Skip to main content
SpringerLink
Log in

Recent Developments in Male Contraception

  • Leading Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Unplanned pregnancies are an ongoing global burden, posing health and economic risks for women, children, and families. Advances in male contraception have been historically stymied by concerning failure rates, problematic side effects, and perceived market limitations. However, increased interest in reliable and reversible options for male contraception have resulted in resurgent efforts to introduce novel contraceptives for men. Hormonal male contraception relies on exogenous androgens and progestogens that suppress gonadotropin production, thereby suppressing testicular testosterone and sperm production. In many men, effective suppression of spermatogenesis can be achieved by androgen-progestin combination therapy. Small-scale contraceptive efficacy studies in couples have demonstrated effectiveness and reversibility with male hormonal methods, but side effects related to mood, sexual desire and cholesterol remain concerning. A number of novel androgens have reached clinical testing as potential contraceptive agents; many of these have both androgenic and progestogenic action in a single, modified steroid, thereby holding promise as single-agent contraceptives. Currently, these novel steroids hold promise as both a “male pill” and long-acting injections. Among non-hormonal methods, studies of reversible vaso-occlusive methods (polymers that block transport of sperm through the vas deferens) are ongoing, but reliable reversibility and long-term safety in men have not been established. Proteins involved in sperm maturation and motility are attractive targets, but to date both specificity and biologic redundancy have been challenges for drug development. In this review, we aim to summarize landmark studies on male contraception, highlight the most recent advances and future development in this important field of public health and medicine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bearak J, Popinchalk A, Alkema L, Sedgh G. Global, regional, and subregional trends in unintended pregnancy and its outcomes from 1990 to 2014: estimates from a Bayesian hierarchical model. Lancet Glob Health. 2018;6:e380–9.

    PubMed  PubMed Central  Google Scholar 

  2. Finer LB, Zolna MR. Declines in unintended pregnancy in the United States, 2008–2011. N Engl J Med. 2016;374:843–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Sonfield A, Kost K, Gold RB, Finer LB. The public costs of births resulting from unintended pregnancies: national and state-level estimates. Perspect Sex Reprod Health. 2011;43:94–102.

    PubMed  Google Scholar 

  4. Herd P, Higgins J, Sicinski K, Merkurieva I. The implications of unintended pregnancies for mental health in later life. Am J Public Health. 2016;106:421–9.

    PubMed  PubMed Central  Google Scholar 

  5. Wendt A, Gibbs CM, Peters S, Hogue CJ. Impact of increasing inter-pregnancy interval on maternal and infant health. Paediatr Perinat Epidemiol. 2012;26(Suppl 1):239–58.

    PubMed  PubMed Central  Google Scholar 

  6. Trussell J. Contraceptive failure in the United States. Contraception. 2011;83:397–404.

    PubMed  PubMed Central  Google Scholar 

  7. Youssef H. The history of the condom. J R Soc Med. 1993;86:226–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Drake MJ, Mills IW, Cranston D. On the chequered history of vasectomy. BJU Int. 1999;84:475–81.

    CAS  PubMed  Google Scholar 

  9. Sundaram A, Vaughan B, Kost K, Bankole A, Finer L, Singh S, Trussell J. Contraceptive failure in the United States: estimates from the 2006–2010 national survey of family growth. Perspect Sex Reprod Health. 2017;49:7–16.

    PubMed  PubMed Central  Google Scholar 

  10. Patel AP, Smith RP. Vasectomy reversal: a clinical update. Asian J Androl. 2016;18:365–71.

    PubMed  PubMed Central  Google Scholar 

  11. World Health Organization Task Force on Methods for the Regulation of Male F. Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men. Fertil Steril. 1996;65:821–829.

  12. Martin CW, Anderson RA, Cheng L, Ho PC, van der Spuy Z, Smith KB, Glasier AF, Everington D, Baird DT. Potential impact of hormonal male contraception: cross-cultural implications for development of novel preparations. Hum Reprod. 2000;15:637–45.

    CAS  PubMed  Google Scholar 

  13. Eberhardt J, van Wersch A, Meikle N. Attitudes towards the male contraceptive pill in men and women in casual and stable sexual relationships. J Fam Plann Reprod Health Care. 2009;35:161–5.

    PubMed  Google Scholar 

  14. Matsumoto AM, Bremner WJ. Stimulation of sperm production by human chorionic gonadotropin after prolonged gonadotropin suppression in normal men. J Androl. 1985;6:137–43.

    CAS  PubMed  Google Scholar 

  15. Coviello AD, Bremner WJ, Matsumoto AM, Herbst KL, Amory JK, Anawalt BD, Yan X, Brown TR, Wright WW, Zirkin BR, Jarow JP. Intratesticular testosterone concentrations comparable with serum levels are not sufficient to maintain normal sperm production in men receiving a hormonal contraceptive regimen. J Androl. 2004;25:931–8.

    CAS  PubMed  Google Scholar 

  16. Liu PY, Swerdloff RS, Anawalt BD, Anderson RA, Bremner WJ, Elliesen J, Gu YQ, Kersemaekers WM, McLachlan RI, Meriggiola MC, Nieschlag E, Sitruk-Ware R, Vogelsong K, Wang XH, Wu FC, Zitzmann M, Handelsman DJ, Wang C. Determinants of the rate and extent of spermatogenic suppression during hormonal male contraception: an integrated analysis. J Clin Endocrinol Metab. 2008;93:1774–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Nieschlag E. Clinical trials in male hormonal contraception. Contraception. 2010;82:457–70.

    CAS  PubMed  Google Scholar 

  18. Chao J, Page ST, Anderson RA. Male contraception. Best Pract Res Clin Obstet Gynaecol. 2014;28:845–57.

    PubMed  PubMed Central  Google Scholar 

  19. Roth MY, Page ST, Bremner WJ. Male hormonal contraception: looking back and moving forward. Andrology. 2016;4:4–12.

    CAS  PubMed  Google Scholar 

  20. Wang C, Festin MP, Swerdloff RS. Male hormonal contraception: where are we now? Curr Obstet Gynecol Rep. 2016;5:38–47.

    PubMed  PubMed Central  Google Scholar 

  21. Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility. Lancet. 1990;336:955–9.

    Google Scholar 

  22. McLachlan RI, McDonald J, Rushford D, Robertson DM, Garrett C, Baker HW. Efficacy and acceptability of testosterone implants, alone or in combination with a 5alpha-reductase inhibitor, for male hormonal contraception. Contraception. 2000;62:73–8.

    CAS  PubMed  Google Scholar 

  23. Turner L, Conway AJ, Jimenez M, Liu PY, Forbes E, McLachlan RI, Handelsman DJ. Contraceptive efficacy of a depot progestin and androgen combination in men. J Clin Endocrinol Metab. 2003;88:4659–67.

    CAS  PubMed  Google Scholar 

  24. Gu YQ, Wang XH, Xu D, Peng L, Cheng LF, Huang MK, Huang ZJ, Zhang GY. A multicenter contraceptive efficacy study of injectable testosterone undecanoate in healthy Chinese men. J Clin Endocrinol Metab. 2003;88:562–8.

    CAS  PubMed  Google Scholar 

  25. Gu Y, Liang X, Wu W, Liu M, Song S, Cheng L, Bo L, Xiong C, Wang X, Liu X, Peng L, Yao K. Multicenter contraceptive efficacy trial of injectable testosterone undecanoate in Chinese men. J Clin Endocrinol Metab. 2009;94:1910–5.

    CAS  PubMed  Google Scholar 

  26. Soufir JC, Meduri G, Ziyyat A. Spermatogenetic inhibition in men taking a combination of oral medroxyprogesterone acetate and percutaneous testosterone as a male contraceptive method. Hum Reprod. 2011;26:1708–14.

    CAS  PubMed  Google Scholar 

  27. Behre HM, Zitzmann M, Anderson RA, Handelsman DJ, Lestari SW, McLachlan RI, Meriggiola MC, Misro MM, Noe G, Wu FC, Festin MP, Habib NA, Vogelsong KM, Callahan MM, Linton KA, Colvard DS. Efficacy and safety of an injectable combination hormonal contraceptive for men. J Clin Endocrinol Metab. 2016;101:4779–88.

    CAS  PubMed  Google Scholar 

  28. Zhang FP, Pakarainen T, Poutanen M, Toppari J, Huhtaniemi I. The low gonadotropin-independent constitutive production of testicular testosterone is sufficient to maintain spermatogenesis. Proc Natl Acad Sci USA. 2003;100:13692–7.

    CAS  PubMed  Google Scholar 

  29. Tom L, Bhasin S, Salameh W, Steiner B, Peterson M, Sokol RZ, Rivier 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;75:476–83.

    CAS  PubMed  Google Scholar 

  30. Pavlou SN, Brewer K, Farley MG, Lindner J, Bastias MC, Rogers BJ, Swift LL, Rivier JE, Vale WW, Conn PM, et al. Combined administration of a gonadotropin-releasing hormone antagonist and testosterone in men induces reversible azoospermia without loss of libido. J Clin Endocrinol Metab. 1991;73:1360–9.

    CAS  PubMed  Google Scholar 

  31. 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;77:427–32.

    CAS  PubMed  Google Scholar 

  32. Behre HM, Kliesch S, Lemcke B, von Eckardstein S, Nieschlag E. Suppression of spermatogenesis to azoospermia by combined administration of GnRH antagonist and 19-nortestosterone cannot be maintained by this non-aromatizable androgen alone. Hum Reprod. 2001;16:2570–7.

    CAS  PubMed  Google Scholar 

  33. Page ST, Amory JK, Anawalt BD, Irwig MS, Brockenbrough AT, Matsumoto AM, Bremner WJ. Testosterone gel combined with depomedroxyprogesterone acetate is an effective male hormonal contraceptive regimen and is not enhanced by the addition of a GnRH antagonist. J Clin Endocrinol Metab. 2006;91:4374–80.

    CAS  PubMed  Google Scholar 

  34. Attardi BJ, Hild SA, Koduri S, Pham T, Pessaint L, Engbring J, Till B, Gropp D, Semon A, Reel JR. The potent synthetic androgens, dimethandrolone (7alpha,11beta-dimethyl-19-nortestosterone) and 11beta-methyl-19-nortestosterone, do not require 5alpha-reduction to exert their maximal androgenic effects. J Steroid Biochem Mol Biol. 2010;122:212–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Attardi BJ, Pham TC, Radler LC, Burgenson J, Hild SA, Reel JR. Dimethandrolone (7alpha,11beta-dimethyl-19-nortestosterone) and 11beta-methyl-19-nortestosterone are not converted to aromatic A-ring products in the presence of recombinant human aromatase. J Steroid Biochem Mol Biol. 2008;110:214–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Attardi BJ, Hild SA, Reel JR. Dimethandrolone undecanoate: a new potent orally active androgen with progestational activity. Endocrinology. 2006;147:3016–26.

    CAS  PubMed  Google Scholar 

  37. Attardi BJ, Marck BT, Matsumoto AM, Koduri S, Hild SA. Long-term effects of dimethandrolone 17beta-undecanoate and 11beta-methyl-19-nortestosterone 17beta-dodecylcarbonate on body composition, bone mineral density, serum gonadotropins, and androgenic/anabolic activity in castrated male rats. J Androl. 2011;32:183–92.

    CAS  PubMed  Google Scholar 

  38. Hild SA, Attardi BJ, Koduri S, Till BA, Reel JR. Effects of synthetic androgens on liver function using the rabbit as a model. J Androl. 2010;31:472–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Hild SA, Marshall GR, Attardi BJ, Hess RA, Schlatt S, Simorangkir DR, Ramaswamy S, Koduri S, Reel JR, Plant TM. Development of l-CDB-4022 as a nonsteroidal male oral contraceptive: induction and recovery from severe oligospermia in the adult male cynomolgus monkey (Macaca fascicularis). Endocrinology. 2007;148:1784–96.

    CAS  PubMed  Google Scholar 

  40. Ayoub R, Page ST, Swerdloff RS, Liu PY, Amory JK, Leung A, Hull L, Blithe D, Christy A, Chao JH, Bremner WJ, Wang C. Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive. Andrology. 2017;5:278–85.

    CAS  PubMed  Google Scholar 

  41. Thirumalai A, Ceponis J, Amory JK, Swerdloff R, Surampudi V, Liu PY, Bremner WJ, Harvey E, Blithe DL, Lee MS, Hull L, Wang C, Page ST. Effects of 28 days of oral dimethandrolone undecanoate in healthy men: a prototype male pill. J Clin Endocrinol Metab. 2018. https://doi.org/10.1210/jc.2018-01452.

    Article  Google Scholar 

  42. Wu S, Yuen F, Swerdloff RS, Pak Y, Thirumalai A, Liu PY, Amory JK, Bai F, Hull L, Blithe DL, Anawalt BD, Parman T, Kim K, Lee MS, Bremner WJ, Page ST, Wang C. Safety and pharmacokinetics of single dose novel oral androgen 11beta-methyl-19-nortestosterone-17beta-dodecylcarbonate in mena. J Clin Endocrinol Metab. 2018. https://doi.org/10.1210/jc.2018-01528.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Kumar N, Didolkar AK, Monder C, Bardin CW, Sundaram K. The biological activity of 7 alpha-methyl-19-nortestosterone is not amplified in male reproductive tract as is that of testosterone. Endocrinology. 1992;130:3677–83.

    CAS  PubMed  Google Scholar 

  44. LaMorte A, Kumar N, Bardin CW, Sundaram K. Aromatization of 7 alpha-methyl-19-nortestosterone by human placental microsomes in vitro. J Steroid Biochem Mol Biol. 1994;48:297–304.

    CAS  PubMed  Google Scholar 

  45. von Eckardstein S, Noe G, Brache V, Nieschlag E, Croxatto H, Alvarez F, Moo-Young A, Sivin I, Kumar N, Small M, Sundaram K, International Committee for Contraception Research TPC. A clinical trial of 7 alpha-methyl-19-nortestosterone implants for possible use as a long-acting contraceptive for men. J Clin Endocrinol Metab. 2003;88:5232–5239.

  46. Walton MJ, Kumar N, Baird DT, Ludlow H, Anderson RA. 7alpha-methyl-19-nortestosterone (MENT) vs testosterone in combination with etonogestrel implants for spermatogenic suppression in healthy men. J Androl. 2007;28:679–88.

    CAS  PubMed  Google Scholar 

  47. Sitruk-Ware R, Nath A. The use of newer progestins for contraception. Contraception. 2010;82:410–7.

    CAS  PubMed  Google Scholar 

  48. Mahabadi V, Amory JK, Swerdloff RS, Bremner WJ, Page ST, Sitruk-Ware R, Christensen PD, Kumar N, Tsong YY, Blithe D, Wang C. Combined transdermal testosterone gel and the progestin nestorone suppresses serum gonadotropins in men. J Clin Endocrinol Metab. 2009;94:2313–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Ilani N, Roth MY, Amory JK, Swerdloff RS, Dart C, Page ST, Bremner WJ, Sitruk-Ware R, Kumar N, Blithe DL, Wang C. A new combination of testosterone and nestorone transdermal gels for male hormonal contraception. J Clin Endocrinol Metab. 2012;97:3476–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Misro M, Guha SK, Singh H, Mahajan S, Ray AR, Vasudevan P. Injectable non-occlusive chemical contraception in the male-I. Contraception. 1979;20:467–73.

    CAS  PubMed  Google Scholar 

  51. Guha SK, Ansari S, Anand S, Farooq A, Misro MM, Sharma DN. Contraception in male monkeys by intra-vas deferens injection of a pH lowering polymer. Contraception. 1985;32:109–18.

    CAS  PubMed  Google Scholar 

  52. Guha SK. Biophysical mechanism-mediated time-dependent effect on sperm of human and monkey vas implanted polyelectrolyte contraceptive. Asian J Androl. 2007;9:221–7.

    PubMed  Google Scholar 

  53. Lohiya NK, Manivannan B, Mishra PK. Ultrastructural changes in the spermatozoa of langur monkeys Presbytis entellus entellus after vas occlusion with styrene maleic anhydride. Contraception. 1998;57:125–32.

    CAS  PubMed  Google Scholar 

  54. Koul V, Srivastav A, Guha SK. Reversibility with sodium bicarbonate of styrene maleic anhydride, an intravasal injectable contraceptive, in male rats. Contraception. 1998;58:227–31.

    CAS  PubMed  Google Scholar 

  55. Lohiya NK, Suthar R, Khandelwal A, Goyal S, Ansari AS, Manivannan B. Sperm characteristics and teratology in rats following vas deferens occlusion with RISUG and its reversal. Int J Androl. 2010;33:e198–206.

    CAS  PubMed  Google Scholar 

  56. Guha SK. Non-invasive reversal of intraluminal vas deferens polymer injection-induced azoospermia–technology. Asian journal of andrology. 1999;1:131–4.

    CAS  PubMed  Google Scholar 

  57. Lohiya NK, Manivannan B, Mishra PK, Pathak N, Balasubramanian SP. Intravasal contraception with styrene maleic anhydride and its noninvasive reversal in langur monkeys (Presbytis entellus entellus). Contraception. 1998;58:119–28.

    CAS  PubMed  Google Scholar 

  58. Manivannan B, Bhande SS, Panneerdoss S, Sriram S, Lohiya NK. Safety evaluation of long-term vas occlusion with styrene maleic anhydride and its non-invasive reversal on accessory reproductive organs in langurs. Asian J Androl. 2005;7:195–204.

    CAS  PubMed  Google Scholar 

  59. Guha SK, Singh G, Anand S, Ansari S, Kumar S, Koul V. Phase I clinical trial of an injectable contraceptive for the male. Contraception. 1993;48:367–75.

    CAS  PubMed  Google Scholar 

  60. Guha SK, Singh G, Ansari S, Kumar S, Srivastava A, Koul V, Das HC, Malhotra RL, Das SK. Phase II clinical trial of a vas deferens injectable contraceptive for the male. Contraception. 1997;56:245–50.

    CAS  PubMed  Google Scholar 

  61. Chaki SP, Das HC, Misro MM. A short-term evaluation of semen and accessory sex gland function in phase III trial subjects receiving intravasal contraceptive RISUG. Contraception. 2003;67:73–8.

    CAS  PubMed  Google Scholar 

  62. Manivannan B, Mishra PK, Lohiya NK. Ultrastructural changes in the vas deferens of langur monkeys Presbytis entellus entellus after vas occlusion with styrene maleic anhydride and after its reversal. Contraception. 1999;59:137–44.

    CAS  PubMed  Google Scholar 

  63. Waller D, Bolick D, Lissner E, Premanandan C, Gamerman G. Azoospermia in rabbits following an intravas injection of Vasalgel. Basic Clin Androl. 2016;26:6.

    PubMed  PubMed Central  Google Scholar 

  64. Waller D, Bolick D, Lissner E, Premanandan C, Gamerman G. Reversibility of Vasalgel male contraceptive in a rabbit model. Basic Clin Androl. 2017;27:8.

    PubMed  PubMed Central  Google Scholar 

  65. Wang Z, Widgren EE, Sivashanmugam P, O’Rand MG, Richardson RT. Association of eppin with semenogelin on human spermatozoa. Biol Reprod. 2005;72:1064–70.

    CAS  PubMed  Google Scholar 

  66. O’Rand MG, Widgren EE, Wang Z, Richardson RT. Eppin: an effective target for male contraception. Mol Cell Endocrinol. 2006;250:157–62.

    PubMed  Google Scholar 

  67. Yenugu S, Richardson RT, Sivashanmugam P, Wang Z, O’Rand MG, French FS, Hall SH. Antimicrobial activity of human EPPIN, an androgen-regulated, sperm-bound protein with a whey acidic protein motif. Biol Reprod. 2004;71:1484–90.

    CAS  PubMed  Google Scholar 

  68. Mitra A, Richardson RT, O’Rand MG. Analysis of recombinant human semenogelin as an inhibitor of human sperm motility. Biol Reprod. 2010;82:489–96.

    CAS  PubMed  Google Scholar 

  69. O’Rand MG, Widgren EE, Beyler S, Richardson RT. Inhibition of human sperm motility by contraceptive anti-eppin antibodies from infertile male monkeys: effect on cyclic adenosine monophosphate. Biol Reprod. 2009;80:279–85.

    PubMed  PubMed Central  Google Scholar 

  70. O’Rand MG, Widgren EE, Sivashanmugam P, Richardson RT, Hall SH, French FS, VandeVoort CA, Ramachandra SG, Ramesh V, Jagannadha Rao A. Reversible immunocontraception in male monkeys immunized with eppin. Science. 2004;306:1189–90.

    PubMed  Google Scholar 

  71. O’Rand MG, Silva EJ, Hamil KG. Non-hormonal male contraception: a review and development of an Eppin based contraceptive. Pharmacol Ther. 2016;157:105–11.

    PubMed  Google Scholar 

  72. Silva EJ, Hamil KG, O’Rand MG. Interacting proteins on human spermatozoa: adaptive evolution of the binding of semenogelin I to EPPIN. PLoS One. 2013;8:e82014.

    PubMed  PubMed Central  Google Scholar 

  73. O’Rand MG, Hamil KG, Adevai T, Zelinski M. Inhibition of sperm motility in male macaques with EP055, a potential non-hormonal male contraceptive. PLoS One. 2018;13:e0195953.

    PubMed  PubMed Central  Google Scholar 

  74. Hild SA, Reel JR, Dykstra MJ, Mann PC, Marshall GR. Acute adverse effects of the indenopyridine CDB-4022 on the ultrastructure of sertoli cells, spermatocytes, and spermatids in rat testes: comparison to the known sertoli cell toxicant Di-n-pentylphthalate (DPP). J Androl. 2007;28:621–9.

    CAS  PubMed  Google Scholar 

  75. Koduri S, Hild SA, Pessaint L, Reel JR, Attardi BJ. Mechanism of action of l-CDB-4022, a potential nonhormonal male contraceptive, in the seminiferous epithelium of the rat testis. Endocrinology. 2008;149:1850–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Pozor MA, Macpherson ML, McDonnell SM, Nollin M, Roser JF, Love C, Runyon S, Thomas BF, Troedsson MH. Indenopyride derivative RTI-4587-073(l): a candidate for male contraception in stallions. Theriogenology. 2013;80:1006–16.

    CAS  PubMed  Google Scholar 

  77. Cheng CY. Toxicants target cell junctions in the testis: insights from the indazole-carboxylic acid model. Spermatogenesis. 2014;4:e981485.

    PubMed  Google Scholar 

  78. Grima J, Silvestrini B, Cheng CY. Reversible inhibition of spermatogenesis in rats using a new male contraceptive, 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide. Biol Reprod. 2001;64:1500–8.

    CAS  PubMed  Google Scholar 

  79. Cheng CY, Mruk D, Silvestrini B, Bonanomi M, Wong CH, Siu MK, Lee NP, Lui WY, Mo MY. AF-2364 [1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide] is a potential male contraceptive: a review of recent data. Contraception. 2005;72:251–61.

    CAS  PubMed  Google Scholar 

  80. Mruk DD, Wong CH, Silvestrini B, Cheng CY. A male contraceptive targeting germ cell adhesion. Nat Med. 2006;12:1323–8.

    CAS  PubMed  Google Scholar 

  81. Tash JS, Attardi B, Hild SA, Chakrasali R, Jakkaraj SR, Georg GI. A novel potent indazole carboxylic acid derivative blocks spermatogenesis and is contraceptive in rats after a single oral dose. Biol Reprod. 2008;78:1127–38.

    CAS  PubMed  Google Scholar 

  82. Vernet N, Dennefeld C, Rochette-Egly C, Oulad-Abdelghani M, Chambon P, Ghyselinck NB, Mark M. Retinoic acid metabolism and signaling pathways in the adult and developing mouse testis. Endocrinology. 2006;147:96–110.

    CAS  PubMed  Google Scholar 

  83. Koubova J, Menke DB, Zhou Q, Capel B, Griswold MD, Page DC. Retinoic acid regulates sex-specific timing of meiotic initiation in mice. Proc Natl Acad Sci USA. 2006;103:2474–9.

    CAS  PubMed  Google Scholar 

  84. Dufour JM, Kim KH. Cellular and subcellular localization of six retinoid receptors in rat testis during postnatal development: identification of potential heterodimeric receptors. Biol Reprod. 1999;61:1300–8.

    CAS  PubMed  Google Scholar 

  85. Chung SS, Wang X, Roberts SS, Griffey SM, Reczek PR, Wolgemuth DJ. Oral administration of a retinoic Acid receptor antagonist reversibly inhibits spermatogenesis in mice. Endocrinology. 2011;152:2492–502.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Chung SS, Wang X, Wolgemuth DJ. Prolonged oral administration of a pan-retinoic acid receptor antagonist inhibits spermatogenesis in mice with a rapid recovery and changes in the expression of influx and efflux transporters. Endocrinology. 2016;157:1601–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Heller CG, Moore DJ, Paulsen CA. Suppression of spermatogenesis and chronic toxicity in men by a new series of bis(dichloroacetyl) diamines. Toxicol Appl Pharmacol. 1961;3:1–11.

    CAS  PubMed  Google Scholar 

  88. Roth MY, Amory JK. Beyond the condom: frontiers in male contraception. Semin Reprod Med. 2016;34:183–90.

    PubMed  PubMed Central  Google Scholar 

  89. Amory JK, Muller CH, Shimshoni JA, Isoherranen N, Paik J, Moreb JS, Amory DW Sr, Evanoff R, Goldstein AS, Griswold MD. Suppression of spermatogenesis by bisdichloroacetyldiamines is mediated by inhibition of testicular retinoic acid biosynthesis. J Androl. 2011;32:111–9.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Metabolism, Endocrinology and Nutrition, University of Washington, 1959 NE Pacific Street, UW Mailbox 356426, Seattle, WA, 98195-6426, USA

    Arthi Thirumalai & Stephanie T. Page

Authors
  1. Arthi Thirumalai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephanie T. Page
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephanie T. Page.

Ethics declarations

No sources of funding were used to assist in the preparation of this manuscript. However, Stephanie Page and Arthi Thirumalai receive funding from the National Institutes of Health through Eunice Kennedy Shriver National Institute of Child Health and Human Development for Clinical Evaluation of Male Contraceptives (Contract number: HHSN275201300025I). Stephanie Page is also supported by the Robert McMillen Professorship in Lipid Research. Stephanie Page was a one-time consultant for Clarus Therapeutics. Arthi Thirumalai has no conflicts of interest that are directly relevant to the content of this manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Thirumalai, A., Page, S.T. Recent Developments in Male Contraception. Drugs 79, 11–20 (2019). https://doi.org/10.1007/s40265-018-1038-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-018-1038-8

Search

Navigation