Download PDF
Semin Reprod Med 2016; 34(03): 183-190
DOI: 10.1055/s-0036-1571435
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Beyond the Condom: Frontiers in Male Contraception

Mara Y. Roth
1   Department of Medicine, Center for Research in Reproduction and Contraception, University of Washington, Seattle, Washington
,
John K. Amory
1   Department of Medicine, Center for Research in Reproduction and Contraception, University of Washington, Seattle, Washington
› Author Affiliations
Further Information

Publication History

Publication Date:
04 March 2016 (online)

    Permissions and Reprints

Abstract

Nearly half of all pregnancies worldwide are unplanned, despite numerous contraceptive options available. No new contraceptive method has been developed for men since the invention of condom. Nevertheless, more than 25% of contraception worldwide relies on male methods. Therefore, novel effective methods of male contraception are of interest. Herein we review the physiologic basis for both male hormonal and nonhormonal methods of contraception. We review the history of male hormonal contraception development, current hormonal agents in development, as well as the potential risks and benefits of male hormonal contraception options for men. Nonhormonal methods reviewed will include both pharmacological and mechanical approaches in development, with specific focus on methods which inhibit the testicular retinoic acid synthesis and action. Multiple hormonal and nonhormonal methods of male contraception are in the drug development pathway, with the hope that a reversible, reliable, safe method of male contraception will be available to couples in the not too distant future.

Keywords

testosterone - retinoic acid - contraception - spermatogenesis
 

  • References

  • 1 Sedgh G, Singh S, Hussain R. Intended and unintended pregnancies worldwide in 2012 and recent trends. Stud Fam Plann 2014; 45 (3) 301-314
    CrossrefPubMedGoogle Scholar
  • 2 Sedgh G, Henshaw S, Singh S, Ahman E, Shah IH. Induced abortion: estimated rates and trends worldwide. Lancet 2007; 370 (9595) 1338-1345
    CrossrefPubMedGoogle Scholar
  • 3 Henshaw SK, Singh S, Haas T. The incidence of abortion worldwide. Int Fam Plann Persp 1999; 25 (Suppl): S30-S38
    CrossrefPubMedGoogle Scholar
  • 4 Sonfield A, Kost K. Public Costs from Unintended Pregnancies and the Role of Public Insurance Programs in Paying for Pregnancy-Related Care: National and State Estimated for 2010. New York: Guttmacher Institute; 2015
    Google Scholar
  • 5 Blumenthal PD, Edelman A. Hormonal contraception. Obstet Gynecol 2008; 112 (3) 670-684
    CrossrefPubMedGoogle Scholar
  • 6 United Nations Department of Economic and Social Affairs, Population Division. Model-Based Estimates and Projections of Family Planning Indicators 2014. New York: United Nations; 2014
    Google Scholar
  • 7 Trussell J. Contraceptive failure in the United States. Contraception 2011; 83 (5) 397-404
    CrossrefPubMedGoogle Scholar
  • 8 Glasier AF, Anakwe R, Everington D , et al. Would women trust their partners to use a male pill?. Hum Reprod 2000; 15 (3) 646-649
    CrossrefPubMedGoogle Scholar
  • 9 Martin CW, Anderson RA, Cheng L , et al. Potential impact of hormonal male contraception: cross-cultural implications for development of novel preparations. Hum Reprod 2000; 15 (3) 637-645
    CrossrefPubMedGoogle Scholar
  • 10 Heinemann K, Saad F, Wiesemes M, White S, Heinemann L. Attitudes toward male fertility control: results of a multinational survey on four continents. Hum Reprod 2005; 20 (2) 549-556
    PubMedGoogle Scholar
  • 11 Hall PF. On the stimulation of testicular steroidogenesis in the rabbit by interstitial cell-stimulating hormone. Endocrinology 1966; 78 (4) 690-698
    CrossrefPubMedGoogle Scholar
  • 12 Amann RP, Howards SS. Daily spermatozoal production and epididymal spermatozoal reserves of the human male. J Urol 1980; 124 (2) 211-215
    PubMedGoogle Scholar
  • 13 Matsumoto AM, Bremner WJ. Modulation of pulsatile gonadotropin secretion by testosterone in man. J Clin Endocrinol Metab 1984; 58 (4) 609-614
    CrossrefPubMedGoogle Scholar
  • 14 McLachlan RI, O'Donnell L, Stanton PG , et al. Effects of testosterone plus medroxyprogesterone acetate on semen quality, reproductive hormones, and germ cell populations in normal young men. J Clin Endocrinol Metab 2002; 87 (2) 546-556
    CrossrefPubMedGoogle Scholar
  • 15 O'Donnell L, Nicholls PK, O'Bryan MK, McLachlan RI, Stanton PG. Spermiation: the process of sperm release. Spermatogenesis 2011; 1 (1) 14-35
    CrossrefPubMedGoogle Scholar
  • 16 World Health Organization. WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction. Cambridge, United Kingdom: Cambridge University Press; 1999
    Google Scholar
  • 17 Cooper TG, Hellenkemper B, Jonckheere J , et al. Azoospermia: virtual reality or possible to quantify?. J Androl 2006; 27 (4) 483-490
    CrossrefPubMedGoogle Scholar
  • 18 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 (4) 821-829
    CrossrefPubMedGoogle Scholar
  • 19 Nieschlag E ; 10th Summit Meeting Group. 10th Summit Meeting consensus: recommendations for regulatory approval for hormonal male contraception. October 22-23, 2006. Contraception 2007; 75 (3) 166-167
    CrossrefPubMedGoogle Scholar
  • 20 Moreau C, Trussell J, Rodriguez G, Bajos N, Bouyer J. Contraceptive failure rates in France: results from a population-based survey. Hum Reprod 2007; 22 (9) 2422-2427
    CrossrefPubMedGoogle Scholar
  • 21 Liu PY, Swerdloff RS, Christenson PD, Handelsman DJ, Wang C ; Hormonal Male Contraception Summit Group. Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet 2006; 367 (9520) 1412-1420
    CrossrefPubMedGoogle Scholar
  • 22 Ly LP, Liu PY, Handelsman DJ. Rates of suppression and recovery of human sperm output in testosterone-based hormonal contraceptive regimens. Hum Reprod 2005; 20 (6) 1733-1740
    CrossrefPubMedGoogle Scholar
  • 23 Nieschlag E, Vorona E, Wenk M, Hemker AK, Kamischke A, Zitzmann M. Hormonal male contraception in men with normal and subnormal semen parameters. Int J Androl 2011; 34 (6, Pt 1): 556-567
    CrossrefPubMedGoogle Scholar
  • 24 Heckel NJ. Production of oligospermia in a man by the use of testosterone propionate. Proc Soc Exp Biol Med 1939; 40: 658-659
    CrossrefPubMedGoogle Scholar
  • 25 World Health Organization. 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 (8721) 955-959
    CrossrefPubMedGoogle Scholar
  • 26 Wu FC, Farley TM, Peregoudov A, Waites GM ; 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 (3) 626-636
    PubMedGoogle Scholar
  • 27 Page ST, Amory JK, Bremner WJ. Advances in male contraception. Endocr Rev 2008; 29 (4) 465-493
    CrossrefPubMedGoogle Scholar
  • 28 Nieschlag E. Clinical trials in male hormonal contraception. Contraception 2010; 82 (5) 457-470
    CrossrefPubMedGoogle Scholar
  • 29 Meriggiola MC, Bremner WJ, Paulsen CA , et al. A combined regimen of cyproterone acetate and testosterone enanthate as a potentially highly effective male contraceptive. J Clin Endocrinol Metab 1996; 81 (8) 3018-3023
    PubMedGoogle Scholar
  • 30 Anawalt BD, Bebb RA, Bremner WJ, Matsumoto AM. A lower dosage levonorgestrel and testosterone combination effectively suppresses spermatogenesis and circulating gonadotropin levels with fewer metabolic effects than higher dosage combinations. J Androl 1999; 20 (3) 407-414
    PubMedGoogle Scholar
  • 31 Bebb RA, Anawalt BD, Christensen 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 (2) 757-762
    PubMedGoogle Scholar
  • 32 Herbst KL, Anawalt BD, Amory JK, Matsumoto AM, Bremner WJ. The male contraceptive regimen of testosterone and levonorgestrel significantly increases lean mass in healthy young men in 4 weeks, but attenuates a decrease in fat mass induced by testosterone alone. J Clin Endocrinol Metab 2003; 88 (3) 1167-1173
    CrossrefPubMedGoogle Scholar
  • 33 Gui YL, He CH, Amory JK , et al. Male hormonal contraception: suppression of spermatogenesis by injectable testosterone undecanoate alone or with levonorgestrel implants in Chinese men. J Androl 2004; 25 (5) 720-727
    CrossrefPubMedGoogle Scholar
  • 34 Anderson RA, Kinniburgh D, Baird DT. Suppression of spermatogenesis by etonogestrel implants with depot testosterone: potential for long-acting male contraception. J Clin Endocrinol Metab 2002; 87 (8) 3640-3649
    CrossrefPubMedGoogle Scholar
  • 35 Brady BM, Amory JK, Perheentupa A , et al. A multicentre study investigating subcutaneous etonogestrel implants with injectable testosterone decanoate as a potential long-acting male contraceptive. Hum Reprod 2006; 21 (1) 285-294
    PubMedGoogle Scholar
  • 36 Mommers E, Kersemaekers WM, Elliesen J , et al. Male hormonal contraception: a double-blind, placebo-controlled study. J Clin Endocrinol Metab 2008; 93 (7) 2572-2580
    CrossrefPubMedGoogle Scholar
  • 37 Kinniburgh D, Anderson RA, Baird DT. Suppression of spermatogenesis with desogestrel and testosterone pellets is not enhanced by addition of finasteride. J Androl 2001; 22 (1) 88-95
    PubMedGoogle Scholar
  • 38 Kinniburgh D, Zhu H, Cheng L, Kicman AT, Baird DT, Anderson RA. Oral desogestrel with testosterone pellets induces consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men. Hum Reprod 2002; 17 (6) 1490-1501
    CrossrefPubMedGoogle Scholar
  • 39 Meriggiola MC, Costantino A, Saad F , et al. Norethisterone enanthate plus testosterone undecanoate for male contraception: effects of various injection intervals on spermatogenesis, reproductive hormones, testis, and prostate. J Clin Endocrinol Metab 2005; 90 (4) 2005-2014
    CrossrefPubMedGoogle Scholar
  • 40 Kamischke A, Heuermann T, Krüger K , et al. An effective hormonal male contraceptive using testosterone undecanoate with oral or injectable norethisterone preparations. J Clin Endocrinol Metab 2002; 87 (2) 530-539
    CrossrefPubMedGoogle Scholar
  • 41 Gu YQ, Tong JS, Ma DZ , et al. Male hormonal contraception: effects of injections of testosterone undecanoate and depot medroxyprogesterone acetate at eight-week intervals in Chinese men. J Clin Endocrinol Metab 2004; 89 (5) 2254-2262
    CrossrefPubMedGoogle Scholar
  • 42 Turner L, Conway AJ, Jimenez M , et al. Contraceptive efficacy of a depot progestin and androgen combination in men. J Clin Endocrinol Metab 2003; 88 (10) 4659-4667
    CrossrefPubMedGoogle Scholar
  • 43 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 U S A 2003; 100 (23) 13692-13697
    CrossrefPubMedGoogle Scholar
  • 44 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 (2) 427-432
    PubMedGoogle Scholar
  • 45 Matthiesson KL, Amory JK, Berger R, Ugoni A, McLachlan RI, Bremner WJ. Novel male hormonal contraceptive combinations: the hormonal and spermatogenic effects of testosterone and levonorgestrel combined with a 5alpha-reductase inhibitor or gonadotropin-releasing hormone antagonist. J Clin Endocrinol Metab 2005; 90 (1) 91-97
    CrossrefPubMedGoogle Scholar
  • 46 Page ST, Amory JK, Anawalt BD , et al. 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 (11) 4374-4380
    CrossrefPubMedGoogle Scholar
  • 47 Kumar N, Koide SS, Tsong Y, Sundaram K. Nestorone: a progestin with a unique pharmacological profile. Steroids 2000; 65 (10–11) 629-636
    CrossrefPubMedGoogle Scholar
  • 48 Mahabadi V, Amory JK, Swerdloff RS , et al. Combined transdermal testosterone gel and the progestin nestorone suppresses serum gonadotropins in men. J Clin Endocrinol Metab 2009; 94 (7) 2313-2320
    CrossrefPubMedGoogle Scholar
  • 49 Roth MY, Shih G, Ilani N , et al. Acceptability of a transdermal gel-based male hormonal contraceptive in a randomized controlled trial. Contraception 2014; 90 (4) 407-412
    CrossrefPubMedGoogle Scholar
  • 50 Ilani N, Roth MY, Amory JK , et al. A new combination of testosterone and nestorone transdermal gels for male hormonal contraception. J Clin Endocrinol Metab 2012; 97 (10) 3476-3486
    CrossrefPubMedGoogle Scholar
  • 51 Attardi BJ, Hild SA, Reel JR. Dimethandrolone undecanoate: a new potent orally active androgen with progestational activity. Endocrinology 2006; 147 (6) 3016-3026
    CrossrefPubMedGoogle Scholar
  • 52 Hild SA, Attardi BJ, Koduri S , et al. Development of dimethandrolone 17B-undecanoate (DMAU) as an oral male hormonal contraceptive: induction of infertility and recovery of fertility in adult male rabbits. Biol Reprod 2008; 78 (93) 174
    PubMedGoogle Scholar
  • 53 Attardi BJ, Marck BT, Matsumoto AM, Koduri S, Hild SA. Long-term effects of dimethandrolone 17β-undecanoate and 11β-methyl-19-nortestosterone 17β-dodecylcarbonate on body composition, bone mineral density, serum gonadotropins, and androgenic/anabolic activity in castrated male rats. J Androl 2011; 32 (2) 183-192
    CrossrefPubMedGoogle Scholar
  • 54 Surampudi P, Page ST, Swerdloff RS , et al. Single, escalating dose pharmacokinetics, safety and food effects of a new oral androgen dimethandrolone undecanoate in man: a prototype oral male hormonal contraceptive. Andrology 2014; 2 (4) 579-587
    CrossrefPubMedGoogle Scholar
  • 55 Ezzati M, Lopez AD, Rodgers A, Murray CJL. Comparative Quantification of Health Risks: Global and Regional Burden of Disease Attributable to Selected Major Risk Factors. Geneva, Switzerland: World Health Organization; 2004
    Google Scholar
  • 56 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 (6) 3677-3683
    PubMedGoogle Scholar
  • 57 Nieschlag E, Kumar N, Sitruk-Ware R. 7α-methyl-19-nortestosterone (MENTR): the population council's contribution to research on male contraception and treatment of hypogonadism. Contraception 2013; 87 (3) 288-295
    CrossrefPubMedGoogle Scholar
  • 58 Anderson RA, Wallace AM, Sattar N, Kumar N, Sundaram K. Evidence for tissue selectivity of the synthetic androgen 7 alpha-methyl-19-nortestosterone in hypogonadal men. J Clin Endocrinol Metab 2003; 88 (6) 2784-2793
    CrossrefPubMedGoogle Scholar
  • 59 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 (2–3) 297-304
    CrossrefPubMedGoogle Scholar
  • 60 von Eckardstein S, Noe G, Brache V , et al; International Committee for Contraception Research, The Population Council. 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 (11) 5232-5239
    CrossrefPubMedGoogle Scholar
  • 61 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 (5) 679-688
    CrossrefPubMedGoogle Scholar
  • 62 Wang C, Cunningham G, Dobs A , et al. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab 2004; 89 (5) 2085-2098
    CrossrefPubMedGoogle Scholar
  • 63 Finkelstein JS, Yu EW, Burnett-Bowie SA. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med 2013; 369 (25) 2457
    CrossrefPubMedGoogle Scholar
  • 64 Meriggiola MC, Cerpolini S, Bremner WJ , et al. Acceptability of an injectable male contraceptive regimen of norethisterone enanthate and testosterone undecanoate for men. Hum Reprod 2006; 21 (8) 2033-2040
    CrossrefPubMedGoogle Scholar
  • 65 Pelusi C, Costantino A, Cerpolini S, Pelusi G, Meriggiola MC, Pasquali R. A placebo-controlled, randomized clinical trial using testosterone undecanoate with injectable norethisterone enanthate: effect on anthropometric, metabolic and biochemical parameters. Int J Androl 2011; 34 (6, Pt 1): 548-555
    CrossrefPubMedGoogle Scholar
  • 66 Cheng CY, Silvestrini B, Grima J , et al. Two new male contraceptives exert their effects by depleting germ cells prematurely from the testis. Biol Reprod 2001; 65 (2) 449-461
    CrossrefPubMedGoogle Scholar
  • 67 Mruk DD, Cheng CY. Testin and actin are key molecular targets of adjudin, an anti-spermatogenic agent, in the testis. Spermatogenesis 2011; 1 (2) 137-146
    CrossrefPubMedGoogle Scholar
  • 68 Mok KW, Mruk DD, Lie PP, Lui WY, Cheng CY. Adjudin, a potential male contraceptive, exerts its effects locally in the seminiferous epithelium of mammalian testes. Reproduction 2011; 141 (5) 571-580
    CrossrefPubMedGoogle Scholar
  • 69 Mruk DD, Wong CH, Silvestrini B, Cheng CY. A male contraceptive targeting germ cell adhesion. Nat Med 2006; 12 (11) 1323-1328
    CrossrefPubMedGoogle Scholar
  • 70 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 (6) 1127-1138
    CrossrefPubMedGoogle Scholar
  • 71 Tash JS, Chakrasali R, Jakkaraj SR , et al. Gamendazole, an orally active indazole carboxylic acid male contraceptive agent, targets HSP90AB1 (HSP90BETA) and EEF1A1 (eEF1A), and stimulates Il1a transcription in rat Sertoli cells. Biol Reprod 2008; 78 (6) 1139-1152
    CrossrefPubMedGoogle Scholar
  • 72 Wolbach SB, Howe PR. Tissue changes following deprivation of fat-soluble A vitamin. J Exp Med 1925; 42 (6) 753-777
    CrossrefPubMedGoogle Scholar
  • 73 Vernet N, Dennefeld C, Rochette-Egly C , et al. Retinoic acid metabolism and signaling pathways in the adult and developing mouse testis. Endocrinology 2006; 147 (1) 96-110
    CrossrefPubMedGoogle Scholar
  • 74 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 U S A 2006; 103 (8) 2474-2479
    CrossrefPubMedGoogle Scholar
  • 75 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 (5) 1300-1308
    CrossrefPubMedGoogle Scholar
  • 76 Kastner P, Mark M, Leid M , et al. Abnormal spermatogenesis in RXR beta mutant mice. Genes Dev 1996; 10 (1) 80-92
    CrossrefPubMedGoogle Scholar
  • 77 Lohnes D, Kastner P, Dierich A, Mark M, LeMeur M, Chambon P. Function of retinoic acid receptor gamma in the mouse. Cell 1993; 73 (4) 643-658
    CrossrefPubMedGoogle Scholar
  • 78 Lufkin T, Lohnes D, Mark M , et al. High postnatal lethality and testis degeneration in retinoic acid receptor alpha mutant mice. Proc Natl Acad Sci U S A 1993; 90 (15) 7225-7229
    CrossrefPubMedGoogle Scholar
  • 79 Schulze GE, Clay RJ, Mezza LE, Bregman CL, Buroker RA, Frantz JD. BMS-189453, a novel retinoid receptor antagonist, is a potent testicular toxin. Toxicol Sci 2001; 59 (2) 297-308
    CrossrefPubMedGoogle Scholar
  • 80 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 (6) 2492-2502
    CrossrefPubMedGoogle Scholar
  • 81 Chung SS, Sung W, Wang X, Wolgemuth DJ. Retinoic acid receptor alpha is required for synchronization of spermatogenic cycles and its absence results in progressive breakdown of the spermatogenic process. Dev Dyn 2004; 230 (4) 754-766
    CrossrefPubMedGoogle Scholar
  • 82 Chung SS, Cuellar RA, Wang X, Reczek PR, Georg GI, Wolgemuth DJ. Pharmacological activity of retinoic acid receptor alpha-selective antagonists in vitro and in vivo. ACS Med Chem Lett 2013; 4 (5) 446-450
    CrossrefPubMedGoogle Scholar
  • 83 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
    CrossrefPubMedGoogle Scholar
  • 84 Heller CG, Flageolle BY, Matson LJ. Histopathology of the human testes as affected by Bis(dichloroacetyl)diamines. Exp Mol Pathol Suppl 1963; 2: 107-114
    PubMedGoogle Scholar
  • 85 Coulston F, Beyler AL, Drobeck HP. The biologic actions of a new series of bis(dichloroacetyl) diamines. Toxicol Appl Pharmacol 1960; 2: 715-731
    CrossrefPubMedGoogle Scholar
  • 86 Amory JK, Muller CH, Shimshoni JA , et al. Suppression of spermatogenesis by bisdichloroacetyldiamines is mediated by inhibition of testicular retinoic acid biosynthesis. J Androl 2011; 32 (1) 111-119
    CrossrefPubMedGoogle Scholar
  • 87 Paik J, Haenisch M, Muller CH , et al. Inhibition of retinoic acid biosynthesis by the bisdichloroacetyldiamine WIN 18,446 markedly suppresses spermatogenesis and alters retinoid metabolism in mice. J Biol Chem 2014; 289 (21) 15104-15117
    CrossrefPubMedGoogle Scholar
  • 88 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 (4) 367-375
    CrossrefPubMedGoogle Scholar
  • 89 Guha SK, Singh G, Ansari S , et al. Phase II clinical trial of a vas deferens injectable contraceptive for the male. Contraception 1997; 56 (4) 245-250
    CrossrefPubMedGoogle Scholar
  • 90 Lohiya NK, Alam I, Hussain M, Khan SR, Ansari AS. RISUG: an intravasal injectable male contraceptive. Indian J Med Res 2014; 140 (Suppl): S63-S72
    PubMedGoogle Scholar
  • 91 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 (6) 460-464
    CrossrefPubMedGoogle Scholar
  • 92 Zhao SC, Lian YH, Yu RC, Zhang SP. Recovery of fertility after removal of polyurethane plugs from the human vas deferens occluded for up to 5 years. Int J Androl 1992; 15 (6) 465-467
    CrossrefPubMedGoogle Scholar