regimens. J Clin Endocrinol Metab 1993; 77:427–432.PubMedCrossRefGoogle Scholar
  4. Bebb RA, Anawalt BD, Christiansen RB, Paulsen CA, Bremner WJ, Matsumoto AM. Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: A promising male contraceptive approach. J Clin Endocrinol Metab 1996; 81:757–62.PubMedCrossRefGoogle Scholar
  5. Behre HM, Baus S, Kliesch S, Keck C, Simoni M, Nieschlag N. Potential of testosterone buciclate for male contraception: endocrine differences betwen responders and non-responders. J Clin Endocrinol Metab 1995; 80:2394–2403.PubMedCrossRefGoogle Scholar
  6. Behre HM, Klein B, Steinmeyer E, McGregor GP, Voigt K, Nieschlag E. Effective suppression of luteinizing hormone and testosterone by single doses of the new gonadotropin-releasing hormone antagonist cetrorelix (SB-75) in normal men. J Clin Endocrinol Metab 1992; 75:393–398.PubMedCrossRefGoogle Scholar
  7. Behre HM, Kliesch S, Puhse G, Reissmann T, Nieschlag E. High loading and low maintenance doses of a gonadotropin-releasing antagonist effectively suppress serum luteinizing hormone, follicle-stimulating hormone, and testosterone in normal men. J Clin Endocrinol Metab 1997; 82:1403–1408.PubMedCrossRefGoogle Scholar
  8. Behre HM, 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.PubMedCrossRefGoogle Scholar
  9. Bhasin S, Heber D, Steiner B, Peterson M, Blaisch B, Campfield LA, Swerdloff RS. Hormonal effects of GnRH agonist in the human male: II. Testosterone enhances gonadotrophin suppression induced by GnRH agonist. Clin Endocrinol 1984; 20:119–128.Google Scholar
  10. Bhasin S, Heber D, Steiner BS, Handelsman DJ, Swerdloff RS. Hormonal effects of gonadotropin-releasing hormone (GnRH) agonist and androgen. J Clin Endocrinol Metab 1985a; 60: 998–1003.PubMedGoogle Scholar
  11. Bhasin S, Steiner B, Swerdloff R. Does constant infusion of gonadotropin-releasing hormone agonist lead to greater suppression of gonadal function in man thanits intermittent administration? Fertil Steril 1985b; 44:96–101.PubMedGoogle Scholar
  12. Bouchard P, Garcia E. Influence of testosterone substitution on sperm suppression by LHRH agonists. Horm Res 1987; 28:175–180.PubMedCrossRefGoogle Scholar
  13. Breton S, Smith PJS, Lui B, Brown D. Acidification of the male reproductive tract by a proton pumping (H+)-ATPase. Nature Medicine 1996; 2:470–472.PubMedCrossRefGoogle Scholar
  14. Chen ZW, Gu YQ, Liang XW, Wu ZG, Yin EJ, Li H. Safety and efficacy of percutaneous injection of polyurethane elastomer (MPU) plugs for vas occlusion in man. Int J Androl 1992; 15:468–472.PubMedGoogle Scholar
  15. Cummings DE, Bremner WJ. Prospects for new hormonal male contraceptives. Endocrinol and Metabol Clinics of North America 1994; 22:893–922.Google Scholar
  16. Cunningham GR, Silverman VE, Kohler DO. Clinical evaluation of testosterone enanthate for induction and maintenance of reversible azoospermia in man. In Hormonal Control of Male Fertility, (Eds.) D. J. Patanelli. DHEW Publication (NIH) 78-1097, pp. 71to 92, 1978.Google Scholar
  17. Diekman AB, Herr JC. Sperm antigen and their use in the development of an immunocontraceptive. Am J Reprod Immunol 1997; 37:111–117.PubMedGoogle Scholar
  18. Edwards JP, Zhi L, Poolay CL, Tagley CM, West SJ, Wang MW, Gottarchis MM, Pathirama C, Shrader WT, Jones TK. Preparation, resolution, and biological evaluation of 5-aryl-1, 2-dihydro-5H-chromeno [3,4-f]quinolines:potent, orally active, nonsteroidal progesterone receptor agonists. J Med Chem 1998; 41:2779–2785.PubMedCrossRefGoogle Scholar
  19. Ellerman DA, Brantug VS, Cohen D, Cuasnicu PS. Potential contraceptive use of an epididymal protein that participates in sperm-egg fusion. Biol Reprod 1996; 54:95.Google Scholar
  20. Ewing L. Effects of testosterone and estradiol, silastic implants, on spermatogenesis in rats and monkeys. In Hormonal Control of Male Fertility. Patanelli DJ (ed) Bethesda: US DHEW Publication No. (NIH) 78-1097 pp 173 to 194, 1978.Google Scholar
  21. Ford WCL, Waites GMH. A reversible contraceptive action of some 6-chloro-6-deoxy sugars in the male rat. J Reprod Fertil 1978; 52:152–157.Google Scholar
  22. Hamann LG, Higuchi RI, Zhi L, Edwards JP, Wang XN, Marschke KB, Kong JW, Farmer LJ, Jones TK. Syntheses and biological activity of a novel series of nonsteroidal, peripherally selective androgen receptor antagonists derived from 1,2-dihydropyridono [5,6-g] quinolines. J Med Chem 1998; 41:623–639.PubMedCrossRefGoogle Scholar
  23. Handelsman DI, Conway AJ, Howe CJ, Turner L, Mackey M-A. Establishing the minimum effective dose and additive effects of depot progestin in suppression of human spermatogenesis by a testosterone depot. J Clin Endocrinol Metab 1996; 81:4113–4121.PubMedCrossRefGoogle Scholar
  24. Handelsman DJ, Conway AJ, Boylan LM. Suppression of human spermatogenesis by testosterone implants in man. J Clin Endocrinol Metab 1992; 75:1326–32.PubMedCrossRefGoogle Scholar
  25. Hayashi M, Fugimoto S, Takano H, Ushoki T, Abe K, Isshikura H, Yoshida M, Kirchoff C, Ishibashi T, Kasahara M. Characterization of a human glycoprotein with potential role in sperm-egg fusion: cDNA cloning, immunohistochemical localization and chromosomal assignment of the gene (AEGL1). Genomics 1996; 32:367–374.PubMedCrossRefGoogle Scholar
  26. Heber D, Swerdloff RS. Male contraception: Synergism of gonadotropin-releasing hormone analog and testosterone in suppressing gonadotropin. Science 1980; 209:936–938.PubMedCrossRefGoogle Scholar
  27. Herr JC. Update on the Center for Recombinant Gamete Contraceptive vaccinogens. Am J Reprod Immunol 1996; 3:184–189.Google Scholar
  28. Hinton BT, Palladino MA, Rudolph D, Labus JC. The epididymis as protector of maturing spermatozoa. Reprod Fertil Dev 1995; 7:731–745.PubMedCrossRefGoogle Scholar
  29. Hinton BT, Palladino MA. Epididymal epithelium: Its contribution to the formation of a luminal fluid microenvironment. Micros Res Tech 1995; 30:67–81.CrossRefGoogle Scholar
  30. Johnson L, Barnard JJ, Rodriguez L, Smith EC, Swerdloff RS, Wang XH, Wang C. Ethnic difference in testicular structure and spermatogenic potential may predispose testes of Asian men to a heightened sensitivity to steroidal contraceptives. 1998 (in press).Google Scholar
  31. Kandeel FR, Swerdloff RS. Role of temperature in the regulation of spermatogenesis and the use ofheating as a method for contraception. Fertil Steril 1988; 40:1–23.Google Scholar
  32. Knuth UA, Nieschlag E. Endocrine approaches to male fertility control. Clinics in Endocrinol Metab 1987; 1:113–131.Google Scholar
  33. Knuth UA, Yeung C, Nieschlag E. Combination of 19 non-testosterone-hexyloxyphenylpropionate (Anadur) and depot medroxyprogesterone-acetate (Clinovir) for male contraception. Fertil Steril 1989: 51:1011–1018.PubMedGoogle Scholar
  34. Kratzschman J, Haendler B, Eberspaecher U, Roosterman D, Donner P, Schleuning WD. The human cystein-rich secretory protein (CRISP) family. Primary structure and tissue distribution of CRISP-1, CRISP-2, AND CRISP-3. Eur J Biochem 1996; 231: 827–836.CrossRefGoogle Scholar
  35. Kumar N, Didolkar AK, Monder C, Bardin CW, Sundaran K. The biological activity of 7 α-methyl-19-nortestosterone is not amplified in male reproductive tract as is that of testosterone. Endocrinology 1992; 130:3677–3683.PubMedCrossRefGoogle Scholar
  36. Li S, Goldstein M, Zhu J, Huber D. The no-scalpel vasectomy. J Urol 1991 145:341–344.PubMedGoogle Scholar
  37. Li S. Percutaneous injection of vas deferens. Chin J Urol 1980; 1:193–198.Google Scholar
  38. Lue YH, Sinha-Hikim AP, Wang C, Leung A, Baravarian S, Reutrakul V, Sangsawan R, Chaichang S, Swereloff RS. Triptolide: a potential male contraceptive. J Andro 1998; 19:479–486.Google Scholar
  39. Mauss J, Borsch G, Bormacher K, Richter E, Leyendecker G. Seminal fluid analyses, serum FSH, LH and testosterone in seven males before, during and after 250 mg testosterone enanthate weekly over 21 weeks. In Patanelli DJ (ed) Hormonal control of male fertility, US DHEW (NIH), Bethesda, pp. 93 to 122, 1978.Google Scholar
  40. Meng GD, Zhu JC, Chen ZW, Wong LT, Zhang GY, Hu YZ, Ding JH, Wang XH, Qian SZ, Wang C, Machin D, Pinol A, Waites GMH. Recovery to normal sperm production following cessation of gossypol treatment: A two center study in China. Int J Androl 1988; 11:1–11.PubMedGoogle Scholar
  41. Meriggiola MC, Bremner WJ, Costantino A, Pavani A, Capelli H, Flamigni C. An oral regimen of cyproterone acetate and testosterone undecanoate for spermatogenic suppression in men. Fertil Steril 1997; 68:844–50.PubMedCrossRefGoogle Scholar
  42. Meriggiola MC, Bremner WJ, Paulsen CA, Valdiserri A, Incorvaia L, Motta R, Pavani A, Capelli M, Flamigni C. A combined regimen of cyproterone acetate and testosterone enanthate as a potentially highly effective male contraceptive. J Clin Endocrinol Metab 1996; 81:3018–23.PubMedCrossRefGoogle Scholar
  43. Mieusset R, Bujan L. Testicular heating and its possible contribution to male fertility: a review. Int J Androl 1995; 18:164–184.Google Scholar
  44. Murty GSRC, Rani CSS, Moudgal NR, Prasad MRN. Effect of passive immunization with specific antiserum to FSH on the spermatogenic process and fertility of male bonnet monkeys (macaca radiata). J Reprod Fertil 1979; (Suppl) 26:147–154.Google Scholar
  45. National Coordinating Group on Male Antifertility Agents. Gossypol: A new antifertility agent for males. Chinese Med 1978; J 4:417–428.Google Scholar
  46. Nieschlag E. Reasons for abandoning immunization against FSH as an approach to fertility regulation. In Zatuchini GI, Goldsmith A, Spieler JM, and Sciana JJ (eds): Male Contraception: Advances and Future Prospects. Philadelphia, Harper & Row, pp. 395–399, 1985.Google Scholar
  47. O’Hern PA, Bambra CS, Isahakia M, Goldberg E. Reversible contraception in female baboons immunized with a synthetic epitope of sperm-specific lactate dehydrogenase. Biol Reprod 1995; 52:331–339.PubMedCrossRefGoogle Scholar
  48. Orgebin-Crist MC. Androgens and epididymal function. In: Pharmacology, Biology, and Clinical Applications of Androgens. S. Bhasin, HL Gabelnick, JM Spieler, RS Swerdloff, C Wang (Eds), Wiley-Liss, Inc., NY, pp 27–38, 1996.Google Scholar
  49. Patanelli DJ (ed) Hormonal control of male fertility. Bethesda: US DHEW Publication No. (NIH) 78-1097, 1978.Google Scholar
  50. Paulsen CA, Bremner WJ, Leonard JM. Male Contraception: Clinical trials. In Mishell, DR Jr (ed), New York: Raven Press, pp. 157–170, 1982.Google Scholar
  51. Pavlou SN, Interlandi JW, Wakefield G, Rivier J, Vale W, Rabin D. Heterogeneity of sperm density profiles following 16-week therapy with continuous infusion of high-dose LHRH analog plus testosterone. JAndrol 1986; 7:228–233.Google Scholar
  52. Pavlou SN, Wakefield GB, Island DP, Hoffman PG, LePage ME, Chan RL, Nerenberg CA, Kovacs WJ. Suppression of pituitary-gonadal function by a potent new luteinizing hormone-releasing hormone antagonist in normal men. J Clin Endocrinol Metab 1987; 64:931–936.PubMedCrossRefGoogle Scholar
  53. Perez Martinez S, Conesa D, Cuasnicu PS. Potential contraceptive use of epididymal proteins: evidence for the participation of specific antibodies against rat epididymal protein DE in male and female fertility inhibition. J Reprod Immunol 1995; 29:31–45.PubMedCrossRefGoogle Scholar
  54. Primakoff P, Woolman-Gamer L, Tung KS, Myles DG. Reversible contraceptive effect of PH-20 immunization in male guinea pigs. Biol Reprod 1997; 56:1142–1146.PubMedCrossRefGoogle Scholar
  55. Qian SZ, Xu Y, Zhang JW. Recent progress in research on tripterygium: a male antifertility plant. Contraception 1995; 51:121–129.CrossRefGoogle Scholar
  56. Qian SZ. Tripterygium Wilfordii: A Chinese herb effective in male fertility regulation. Contraception 1987; 36:247–263.CrossRefGoogle Scholar
  57. Roy S. Experience in the development of hormonal contraceptive for the male. In Recent Advances in Human Reproduction, Asch RH (ed) Rome: Fondazione per gli Studi Sulla Riproduzione Umana pp. 95–104, 1985.Google Scholar
  58. Schearer SB, Alvarez-Sanchez F, Anselmo J, Brenner P, Continlo E, Latham-Foundes A, Frick J, Heinild B, Johansson EDB. Hormonal contraception for men. Int J Andrology 1978; Suppl 2:680–712.Google Scholar
  59. Sinha Hikim AP, Wang C, Leung A, Swerdloff RS. Involvement of apoptosis in the induction of germ cell degeneration in adult rats after gonadotropin-releasing hormone antagonist treatment. Endocrinology 1995; 136:2770–2775.CrossRefGoogle Scholar
  60. Sinha-Hikim A, Wang C, Lue YH, Johnson L, Wang XH, Swerdloff RS. Spontaneous germ cell apoptosis in human: evidence for ethnic differences in thesusceptability of germ cells to programmed cell death. J Clin Endocrinol Metab 1998; 83:152–156.CrossRefGoogle Scholar
  61. Swerdloff RS, Bagatell CJ, Wang C, Anawalt BD, Steiner B, Berman N, Bremner WJ. Suppression of spermatogenesis in man induced by Nal-Glu gonadotropin releasing hormone antagonist and testosterone enanthate is maintained by testosterone enanthate alone. J Clin Endocrinol Metab 1998 (in press).Google Scholar
  62. Swerdloff RS, Palacios A, McClure RD, Campfield LA, Brosman SA. Clinical evaluation of testosterone enanthate in the reversible suppression of spermatogenesis in the human male: efficacy, mechanism of action, and adverse effects. In Patanelli DJ (ed) Hormonal control of male fertility, US DHEW (NIH), Bethesda, pp. 41 to 70, 1978.Google Scholar
  63. Tapanainen JA, Ailtomaki K, Min J, Vaskivuo T, Huhtaniemi IT. Men homozygous for an inactivating mutation of the follicle-stimulating hormone (FSH) receptor gene present variable suppression of spermatogenesis and fertility. Nature Genetics 1997; 15:205–6.PubMedCrossRefGoogle Scholar
  64. Tom L, Bhasin S, Salameh W, Steiner B, Peterson M, Sokol RZ, Riveier J, Vale W, Swerdloff RS. Induction of azoospermia in normal men with combined Nal-Glu gonadotropin-releasing hormone antagonist and testosterone enanthate. J Clin Endocrinol Metab 1992; 75:476–483.PubMedCrossRefGoogle Scholar
  65. Trussel J, Kost K. Contraceptive failure in the United States: A critical review of literature. Studies in Family Planning 1987; 18:237–283.CrossRefGoogle Scholar
  66. Waites GMH, Wang C, Griffin PD. Gossypol: reasons for its failure to be accepted as a safe, reversible male antifertility drug. Int J Androl 1998; 21:8–12.PubMedCrossRefGoogle Scholar
  67. Waites GMH. Male fertility regulation: the challenges for the year 2000. Br Med Bulletin 1993; 49:210–221.Google Scholar
  68. Wang C, Berman NG, Veldhuis JD, Der T, McDonald V, Steiner B, Swerdloff RS. Graded testosterone infusions distinguish gonadotropin negative feedback responsiveness in Asian and White men —A Clinical Research Center Study. J Clin Endocrinol Metab 1998; 83:870–876.PubMedCrossRefGoogle Scholar
  69. Wang C, McDonald V, Leung A, Superlano L, Berman N, Hull L, Swerdloff RS. Effect of increased scrotal temperature on sperm production in normal men. Fertil Steril 1997; 68:334–354.PubMedCrossRefGoogle Scholar
  70. Wang C, Swerdloff RS, Waites GMH. Male contraception: 1993 and beyond. In Van Look PFA & Perez-Palacio (eds) Contraceptive Research and Development 1984 to 1994, Delhi: Oxford University Press, pp. 121–134, 1994.Google Scholar
  71. Wang C, Yeung KK. Use of low-dosage cyprosterone acetate as a male contraceptive. Contraception 1980; 21:245–272.PubMedCrossRefGoogle Scholar
  72. World Health Organization Special Programme of Research, Development and Research Training in Human Reproduction. Annual and Biennial Reports. WHO: Geneva, 1972–1995.Google Scholar
  73. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia in normal men. Lancet 1990; 336:955–59.CrossRefGoogle Scholar
  74. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men. Fertil Steril 1996; 65:821–9.Google Scholar
  75. World Health Organization Task Force on Methods for the Regulation of Male Fertility Comparison of two androgens plus depo-medroxyprogesterone acetate for suppression to azoospermia in Indonesian men. Fertil Steril 1993; 60:1062–68.Google Scholar
  76. World Health Organization. Reproductive health research: the new directions. Biennial Report (1996-1997). World Health Organization, Geneva, 1998.Google Scholar
  77. Wu FCW, Farley TMM, Peregoudov A, Waites GMH, World Health Organization Task Force on Methods for the Regulation of Male Fertility. Effects of testosterone enanthate in normal men: experience from a multicenter contraceptive efficacy study. Fertil Steril 1996; 65:626–36.PubMedGoogle Scholar
  78. Zhao SC, Zhang SP, Yu RC. Intravasal injection of formed-in-place silicone rubber as a method of vas occlusion. Int J Androl 1992; 15:460–464.PubMedGoogle Scholar
  79. Zhi L, Tegley CM, Kallel EA, Marschke KB, Mais DE, Gottardis MM, Jones TK. 5-Aryl-1,2-dihydrochromeno [3-4-fJquinolines: a novel class of nonsteroidal human progesterone receptor agonists. J Med Chem 1998; 41:291–302.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • C. Wang
    • 1
  • R. S. Swerdloff
    • 1
  1. 1.Harbor-UCLA Medical CenterTorrance

Personalised recommendations