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Semin Reprod Med 2023; 41(06): 279-286
DOI: 10.1055/s-0043-1777757
DOI: 10.1055/s-0043-1777757
Review Article
Male Contraception
Funding This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, a branch of the National Institute of Health via grant R01HD098039.
Abstract
Approximately 40 to 50% of pregnancies are unintended. Contraceptive use significantly reduces the risk of unintended pregnancy. Approximately 70% of couples' contraceptive use is female and 30% is male, attributable to the reliance on condoms and vasectomies. Unfortunately, many women cannot use currently available contraceptives due to medical contraindications or side effects. At the same time, men want additional safe and effective contraceptive methods. Because of this, work to develop novel, safe, and effective male contraceptives is underway. This review will briefly discuss the pros and cons of condoms and vasectomies, and then describe research into the development of novel methods of male contraception, by the mechanism of action of the contraceptive. First, we will discuss male contraceptives that block sperm transmission. Next, we will discuss male contraceptives that impair sperm production. Lastly, we will discuss male contraceptives that impair sperm function.
Disclosure Statement
The author has received research funding from Ferring Pharmaceuticals.
Publication History
Article published online:
19 December 2023
© 2023. Thieme. All rights reserved.
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References
- 1 Bearak J, Popinchalk A, Ganatra B. et al. Unintended pregnancy and abortion by income, region, and the legal status of abortion: estimates from a comprehensive model for 1990-2019. Lancet Glob Health 2020; 8 (09) e1152-e1161
- 2 Finer LB, Zolna MR. Declines in unintended pregnancy in the United States, 2008-2011. N Engl J Med 2016; 374 (09) 843-852
- 3 Kost K, Zona M, Murro R. Pregnancies in the United States by desire for pregnancy: estimates for 2009, 2011, 2013, and 2015. Demography. April 27, 2023 online ahead of print
- 4 Jones RK, Kirstein M, Philbin J. Abortion incidence and service availability in the United States, 2020. Perspect Sex Reprod Health 2022; 54 (04) 128-141
- 5 Sonfield A, Hasstedt K, Gold RB. Moving forward: Family planning in the era of health reform. New York: Guttmacher Institute; 2014. Accessed November 27, 2023 at: https://www.guttmacher.org/report/moving-forward-family-planning-era-health-reform
- 6 Cleland J. The complex relationship between contraception and abortion. Best Pract Res Clin Obstet Gynaecol 2020; 62: 90-100
- 7 Speidel JJ, Grossman RA. Addressing global health, economic, and environmental problems through family planning. Obstet Gynecol 2011; 117 (06) 1394-1398
- 8 Daniels K, Daugherty J, Jones J, Mosher W. Current contraceptive use and variation by selected characteristics among women aged 15–44: US, 2011–2013. Natl Health Stat Rep 2015; 86: 1-14
- 9 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 (02) 549-556
- 10 Glasier AF, Anakwe R, Everington D. et al. Would women trust their partners to use a male pill?. Hum Reprod 2000; 15 (03) 646-649
- 11 Sundaram A, Vaughan B, Kost K. et al. Contraceptive failure from the 2006–2010 national survey of family growth. Perspect Sex Reprod Health 2017; 49: 7-16
- 12 DʼAnna LH, Korosteleva O, Warner L. et al; RESPECT-2 Study Group. Factors associated with condom use problems during vaginal sex with main and non-main partners. Sex Transm Dis 2012; 39 (09) 687-693
- 13 Fennell J. “And isn't that the point?”: pleasure and contraceptive decisions. Contraception 2014; 89 (04) 264-270
- 14 Walsh TL, Frezieres RG, Peacock K, Nelson AL, Clark VA, Bernstein L. Evaluation of the efficacy of a nonlatex condom: results from a randomized, controlled clinical trial. Perspect Sex Reprod Health 2003; 35 (02) 79-86
- 15 Ostrowski KA, Holt SK, Haynes B, Davies BJ, Fuchs EF, Walsh TJ. Evaluation of vasectomy trends in the United States. Urology 2018; 118: 76-79
- 16 Jamieson DJ, Costello C, Trussell J, Hillis SD, Marchbanks PA, Peterson HB. US Collaborative Review of Sterilization Working Group. The risk of pregnancy after vasectomy. Obstet Gynecol 2004; 103 (5, Pt 1): 848-850
- 17 Li S-Q, Goldstein M, Zhu J, Huber D. The no-scalpel vasectomy. J Urol 1991; 145 (02) 341-344
- 18 Tandon S, Sabanegh Jr E. Chronic pain after vasectomy: a diagnostic and treatment dilemma. BJU Int 2008; 102 (02) 166-169
- 19 Polackwich AS, Tadros NN, Ostrowski KA. et al. Vasectomy reversal for postvasectomy pain: a study and literature review. Urology 2015; 86 (02) 269-272
- 20 Jequier AM. Vasectomy related infertility: a major and costly medical problem. Hum Reprod 1998; 13 (07) 1757-1759
- 21 Belker AM, Thomas Jr AJ, Fuchs EF, Konnak JW, Sharlip ID. Results of 1,469 microsurgical vasectomy reversals by the Vasovasostomy Study Group. J Urol 1991; 145 (03) 505-511
- 22 Heidenreich A, Bonfig R, Wilbert DM, Strohmaier WL, Engelmann UH. Risk factors for antisperm antibodies in infertile men. Am J Reprod Immunol 1994; 31 (2-3): 69-76
- 23 Guha SK, Singh G, Ansari S. et al. Phase II clinical trial of a vas deferens injectable contraceptive for the male. Contraception 1997; 56 (04) 245-250
- 24 Sharma RS, Mathur AK, Singh R. et al. Safety & efficacy of an intravasal, one-time injectable & non-hormonal male contraceptive (RISUG): a clinical experience. Indian J Med Res 2019; 150 (01) 81-86
- 25 Khilwani B, Badar A, Ansari AS, Lohiya NK. RISUG® as a male contraceptive: journey from bench to bedside. Basic Clin Androl 2020; 30: 2
- 26 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
- 27 Colagross-Schouten A, Lemoy MJ, Keesler RI, Lissner E, VandeVoort CA. The contraceptive efficacy of intravas injection of Vasalgel™ for adult male rhesus monkeys. Basic Clin Androl 2017; 27: 4
- 28 Waller D, Bolick D, Lissner E. et al. Reversibility of Vasalgel™ male contraceptive in a rabbit model. Basic Clin Androl 2016; 26: 6
- 29 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 (06) 460-464
- 30 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 (06) 465-467
- 31 Wang ZQ, Liu ZQ, Zhao CH. et al. An ultrasound induced self-clearance hydrogel for male reversible contraception. ACS Nano 2022; 16 (04) 5515-5528
- 32 Anderson P, Bolton D, Lawrentschuk N. Preliminary results of a first in human dose-ranging clinical trial of ADAM, a non-hormonal hydrogel-based male contraceptive (abstract PD42–08). J Urol
- 33 Homonnai ZT, Shilon M, Paz GF. Phenoxybenzamine – an effective male contraceptive pill. Contraception 1984; 29 (05) 479-491
- 34 Kobayashi K, Masumori N, Kato R, Hisasue S, Furuya R, Tsukamoto T. Orgasm is preserved regardless of ejaculatory dysfunction with selective alpha1A-blocker administration. Int J Impot Res 2009; 21 (05) 306-310
- 35 Bhat GS, Shastry A. A prospective double-blind, randomized, placebo-controlled study to evaluate the efficacy of silodosin 8 mg as an on-demand, reversible, nonhormonal oral contraceptive for males: a pilot study. World J Urol 2020; 38 (03) 747-751
- 36 Heller CH, Clermont Y. Kinetics of the germinal epithelium in man. Recent Prog Horm Res 1964; 20: 545-575
- 37 Gonzalez D, Narasimman M, Best JC, Ory J, Ramasamy R. Clinical update on home testing for male fertility. World J Mens Health 2021; 39 (04) 615-625
- 38 Heckel NJ. Production of oligozoospermia in a man by the use of testosterone propionate. Proc Soc Exp Biol Med 1939; 40: 658-659
- 39 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
- 40 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 (04) 821-829
- 41 Aaltonen P, Amory JK, Anderson RA. et al. 10th Summit Meeting consensus: recommendations for regulatory approval for hormonal male contraception. J Androl 2007; 28 (03) 362-363
- 42 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
- 43 Gu YQ, Wang XH, Xu D. et al. A multicenter contraceptive efficacy study of injectable testosterone undecanoate in healthy Chinese men. J Clin Endocrinol Metab 2003; 88 (02) 562-568
- 44 Gu Y, Liang X, Wu W. et al. Multicenter contraceptive efficacy trial of injectable testosterone undecanoate in Chinese men. J Clin Endocrinol Metab 2009; 94 (06) 1910-1915
- 45 Meriggiola MC, Bremner WJ. Progestin-androgen combination regimens for male contraception. J Androl 1997; 18 (03) 240-244
- 46 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
- 47 Behre HM, Zitzmann M, Anderson RA. et al. Efficacy and safety of an injectable combination hormonal contraceptive for men. J Clin Endocrinol Metab 2016; 101 (12) 4779-4788
- 48 Amory JK, Blithe DL, Sitruk-Ware R. et al. Design of an international male contraceptive efficacy trial using a self-administered daily transdermal gel containing testosterone and segesterone acetate (Nestorone). Contraception 2023; 124: 110064
- 49 Page ST, Amory JK. Male hormonal contraceptive - are we there yet?. Nat Rev Endocrinol 2018; 14 (12) 685-686
- 50 Poromaa IS, Segebladh B. Adverse mood symptoms with oral contraceptives. Acta Obstet Gynecol Scand 2012; 91 (04) 420-427
- 51 National Collaborative Team on the clinical study of Gossypol as a male antifertility agent. The study of gossypol in 8,806 men. Reprod Contracept 1985; 5: 5-11
- 52 Waites GM, Wang C, Griffin PD. Gossypol: reasons for its failure to be accepted as a safe, reversible male antifertility drug. Int J Androl 1998; 21 (01) 8-12
- 53 Wolbach SB, Howe PR. Tissue changes following deprivation of fat soluble A Vitamin. J Exp Med 1925; 42 (06) 753-777
- 54 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 (01) 96-110
- 55 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
- 56 Topping T, Griswold MD. Global deletion of ALDH1A1 and ALDH1A2 genes does not affect viability but blocks spermatogenesis. Front Endocrinol (Lausanne) 2022; 13: 871225
- 57 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 (02) 297-308
- 58 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 (06) 2492-2502
- 59 Kyzer JL, Noman MAA, Cuellar RAD. et al. Investigation of selective retinoic acid receptor alpha antagonist ER-50891 and related analogs for male contraception. Arch Pharm (Weinheim) 2023; 356 (07) e2300031
- 60 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
- 61 Beyler AL, Potts GO, Coulston F, Surrey AR. The selective testicular effects of certain bis(dichloroacetyl)diamines. Endocrinology 1961; 69: 819-833
- 62 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 (01) 111-119
- 63 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
- 64 Chen Y, Zhu JY, Hong KH. et al. Structural basis of ALDH1A2 inhibition by irreversible and reversible small molecule inhibitors. ACS Chem Biol 2018; 13 (03) 582-590
- 65 Glover TD, Young DH. Temperature and the production of spermatozoa. Fertil Steril 1963; 14: 441-450
- 66 Mieusset R, Grandjean H, Mansat A, Pontonnier F. Inhibiting effect of artificial cryptorchidism on spermatogenesis. Fertil Steril 1985; 43 (04) 589-594
- 67 Shafik A. Contraceptive efficacy of polyester-induced azoospermia in normal men. Contraception 1992; 45 (05) 439-451
- 68 Joubert S, Tcherdukian J, Mieusset R, Perrin J. Thermal male contraception: a study of users' motivation, experience, and satisfaction. Andrology 2022; 10 (08) 1500-1510
- 69 O'Rand MG, Widgren EE, Hamil KG, Silva EJ, Richardson RT. Functional studies of EPPIN. Biochem Soc Trans 2011; 39 (05) 1447-1449
- 70 O'rand MG, Widgren EE, Sivashanmugam P. et al. Reversible immunocontraception in male monkeys immunized with EPPIN. Science 2004; 306 (5699): 1189-1190
- 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: 105-111
- 72 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 (04) e0195953
- 73 Gomes AAS, Santos NCM, Rosa LR. et al. Interactions of the male contraceptive target EPPIN with semenogelin-1 and small organic ligands. Sci Rep 2023; 13 (01) 14382
- 74 Ren D, Navarro B, Perez G. et al. A sperm ion channel required for sperm motility and male fertility. Nature 2001; 413 (6856): 603-609
- 75 Qi H, Moran MM, Navarro B. et al. All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility. Proc Natl Acad Sci U S A 2007; 104 (04) 1219-1223
- 76 Avenarius MR, Hildebrand MS, Zhang Y. et al. Human male infertility caused by mutations in the CATSPER1 channel protein. Am J Hum Genet 2009; 84 (04) 505-510
- 77 Carlson AE, Burnett LA, del Camino D. et al. Pharmacological targeting of native CatSper channels reveals a required role in maintenance of sperm hyperactivation. PLoS One 2009; 4 (08) e6844
- 78 Lishko PV. Contraception: search for an ideal unisex mechanism by targeting ion channels. Trends Biochem Sci 2016; 41 (10) 816-818
- 79 Schreiber M, Wei A, Yuan A, Gaut J, Saito M, Salkoff L. Slo3, a novel pH-sensitive K+ channel from mammalian spermatocytes. J Biol Chem 1998; 273 (06) 3509-3516
- 80 Santi CM, Martínez-López P, de la Vega-Beltrán JL. et al. The SLO3 sperm-specific potassium channel plays a vital role in male fertility. FEBS Lett 2010; 584 (05) 1041-1046
- 81 Lyon M, Li P, Ferreira JJ. et al. A selective inhibitor of the sperm-specific potassium channel SLO3 impairs human sperm function. Proc Natl Acad Sci U S A 2023; 120 (04) e2212338120
- 82 Liu R, Yan Z, Fan Y. et al. Bi-allelic variants in KCNU1 cause impaired acrosome reactions and male infertility. Hum Reprod 2022; 37 (07) 1394-1405
- 83 Balbach M, Ghanem L, Rossetti T. et al. Soluble adenylyl cyclase inhibition prevents human sperm functions essential for fertilization. Mol Hum Reprod 2021; 27 (09) gaab054
- 84 Balbach M, Rossetti T, Ferreira J. et al. On-demand male contraception via acute inhibition of soluble adenylyl cyclase. Nat Commun 2023; 14 (01) 637
- 85 Qian SZ. Tripterygium wilfordii, a Chinese herb effective in male fertility regulation. Contraception 1987; 36 (03) 335-345
- 86 Huynh PN, Hikim AP, Wang C. et al. Long-term effects of triptolide on spermatogenesis, epididymal sperm function, and fertility in male rats. J Androl 2000; 21 (05) 689-699
- 87 Chang Z, Qin W, Zheng H. et al. Triptonide is a reversible non-hormonal male contraceptive agent in mice and non-human primates. Nat Commun 2021; 12 (01) 1253