Skip to main content
SpringerLink
Log in

Non-Hormonal Approaches to Male Contraception

  • Chapter
  • First Online:
Andrology

  • 600 Accesses

Abstract

Technology for non-hormonal male contraception can range from application of biologics (large molecules) such as antibody vaccine and mRNA, vas deferens polymeric injection, or small molecules, including natural products as agonists or antagonists of reproductive tissue protein targets. The mechanism of action for these contraceptive agents is to affect sperm production, sperm function, or sperm transport. One prevailing rationale for pursuing non-hormonal contraceptive agents is the concept of little-to-no side effects. This remains to be seen as research and development into non-hormonal methods have proven difficult over the years and selectively or exclusively targeting reproductive tissue proteins as drug targets are in early stages.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Akbari A, Pipitone GB, Anvar Z, Jaafarinia M, Ferrari M, Carrera P, Totonchi M (2019) ADCY10 frameshift variant leading to severe recessive asthenozoospermia and segregating with absorptive hypercalciuria. Hum Reprod 34:1155–1164

    CAS  PubMed  Google Scholar 

  • Amory JK, Arnold S, Lardone MC, Piottante A, Ebensperger M, Isoherranen N, Muller CH, Walsh T, Castro A (2014) Levels of the retinoic acid synthesizing enzyme aldehyde dehydrogenase-1A2 are lower in testicular tissue from men with infertility. Fertil Steril 101:960–966

    CAS  PubMed  PubMed Central  Google Scholar 

  • Anamthathmakula P, Winuthayanon W (2020) Mechanism of semen liquefaction and its potential for a novel non-hormonal contraception. Biol Reprod 103:411–426

    PubMed  PubMed Central  Google Scholar 

  • Anderson DJ, Johnson PM, Alexander NJ, Jones WR, David Griffin P (1987) Monoclonal antibodies to human trophoblast and sperm antigens: report of two WHO-sponsored workshops, June 30, 1986—Toronto, Canada. J Reprod Immunol 10:231–257

    CAS  PubMed  Google Scholar 

  • Anderson DJ, Politch JA, Cone RA, Zeitlin L, Lai SK, Santangelo PJ, Moench TR, Whaley KJ (2020) Engineering monoclonal antibody-based contraception and multipurpose prevention technologies. Biol Reprod 103:275–285

    PubMed  PubMed Central  Google Scholar 

  • Aydin H, Sultana A, Li S, Thavalingam A, Lee JE (2016) Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex. Nature 534:562–565

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ayoub AM, Hawk LML, Herzig RJ, Jiang J, Wisniewski AJ, Gee CT, Zhao P, Zhu JY, Berndt N, Offei-Addo NK, Scott TG, Qi J, Bradner JE, Ward TR, Schönbrunn E, Georg GI, Pomerantz WCK (2017) BET Bromodomain inhibitors with one-step synthesis discovered from virtual screen. J Med Chem 60:4805–4817

    CAS  PubMed  PubMed Central  Google Scholar 

  • Balbach M, Fushimi M, Huggins DJ, Steegborn C, Meinke PT, Levin LR, Buck J (2020) Optimization of lead compounds into on-demand, nonhormonal contraceptives: leveraging a public-private drug discovery institute collaboration. Biol Reprod 103:176–182

    PubMed  PubMed Central  Google Scholar 

  • Barton BE, Rock JK, Willie AM, Harris EA, Finnerty RM, Herrera GG, Anamthathmakula P, Winuthayanon W (2020) Serine protease inhibitor disrupts sperm motility leading to reduced fertility in female mice. Biol Reprod 103:400–410

    PubMed  PubMed Central  Google Scholar 

  • Bearak J, Popinchalk A, Alkema L, Sedgh G (2018) Global, regional, and subregional trends in unintended pregnancy and its outcomes from 1990 to 2014: estimates from a Bayesian hierarchical model. Lancet Glob Health 6:e380–ee89

    PubMed  PubMed Central  Google Scholar 

  • Bertrand JT, Ross J, Sullivan TM, Hardee K, Shelton JD (2020) Contraceptive method mix: updates and implications. Glob Health Sci Pract 8:666–679

    PubMed  PubMed Central  Google Scholar 

  • Buck J, Sinclair ML, Schapal L, Cann MJ, Levin LR (1999) Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals. Proc Natl Acad Sci U S A 96:79–84

    CAS  PubMed  PubMed Central  Google Scholar 

  • Carlson AE, Burnett LA, del Camino D, Quill TA, Hille B, Chong JA, Moran MM, Babcock DF (2009) Pharmacological targeting of native CatSper channels reveals a required role in maintenance of sperm hyperactivation. PLoS One 4:e6844

    PubMed  PubMed Central  Google Scholar 

  • Chavez JC, Ferreira JJ, Butler A, De La Vega Beltran JL, Trevino CL, Darszon A, Salkoff L, Santi CM (2014) SLO3 K+ channels control calcium entry through CATSPER channels in sperm. J Biol Chem 289:32266–32275

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen Y, Zhu JY, Hong KH, Mikles DC, Georg GI, Goldstein AS, Amory JK, Schonbrunn E (2018) Structural basis of ALDH1A2 inhibition by irreversible and reversible small molecule inhibitors. ACS Chem Biol 13:582–590

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cho C (2012) Testicular and epididymal ADAMs: expression and function during fertilization. Nat Rev Urol 9:550–560

    CAS  PubMed  Google Scholar 

  • Chung SSW, Wang X, Roberts SS, Griffey SM, Reczek PR, Wolgemuth DJ (2011) Oral administration of a retinoic acid receptor antagonist reversibly inhibits spermatogenesis in mice. Endocrinology 152:2492–2502

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chung SS, Wang X, Wolgemuth DJ (2016) 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 157:1601–1612

    CAS  PubMed  PubMed Central  Google Scholar 

  • Clausen MJ, Nissen P, Poulsen H (2011) The pumps that fuel a sperm’s journey. Biochem Soc Trans 39:741–745

    CAS  PubMed  Google Scholar 

  • Colagross-Schouten A, Lemoy MJ, Keesler RI, Lissner E, VandeVoort CA (2017) The contraceptive efficacy of intravas injection of Vasalgel for adult male rhesus monkeys. Basic Clin Androl 27:4

    PubMed  PubMed Central  Google Scholar 

  • Cormier N, McGlone JJ, Leszyk J, Hardy DM (2018) Immunocontraceptive target repertoire defined by systematic identification of sperm membrane alloantigens in a single species. PLoS One 13:e0190891

    PubMed  PubMed Central  Google Scholar 

  • Coutinho EM (2002) Gossypol: a contraceptive for men. Contraception 65:259–263

    CAS  PubMed  Google Scholar 

  • Crapster JA, Rack PG, Hellmann ZJ, Le AD, Adams CM, Leib RD, Elias JE, Perrino J, Behr B, Li Y, Lin J, Zeng H, Chen JK (2020) HIPK4 is essential for murine spermiogenesis. elife 9:e50209

    CAS  PubMed  PubMed Central  Google Scholar 

  • D’Francisco F, Merlo ML, Vercellini R, Blanco P, Barbeito C, Gobello C (2019) Effect of the indenopyridine RTI-4587-073 (l) on feline testicle. Anim Reprod Sci 205:10–17

    PubMed  Google Scholar 

  • Esposito G, Jaiswal BS, Xie F, Krajnc-Franken MA, Robben TJ, Strik AM, Kuil C, Philipsen RL, van Duin M, Conti M, Gossen JA (2004) Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect. Proc Natl Acad Sci U S A 101:2993–2998

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fujihara Y, Lu Y, Noda T, Oji A, Larasati T, Kojima-Kita K, Yu Z, Matzuk RM, Matzuk MM, Ikawa M (2020) Spermatozoa lacking fertilization influencing membrane protein (FIMP) fail to fuse with oocytes in mice. Proc Natl Acad Sci U S A 117:9393–9400

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gaikwad AS, Anderson AL, Merriner DJ, O’Connor AE, Houston BJ, Aitken RJ, O’Bryan MK, Nixon B (2019) GLIPR1L1 is an IZUMO-binding protein required for optimal fertilization in the mouse. BMC Biol 17:86

    PubMed  PubMed Central  Google Scholar 

  • Gaucher J, Boussouar F, Montellier E, Curtet S, Buchou T, Bertrand S, Hery P, Jounier S, Depaux A, Vitte AL, Guardiola P, Pernet K, Debernardi A, Lopez F, Holota H, Imbert J, Wolgemuth DJ, Gerard M, Rousseaux S, Khochbin S (2012) Bromodomain-dependent stage-specific male genome programming by Brdt. EMBO J 31:3809–3820

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hawkinson JE, Sinville R, Mudaliar D, Shetty J, Ward T, Herr JC, Georg GI (2017) Potent pyrimidine and Pyrrolopyrimidine inhibitors of testis-specific serine/threonine kinase 2 (TSSK2). ChemMedChem 12:1857–1865

    CAS  PubMed  PubMed Central  Google Scholar 

  • Heinemann K, Saad F, Wiesemes M, White S, Heinemann L (2005) Attitudes toward male fertility control: results of a multinational survey on four continents. Hum Reprod 20:549–556

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Hikim AP, Lue YH, Wang C, Reutrakul V, Sangsuwan R, Swerdloff RS (2000) Posttesticular antifertility action of triptolide in the male rat: evidence for severe impairment of cauda epididymal sperm ultrastructure. J Androl 21:431–437

    CAS  PubMed  Google Scholar 

  • Hild SA, Marshall GR, Attardi BJ, Hess RA, Schlatt S, Simorangkir DR, Ramaswamy S, Koduri S, Reel JR, Plant TM (2007) 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 148:1784–1796

    CAS  PubMed  Google Scholar 

  • Huynh PN, Hikim AP, Wang C, Stefonovic K, Lue YH, Leung A, Atienza V, Baravarian S, Reutrakul V, Swerdloff RS (2000) Long-term effects of triptolide on spermatogenesis, epididymal sperm function, and fertility in male rats. J Androl 21:689–699

    CAS  PubMed  Google Scholar 

  • Isojima S, Kameda K, Tsuji Y, Shigeta M, Ikeda Y, Koyama K (1987) Establishment and characterization of a human hybridoma secreting monoclonal antibody with high titers of sperm immobilizing and agglutinating activities against human seminal plasma. J Reprod Immunol 10:67–78

    CAS  PubMed  Google Scholar 

  • Jimenez T, McDermott JP, Sanchez G, Blanco G (2011) Na,K-ATPase alpha4 isoform is essential for sperm fertility. Proc Natl Acad Sci U S A 108:644–649

    CAS  PubMed  Google Scholar 

  • Khilwani B, Badar A, Ansari AS, Lohiya NK (2020) RISUG® as a male contraceptive: journey from bench to bedside. Basic Clin Androl 30:2

    PubMed  PubMed Central  Google Scholar 

  • Konrad L, Dietze R, Kirch U, Kirch H, Eva A, Scheiner-Bobis G (2011) Cardiotonic steroids trigger non-classical testosterone signaling in sertoli cells via the alpha4 isoform of the sodium pump. Biochim Biophys Acta 1813:2118–2124

    CAS  PubMed  Google Scholar 

  • Kupchan SM, Court WA, Dailey RG Jr, Gilmore CJ, Bryan RF (1972) Triptolide and tripdiolide, novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii. J Am Chem Soc 94:7194–7195

    CAS  PubMed  Google Scholar 

  • Lamas-Toranzo I, Hamze JG, Bianchi E, Fernández-Fuertes B, Pérez-Cerezales S, Laguna-Barraza R, Fernández-González R, Lonergan P, Gutiérrez-Adán A, Wright GJ, Jiménez-Movilla M, Bermejo-Álvarez P (2020) TMEM95 is a sperm membrane protein essential for mammalian fertilization. elife 9:e53913

    PubMed  PubMed Central  Google Scholar 

  • Law RP, Atkinson SJ, Bamborough P, Chung CW, Demont EH, Gordon LJ, Lindon M, Prinjha RK, Watson AJB, Hirst DJ (2018) Discovery of Tetrahydroquinoxalines as Bromodomain and extra-terminal domain (BET) inhibitors with selectivity for the second Bromodomain. J Med Chem 61:4317–4334

    CAS  PubMed  Google Scholar 

  • Lim S, Kierzek M, O’Connor AE, Brenker C, Merriner DJ, Okuda H, Volpert M, Gaikwad A, Bianco D, Potter D, Prabhakar R, Strünker T, O’Bryan MK (2019) CRISP2 is a regulator of multiple aspects of sperm function and male fertility. Endocrinology 160:915–924

    CAS  PubMed  Google Scholar 

  • Lindsay KE, Vanover D, Thoresen M, King H, Xiao P, Badial P, Araínga M, Park SB, Tiwari PM, Peck HE, Blanchard EL, Feugang JM, Olivier AK, Zurla C, Villinger F, Woolums AR, Santangelo PJ (2020) Aerosol delivery of synthetic mRNA to vaginal mucosa leads to durable expression of broadly neutralizing antibodies against HIV. Mol Ther 28:805–819

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lishko PV, Kirichok Y, Ren D, Navarro B, Chung JJ, Clapham DE (2012) The control of male fertility by spermatozoan ion channels. Annu Rev Physiol 74:453–475

    CAS  PubMed  Google Scholar 

  • Liu GZ, Lyle KC (1987) Clinical trial of gossypol as a male contraceptive drug. Part 2. Hypokalemia study. Fertil Steril 48:462–465

    CAS  PubMed  Google Scholar 

  • Liu GZ, Lyle KC, Cao J (1987) Clinical trial of gossypol as a male contraceptive drug. Part I. efficacy study. Fertil Steril 48:459–461

    CAS  PubMed  Google Scholar 

  • Lorenzetti D, Poirier C, Zhao M, Overbeek PA, Harrison W, Bishop CE (2014) A transgenic insertion on mouse chromosome 17 inactivates a novel immunoglobulin superfamily gene potentially involved in sperm-egg fusion. Mamm Genome 25:141–148

    CAS  PubMed  Google Scholar 

  • Louvandini H, Corrêa PS, Amorín R, Liu L, Ieda EH, Jimenez CR, Tsai SM, McManus CM, Peñagaricano F (2020) Gestational and lactational exposure to gossypol alters the testis transcriptome. BMC Genomics 21:59

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lue Y, Sinha Hikim AP, Wang C, Leung A, Baravarian S, Reutrakul V, Sangsawan R, Chaichana S, Swerdloff RS (1998) Triptolide: a potential male contraceptive. J Androl 19:479–486

    CAS  PubMed  Google Scholar 

  • Lufkin T, Lohnes D, Mark M, Dierich A, Gorry P, Gaub MP, Lemeur M, Chambon P (1993) High postnatal lethality and testis degeneration in retinoic acid receptor alpha mutant mice. Proc Natl Acad Sci 90:7225–7229

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matlin SA, Belenguer A, Stacey VE, Qian SZ, Xu Y, Zhang JW, Sanders JK, Amor SR, Pearce CM (1993) Male antifertility compounds from Tripterygium wilfordii hook f. Contraception 47:387–400

    CAS  PubMed  Google Scholar 

  • Matzuk MM, McKeown MR, Filippakopoulos P, Li Q, Ma L, Agno JE, Lemieux ME, Picaud S, Yu RN, Qi J, Knapp S, Bradner JE (2012) Small-molecule inhibition of BRDT for male contraception. Cell 150:673–684

    CAS  PubMed  PubMed Central  Google Scholar 

  • McDermott J, Sanchez G, Nangia AK, Blanco G (2015) Role of human Na,K-ATPase alpha 4 in sperm function, derived from studies in transgenic mice. Mol Reprod Dev 82:167–181

    CAS  PubMed  PubMed Central  Google Scholar 

  • Miller MR, Mannowetz N, Iavarone AT, Safavi R, Gracheva EO, Smith JF, Hill RZ, Bautista DM, Kirichok Y, Lishko PV (2016) Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone. Science 352:555–559

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mok KW, Mruk DD, Lie PP, Lui WY, Cheng CY (2011) Adjudin, a potential male contraceptive, exerts its effects locally in the seminiferous epithelium of mammalian testes. Reproduction 141:571–580

    CAS  PubMed  PubMed Central  Google Scholar 

  • Noda T, Lu Y, Fujihara Y, Oura S, Koyano T, Kobayashi S, Matzuk MM, Ikawa M (2020) Sperm proteins SOF1, TMEM95, and SPACA6 are required for sperm-oocyte fusion in mice. Proc Natl Acad Sci U S A 117:11493–11502

    CAS  PubMed  PubMed Central  Google Scholar 

  • Noman MAA, Kyzer JL, Chung SSW, Wolgemuth DJ, Georg GI (2020) Retinoic acid receptor antagonists for male contraception: current status. Biol Reprod 103:390–399

    PubMed  PubMed Central  Google Scholar 

  • Norton EJ, Diekman AB, Westbrook VA, Flickinger CJ, Herr JC (2001) RASA, a recombinant single-chain variable fragment (scFv) antibody directed against the human sperm surface: implications for novel contraceptives. Hum Reprod 16:1854–1860

    CAS  PubMed  Google Scholar 

  • O’Rand MG, Widgren EE, Sivashanmugam P, Richardson RT, Hall SH, French FS, VandeVoort CA, Ramachandra SG, Ramesh V, Rao AJ (2004) Reversible immunocontraception in male monkeys immunized with eppin. Science 306:1189–1190

    PubMed  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  • Oberheide K, Puchkov D, Jentsch TJ (2017) Loss of the Na(+)/H(+) exchanger NHE8 causes male infertility in mice by disrupting acrosome formation. J Biol Chem 292:10845–10854

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ohto U, Ishida H, Krayukhina E, Uchiyama S, Inoue N, Shimizu T (2016) Structure of IZUMO1-JUNO reveals sperm-oocyte recognition during mammalian fertilization. Nature 534:566–569

    CAS  PubMed  Google Scholar 

  • Pozor MA, Macpherson ML, McDonnell SM, Nollin M, Roser JF, Love C, Runyon S, Thomas BF, Troedsson MH (2013) Indenopyride derivative RTI-4587-073(l): a candidate for male contraception in stallions. Theriogenology 80:1006–1016

    CAS  PubMed  Google Scholar 

  • Prajogo B, Pramesti D, Musta’ina S (2014) ASA 2014 meeting abstract-study on contraceptive effect of ethanol extracted Justicia gendarussa burm. F. leaves in fertile men: phase 2 clinical trial. Andrology 2:69

    Google Scholar 

  • Qian SZ (1987) Tripterygium wilfordii, a Chinese herb effective in male fertility regulation. Contraception 36:335–345

    CAS  PubMed  Google Scholar 

  • Qian SZ, Zhong CQ, Xu Y (1986) Effect of Tripterygium wilfordii Hook. f. on the fertility of rats. Contraception 33:105–110

    CAS  PubMed  Google Scholar 

  • Ren D, Navarro B, Perez G, Jackson AC, Hsu S, Shi Q, Tilly JL, Clapham DE (2001) A sperm ion channel required for sperm motility and male fertility. Nature 413:603–609

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rennhack A, Schiffer C, Brenker C, Fridman D, Nitao ET, Cheng YM, Tamburrino L, Balbach M, Stolting G, Berger TK, Kierzek M, Alvarez L, Wachten D, Zeng XH, Baldi E, Publicover S, Kaupp UB, Strunker T (2018) A novel cross-species inhibitor to study the function of CatSper Ca(2+) channels in sperm. Br J Pharmacol 5(15):3144–3161

    Google Scholar 

  • Russell DL, Brown HM, Dunning KR (2015) ADAMTS proteases in fertility. Matrix Biol 44–46:54–63

    PubMed  Google Scholar 

  • Salicioni AM, Gervasi MG, Sosnik J, Tourzani DA, Nayyab S, Caraballo DA, Visconti PE (2020) Testis-specific serine kinase protein family in male fertility and as targets for non-hormonal male contraception. Biol Reprod 103:264–274

    PubMed  PubMed Central  Google Scholar 

  • Sato E, Segal SJ, Koide SS (1985) Interaction of 14 C-gossypol with human sperm. Adv Contracept Deliv Syst 1:69–74

    Google Scholar 

  • Shang E, Nickerson HD, Wen D, Wang X, Wolgemuth DJ (2007) The first bromodomain of Brdt, a testis-specific member of the BET sub-family of double-bromodomain-containing proteins, is essential for male germ cell differentiation. Development 134:3507–3515

    CAS  PubMed  Google Scholar 

  • Shang P, Baarends WM, Hoogerbrugge J, Ooms MP, van Cappellen WA, de Jong AA, Dohle GR, van Eenennaam H, Gossen JA, Grootegoed JA (2010) Functional transformation of the chromatoid body in mouse spermatids requires testis-specific serine/threonine kinases. J Cell Sci 123:331–339

    CAS  PubMed  Google Scholar 

  • Sharma RS, Mathur AK, Singh R, Das HC, Singh GJ, Toor DPS, Guha SK (2019) Safety & efficacy of an intravasal, one-time injectable & non-hormonal male contraceptive (RISUG): a clinical experience. Indian J Med Res 150:81–86

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sheng-Cai Z, Yi-He L, Yu R-C, Shu-Ping Z (1992) Recovery of fertility after removal of polyurethane plugs from the human vas deferens occluded for up to 5 years. Int J Androl 15:465–467

    Google Scholar 

  • Shetty J, Sinville R, Shumilin IA, Minor W, Zhang J, Hawkinson JE, Georg GI, Flickinger CJ, Herr JC (2016) Recombinant production of enzymatically active male contraceptive drug target hTSSK2—localization of the TSKS domain phosphorylated by TSSK2. Protein Expr Purif 121:88–96

    CAS  PubMed  PubMed Central  Google Scholar 

  • Spiridonov NA, Wong L, Zerfas PM, Starost MF, Pack SD, Paweletz CP, Johnson GR (2005) Identification and characterization of SSTK, a serine/threonine protein kinase essential for male fertility. Mol Cell Biol 25:4250–4261

    CAS  PubMed  PubMed Central  Google Scholar 

  • Suarez SS (2016) Mammalian sperm interactions with the female reproductive tract. Cell Tissue Res 363:185–194

    PubMed  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  • Syeda SS, Sanchez G, Hong KH, Hawkinson JE, Georg GI, Blanco G (2018) Design, synthesis, and in vitro and in vivo evaluation of ouabain analogues as potent and selective Na,K-ATPase alpha4 isoform inhibitors for male contraception. J Med Chem 61:1800–1820

    CAS  PubMed  PubMed Central  Google Scholar 

  • Syeda SS, Sánchez G, McDermott JP, Hong KH, Blanco G, Georg GI (2020) The Na+ and K+ transport system of sperm (ATP1A4) is essential for male fertility and an attractive target for male contraception. Biol Reprod 103:343–356

    PubMed  PubMed Central  Google Scholar 

  • Tash JS, Attardi B, Hild SA, Chakrasali R, Jakkaraj SR, Georg GI (2008) A novel potent indazole carboxylic acid derivative blocks spermatogenesis and is contraceptive in rats after a single oral dose. Biol Reprod 78:1127–1138

    CAS  PubMed  Google Scholar 

  • Vasiliou V, Bairoch A, Tipton KF, Nebert DW (1999) Eukaryotic aldehyde dehydrogenase (ALDH) genes: human polymorphisms, and recommended nomenclature based on divergent evolution and chromosomal mapping. Pharmacogenetics 9:421–434

    CAS  PubMed  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  • Wang D, King SM, Quill TA, Doolittle LK, Garbers DL (2003) A new sperm-specific Na+/H+ exchanger required for sperm motility and fertility. Nat Cell Biol 5:1117–1122

    CAS  PubMed  Google Scholar 

  • Wang D, Hu J, Bobulescu IA, Quill TA, McLeroy P, Moe OW, Garbers DL (2007) A sperm-specific Na+/H+ exchanger (sNHE) is critical for expression and in vivo bicarbonate regulation of the soluble adenylyl cyclase (sAC). Proc Natl Acad Sci 104:9325–9330

    CAS  PubMed  PubMed Central  Google Scholar 

  • Widyowati R, Agil M (2018) Chemical constituents and bioactivities of several Indonesian plants typically used in Jamu. Chem Pharm Bull 66:506–518

    CAS  Google Scholar 

  • Wisniewski A, Georg GI (2020) BET proteins: investigating BRDT as a potential target for male contraception. Bioorg Med Chem Lett 30:126958

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu B, Hao Z, Jha KN, Zhang Z, Urekar C, Digilio L, Pulido S, Strauss JF 3rd, Flickinger CJ, Herr JC (2008) Targeted deletion of Tssk1 and 2 causes male infertility due to haploinsufficiency. Dev Biol 319:211–222

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yamaguchi R, Muro Y, Isotani A, Tokuhiro K, Takumi K, Adham I, Ikawa M, Okabe M (2009) Disruption of ADAM3 impairs the migration of sperm into oviduct in mouse. Biol Reprod 81:142–146

    CAS  PubMed  Google Scholar 

  • Yu DY (1983) One hundred and forty-four cases of rheumatoid arthritis treated with Tripterygium wilfordii. J Tradit Chin Med 3:125–129

    CAS  PubMed  Google Scholar 

  • Zhang H, Su D, Yang Y, Zhang W, Liu Y, Bai G, Ma M, Ma Y, Zhang S (2010) Some single-nucleotide polymorphisms of the TSSK2 gene may be associated with human spermatogenesis impairment. J Androl 31:388–392

    PubMed  Google Scholar 

  • Zhang Z, Yang Y, Wu H, Zhang H, Zhang H, Mao J, Liu D, Zhao L, Lin H, Tang W, Hong K, Jiang H (2017) Sodium-hydrogen-exchanger expression in human sperm and its relationship with semen parameters. J Assist Reprod Genet 34:795–801

    PubMed  PubMed Central  Google Scholar 

  • Zhao S-C (1990) Vas deferens occlusion by percutaneous injection of polyurethane elastomer plugs: clinical experience and reversibility. Contraception 41:453–459

    CAS  PubMed  Google Scholar 

  • Zhen QS, Ye X, Wei ZJ (1995) Recent progress in research on tripterygium: a male antifertility plant. Contraception 51:121–129

    CAS  PubMed  Google Scholar 

  • Zhen-Wen C, Yi-Qun G, Liang X-W, Wu Z-G, Er-Jing Y, Hong L (1992) Safety and efficacy of percutaneous injection of polyurethane elastomer (MPU) plugs for vas occlusion in man. Int J Androl 15:468–472

    Google Scholar 

  • Ziaei S, Halaby R (2016) Immunosuppressive, anti-inflammatory and anti-cancer properties of triptolide: a mini review. Avicenna J Phytomed 6:149–164

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Contraceptive Development Program, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

    Diana L. Blithe & Min S. Lee

Authors
  1. Diana L. Blithe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Min S. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Diana L. Blithe or Min S. Lee .

Editor information

Editors and Affiliations

  1. Center for Reproductive Medicine and Andrology, University Hospital Münster, Münster, Germany

    Eberhard Nieschlag

  2. Center for Reproductive Medicine and Andrology, University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg, Halle (Saale), Germany

    Hermann M. Behre

  3. Center for Reproductive Medicine and Andrology, University Hospital Münster, Münster, Germany

    Sabine Kliesch

  4. Center for Reproductive Medicine and Andrology, University Hospital Münster, Münster, Germany

    Susan Nieschlag

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Blithe, D.L., Lee, M.S. (2023). Non-Hormonal Approaches to Male Contraception. In: Nieschlag, E., Behre, H.M., Kliesch, S., Nieschlag, S. (eds) Andrology. Springer, Cham. https://doi.org/10.1007/978-3-031-31574-9_48

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-31574-9_48

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-31573-2

  • Online ISBN: 978-3-031-31574-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation