male contraceptive#Pharmaceutical methods

In the 21st century, surveys indicated that around half of men in countries across the world have been interested in using a variety of novel contraceptive methods,{{cite journal | vauthors = Glasier A | title = Acceptability of contraception for men: a review | journal = Contraception | volume = 82 | issue = 5 | pages = 453–456 | date = November 2010 | pmid = 20933119 | doi = 10.1016/j.contraception.2010.03.016 }}{{cite journal | vauthors = Heinemann K, Saad F, Wiesemes M, White S, Heinemann L | title = Attitudes toward male fertility control: results of a multinational survey on four continents | journal = Human Reproduction | volume = 20 | issue = 2 | pages = 549–556 | date = February 2005 | pmid = 15608042 | doi = 10.1093/humrep/deh574 }}{{Cite web | vauthors = Friedman M |date=2019 |title=Interest Among U.S. Men for New Male Contraceptive Options |url=https://www.malecontraceptive.org/uploads/1/3/1/9/131958006/mci_consumerresearchstudy.pdf |access-date=Oct 12, 2023 |website=Male Contraceptive Initiative}} and men in clinical trials for male contraceptives have reported high levels of satisfaction with the products.{{cite journal | vauthors = Nguyen BT, Farrant MT, Anawalt BD, Yuen F, Thirumalai A, Amory JK, Swerdloff RS, Bremner WJ, Liu PY, Blithe DL, Page ST, Wang C | title = Acceptability of oral dimethandrolone undecanoate in a 28-day placebo-controlled trial of a hormonal male contraceptive prototype | journal = Contraception | volume = 102 | issue = 1 | pages = 52–57 | date = July 2020 | pmid = 32298717 | pmc = 7287214 | doi = 10.1016/j.contraception.2020.04.006 }} Women worldwide have also shown a high level of interest in new male contraceptives, and though both male and female partners could use their own contraceptives simultaneously, women in long-term relationships have indicated a high degree of trust in their male partner's ability to successfully manage contraceptive use.

A modelling study from 2018 suggested that even partial adoption of new male contraceptives would significantly reduce unintended pregnancy rates around the globe,{{cite journal | vauthors = Dorman E, Perry B, Polis CB, Campo-Engelstein L, Shattuck D, Hamlin A, Aiken A, Trussell J, Sokal D | title = Modeling the impact of novel male contraceptive methods on reductions in unintended pregnancies in Nigeria, South Africa, and the United States | journal = Contraception | volume = 97 | issue = 1 | pages = 62–69 | date = January 2018 | pmid = 28887053 | pmc = 5732079 | doi = 10.1016/j.contraception.2017.08.015 }} which remain at nearly 50%, even in developed countries where women have access to modern contraceptives.{{cite journal | vauthors = Sedgh G, Singh S, Hussain R | title = Intended and unintended pregnancies worldwide in 2012 and recent trends | journal = Studies in Family Planning | volume = 45 | issue = 3 | pages = 301–314 | date = September 2014 | pmid = 25207494 | pmc = 4727534 | doi = 10.1111/j.1728-4465.2014.00393.x }}{{cite journal | vauthors = Finer LB, Zolna MR | title = Declines in Unintended Pregnancy in the United States, 2008-2011 | journal = The New England Journal of Medicine | volume = 374 | issue = 9 | pages = 843–852 | date = March 2016 | pmid = 26962904 | pmc = 4861155 | doi = 10.1056/NEJMsa1506575 }} Unintended pregnancies are associated with negative socioeconomic, educational, and health outcomes for women, men, and the resulting children (especially in historically marginalized communities),{{cite journal | vauthors = Singh S, Sedgh G, Hussain R | title = Unintended pregnancy: worldwide levels, trends, and outcomes | journal = Studies in Family Planning | volume = 41 | issue = 4 | pages = 241–250 | date = December 2010 | pmid = 21465725 | doi = 10.1111/j.1728-4465.2010.00250.x }}{{cite journal | vauthors = Herd P, Higgins J, Sicinski K, Merkurieva I | title = The Implications of Unintended Pregnancies for Mental Health in Later Life | journal = American Journal of Public Health | volume = 106 | issue = 3 | pages = 421–429 | date = March 2016 | pmid = 26691118 | pmc = 4815713 | doi = 10.2105/AJPH.2015.302973 }}{{cite journal | vauthors = Finer LB, Sonfield A | title = The evidence mounts on the benefits of preventing unintended pregnancy | journal = Contraception | volume = 87 | issue = 2 | pages = 126–127 | date = February 2013 | pmid = 23305754 | doi = 10.1016/j.contraception.2012.12.005 }}{{cite journal | vauthors = Gipson JD, Koenig MA, Hindin MJ | title = The effects of unintended pregnancy on infant, child, and parental health: a review of the literature | journal = Studies in Family Planning | volume = 39 | issue = 1 | pages = 18–38 | date = March 2008 | pmid = 18540521 | doi = 10.1111/j.1728-4465.2008.00148.x }}{{cite journal | vauthors = Trussell J | title = The cost of unintended pregnancy in the United States | journal = Contraception | volume = 75 | issue = 3 | pages = 168–170 | date = March 2007 | pmid = 17303484 | doi = 10.1016/j.contraception.2006.11.009 }}{{cite journal | vauthors = Wise A, Geronimus AT, Smock PJ | title = The Best of Intentions: A Structural Analysis of the Association between Socioeconomic Disadvantage and Unintended Pregnancy in a Sample of Mothers from the National Longitudinal Survey of Youth (1979) | journal = Women's Health Issues | volume = 27 | issue = 1 | pages = 5–13 | date = 2017 | pmid = 27913056 | pmc = 5219931 | doi = 10.1016/j.whi.2016.10.006 }}{{cite journal | vauthors = Trussell J, Henry N, Hassan F, Prezioso A, Law A, Filonenko A | title = Burden of unintended pregnancy in the United States: potential savings with increased use of long-acting reversible contraception | journal = Contraception | volume = 87 | issue = 2 | pages = 154–161 | date = February 2013 | pmid = 22959904 | pmc = 3659779 | doi = 10.1016/j.contraception.2012.07.016 }} and 60% of unintended pregnancies end in abortions, many of which are unsafe and can lead to women's harm or death. Therefore, the development of new male contraceptives has the potential to improve racial, economic, and gender equality across the world, advance reproductive justice and reproductive autonomy for all people, and save lives.

File:Open Vasectomy .jpeg

{{Main|Vasectomy}}

Vasectomy is surgical procedure for permanent male sterilization usually performed in a physician's office in an outpatient procedure.{{Cite book |title=Contraceptive Technology |vauthors=Hatcher RA |publisher=Managing Contraception LLC |year=2023 |isbn=978-1-284-29926-7 |edition=22nd |language=en}} During the procedure, the vasa deferentia of a patient are severed, and then tied or sealed to prevent sperm from being released during ejaculation.{{Cite web |title=Male Vasectomy Procedure {{!}} What is a Vasectomy? |url=https://www.plannedparenthood.org/learn/birth-control/vasectomy |access-date=2024-01-26 |website=www.plannedparenthood.org |language=en}} Vasectomy is an effective procedure, with less than 0.15% of partners becoming pregnant within the first 12 months after the procedure.{{Cite web |date=2020-01-23 |title=Contraceptive Effectiveness in the United States |url=https://www.guttmacher.org/fact-sheet/contraceptive-effectiveness-united-states |access-date=2023-10-12 |website=Guttmacher Institute |language=en}} Vasectomy is also a widely reliable and safe method of contraception, and complications are both rare and minor.{{cite journal | vauthors = Yang F, Li J, Dong L, Tan K, Huang X, Zhang P, Liu X, Chang D, Yu X | title = Review of Vasectomy Complications and Safety Concerns | language = English | journal = The World Journal of Men's Health | volume = 39 | issue = 3 | pages = 406–418 | date = July 2021 | pmid = 32777870 | pmc = 8255399 | doi = 10.5534/wjmh.200073 }}{{Cite web |date=2022-02-18 |title=How effective is vasectomy? | work = NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development |url=https://www.nichd.nih.gov/health/topics/vasectomy/conditioninfo/effective |access-date=2023-10-12 |language=en}} Vasectomies can be reversed, though rates of successful reversal decline as the time since vasectomy increases, and the procedure is technically difficult and often costly.{{cite journal | vauthors = Patel AP, Smith RP | title = Vasectomy reversal: a clinical update | journal = Asian Journal of Andrology | volume = 18 | issue = 3 | pages = 365–371 | date = 2016 | pmid = 26975488 | pmc = 4854082 | doi = 10.4103/1008-682x.175091 | doi-access = free }}

File:Kondom.jpg

{{Main|Condom}}

A condom is a barrier device made of latex or thin plastic film that is rolled onto an erect penis before intercourse and retains ejaculated semen, thereby preventing pregnancy.{{Cite web |title=Condoms {{!}} How to Put On a Condom Video |url=https://www.plannedparenthood.org/learn/birth-control/condom |access-date=2024-01-26 |website=www.plannedparenthood.org |language=en}} Condoms are less effective at preventing pregnancy than vasectomy or modern methods of female contraception, with a real-world failure rate of 13%. However, condoms have the advantage of providing protection against some sexually transmitted infections such as HIV/AIDS.{{Cite web |title=What are the Benefits and Advantages of Using Condoms? |url=https://www.plannedparenthood.org/learn/birth-control/condom/what-are-the-benefits-of-condoms |access-date=2023-10-12 |website=www.plannedparenthood.org |language=en}}{{cite book | vauthors = Trussell J | chapter = Contraceptive efficacy. | veditors = Hatcher RA, Trussell J, Nelson AL, Cates W, Stewart FH, Kowal D | title = Contraceptive Technology | edition = Nineteenth Revised | location = New York NY | publisher = Ardent Media | date = 2007 | chapter-url=http://www.contraceptivetechnology.com/table.html |archive-url=https://web.archive.org/web/20080531095926/http://www.contraceptivetechnology.com/table.html |archive-date=2008-05-31 |access-date=2016-10-10 }} Condoms may be combined with other forms of contraception (such as spermicide) for greater protection.{{cite journal | vauthors = Kestelman P, Trussell J | title = Efficacy of the simultaneous use of condoms and spermicides | journal = Family Planning Perspectives | volume = 23 | issue = 5 | pages = 226–7, 232 | year = 1991 | pmid = 1743276 | doi = 10.2307/2135759 | jstor = 2135759 }}

{{Main|Coitus interruptus}}

The withdrawal method, also known as coitus interruptus or pulling out, is a behavior that involves halting penile-vaginal intercourse to remove the penis out and away from the vagina prior to ejaculation.{{Cite web |title=Pull Out Method {{!}} Withdrawal Method {{!}} What is Pulling Out? |url=https://www.plannedparenthood.org/learn/birth-control/withdrawal-pull-out-method |access-date=2024-01-26 |website=www.plannedparenthood.org |language=en}}{{cite book |title=Sexuality Now: Embracing Diversity |vauthors=Carroll JL |date=2012 |publisher=Cengage Learning |isbn=978-1-111-83581-1}}{{page needed|date=August 2021}} Withdrawal is considered a less-effective contraceptive method, with typical-use failure rates around 20%. However, it requires no equipment or medical procedures.

Researchers have been working to generate novel male contraceptives with diverse mechanisms of action and possible delivery methods, including long-acting reversible contraceptives (LARCs), daily transdermal gels, daily and on-demand oral pills, monthly injectables, and implants.{{Cite web |title=What Is In Development |url=https://www.malecontraceptive.org/what-is-in-development.html |access-date=2023-10-12 |website=Male Contraceptive Initiative |language=en}}{{cite journal | vauthors = Abbe CR, Page ST, Thirumalai A | title = Male Contraception | journal = The Yale Journal of Biology and Medicine | volume = 93 | issue = 4 | pages = 603–613 | date = September 2020 | pmid = 33005125 | pmc = 7513428 }}{{cite journal | vauthors = Anderson DJ, Johnston DS | title = A brief history and future prospects of contraception | journal = Science | volume = 380 | issue = 6641 | pages = 154–158 | date = April 2023 | pmid = 37053322 | pmc = 10615352 | doi = 10.1126/science.adf9341 | s2cid = 258112296 | bibcode = 2023Sci...380..154A }} Efforts to develop male contraceptives have been ongoing for many decades, but progress has been slowed by a lack of funding and industry involvement. As of 2024, most funding for male contraceptive research is derived from government or philanthropic sources.{{Cite web | vauthors = Wang CC |title=Male Birth Control Is in Development, but Barriers Still Stand in the Way |url=https://www.scientificamerican.com/article/male-birth-control-is-in-development-but-barriers-still-stand-in-the-way/ |access-date=2023-10-12 |website=Scientific American |language=en}}{{Cite journal | vauthors = Vitale G | date = November 2022 | volume = 100 | issue = 41 |title=Birth control for men |url=https://cen.acs.org/pharmaceuticals/drug-development/Birth-control-men-male-contraception/100/i41 |access-date=2023-10-12 | journal = Chemical & Engineering News |language=en}}{{Cite web | vauthors = Sitruk-Ware R |date=2018-05-11 |title=Getting contraceptives for men to the market will take pharma's help |url=https://www.statnews.com/2018/05/11/contraceptives-for-men-pharma/ |access-date=2023-10-12 |website=STAT |language=en-US}}{{Cite web |title=G-Finder data portal |url=https://gfinderdata.policycuresresearch.org/pages/data-visualisations/allSexualReproductiveHealthDiseases |access-date=Oct 12, 2023 |website=Policy Cures Research}}

Novel male contraceptives could work by blocking various steps of the sperm development process, blocking sperm release, or interfering with any of the sperm functions necessary to reach and fertilize an egg in the female reproductive tract.{{Cite web |title=Mechanisms of Male Contraception |url=https://www.malecontraceptive.org/mechanisms-of-male-contraception.html |access-date=2023-10-12 |website=Male Contraceptive Initiative |language=en}} Advantages and disadvantages of each of these approaches will be discussed below, along with relevant examples of products in development.

These methods work by preventing the testes from producing sperm, or interfering with sperm production in a way that leads to the production of nonfunctional sperm.{{Cite web |title=Spermatogenesis – Mechanisms of Male Contraception |url=http://www.malecontraceptive.org/1/post/2019/02/spermatogenesis-mechanisms-of-male-contraception.html |access-date=2024-01-27 |website=Male Contraceptive Initiative |language=en}} This approach can be accomplished by either hormonal or nonhormonal small-molecule drugs, or potentially by thermal methods. The effectiveness of contraceptives in this group can be easily assessed microscopically, by measuring sperm count or abnormalities in sperm shape, but because spermatogenesis takes approximately 70 days to complete,{{cite journal | vauthors = Amann RP | title = The cycle of the seminiferous epithelium in humans: a need to revisit? | journal = Journal of Andrology | volume = 29 | issue = 5 | pages = 469–487 | date = 10 September 2008 | pmid = 18497337 | doi = 10.2164/jandrol.107.004655 }} these methods are likely to require approximately three months of use before they become effective, and approaches that halt sperm production at an early stage of the process may result in reduced testicular size. Methods have been suggested in the 1980s.{{cite journal | vauthors = Palacios A, McClure RD, Campfield A, Swerdloff RS | title = Effect of testosterone enanthate on testis size | journal = The Journal of Urology | volume = 126 | issue = 1 | pages = 46–48 | date = July 1981 | pmid = 6788960 | doi = 10.1016/s0022-5347(17)54372-4 }}

Hormonal contraceptives for men work similarly to hormonal female methods, using steroids to interrupt the hypothalamic-pituitary-gonadal axis and thereby block sperm production. Administering external androgens and progestogens suppresses secretion of the gonadotropins LH and FSH, which impairs testosterone production and sperm generation in the testes, leading to reduced sperm counts in ejaculates within 4–12 weeks of use.{{cite journal | vauthors = Page ST, Blithe D, Wang C | title = Hormonal Male Contraception: Getting to Market | journal = Frontiers in Endocrinology | volume = 13 | pages = 891589 | date = 2022 | pmid = 35721718 | pmc = 9203677 | doi = 10.3389/fendo.2022.891589 | doi-access = free }} However, since the contraceptives contain testosterone or related androgens, the levels of androgens in the blood remain relatively constant, thereby limiting side effects and maintaining masculine secondary sex characteristics like muscle mass and hair growth.

Multiple methods of male hormonal contraception have been tested in clinical trials since the 1990s, and although one trial was halted early, leading to a large amount of press attention,{{cite journal | vauthors = 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 | title = Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 101 | issue = 12 | pages = 4779–4788 | date = December 2016 | pmid = 27788052 | doi = 10.1210/jc.2016-2141 | doi-access = free }}{{cite journal | vauthors = Abbe C, Roxby AC | title = Assessing safety in hormonal male contraception: a critical appraisal of adverse events reported in a male contraceptive trial | journal = BMJ Sexual & Reproductive Health | volume = 46 | issue = 2 | pages = 139–146 | date = April 2020 | pmid = 31754066 | pmc = 8029306 | doi = 10.1136/bmjsrh-2018-200206 }}{{Cite news |date=3 November 2016 |title=Male Birth Control Study Killed After Men Report Side Effects |url=https://www.npr.org/sections/health-shots/2016/11/03/500549503/male-birth-control-study-killed-after-men-complain-about-side-effects |access-date=18 December 2023 |work=National Public Radio}}{{Cite web | vauthors = Scutti S |date=2016-10-31 |title=Male birth control shot found effective, but side effects cut study short |url=https://www.cnn.com/2016/10/30/health/male-birth-control/index.html |access-date=2023-12-18 |website=CNN |language=en}}{{Cite web | vauthors = Hafner J | date = November 2016 |title=Male birth control study nixed after men can't handle side effects women face daily |url=https://www.usatoday.com/story/news/nation-now/2016/11/01/male-birth-control-study-nixed-after-men-cant-handle-side-effects-women-face-daily/93088124/ |access-date=2023-12-18 |website=USA Today |language=en-US}} most hormonal male contraceptives have been found to be effective, reversible, and well-tolerated.{{cite journal | vauthors = | title = Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility | journal = Lancet | volume = 336 | issue = 8721 | pages = 955–959 | date = October 1990 | pmid = 1977002 | doi = 10.1016/0140-6736(90)92416-F | s2cid = 25825354 }}{{cite journal | title = Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men | journal = Fertility and Sterility | volume = 65 | issue = 4 | pages = 821–829 | date = April 1996 | pmid = 8654646 | doi = 10.1016/S0015-0282(16)58221-1 | author1 = World Health Organization Task Force on Methods for the Regulation of Male Fertility }}{{cite journal | vauthors = McLachlan RI, McDonald J, Rushford D, Robertson DM, Garrett C, Baker HW | title = Efficacy and acceptability of testosterone implants, alone or in combination with a 5alpha-reductase inhibitor, for male hormonal contraception | journal = Contraception | volume = 62 | issue = 2 | pages = 73–78 | date = August 2000 | pmid = 11102590 | doi = 10.1016/S0010-7824(00)00139-6 }}{{cite journal | vauthors = Turner L, Conway AJ, Jimenez M, Liu PY, Forbes E, McLachlan RI, Handelsman DJ | title = Contraceptive efficacy of a depot progestin and androgen combination in men | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 10 | pages = 4659–4667 | date = October 2003 | pmid = 14557437 | doi = 10.1210/jc.2003-030107 }}{{cite journal | vauthors = Gu Y, Liang X, Wu W, Liu M, Song S, Cheng L, Bo L, Xiong C, Wang X, Liu X, Peng L, Yao K | title = Multicenter contraceptive efficacy trial of injectable testosterone undecanoate in Chinese men | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 94 | issue = 6 | pages = 1910–1915 | date = June 2009 | pmid = 19293262 | doi = 10.1210/jc.2008-1846 | doi-access = free }}{{cite journal | vauthors = Gu YQ, Wang XH, Xu D, Peng L, Cheng LF, Huang MK, Huang ZJ, Zhang GY | title = A multicenter contraceptive efficacy study of injectable testosterone undecanoate in healthy Chinese men | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 2 | pages = 562–568 | date = February 2003 | pmid = 12574181 | doi = 10.1210/jc.2002-020447 | doi-access = free }}

{{as of|2024}}, the following hormonal male contraceptive products are in clinical trials:

• NES/T (Nesterone/Testosterone gel) is a transdermal gel that users apply to the upper arms and shoulders once daily.{{Cite web |date=2023-03-01 |title=With a New Gel, the Future of Male Birth Control Looks Bright |url=https://news.yahoo.com/gel-future-male-birth-control-140000146.html |access-date=2023-10-09 |website=Yahoo News |language=en-US}}{{Cite web |date=2022-02-22 |title=What Happens When Men Take Hormonal Birth Control? |url=https://www.cosmopolitan.com/health-fitness/a38954452/male-contraceptive-gel-trial/ |access-date=2023-10-12 |website=Cosmopolitan |language=en-US}} Developed as a collaboration between the NICHD and Population Council, NES/T is in a phase II clinical trial,{{ClinicalTrialsGov|NCT03452111|Study of Daily Application of Nestorone (NES) and Testosterone (T) Combination Gel for Male Contraception}} where it is being evaluated for safety and efficacy, with healthy couples relying on it as their only means of birth control.{{cite journal | vauthors = Amory JK, Blithe DL, Sitruk-Ware R, Swerdloff RS, Bremner WJ, Dart C, Liu PY, Thirumalai A, Nguyen BT, Anawalt BD, Lee MS, Page ST, Wang C | title = Design of an international male contraceptive efficacy trial using a self-administered daily transdermal gel containing testosterone and segesterone acetate (Nestorone) | journal = Contraception | volume = 124 | pages = 110064 | date = August 2023 | pmid = 37210024 | doi = 10.1016/j.contraception.2023.110064 | s2cid = 258800752 | doi-access = free }}{{cite journal | vauthors = Ilani N, Roth MY, Amory JK, Swerdloff RS, Dart C, Page ST, Bremner WJ, Sitruk-Ware R, Kumar N, Blithe DL, Wang C | title = A new combination of testosterone and nestorone transdermal gels for male hormonal contraception | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 97 | issue = 10 | pages = 3476–3486 | date = October 2012 | pmid = 22791756 | pmc = 3462927 | doi = 10.1210/jc.2012-1384 }}{{cite journal | vauthors = Roth MY, Shih G, Ilani N, Wang C, Page ST, Bremner WJ, Swerdloff RS, Sitruk-Ware R, Blithe DL, Amory JK | title = Acceptability of a transdermal gel-based male hormonal contraceptive in a randomized controlled trial | journal = Contraception | volume = 90 | issue = 4 | pages = 407–412 | date = October 2014 | pmid = 24981149 | pmc = 4269220 | doi = 10.1016/j.contraception.2014.05.013 }}{{cite journal | vauthors = Anawalt BD, Roth MY, Ceponis J, Surampudi V, Amory JK, Swerdloff RS, Liu PY, Dart C, Bremner WJ, Sitruk-Ware R, Kumar N, Blithe DL, Page ST, Wang C | title = Combined nestorone-testosterone gel suppresses serum gonadotropins to concentrations associated with effective hormonal contraception in men | journal = Andrology | volume = 7 | issue = 6 | pages = 878–887 | date = November 2019 | pmid = 30969032 | pmc = 6768743 | doi = 10.1111/andr.12603 }}
• DMAU (Dimethandrolone undecanoate) is a steroid-based contraceptive molecule with both androgenic and progestational activities, which allows it to be used as a single agent. DMAU has been tested in clinical trials in both oral{{Cite journal | vauthors = Jacobsohn T, Nguyen B, Fernando F, Brown J, Blithe D, Lee M, Yuen F, Swerdloff R, Liu P, Wang C, Farrant M, Anawalt B, Thirumalai A, Bremner W, Page S |date= 2022|title=ODP644 Oral Dosing of Progestogenic Androgens for Male Contraception Show Low Serum Testosterone and High Acceptability in Placebo-Controlled Trials |journal=Journal of the Endocrine Society |volume=6 |issue=Supplement_1 |pages=A676 |doi=10.1210/jendso/bvac150.1398 |doi-access=free |pmc=9625429 }} and injectable forms.{{ClinicalTrialsGov|NCT02927210|Injectable DMAU for Male Contraception in Healthy Male Volunteers (CCN015) (DMAU)}}
• 11β-MNTDC is another dual-function molecule (progestogenic androgen) in clinical development as an oral contraceptive for men.{{cite journal | vauthors = Nguyen BT, Yuen F, Farrant M, Thirumalai A, Fernando F, Amory JK, Swerdloff RS, Anawalt BD, Blithe DL, Long JE, Liu PY, Page ST, Wang C | title = Acceptability of the oral hormonal male contraceptive prototype, 11β-methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC), in a 28-day placebo-controlled trial | journal = Contraception | volume = 104 | issue = 5 | pages = 531–537 | date = November 2021 | pmid = 34153318 | pmc = 8995005 | doi = 10.1016/j.contraception.2021.06.009 }}

Some anabolic steroids may exhibit suppressive effects on spermatogenesis, but none are being investigated for use as a male contraceptive.{{cite journal | vauthors = El Osta R, Almont T, Diligent C, Hubert N, Eschwège P, Hubert J | title = Anabolic steroids abuse and male infertility | journal = Basic and Clinical Andrology | volume = 26 | pages = 2 | date = 2016 | pmid = 26855782 | pmc = 4744441 | doi = 10.1186/s12610-016-0029-4 | doi-access = free }}

Non-hormonal contraceptives for men are a diverse group of molecules that act by inhibiting any of the many proteins involved in sperm production, release, or function. Because sperm cells are highly specialized, they express many proteins that are rare in the rest of the human body.{{cite journal | vauthors = Chen SR, Batool A, Wang YQ, Hao XX, Chang CS, Cheng CY, Liu YX | title = The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon's head to tail | journal = Cell Death & Disease | volume = 7 | issue = 11 | pages = e2472 | date = November 2016 | pmid = 27831554 | pmc = 5260884 | doi = 10.1038/cddis.2016.344 }}{{cite journal | vauthors = Zheng LP, Wang HF, Li BM, Zeng XH | title = Sperm-specific ion channels: targets holding the most potential for male contraceptives in development | journal = Contraception | volume = 88 | issue = 4 | pages = 485–491 | date = October 2013 | pmid = 23845210 | doi = 10.1016/j.contraception.2013.06.002 }}{{cite journal | vauthors = Robertson MJ, Kent K, Tharp N, Nozawa K, Dean L, Mathew M, Grimm SL, Yu Z, Légaré C, Fujihara Y, Ikawa M, Sullivan R, Coarfa C, Matzuk MM, Garcia TX | title = Large-scale discovery of male reproductive tract-specific genes through analysis of RNA-seq datasets | journal = BMC Biology | volume = 18 | issue = 1 | pages = 103 | date = August 2020 | pmid = 32814578 | pmc = 7436996 | doi = 10.1186/s12915-020-00826-z | doi-access = free }} This suggests the possibility that non-hormonal contraceptives that specifically block these sperm proteins could have fewer side effects than hormonal contraceptives, since sex steroid receptors are found in tissues throughout the body.{{cite journal | vauthors = Johnston DS, Goldberg E | title = Preclinical contraceptive development for men and women | journal = Biology of Reproduction | volume = 103 | issue = 2 | pages = 147–156 | date = August 2020 | pmid = 32561907 | pmc = 7496738 | doi = 10.1093/biolre/ioaa076 }} Non-hormonal contraceptives can work by blocking spermatogenesis, sperm release, or mature sperm function, resulting in products with a wide variety of usage patterns, from slow onset to on-demand usage.{{Cite web |title=Mechanisms of Male Contraception |url=https://www.malecontraceptive.org/mechanisms-of-male-contraception.html |access-date=2024-01-30 |website=Male Contraceptive Initiative |language=en}} Contraceptives targeting mature sperm functions could even be taken by both sperm-producing and egg producing people. Challenges of non-hormonal contraceptive development include bioavailability and delivery past the blood-testis barrier.{{cite journal | vauthors = Cheng CY, Mruk DD | title = The blood-testis barrier and its implications for male contraception | journal = Pharmacological Reviews | volume = 64 | issue = 1 | pages = 16–64 | date = January 2012 | pmid = 22039149 | pmc = 3250082 | doi = 10.1124/pr.110.002790 | veditors = Sibley DR }}

{{as of|2024}}, the following non-hormonal male contraceptive product is in clinical trials:

• YCT529, a retinoic acid receptor antagonist, began a Phase 1 clinical trial in 2023{{ClinicalTrialsGov|NCT06094283|First in Human Study Evaluating Single Ascending Oral Doses of YCT-529 in Healthy Males}} organized by the US startup YourChoice Pharmaceuticals. The clinical test on humans is done by the UK company Quotient Sciences.{{cite press release |title=A non-hormonal pill could soon expand men's birth control options |url=https://www.acs.org/pressroom/newsreleases/2022/march/non-hormonal-pill-could-soon-expand-mens-birth-control-options.html |publisher=American Chemical Society |date=23 March 2022 }}{{Cite web |date=13 December 2023 |title=YourChoice Therapeutics begins first-in-human trial for male birth control pill |url=https://www.pharmacy.umn.edu/news/yourchoice-therapeutics-begins-first-human-trial-male-birth-control-pill |access-date=2023-12-18 |website=University of Minnesota College of Pharmacy |language=en}}{{cite web|url=https://www.biotechniques.com/drug-discovery-development/is-that-an-oral-male-contraceptive-on-the-horizon/|title=Is that an oral male contraceptive on the horizon?|date=30 March 2022 }} It was originally planned in 2022 instead of 2023, with an expected marketing date 5 years later.{{cite web|url=https://www.biotechniques.com/drug-discovery-development/is-that-an-oral-male-contraceptive-on-the-horizon/|title=Is that an oral male contraceptive on the horizon?|date=30 March 2022 }}

{{as of|2024}}, the following non-hormonal male contraceptive products are in preclinical development:

• BRDT inhibitors such as JQ1 have been shown to produce reversible sterility in male mice by blocking chromatin remodeling,{{cite press release |title=A male contraceptive pill in the making? |url=https://www.eurekalert.org/news-releases/707224 |work=EurekAlert! |publisher=Dana-Farber Cancer Institute |date=16 August 2012 }}{{cite journal | vauthors = Matzuk MM, McKeown MR, Filippakopoulos P, Li Q, Ma L, Agno JE, Lemieux ME, Picaud S, Yu RN, Qi J, Knapp S, Bradner JE | title = Small-molecule inhibition of BRDT for male contraception | journal = Cell | volume = 150 | issue = 4 | pages = 673–684 | date = August 2012 | pmid = 22901802 | pmc = 3420011 | doi = 10.1016/j.cell.2012.06.045 }}{{cite journal | vauthors = Wisniewski A, Georg GI | title = BET proteins: Investigating BRDT as a potential target for male contraception | journal = Bioorganic & Medicinal Chemistry Letters | volume = 30 | issue = 6 | pages = 126958 | date = March 2020 | pmid = 32019712 | pmc = 7023680 | doi = 10.1016/j.bmcl.2020.126958 }} and efforts to develop and evaluate new small-molecule inhibitors with improved pharmacokinetic properties are ongoing.{{cite journal | vauthors = Yu Z, Ku AF, Anglin JL, Sharma R, Ucisik MN, Faver JC, Li F, Nyshadham P, Simmons N, Sharma KL, Nagarajan S, Riehle K, Kaur G, Sankaran B, Storl-Desmond M, Palmer SS, Young DW, Kim C, Matzuk MM | title = Discovery and characterization of bromodomain 2-specific inhibitors of BRDT | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 118 | issue = 9 | date = March 2021 | pmid = 33637650 | pmc = 7936271 | doi = 10.1073/pnas.2021102118 | bibcode = 2021PNAS..11821102Y | doi-access = free }}{{cite journal | vauthors = Modukuri RK, Yu Z, Tan Z, Ta HM, Ucisik MN, Jin Z, Anglin JL, Sharma KL, Nyshadham P, Li F, Riehle K, Faver JC, Duong K, Nagarajan S, Simmons N, Palmer SS, Teng M, Young DW, Yi JS, Kim C, Matzuk MM | title = Discovery of potent BET bromodomain 1 stereoselective inhibitors using DNA-encoded chemical library selections | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 119 | issue = 22 | pages = e2122506119 | date = May 2022 | pmid = 35622893 | pmc = 9295786 | doi = 10.1073/pnas.2122506119 | doi-access = free | bibcode = 2022PNAS..11922506M }}
• Several testis-specific kinases have been linked to male infertility in mice and/or humans, and inhibitors of several of these kinases, such as the testis-specific serine kinases{{cite journal | vauthors = Salicioni AM, Gervasi MG, Sosnik J, Tourzani DA, Nayyab S, Caraballo DA, Visconti PE | title = Testis-specific serine kinase protein family in male fertility and as targets for non-hormonal male contraception† | journal = Biology of Reproduction | volume = 103 | issue = 2 | pages = 264–274 | date = August 2020 | pmid = 32337545 | pmc = 7401350 | doi = 10.1093/biolre/ioaa064 }}{{cite journal | vauthors = Long JE, Lee MS, Blithe DL | title = Male Contraceptive Development: Update on Novel Hormonal and Nonhormonal Methods | journal = Clinical Chemistry | volume = 65 | issue = 1 | pages = 153–160 | date = January 2019 | pmid = 30602479 | doi = 10.1373/clinchem.2018.295089 }}{{cite journal | vauthors = Kadiyska T, Tourtourikov I, Dabchev K, Madzharova D, Tincheva S, Spandidos DA, Zoumpourlis V | title = Role of testis‑specific serine kinase 1B in undiagnosed male infertility | journal = Molecular Medicine Reports | volume = 25 | issue = 6 | date = June 2022 | pmid = 35485285 | pmc = 9073834 | doi = 10.3892/mmr.2022.12720 }} and Cyclin-dependent kinase 2{{cite journal | vauthors = Faber EB, Wang N, Georg GI | title = Review of rationale and progress toward targeting cyclin-dependent kinase 2 (CDK2) for male contraception† | journal = Biology of Reproduction | volume = 103 | issue = 2 | pages = 357–367 | date = August 2020 | pmid = 32543655 | doi = 10.1093/biolre/ioaa107 | pmc = 7523694 }}{{cite journal | vauthors = Faber EB, Sun L, Tang J, Roberts E, Ganeshkumar S, Wang N, Rasmussen D, Majumdar A, Hirsch LE, John K, Yang A, Khalid H, Hawkinson JE, Levinson NM, Chennathukuzhi V, Harki DA, Schönbrunn E, Georg GI | title = Development of allosteric and selective CDK2 inhibitors for contraception with negative cooperativity to cyclin binding | journal = Nature Communications | volume = 14 | issue = 1 | pages = 3213 | date = June 2023 | pmid = 37270540 | doi = 10.1038/s41467-023-38732-x | pmc = 10239507 | bibcode = 2023NatCo..14.3213F }}{{cite journal | vauthors = Faber EB, Wang N, John K, Sun L, Wong HL, Burban D, Francis R, Tian D, Hong KH, Yang A, Wang L, Elsaid M, Khalid H, Levinson NM, Schönbrunn E, Hawkinson JE, Georg GI | title = Screening through Lead Optimization of High Affinity, Allosteric Cyclin-Dependent Kinase 2 (CDK2) Inhibitors as Male Contraceptives That Reduce Sperm Counts in Mice | journal = Journal of Medicinal Chemistry | volume = 66 | issue = 3 | pages = 1928–1940 | date = February 2023 | pmid = 36701569 | doi = 10.1021/acs.jmedchem.2c01731 | s2cid = 256302901 | pmc = 11556300 }} are in medicinal chemistry development.
• The retinoic acid signalling pathway has been known since the late 1950s to be necessary for spermatogenesis in rodents and humans, and various attempts have been made to develop male contraceptives that work by blocking different enzymes in this pathway.{{cite journal |vauthors=Kean S |date=October 2012 |title=Contraception research. Reinventing the pill: male birth control |journal=Science |volume=338 |issue=6105 |pages=318–320 |doi=10.1126/science.338.6105.318 |pmid=23087225}}{{cite journal |vauthors=Noman MA, Kyzer JL, Chung SS, Wolgemuth DJ, Georg GI |date=August 2020 |title=Retinoic acid receptor antagonists for male contraception: current status† |journal=Biology of Reproduction |volume=103 |issue=2 |pages=390–399 |doi=10.1093/biolre/ioaa122 |pmc=7401398 |pmid=32671394}}{{cite journal |vauthors=Chung SS, Wang X, Roberts SS, Griffey SM, Reczek PR, Wolgemuth DJ |date=June 2011 |title=Oral administration of a retinoic Acid receptor antagonist reversibly inhibits spermatogenesis in mice |journal=Endocrinology |volume=152 |issue=6 |pages=2492–2502 |doi=10.1210/en.2010-0941 |pmc=3100616 |pmid=21505053}}{{Cite web | vauthors = Anthes E | date = 3 August 2017 |title=Why We Can't Have the Male Pill |url=https://www.bloomberg.com/news/features/2017-08-03/why-we-can-t-have-the-male-pill |access-date=2024-05-07 | work = Bloomberg }}{{cite journal |vauthors=Thirumalai A, Amory JK |date=June 2021 |title=Emerging approaches to male contraception |journal=Fertility and Sterility |volume=115 |issue=6 |pages=1369–1376 |doi=10.1016/j.fertnstert.2021.03.047 |pmc=8169637 |pmid=33931201}} As of 2024, efforts are underway to develop inhibitors of ALDH1A2, Retinoic acid receptor alpha,{{cite journal | vauthors = Noman MA, Kyzer JL, Chung SS, Wolgemuth DJ, Georg GI | title = Retinoic acid receptor antagonists for male contraception: current status† | journal = Biology of Reproduction | volume = 103 | issue = 2 | pages = 390–399 | date = August 2020 | pmid = 32671394 | pmc = 7401398 | doi = 10.1093/biolre/ioaa122 }}{{cite journal | vauthors = Kyzer JL, Noman MA, Cuellar RA, Chung SS, Maitra S, Naqvi T, Hawkinson JE, Wolgemuth DJ, Georg GI | title = Investigation of selective retinoic acid receptor alpha antagonist ER-50891 and related analogs for male contraception | journal = Archiv der Pharmazie | volume = 356 | issue = 7 | pages = e2300031 | date = July 2023 | pmid = 37154197 | doi = 10.1002/ardp.202300031 }} and SMRT.{{cite journal | vauthors = Hong SH, Castro G, Wang D, Nofsinger R, Kane M, Folias A, Atkins AR, Yu RT, Napoli JL, Sassone-Corsi P, de Rooij DG, Liddle C, Downes M, Evans RM | title = Targeting nuclear receptor corepressors for reversible male contraception | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 121 | issue = 9 | pages = e2320129121 | date = February 2024 | pmid = 38377195 | pmc = 10907271 | doi = 10.1073/pnas.2320129121 | bibcode = 2024PNAS..12120129H }}

New male contraceptive methods could be available before 2030, assuming smooth development and clinical trials.{{cite journal |last1=Kim |first1=Jongwon |last2=So |first2=Byeongchan |last3=Heo |first3=Yongki |last4=So |first4=Hongyun |last5=Jo |first5=Jung Ki |title=Advances in Male Contraception: When Will the Novel Male Contraception be Available? |journal=World Journal of Men's Health |volume=42 |issue=3 |pages=487–501 |date=July 2024 |doi=10.5534/wjmh.230118 |pmid=38164023 |url=https://doi.org/10.5534/wjmh.230118|pmc=11216971 }}

{{Main|Heat-based contraception}}Prolonged testicular heating had been shown to reduce sperm counts in 1941,{{cite journal | vauthors = Macleod J, Hotchkiss RS |title=The Effect of Hyperpyrexia Upon Spermatozoa Counts in Men |journal=Endocrinology |date=May 1941 |volume=28 |issue=5 |pages=780–784 |doi=10.1210/endo-28-5-780 }} considered as a method of birth control after 1968 and in the 1980s{{cite journal | vauthors = Kandeel FR, Swerdloff RS | title = Role of temperature in regulation of spermatogenesis and the use of heating as a method for contraception | journal = Fertility and Sterility | volume = 49 | issue = 1 | pages = 1–23 | date = January 1988 | pmid = 3275550 | doi = 10.1016/S0015-0282(16)59640-X | doi-access = free }}{{cite journal | vauthors = Robinson D, Rock J, Menkin MF | title = Control of human spermatogenesis by induced changes of intrascrotal temperature | journal = JAMA | volume = 204 | issue = 4 | pages = 290–297 | date = April 1968 | pmid = 5694622 | doi = 10.1001/jama.1968.03140170006002 }} No modern clinical trials have demonstrated the safety, contraceptive effectiveness, or reversibility of this approach. Various devices are in early preclinical stages of development, and as of 2017 some approaches have been used by men through self-experimentation.{{cite journal | vauthors = Soufir JC | title = Hormonal, chemical and thermal inhibition of spermatogenesis: contribution of French teams to international data with the aim of developing male contraception in France | journal = Basic and Clinical Andrology | volume = 27 | pages = 3 | date = 2017 | pmid = 28101363 | pmc = 5237323 | doi = 10.1186/s12610-016-0047-2 | doi-access = free }}{{Cite web | vauthors = Labourie P, Ferrari B |date=2023-08-30 |title=I Made My Own DIY Birth Control By Pushing My Balls Into My Body |url=https://www.vice.com/en/article/heat-based-contraception-for-men/ |access-date=2023-10-13 |website=Vice |language=en}} As of 2015, the mechanism by which heating disrupts spermatogenesis was still not fully understood.{{cite journal | vauthors = Durairajanayagam D, Agarwal A, Ong C | title = Causes, effects and molecular mechanisms of testicular heat stress | journal = Reproductive Biomedicine Online | volume = 30 | issue = 1 | pages = 14–27 | date = January 2015 | pmid = 25456164 | doi = 10.1016/j.rbmo.2014.09.018 | doi-access = free }} There have been theoretical concerns that prolonged heating could increase the risk of testicular cancer since the inborn birth defect of cryptorchidism carries a risk of testicular cancer{{cite journal | vauthors = Wood HM, Elder JS | title = Cryptorchidism and testicular cancer: separating fact from fiction | journal = The Journal of Urology | volume = 181 | issue = 2 | pages = 452–461 | date = February 2009 | pmid = 19084853 | doi = 10.1016/j.juro.2008.10.074 }} or that heating could damage sperm DNA, resulting in harm to potential offspring.{{cite journal | vauthors = Ahmad G, Moinard N, Esquerré-Lamare C, Mieusset R, Bujan L | title = Mild induced testicular and epididymal hyperthermia alters sperm chromatin integrity in men | journal = Fertility and Sterility | volume = 97 | issue = 3 | pages = 546–553 | date = March 2012 | pmid = 22265039 | doi = 10.1016/j.fertnstert.2011.12.025 | doi-access = free }}

These approaches work by either physically or chemically preventing the emission of sperm during ejaculation, and are likely to be effective on-demand.

α1-adrenoceptor antagonists and P2X1 antagonists have been shown to inhibit smooth muscle contractions in the vas deferens during ejaculation, and therefore prevent the release of semen and sperm while maintaining the sensation of orgasm.{{cite journal | vauthors = White CW, Choong YT, Short JL, Exintaris B, Malone DT, Allen AM, Evans RJ, Ventura S | title = Male contraception via simultaneous knockout of α1A-adrenoceptors and P2X1-purinoceptors in mice | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 51 | pages = 20825–20830 | date = December 2013 | pmid = 24297884 | pmc = 3870707 | doi = 10.1073/pnas.1318624110 | doi-access = free }}{{cite journal | vauthors = Bennetts FM, Mobbs JI, Ventura S, Thal DM | title = The P2X1 receptor as a therapeutic target | journal = Purinergic Signalling | volume = 18 | issue = 4 | pages = 421–433 | date = December 2022 | pmid = 35821454 | pmc = 9832217 | doi = 10.1007/s11302-022-09880-4 }} Various molecules in these categories are under consideration as possible on-demand male contraceptives.

• Silodosin and Tamsulosin are α1-adrenoceptor antagonists approved to treat Benign Prostatic Hyperplasia, and their ejaculation-blocking effects have been evaluated in humans.{{cite journal | vauthors = Bhat GS, Shastry A | title = 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 | journal = World Journal of Urology | volume = 38 | issue = 3 | pages = 747–751 | date = March 2020 | pmid = 31076850 | doi = 10.1007/s00345-019-02806-7 | s2cid = 149444504 }}{{cite journal | vauthors = Kobayashi K, Masumori N, Hisasue S, Kato R, Hashimoto K, Itoh N, Tsukamoto T | title = Inhibition of Seminal emission is the main cause of anejaculation induced by a new highly selective alpha1A-blocker in normal volunteers | journal = The Journal of Sexual Medicine | volume = 5 | issue = 9 | pages = 2185–2190 | date = September 2008 | pmid = 18399947 | doi = 10.1111/j.1743-6109.2008.00779.x }}{{cite journal | vauthors = Kobayashi K, Masumori N, Kato R, Hisasue S, Furuya R, Tsukamoto T | title = Orgasm is preserved regardless of ejaculatory dysfunction with selective alpha1A-blocker administration | journal = International Journal of Impotence Research | volume = 21 | issue = 5 | pages = 306–310 | date = September 2009 | pmid = 19536124 | doi = 10.1038/ijir.2009.27 | pmc = 2834370 }}{{cite journal | vauthors = Capogrosso P, Serino A, Ventimiglia E, Boeri L, Dehò F, Damiano R, Briganti A, Montorsi F, Salonia A | title = Effects of silodosin on sexual function - realistic picture from the everyday clinical practice | journal = Andrology | volume = 3 | issue = 6 | pages = 1076–1081 | date = November 2015 | pmid = 26446512 | doi = 10.1111/andr.12095 }}{{cite web |date=10 January 2010 |title=CHMP Assessment Report for Silodyx (International Nonproprietary Name: silodosin) |url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001209/WC500074188.pdf |publisher=Europeans Medicine Agency |access-date=7 November 2014 |archive-date=4 March 2016 |archive-url=https://web.archive.org/web/20160304050256/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001209/WC500074188.pdf |url-status=dead }} A patent for their use as contraceptives was filed in 2023 and approved in 2024.{{Cite patent|country = US | number = 20230145374 |title=Non-hormonal compositions and methods for male contraception | inventor = El Glaoui G, El Glaoui M, Perrin P, Droupy S, Agathon-Meriau V | assign = Laboratoires Majorelle Pharmajor International Laboratoires Major SAS | gdate = 9 April 2024|url=https://patents.google.com/patent/US20230145374A1/en}} Other α1-adrenoceptor antagonists such as phenoxybenzamine have shown inhibition of ejaculation as a side effect, and have been investigated as potential male contraceptives, but work on these molecules is not active as of 2024.{{Cite web |title=Clean Sheets Pill |url=https://www.parsemus.org/humanhealth/clean-sheets-pill/ |access-date=2024-05-11 |website=Parsemus Foundation |language=en-US}}{{cite journal | vauthors = Greenberg HR, Carrillo C | title = Thioridazine-induced inhibition of masturbatory ejaculation in an adolescent | journal = The American Journal of Psychiatry | volume = 124 | issue = 7 | pages = 991–993 | date = January 1968 | pmid = 5688684 | doi = 10.1176/ajp.124.7.991 }}{{cite journal | vauthors = Homonnai ZT, Shilon M, Paz GF | title = Phenoxybenzamine--an effective male contraceptive pill | journal = Contraception | volume = 29 | issue = 5 | pages = 479–491 | date = May 1984 | pmid = 6430643 | doi = 10.1016/0010-7824(84)90022-2 }}{{cite journal | vauthors = Kjaergaard N, Kjaergaard B, Lauritsen JG | title = Prazosin, an adrenergic blocking agent inadequate as male contraceptive pill | journal = Contraception | volume = 37 | issue = 6 | pages = 621–629 | date = June 1988 | pmid = 2899490 | doi = 10.1016/0010-7824(88)90008-X }}{{cite journal | vauthors = Amobi NI, Smith IC | title = Differential inhibition in the human vas deferens by phenoxybenzamine: a possible mechanism for its contraceptive action | journal = Journal of Reproduction and Fertility | volume = 103 | issue = 2 | pages = 215–221 | date = March 1995 | pmid = 7616492 | doi = 10.1530/jrf.0.1030215 }}{{cite journal | vauthors = Amobi N, Guillebaud J, Kaisary A, Lloyd-Davies RW, Turner E, Smith IC | title = Contractile actions of imidazoline alpha-adrenoceptor agonists and effects of noncompetitive alpha1-adrenoceptor antagonists in human vas deferens | journal = European Journal of Pharmacology | volume = 462 | issue = 1–3 | pages = 169–177 | date = February 2003 | pmid = 12591110 | doi = 10.1016/S0014-2999(03)01346-3 }}
• Novel small molecule P2X1 antagonists are also in early screening and development as potential ejaculation blockers as of 2024.{{cite journal | vauthors = Mathiew M, Dennis BM, Bennetts F, Su NN, Nguyen N, Botteon A, Baell JB, Ventura S | title = Synthesis of 2-phenyl-5,6,7,8-tetrahydroquinoxaline derivatives and screening for P2X1-purinoceptor antagonist activity in isolated preparations of rat vas deferens, for translation into a male contraceptive† | journal = Biology of Reproduction | volume = 103 | issue = 2 | pages = 323–332 | date = August 2020 | pmid = 32648904 | pmc = 7526726 | doi = 10.1093/biolre/ioaa117 }}{{cite journal | vauthors = Eise NT, Simpson JS, Thompson PE, Ventura S | title = Aqueous extracts of Urtica dioica (stinging nettle) leaf contain a P2-purinoceptor antagonist-Implications for male fertility | journal = PLOS ONE | volume = 17 | issue = 7 | pages = e0271735 | date = 2022-07-28 | pmid = 35900970 | pmc = 9333203 | doi = 10.1371/journal.pone.0271735 | bibcode = 2022PLoSO..1771735E | doi-access = free | veditors = Quintas LE }}

{{Main|Vas-occlusive contraception}}

File:Vas-occlusive Contraception Diagram.svg

Vas-occlusive contraception is a form of male contraception that blocks sperm transport in the vas deferens, the tubes that carry sperm from the epididymis to the ejaculatory ducts.

Vas-occlusive contraception provides a contraceptive effect through physical blockage of the vas deferens, the duct connecting the epididymis to the urethra. While a vasectomy excises, or removes, a piece of each vas deferens and occludes the remaining open ends of the duct, vas-occlusive methods aim to block the duct while leaving it intact. Vas-occlusive methods generally aim to create long-acting reversible options, through a second procedure that removes the blockage.{{Cite web |title=Sperm Transport – Mechanisms of Male Contraception |url=http://www.malecontraceptive.org/1/post/2019/03/sperm-transport-mechanisms-of-male-contraception.html |access-date=2024-01-30 |website=Male Contraceptive Initiative |language=en}} However, full reversibility remains questionable, since animal and human studies have shown sperm abnormalities, incomplete recovery of sperm parameters, and the development of fertility-impairing antibodies against one's own sperm after blockage removal.{{cite journal | vauthors = Silva AF, Ramalho-Santos J, Amaral S | title = The impact of antisperm antibodies on human male reproductive function: an update | journal = Reproduction | volume = 162 | issue = 4 | pages = R55–R71 | date = September 2021 | pmid = 34338216 | doi = 10.1530/REP-21-0123 }}{{cite journal | vauthors = Shibahara H, Wakimoto Y, Fukui A, Hasegawa A | title = Anti-sperm antibodies and reproductive failures | journal = American Journal of Reproductive Immunology | volume = 85 | issue = 4 | pages = e13337 | date = April 2021 | pmid = 32885505 | doi = 10.1111/aji.13337 | s2cid = 221496379 }}{{cite journal | vauthors = Francavilla F, Santucci R, Barbonetti A, Francavilla S | title = Naturally-occurring antisperm antibodies in men: interference with fertility and clinical implications. An update | journal = Frontiers in Bioscience | volume = 12 | issue = 8–12 | pages = 2890–2911 | date = May 2007 | pmid = 17485267 | doi = 10.2741/2280 }}{{cite journal | vauthors = Zhao SC, Lian YH, Yu RC, Zhang SP | title = Recovery of fertility after removal of polyurethane plugs from the human vas deferens occluded for up to 5 years | journal = International Journal of Andrology | volume = 15 | issue = 6 | pages = 465–467 | date = December 1992 | pmid = 1483735 | doi = 10.1111/j.1365-2605.1992.tb01139.x }}{{cite book |doi=10.1016/s0074-7696(00)99006-5 |title=Cellular responses to vasectomy |series=International Review of Cytology |date=2000 | vauthors = McDonald SW |volume=199 |pages=295–339 |pmid=10874581 |isbn=978-0-12-364603-3 }}

{{as of|2024}}, the following vas-occlusive male contraceptive products are in clinical trials:

• RISUG is an injectable male contraceptive vas-occlusive gel that has been in development in India since the 1970s,{{cite journal | vauthors = Khilwani B, Badar A, Ansari AS, Lohiya NK | title = RISUG^® as a male contraceptive: journey from bench to bedside | journal = Basic and Clinical Andrology | volume = 30 | pages = 2 | date = 2020 | pmid = 32082579 | pmc = 7017607 | doi = 10.1186/s12610-020-0099-1 | doi-access = free }}{{Cite web |date=2017-04-04 |title=Male contraceptive is being blocked by drug companies who make billions from the female pill |url=https://www.independent.co.uk/news/business/news/male-contraceptive-block-drug-companies-examples-female-pill-injection-india-startup-big-pharma-a7665511.html |access-date=2023-10-12 |website=The Independent |language=en |vauthors=Altstedter A}} and has shown high effectiveness at pregnancy prevention in multiple clinical trials through Phase III in India,{{cite journal |vauthors=Sharma RS, Mathur AK, Singh R, Das HC, Singh GJ, Toor DP, Guha SK |date=July 2019 |title=Safety & efficacy of an intravasal, one-time injectable & non-hormonal male contraceptive (RISUG): A clinical experience |journal=The Indian Journal of Medical Research |language=en-US |volume=150 |issue=1 |pages=81–86 |doi=10.4103/ijmr.IJMR_635_18 |pmc=6798614 |pmid=31571633 |doi-access=free}}{{cite journal |vauthors=Guha SK, Singh G, Ansari S, Kumar S, Srivastava A, Koul V, Das HC, Malhotra RL, Das SK |date=October 1997 |title=Phase II clinical trial of a vas deferens injectable contraceptive for the male |url=http://eprint.iitd.ac.in/bitstream/2074/394/1/guhapha97.pdf |url-status=dead |journal=Contraception |volume=56 |issue=4 |pages=245–250 |doi=10.1016/s0010-7824(97)00142-x |pmid=9408706 |archive-url=https://web.archive.org/web/20170921224918/http://eprint.iitd.ac.in/bitstream/2074/394/1/guhapha97.pdf |archive-date=2017-09-21 |access-date=2021-08-14}} though the results of the largest phase III study were published in a questionably peer-reviewed predatory journal.{{Cite web |date=2023-10-19 |title=ICMR completes clinical trials of world's first injectable male contraceptive; study claims it's safe |url=https://www.newindianexpress.com/nation/2023/Oct/19/icmr-completes-clinical-trials-of-worlds-first-injectable-male-contraceptive-study-claims-its-saf-2625398.html |access-date=2024-05-10 |website=The New Indian Express |language=en}} RISUG is proposed to be reversed through a second injection that dissolves the polymer,{{cite journal |vauthors=Ansari AS, Badar A, Balasubramanian K, Lohiya NK |date=2017 |title=Contraception with RISUG^® and functional reversal through DMSO and NaHCO₃ in male rabbits |journal=Asian Journal of Andrology |volume=19 |issue=4 |pages=389–395 |doi=10.4103/1008-682X.185000 |pmc=5507081 |pmid=27586026 |doi-access=free}} but as of 2024, reversibility and return to fertility after removal of RISUG have not been shown in humans. As of 2022, RISUG was awaiting approval from the Drug Controller General of India for mass production.{{Cite journal | vauthors = Lohiya NK, Ansari AS, Sadasukhi TC, Pachera S, Khilwani B, Dhaked RK|date=2022-12-20 |title=RISUG® offers early contraception: An experience during Phase III clinical trials |url=https://jrhm.org/risug-offers-early-contraception-an-experience-during-phase-iii-clinical-trials/ |journal=Journal of Reproductive Healthcare and Medicine |language=en |volume=3 |pages=11 |doi=10.25259/JRHM_8_2022 |issn=2768-1114|doi-access=free }}
• ADAM is a hydrogel-based male contraceptive implant in early clinical development{{ClinicalTrialsGov|NCT05134428|Safety Evaluation of the ADAM System}} by Contraline, Inc.{{Cite web |date=2022-11-10 |title=Contraline Announces First Patients Successfully Implanted in Male Contraceptive Study |url=https://www.businesswire.com/news/home/20221110005120/en/Contraline-Announces-First-Patients-Successfully-Implanted-in-Male-Contraceptive-Study |access-date=2023-10-13 |website=www.businesswire.com |language=en}} The implant is administered to a user in a procedure similar to a no-scalpel vasectomy, and is proposed to provide protection from pregnancy for approximately two years, after which the hydrogel degrades, thereby restoring fertility.{{Cite web |title=Male contraceptive implanted at Epworth Freemasons in world first - Epworth HealthCare |url=https://www.epworth.org.au/newsroom/male-contraceptive-implanted-at-epworth-freemasons-in-world-first |access-date=2023-10-13 |website=www.epworth.org.au |language=en}}

{{as of|2024}}, the following vas-occlusive male contraceptive products are in preclinical development:

• Plan A, formerly known as Vasalgel, is an adaptation of the polymer used in RISUG, which as of 2024 is in preclinical development in the United States by NEXT life sciences.{{Cite web |title=Home |url=https://nextlifesciences.org/ |access-date=2023-10-13 |website=NEXT Life Sciences |language=en-US}}{{cite web|url=https://www.parsemus.org/projects/vasalgel/|title=Vasalgel, a Multi-year Contraceptive|access-date=19 February 2018}}{{Cite web |date=2023-06-02 |title=$1.55M Raised for Plan A™ Male Birth Control Product, Seeking Clinical Trials in 2023 |url=https://finance.yahoo.com/news/1-55m-raised-plan-male-140000712.html |access-date=2023-10-12 |website=Yahoo Finance |language=en-US}}{{cite journal | vauthors = Waller D, Bolick D, Lissner E, Premanandan C, Gamerman G | title = Reversibility of Vasalgel™ male contraceptive in a rabbit model | journal = Basic and Clinical Andrology | volume = 27 | pages = 8 | date = 2017 | pmid = 28417005 | pmc = 5381074 | doi = 10.1186/s12610-017-0051-1 | doi-access = free }}{{cite journal | vauthors = Colagross-Schouten A, Lemoy MJ, Keesler RI, Lissner E, VandeVoort CA | title = The contraceptive efficacy of intravas injection of Vasalgel™ for adult male rhesus monkeys | journal = Basic and Clinical Andrology | volume = 27 | pages = 4 | date = 2017 | pmid = 28191316 | pmc = 5294830 | doi = 10.1186/s12610-017-0048-9 | doi-access = free }}{{cite journal | vauthors = Waller D, Bolick D, Lissner E, Premanandan C, Gamerman G | title = Azoospermia in rabbits following an intravas injection of Vasalgel ™ | journal = Basic and Clinical Andrology | volume = 26 | pages = 6 | date = 2016 | pmid = 27030808 | pmc = 4812607 | doi = 10.1186/s12610-016-0033-8 | doi-access = free }}
• Other methods for vas occlusion have been proposed, though these methods are largely in very early development.{{cite journal | vauthors = Wang ZQ, Liu ZQ, Zhao CH, Zhang K, Kang ZJ, Qu TR, Zeng FS, Guo PY, Tong ZC, Wang CL, Wang KL, Wang HL, Xu YS, Wang WH, Chu ML, Wang L, Qiao ZY, Wang H, Xu W | title = An Ultrasound-Induced Self-Clearance Hydrogel for Male Reversible Contraception | journal = ACS Nano | volume = 16 | issue = 4 | pages = 5515–5528 | date = April 2022 | pmid = 35352555 | doi = 10.1021/acsnano.1c09959 | s2cid = 247791477 }}{{cite journal | vauthors = Ding W, Chen Z, Gu Y, Chen Z, Zheng Y, Sun F | title = Magnetic Testis Targeting and Magnetic Hyperthermia for Noninvasive, Controllable Male Contraception via Intravenous Administration | journal = Nano Letters | volume = 21 | issue = 14 | pages = 6289–6297 | date = July 2021 | pmid = 34232048 | doi = 10.1021/acs.nanolett.1c02181 | s2cid = 235756835 | bibcode = 2021NanoL..21.6289D }}{{Cite web |title=This is how the Bimek SLV works |url=http://bimek.com/this-is-how-the-bimek-slv-works/ |access-date=2024-01-14 |website=bimek.com |language=en}}{{cite journal | vauthors = Kjaergaard N, Kjaergaard B, Lauritsen JG | title = Prazosin, an adrenergic blocking agent inadequate as male contraceptive pill | journal = Contraception | volume = 37 | issue = 6 | pages = 621–629 | date = June 1988 | pmid = 2899490 | doi = 10.1016/0010-7824(88)90008-x }}

Research into new, more acceptable designs of condoms is ongoing.{{Cite web |title=The search to make a perfect condom |url=https://www.bbc.com/future/article/20210423-how-grass-and-gel-could-make-condoms-better |access-date=2023-10-12 |website=www.bbc.com |language=en |vauthors=Lee C|date=25 April 2021 }}{{Cite web | vauthors = Jordyn T |date=2015-11-18 |title=2 Years Later, Here's What Happened to Bill Gates' Condoms of the Future |url=https://www.mic.com/articles/128850/bill-and-melinda-gates-foundation-condom-contest-where-are-they-now |access-date=2024-01-30 |website=Mic |language=en}}

These approaches work by blocking functions that mature sperm need in order to reach and fertilize an egg in the female reproductive tract, such as motility, capacitation, semen liquification, or fertilization. Drugs or devices that target mature sperm are likely to be effective on-demand (taken just before intercourse), and could even be delivered either in sperm-producing or egg-producing bodies, leading to unisex contraceptives.{{cite thesis |id={{ProQuest|2884070213}} | vauthors = Skinner WM |date=2022 |title=Investigating Sperm-Specific Proteins and Physiology to Inform Development of Non-Hormonal, Unisex Contraception }}{{page needed|date=February 2024}}{{cite journal | vauthors = Lishko PV | title = Contraception: Search for an Ideal Unisex Mechanism by Targeting Ion Channels | journal = Trends in Biochemical Sciences | volume = 41 | issue = 10 | pages = 816–818 | date = October 2016 | pmid = 27545067 | pmc = 5364274 | doi = 10.1016/j.tibs.2016.08.002 }}

{{as of|2024}}, the following non-hormonal male contraceptive approaches are in preclinical or early development:

• Short-term inhibition of soluble adenylyl cyclase has been demonstrated to temporarily impair sperm motility and capacitation, and thereby block fertility in mice. Medicinal chemistry efforts are underway to develop molecules that could be used as on-demand contraceptives.{{cite journal | vauthors = Balbach M, Rossetti T, Ferreira J, Ghanem L, Ritagliati C, Myers RW, Huggins DJ, Steegborn C, Miranda IC, Meinke PT, Buck J, Levin LR | title = On-demand male contraception via acute inhibition of soluble adenylyl cyclase | journal = Nature Communications | volume = 14 | issue = 1 | pages = 637 | date = February 2023 | pmid = 36788210 | pmc = 9929232 | doi = 10.1038/s41467-023-36119-6 | bibcode = 2023NatCo..14..637B }}{{cite journal | vauthors = Balbach M, Ghanem L, Rossetti T, Kaur N, Ritagliati C, Ferreira J, Krapf D, Puga Molina LC, Santi CM, Hansen JN, Wachten D, Fushimi M, Meinke PT, Buck J, Levin LR | title = Soluble adenylyl cyclase inhibition prevents human sperm functions essential for fertilization | journal = Molecular Human Reproduction | volume = 27 | issue = 9 | date = September 2021 | pmid = 34463764 | pmc = 8473925 | doi = 10.1093/molehr/gaab054 }}{{Cite web |title=Male Birth Control Drug 'Stops Sperm in Their Tracks' in Study of Mice |url=https://www.smithsonianmag.com/smart-news/male-birth-control-drug-stops-sperm-in-their-tracks-in-study-of-mice-180981645/ |access-date=2023-10-12 |website=Smithsonian Magazine |language=en |vauthors=Sullivan W}}
• EP055 is a non-hormonal contraceptive molecule in development that works by targeting the sperm protein Eppin and blocking the initiation of sperm motility after ejaculation.{{cite journal | vauthors = Gomes AA, Santos NC, Rosa LR, Borges RJ, Fontes MR, Hamil KG, O'Rand MG, Silva EJ | title = Interactions of the male contraceptive target EPPIN with semenogelin-1 and small organic ligands | journal = Scientific Reports | volume = 13 | issue = 1 | pages = 14382 | date = September 2023 | pmid = 37658081 | pmc = 10474283 | doi = 10.1038/s41598-023-41365-1 | bibcode = 2023NatSR..1314382G }}{{cite journal | vauthors = O'Rand MG, Hamil KG, Adevai T, Zelinski M | title = Inhibition of sperm motility in male macaques with EP055, a potential non-hormonal male contraceptive | journal = PLOS ONE | volume = 13 | issue = 4 | pages = e0195953 | date = 2018 | pmid = 29672554 | pmc = 5908160 | doi = 10.1371/journal.pone.0195953 | bibcode = 2018PLoSO..1395953O | doi-access = free }}{{Cite web |date=2023-12-14 |title=A birth control pill for men? How a UNC scientist-turned-entrepreneur plans to curb unintended pregnancies. | work = Innovate Carolina {{!}} UNC Innovation & Entrepreneurship |url=https://innovate.unc.edu/birth-control-pill-for-men-how-a-unc-scientist-turned-entrepreneur-plans-to-curb-unintended-pregnancies/ |access-date=2023-12-21 |language=en-US}}
• Inhibitors of various sperm ion channels/transporters such as CatSper,{{cite journal | vauthors = Luque GM, Schiavi-Ehrenhaus LJ, Jabloñski M, Balestrini PA, Novero AG, Torres NI, Osycka-Salut CE, Darszon A, Krapf D, Buffone MG | title = High-throughput screening method for discovering CatSper inhibitors using membrane depolarization caused by external calcium chelation and fluorescent cell barcoding | journal = Frontiers in Cell and Developmental Biology | volume = 11 | pages = 1010306 | date = 2023 | pmid = 36743410 | pmc = 9892719 | doi = 10.3389/fcell.2023.1010306 | doi-access = free }}{{cite journal | vauthors = Smith JF, Syritsyna O, Fellous M, Serres C, Mannowetz N, Kirichok Y, Lishko PV | title = Disruption of the principal, progesterone-activated sperm Ca2+ channel in a CatSper2-deficient infertile patient | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 17 | pages = 6823–6828 | date = April 2013 | pmid = 23530196 | pmc = 3637729 | doi = 10.1073/pnas.1216588110 | doi-access = free }} sNHE,{{cite journal | vauthors = Cavarocchi E, Whitfield M, Chargui A, Stouvenel L, Lorès P, Coutton C, Arnoult C, Santulli P, Patrat C, Thierry-Mieg N, Ray PF, Dulioust E, Touré A | title = The sodium/proton exchanger SLC9C1 (sNHE) is essential for human sperm motility and fertility | journal = Clinical Genetics | volume = 99 | issue = 5 | pages = 684–693 | date = May 2021 | pmid = 33462806 | doi = 10.1111/cge.13927 | s2cid = 231642168 | url = https://hal.archives-ouvertes.fr/hal-03369825/file/Cavarocchi-et-al_2021.pdf }} Slo3,{{cite journal | vauthors = Tan Z, Garcia TX | title = SLO3 in the fast lane: The latest male contraceptive target with a promising small-molecule inhibitor | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 120 | issue = 8 | pages = e2221758120 | date = February 2023 | pmid = 36791103 | pmc = 9974486 | doi = 10.1073/pnas.2221758120 | doi-access = free | bibcode = 2023PNAS..12021758T }}{{cite journal | vauthors = Lyon M, Li P, Ferreira JJ, Lazarenko RM, Kharade SV, Kramer M, McClenahan SJ, Days E, Bauer JA, Spitznagel BD, Weaver CD, Borrego Alvarez A, Puga Molina LC, Lybaert P, Khambekar S, Liu A, Lindsley CW, Denton J, Santi CM | title = A selective inhibitor of the sperm-specific potassium channel SLO3 impairs human sperm function | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 120 | issue = 4 | pages = e2212338120 | date = January 2023 | pmid = 36649421 | doi = 10.1073/pnas.2212338120 | doi-access = free | pmc = 9942793 | bibcode = 2023PNAS..12012338L }} and NKAα4,{{cite journal | vauthors = Syeda SS, Sánchez G, McDermott JP, Hong KH, Blanco G, Georg GI | title = The Na+ and K+ transport system of sperm (ATP1A4) is essential for male fertility and an attractive target for male contraception† | journal = Biology of Reproduction | volume = 103 | issue = 2 | pages = 343–356 | date = August 2020 | pmid = 32588885 | pmc = 7401355 | doi = 10.1093/biolre/ioaa093 }}{{cite journal | vauthors = Numata S, McDermott JP, Blanco G | title = Genetic Ablation of Na,K-ATPase α4 Results in Sperm Energetic Defects | journal = Frontiers in Cell and Developmental Biology | volume = 10 | pages = 911056 | date = 2022 | pmid = 35693932 | pmc = 9178190 | doi = 10.3389/fcell.2022.911056 | doi-access = free }}{{cite journal | vauthors = Syeda SS, Sánchez G, Hong KH, Hawkinson JE, Georg GI, Blanco G | title = Design, Synthesis, and in Vitro and in Vivo Evaluation of Ouabain Analogues as Potent and Selective Na,K-ATPase α4 Isoform Inhibitors for Male Contraception | journal = Journal of Medicinal Chemistry | volume = 61 | issue = 5 | pages = 1800–1820 | date = March 2018 | pmid = 29291372 | doi = 10.1021/acs.jmedchem.7b00925 | pmc = 5846083 }}{{cite web | vauthors = Georg G, Hawkinson J, Syeda S | work = The Conversation | via = The Smithsonian Magazine | date = 31 January 2018 |title= Heart-Stopping Arrow Poison Could be Key to Male Birth Control |url=https://www.smithsonianmag.com/science-nature/arrow-poison-key-male-birth-control-180967985/}} are in development. These inhibitors generally act to block sperm motility and/or capacitation, and have the potential to be administered either systemically in males or through vaginal delivery in females.{{cite journal | vauthors = Mariani NA, Silva JV, Fardilha M, Silva EJ | title = Advances in non-hormonal male contraception targeting sperm motility | journal = Human Reproduction Update | volume = 29 | issue = 5 | pages = 545–569 | date = September 2023 | pmid = 37141450 | doi = 10.1093/humupd/dmad008 }}
• Blocking prostate-derived serine proteases, such as PSA, is under consideration as a way to prevent semen liquifaction and therefore trap sperm in the ejaculate and prevent it from crossing through the cervix towards the egg.{{cite journal | vauthors = Anamthathmakula P, Winuthayanon W | title = Mechanism of semen liquefaction and its potential for a novel non-hormonal contraception† | journal = Biology of Reproduction | volume = 103 | issue = 2 | pages = 411–426 | date = August 2020 | pmid = 32529252 | pmc = 7523691 | doi = 10.1093/biolre/ioaa075 }}{{cite journal | vauthors = Anamthathmakula P, Erickson JA, Winuthayanon W | title = Blocking serine protease activity prevents semenogelin degradation leading to hyperviscous semen in humans | journal = Biology of Reproduction | volume = 106 | issue = 5 | pages = 879–887 | date = May 2022 | pmid = 35098308 | doi = 10.1093/biolre/ioac023 | pmc = 9113478 }}
• Sperm-specific metabolic enzymes needed to power motility, such as Lactate Dehydrogenase C,{{cite journal | vauthors = Iida-Norita R, Miyata H, Kaneda Y, Emori C, Noda T, Nakagawa T, Matzuk MM, Ikawa M | title = Generation of humanized LDHC knock-in mice as a tool to assess human LDHC-targeting contraceptive drugs | journal = Andrology | volume = 11 | issue = 5 | pages = 840–848 | date = July 2023 | pmid = 36464740 | doi = 10.1111/andr.13359 | s2cid = 254245669 }}{{cite journal | vauthors = Goldberg E | title = The sperm-specific form of lactate dehydrogenase is required for fertility and is an attractive target for male contraception (a review) | journal = Biology of Reproduction | volume = 104 | issue = 3 | pages = 521–526 | date = March 2021 | pmid = 33252126 | doi = 10.1093/biolre/ioaa217 }} GAPDHS,{{cite journal | vauthors = Danshina PV, Qu W, Temple BR, Rojas RJ, Miley MJ, Machius M, Betts L, O'Brien DA | title = Structural analyses to identify selective inhibitors of glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme | journal = Molecular Human Reproduction | volume = 22 | issue = 6 | pages = 410–426 | date = June 2016 | pmid = 26921398 | pmc = 4884916 | doi = 10.1093/molehr/gaw016 }}{{cite journal | vauthors = Sexton JZ, Danshina PV, Lamson DR, Hughes M, House AJ, Yeh LA, O'Brien DA, Williams KP | title = Development and Implementation of a High Throughput Screen for the Human Sperm-Specific Isoform of Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDHS) | journal = Current Chemical Genomics | volume = 5 | pages = 30–41 | date = 2011-07-04 | pmid = 21760877 | doi = 10.2174/1875397301105010030 | pmc = 3134944 }} are also being evaluated as inhibition targets for developing male contraceptives.

Although some people question whether men would be interested in managing their own contraceptives{{Cite news | vauthors = Filipovic J |date=2023-12-18 |title=Scientists are on the verge of a male birth-control pill. Will men take it? |url= https://www.theguardian.com/commentisfree/2023/dec/18/male-birth-control-will-men-take-it |access-date=2024-02-02 |work=The Guardian |language=en-GB |issn=0261-3077}} or whether women would trust their male partners to do so successfully,{{Cite news |date=2019-10-21 |title=Are we ready for men to take the pill? |url=https://www.bbc.com/news/health-49879667 |access-date=2024-02-02 |language=en-GB}} studies consistently show that men around the world have significant levels of interest in novel forms of male contraception{{cite journal | vauthors = Reynolds-Wright JJ, Cameron NJ, Anderson RA | title = Will Men Use Novel Male Contraceptive Methods and Will Women Trust Them? A Systematic Review | journal = Journal of Sex Research | volume = 58 | issue = 7 | pages = 838–849 | date = September 2021 | pmid = 33900134 | doi = 10.1080/00224499.2021.1905764 | hdl = 20.500.11820/d54d8a6a-eaa6-47d4-9204-4bdf87fc920b | url = https://www.pure.ed.ac.uk/ws/files/200401529/20_310.R2_Proof_hi.pdf | hdl-access = free }}{{Cite web |title=Nearly half of US men interested in taking new male contraceptives post-Dobbs decision |url=http://www.malecontraceptive.org/2/post/2023/06/nearly-half-of-us-men-interested-in-taking-new-male-contraceptives-post-dobbs-decision.html |access-date=2024-02-02 |website=Male Contraceptive Initiative |language=en}}{{cite journal | vauthors = Buck KA, Stadick JL, Frazier ML | title = Preparing for sperm-targeted contraception: College students' perceptions and intentions related to non-hormonal intravas injectable gel | journal = Public Health Nursing | volume = 37 | issue = 5 | pages = 639–646 | date = September 2020 | pmid = 32627239 | doi = 10.1111/phn.12761 | s2cid = 220367503 }}{{cite journal | vauthors = Amouroux M, Mieusset R, Desbriere R, Opinel P, Karsenty G, Paci M, Fernandes S, Courbiere B, Perrin J | title = Are men ready to use thermal male contraception? Acceptability in two French populations: New fathers and new providers | journal = PLOS ONE | volume = 13 | issue = 5 | pages = e0195824 | date = 2018 | pmid = 29813095 | pmc = 5973589 | doi = 10.1371/journal.pone.0195824 | bibcode = 2018PLoSO..1395824A | doi-access = free }} and that women in committed relationships would generally trust their male partners to manage the contraceptive burden in the relationship. Additionally, males participating in various contraceptive clinical trials have reported high satisfaction with the products they were using.

Studies on potential uptake indicate that in most countries, more than half of men surveyed would be willing to use a new method of male contraception.{{cite journal | vauthors = Weston GC, Schlipalius ML, Bhuinneain MN, Vollenhoven BJ | title = Will Australian men use male hormonal contraception? A survey of a postpartum population | journal = The Medical Journal of Australia | volume = 176 | issue = 5 | pages = 208–210 | date = March 2002 | pmid = 11999235 | doi = 10.5694/j.1326-5377.2002.tb04374.x | s2cid = 14438520 }}{{cite journal | vauthors = Sax MR, Hurley EG, Rossi RA, Thakore S, Hasija A, Sroga-Rios J | title = Young Adult Males' Perspectives of Male Hormonal Contraception | journal = Southern Medical Journal | volume = 114 | issue = 2 | pages = 73–76 | date = February 2021 | pmid = 33537786 | doi = 10.14423/SMJ.0000000000001204 | s2cid = 231804527 }}{{cite journal | vauthors = Martin CW, Anderson RA, Cheng L, Ho PC, van der Spuy Z, Smith KB, Glasier AF, Everington D, Baird DT | title = Potential impact of hormonal male contraception: cross-cultural implications for development of novel preparations | journal = Human Reproduction | volume = 15 | issue = 3 | pages = 637–645 | date = March 2000 | pmid = 10686211 | doi = 10.1093/humrep/15.3.637 }} Interestingly, some of the highest rates were reported in low-income countries like Nigeria and Bangladesh where 76% of men surveyed indicated that they would be willing to use a new method within the first 12 months that it is available. This is particularly compelling, since it has been estimated that a mere 10% uptake of new male contraceptive methods could avert nearly 40% of unintended pregnancies in Nigeria. Across the world, many young and middle-aged men especially want the ability to control their own fertility, and are not well-served by existing family planning programs.{{cite journal | vauthors = Marcell AV, Gibbs SE, Choiriyyah I, Sonenstein FL, Astone NM, Pleck JH, Dariotis JK | title = National Needs of Family Planning Among US Men Aged 15 to 44 Years | journal = American Journal of Public Health | volume = 106 | issue = 4 | pages = 733–739 | date = April 2016 | pmid = 26890180 | pmc = 4815999 | doi = 10.2105/AJPH.2015.303037 }}

Although a phase II trial for an injectable male contraceptive was halted in 2011 by an independent data safety monitoring board due likely to rare adverse effects experienced by some participants,{{Cite journal |title=ISRCTN |url=https://www.isrctn.com/holding |access-date=2024-02-02 |website=www.isrctn.com |doi=10.1186/isrctn07760234|doi-access= free| vauthors = Vogelsong K |url-access=subscription }} leading many popular articles to suggest men could not tolerate side effects similar to those that many women endure on hormonal birth control,{{Cite web |date=2016-11-07 |title=Did gender bias kill hormonal birth control for men? |url=https://www.pbs.org/newshour/health/gender-bias-kill-male-birth-control |access-date=2024-02-22 |website=PBS NewsHour |language=en-us}} in reality more than 80% of the study's male participants stated at the end of the trial that they were satisfied with the contraceptive injection, and would be willing to use the method if it were available.{{cite journal | vauthors = 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 | title = Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 101 | issue = 12 | pages = 4779–4788 | date = December 2016 | pmid = 27788052 | doi = 10.1210/jc.2016-2141 }} Subsequent hormonal male contraceptive clinical trials have progressed successfully, showing high levels of efficacy and acceptability among the participants.{{cite journal | vauthors = 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 | title = Effects of 28 Days of Oral Dimethandrolone Undecanoate in Healthy Men: A Prototype Male Pill | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 104 | issue = 2 | pages = 423–432 | date = February 2019 | pmid = 30252061 | pmc = 6306388 | doi = 10.1210/jc.2018-01452 }}

It is sometimes assumed that women won't trust men to take contraceptives, since women would bear the consequences of a male partner's missed dose or misuse. Of course, male contraceptive options would not have to replace female contraceptives, and in casual sexual encounters both partners may prefer to independently control their own contraceptive methods. On the other hand, some long-term couples might want only one partner to bear the contraceptive burden. Indeed, there is evidence that a large proportion of women in relationships in many countries around the world would trust their partners to take a potential male method,{{cite journal | vauthors = Glasier AF, Anakwe R, Everington D, Martin CW, van der Spuy Z, Cheng L, Ho PC, Anderson RA | title = Would women trust their partners to use a male pill? | journal = Human Reproduction | volume = 15 | issue = 3 | pages = 646–649 | date = March 2000 | pmid = 10686212 | doi = 10.1093/humrep/15.3.646 }} and many women want more male partner involvement in their own reproductive health services.{{Cite journal | vauthors = Zolna MR, Frost JJ, Lindberg LD |date=2011-06-07 |title=Couple-Focused Services in Publicly Funded Family Planning Clinics: Identifying the Need, 2009 |url=https://www.guttmacher.org/report/couple-focused-services-publicly-funded-family-planning-clinics-identifying-need-2009 |journal=Guttmacher Institute |language=en}} Further, current contraceptive use data show that more than a quarter of women worldwide already rely on male-controlled methods for contraception (such as condoms and vasectomy),{{Cite book |url=https://www.un-ilibrary.org/content/books/9789210046527 |title=Contraceptive Use by Method 2019: Data Booklet |date=2019-12-10 |publisher=United Nations |isbn=978-92-1-004652-7 |language=en |doi=10.18356/1bd58a10-en|s2cid=241385492 }} and this figure could grow as more male contraceptive methods become available.

Despite the fact that modern female pharmaceutical contraception has been on the market since the 1960s,{{cite journal | vauthors = McCracken JA | title = Reflections on the 50th anniversary of the birth control pill | journal = Biology of Reproduction | volume = 83 | issue = 4 | pages = 684–686 | date = October 2010 | pmid = 20811017 | doi = 10.1095/biolreprod.110.087809 }} 40-50% of pregnancies are still unintended worldwide, leading to an approximate total of 121 million unintended pregnancies annually.{{cite journal | vauthors = Finer LB, Zolna MR | title = Declines in Unintended Pregnancy in the United States, 2008-2011 | journal = The New England Journal of Medicine | volume = 374 | issue = 9 | pages = 843–852 | date = March 2016 | pmid = 26962904 | pmc = 4861155 | doi = 10.1056/NEJMsa1506575 }}{{cite journal | vauthors = Finer LB, Zolna MR | title = Unintended pregnancy in the United States: incidence and disparities, 2006 | journal = Contraception | volume = 84 | issue = 5 | pages = 478–485 | date = November 2011 | pmid = 22018121 | pmc = 3338192 | doi = 10.1016/j.contraception.2011.07.013 | citeseerx = 10.1.1.295.8407 }} Importantly, most studies on unintended pregnancies only measure women's intentions about the pregnancy, and so pregnancies that were unintended by men are understudied and may be under-reported.{{cite journal | vauthors = Kågesten A, Bajos N, Bohet A, Moreau C | title = Male experiences of unintended pregnancy: characteristics and prevalence | journal = Human Reproduction | volume = 30 | issue = 1 | pages = 186–196 | date = January 2015 | pmid = 25316449 | pmc = 4262464 | doi = 10.1093/humrep/deu259 }} Unintended pregnancies have been shown to be linked with a wide variety of negative outcomes on mental and physical health, as well as educational and socioeconomic attainment in both parents and the children born of unintended pregnancies.

Surprisingly, although the rate of unintended pregnancies (per 1000 women of childbearing age) is higher in developing countries,{{cite journal | vauthors = Sedgh G, Singh S, Hussain R | title = Intended and unintended pregnancies worldwide in 2012 and recent trends | journal = Studies in Family Planning | volume = 45 | issue = 3 | pages = 301–314 | date = September 2014 | pmid = 25207494 | pmc = 4727534 | doi = 10.1111/j.1728-4465.2014.00393.x | citeseerx = 10.1.1.678.2268 }}{{cite journal | vauthors = Bearak J, Popinchalk A, Alkema L, Sedgh G | title = Global, regional, and subregional trends in unintended pregnancy and its outcomes from 1990 to 2014: estimates from a Bayesian hierarchical model | journal = The Lancet. Global Health | volume = 6 | issue = 4 | pages = e380–e389 | date = April 2018 | pmid = 29519649 | pmc = 6055480 | doi = 10.1016/S2214-109X(18)30029-9 }}{{cite journal | vauthors = Bearak JM, Alkema L, Kantorová V, Casterline J | title = Alignment between Desires and Outcomes among Women Wanting to Avoid Pregnancy: A Global Comparative Study of "Conditional" Unintended Pregnancy Rates | journal = Studies in Family Planning | volume = 54 | issue = 1 | pages = 265–280 | date = March 2023 | pmid = 36811721 | doi = 10.1111/sifp.12234 | doi-access = free }} the percentage of pregnancies that are unintended is actually higher in developed countries, since a lower proportion of women in developed countries are intending to conceive at any given time. Research indicates that unmet need for modern contraception is the cause of 84% of unintended pregnancies in developing countries.{{Cite web |date=2017-06-23 |title=Adding It Up: Investing in Contraception and Maternal and Newborn Health, 2017 | work = Guttmacher Institute |url=https://www.guttmacher.org/fact-sheet/adding-it-up-contraception-mnh-2017 |access-date=2024-02-07 |language=en}} In the United States, which has a higher unintended pregnancy rate than many other developed nations,{{Cite web |date=2012-01-26 |title=Unintended Pregnancy in the United States | work = Guttmacher Institute |url=https://www.guttmacher.org/fact-sheet/unintended-pregnancy-united-states |access-date=2024-02-07 |language=en}} one important reason that women cite for nonuse of contraceptives is concerns about the side effects of existing products.{{cite journal | vauthors = Mosher W, Jones J, Abma J | title = Nonuse of contraception among women at risk of unintended pregnancy in the United States | journal = Contraception | volume = 92 | issue = 2 | pages = 170–176 | date = August 2015 | pmid = 25998937 | pmc = 6413311 | doi = 10.1016/j.contraception.2015.05.004 }} Taken together, these statistics suggests that the current suite of contraceptives is insufficient to meet the fertility planning needs of people across the world, and therefore the introduction of new male contraceptives is likely to decrease the stubbornly high global rates of unintended pregnancy.

International market research indicates that 49% of men in the United states and 76% of men in Nigeria would try a novel male contraceptive within the first year of its existence. Independent modelling predicts that even if real-world usage is only 10% as high as the market research suggests, the introduction of a male contraceptive would avert roughly 200,000 unintended pregnancies per year in the USA and Nigeria each.

Fathers with unintended births report lower proportions of happiness than in fathers with intentional births{{cite journal | vauthors = Lindberg LD, Kost K | title = Exploring U.S. men's birth intentions | journal = Maternal and Child Health Journal | volume = 18 | issue = 3 | pages = 625–633 | date = April 2014 | pmid = 23793481 | pmc = 3844082 | doi = 10.1007/s10995-013-1286-x }} and unintended fatherhood for men in their early 30s is associated with a significant increase in depressive symptoms.{{cite journal | vauthors = Maximova K, Quesnel-Vallée A | title = Mental health consequences of unintended childlessness and unplanned births: gender differences and life course dynamics | journal = Social Science & Medicine | volume = 68 | issue = 5 | pages = 850–857 | date = March 2009 | pmid = 19097676 | pmc = 3762744 | doi = 10.1016/j.socscimed.2008.11.012 }} In addition, men in insecure financial situations are more likely to report a recent unintended pregnancy, and supporting and raising a child brings significant costs that can exacerbate financial insecurity.{{cite journal | vauthors = Hamm M, Miller E, Jackson Foster L, Browne M, Borrero S | title = "The Financial Is the Main Issue, It's Not Even the Child": Exploring the Role of Finances in Men's Concepts of Fatherhood and Fertility Intention | journal = American Journal of Men's Health | volume = 12 | issue = 4 | pages = 1074–1083 | date = July 2018 | pmid = 29774803 | pmc = 6131444 | doi = 10.1177/1557988318775189 }}{{Cite journal | vauthors = Smith I, Youssef GJ, Shatte A, Teague SJ, Knight T, Macdonald JA |date=2022 |title="You are not alone": A big data and qualitative analysis of men's unintended fatherhood |url= https://researchonline.jcu.edu.au/73677/1/73677.pdf|journal=SSM - Qualitative Research in Health |language=en |volume=2 |pages=100085 |doi=10.1016/j.ssmqr.2022.100085|s2cid=248211972 }} More broadly, access to effective and reliable contraception would advance men's ability to "maintain personal bodily autonomy, have children, not have children, and parent the children we have in safe and sustainable communities" in accordance with the principles of Reproductive Justice.{{Cite web |title=Reproductive Justice |url=https://www.sistersong.net/reproductive-justice |access-date=2024-02-08 |website=Sister Song |language=en-US}}

Family planning has been found to be associated with overall well-being and is one of the most efficient tools for women's empowerment.{{Cite journal |vauthors=Monjok E |date=May 2010 |title=Contraceptive practices in Nigeria: Literature review and recommendation for future policy decisions |journal=Open Access Journal of Contraception |pages=9 |doi=10.2147/oajc.s9281 |doi-access=free}}{{cite journal |vauthors=Allen RH |date=November 2007 |title=The role of family planning in poverty reduction |journal=Obstetrics and Gynecology |volume=110 |issue=5 |pages=999–1002 |doi=10.1097/01.AOG.0000287063.32004.23 |pmid=17978110}}{{cite book |title=Reproductive Health -- the Missing Millennium Development Goal |vauthors=Campbell-White A, Merrick TW, Yazbeck AS |date=2006 |isbn=978-0-8213-6613-4 |doi=10.1596/978-0-8213-6613-4|doi-broken-date=23 May 2025 }} Positive outcomes of effective birth control include improvements in women's health, self-agency, education, labor force participation, financial stability, as well as decreases in pregnancy-related deaths,{{cite journal |vauthors=Finlay JE, Lee MA |date=June 2018 |title=Identifying Causal Effects of Reproductive Health Improvements on Women's Economic Empowerment Through the Population Poverty Research Initiative |journal=The Milbank Quarterly |volume=96 |issue=2 |pages=300–322 |doi=10.1111/1468-0009.12326 |pmc=5987803 |pmid=29870117}}{{cite report | vauthors = Kavanaugh ML, Anderson RM | title = Contraception and Beyond: The Health Benefits of Services Provided at Family Planning Centers [Internet]. | publisher = Guttmacher Institute | date = 2013 | url = https://www.guttmacher.org/report/contraception-and-beyond-health-benefits-services-provided-family-planning-centers

}}{{cite report | vauthors = Bernstein A, Jones KM | title = The Economic Effects of Contraceptive Access: A Review of the Evidence - Key Findings from the Literature [Internet]. | publisher = Institute for Women’s Policy Research | date = September 2019 | access-date = 8 February 2024 | url = https://policycommons.net/artifacts/4825153/the-economic-effects-of-contraceptive-access/5661869/ }} and these positive social and health impacts may be further realized by the addition of novel male and unisex methods. New male contraceptive options would not come at the expense of women’s reproductive autonomy, since women would still be able to take advantage of all of the contraceptive methods available to them, choose to have both partners use their own contraceptive methods at the same time, or rely solely on their male partners’ form of contraception.

Interventions encouraging male engagement in couples' reproductive health and decisionmaking have shown positive outcomes related to promoting more equitable gender norms in the context of family planning,{{cite journal | vauthors = Hardee K, Croce-Galis M, Gay J | title = Are men well served by family planning programs? | journal = Reproductive Health | volume = 14 | issue = 1 | pages = 14 | date = January 2017 | pmid = 28115004 | pmc = 5260026 | doi = 10.1186/s12978-017-0278-5 | doi-access = free }} and increased joint decision making in couples. It is reasonable to assume from these data that increasing male involvement as contraceptive users will further improve gender equity.{{cite report | title = Increasing Men's Engagement to Improve Family Planning Programs in South Asia [Internet]. | work = FHI360 (Family Health International) | location = Research Triangle Park, NC | date = 2012 | access-date = 8 February 2024 | url = https://www.fhi360.org/resource/increasing-mens-engagement-improve-family-planning-programs-south-asia }}

While this article has used the term "male" contraception for clarity, these contraceptives are most accurately described as "sperm-targeting" contraceptives, since they would work effectively in any body that produces sperm, regardless of that person's gender identity or external genitalia. Importantly, contraceptives that block functions of mature sperm could be delivered in a unisex manner, incapacitating sperm before ejaculation in sperm-producing people, or after sperm arrives in the body of egg-producing people.

Transgender, nonbinary, and intersex people are underserved by current contraceptive options. For example, many trans men can become pregnant (both intentionally and unintentionally),{{cite journal | vauthors = Light AD, Obedin-Maliver J, Sevelius JM, Kerns JL | title = Transgender men who experienced pregnancy after female-to-male gender transitioning | journal = Obstetrics and Gynecology | volume = 124 | issue = 6 | pages = 1120–1127 | date = December 2014 | pmid = 25415163 | doi = 10.1097/aog.0000000000000540 | s2cid = 36023275 | url = https://escholarship.org/uc/item/3dz427qw }} but may prefer not to use estrogen- or progestin-containing hormonal birth control (both because of the social classification of these hormones as "female sex hormones" and because of a fear they will interfere with masculinizing hormone therapy, although the American College of Obstetricians and Gynecologists states that these hormonal contraceptives have little effect on masculinization.){{cite journal | vauthors = Francis A, Jasani S, Bachmann G | title = Contraceptive challenges and the transgender individual | journal = Women's Midlife Health | volume = 4 | issue = 1 | pages = 12 | date = 2018-07-13 | pmid = 30766722 | pmc = 6297942 | doi = 10.1186/s40695-018-0042-1 | doi-access = free }}{{cite journal | vauthors = Nisly NL, Imborek KL, Miller ML, Kaliszewski SD, Williams RM, Krasowski MD | title = Unique Primary Care Needs of Transgender and Gender Non-Binary People | journal = Clinical Obstetrics and Gynecology | volume = 61 | issue = 4 | pages = 674–686 | date = December 2018 | pmid = 30339607 | doi = 10.1097/grf.0000000000000404 | s2cid = 53009782 }}{{Cite web |title=Health Care for Transgender and Gender Diverse Individuals |url=https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2021/03/health-care-for-transgender-and-gender-diverse-individuals |access-date=2024-02-09 |website=www.acog.org |language=en}} Trans women who have not had gender-affirming genital surgery may have similar unmet contraceptive needs as those of cisgender men, since gender-affirming hormonal therapy is not effective contraception. Nonbinary and intersex people may be less likely to use current methods of birth control, since they are popularly categorized by the labels "male" and "female", which may not match an individual's gender identity or may invoke feelings of gender dysphoria. This dynamic may contribute to the higher rates of unintended pregnancies seen in the LGBTQ+ community as compared to heterosexual peers,{{cite journal | vauthors = Everett BG, McCabe KF, Hughes TL | title = Sexual Orientation Disparities in Mistimed and Unwanted Pregnancy Among Adult Women | journal = Perspectives on Sexual and Reproductive Health | volume = 49 | issue = 3 | pages = 157–165 | date = September 2017 | pmid = 28598550 | pmc = 5819992 | doi = 10.1363/psrh.12032 }}{{cite journal | vauthors = Hodson K, Meads C, Bewley S | title = Lesbian and bisexual women's likelihood of becoming pregnant: a systematic review and meta-analysis | journal = BJOG | volume = 124 | issue = 3 | pages = 393–402 | date = February 2017 | pmid = 27981741 | pmc = 5299536 | doi = 10.1111/1471-0528.14449 }}{{cite journal | vauthors = Lindley LL, Walsemann KM | title = Sexual Orientation and Risk of Pregnancy Among New York City High-School Students | journal = American Journal of Public Health | volume = 105 | issue = 7 | pages = 1379–1386 | date = July 2015 | pmid = 25973807 | pmc = 4463368 | doi = 10.2105/ajph.2015.302553 }} which could in theory be ameliorated by the introduction of unisex contraceptives.

Novel male contraceptive options are predicted to reduce the incidence unintended pregnancies,{{Cite web |title=International Market Research |url=https://www.malecontraceptive.org/international-market-research.html |access-date=2024-02-09 |website=Male Contraceptive Initiative |language=en}} and being the product of an intended rather than unintended pregnancy has been shown to correlate with improved health and wellbeing outcomes in children.{{Cite journal | vauthors = David HP |date=1992 |title=Born Unwanted: Long-Term Developmental Effects of Denied Abortion |journal=Journal of Social Issues |volume=48 |issue=3 |pages=163–181 |doi=10.1111/j.1540-4560.1992.tb00902.x |issn=0022-4537}}{{cite journal | vauthors = David HP | title = Born unwanted, 35 years later: the Prague study | journal = Reproductive Health Matters | volume = 14 | issue = 27 | pages = 181–190 | date = May 2006 | pmid = 16713893 | doi = 10.1016/s0968-8080(06)27219-7 }} Additionally, reduced family size correlates with improved educational outcomes,{{Cite journal | vauthors = Downey DB |date=1995 |title=When Bigger Is Not Better: Family Size, Parental Resources, and Children's Educational Performance |journal=American Sociological Review |volume=60 |issue=5 |pages=746–761 |doi=10.2307/2096320 |jstor=2096320 |issn=0003-1224}} and children born after the introduction of family planning programs in the USA experienced a reduction in poverty rates, both in childhood and adulthood.{{cite journal | vauthors = Bailey MJ, Malkova O, Norling J | title = Do family planning programs decrease poverty? Evidence from public census data. | journal = CESifo Economic Studies | volume = 60 | issue = 2 | pages = 312–337 | date = 2014-03-06 | pmid = 25346655 | pmc = 4206087 | doi = 10.1093/cesifo/ifu011 }}

Unintended pregnancies rates increase as income decreases, both between countries{{cite journal | vauthors = Bearak J, Popinchalk A, Ganatra B, Moller AB, Tunçalp Ö, Beavin C, Kwok L, Alkema L | title = Unintended pregnancy and abortion by income, region, and the legal status of abortion: estimates from a comprehensive model for 1990-2019 | journal = The Lancet. Global Health | volume = 8 | issue = 9 | pages = e1152–e1161 | date = September 2020 | pmid = 32710833 | doi = 10.1016/s2214-109x(20)30315-6 | doi-access = free | hdl = 20.500.14005/1317 | hdl-access = free }} and between socioeconomic and racial groups within a given country.{{cite journal | vauthors = Finer LB, Zolna MR | title = Unintended pregnancy in the United States: incidence and disparities, 2006 | journal = Contraception | volume = 84 | issue = 5 | pages = 478–485 | date = November 2011 | pmid = 22018121 | pmc = 3338192 | doi = 10.1016/j.contraception.2011.07.013 }}  Women of color, especially Black women, in the United States and other developed countries have dramatically higher rates of death during and after birth and worse maternal health outcomes, due in part to systemic discrimination.{{cite journal | vauthors = Singh GK | title = Trends and Social Inequalities in Maternal Mortality in the United States, 1969-2018 | journal = International Journal of MCH and AIDS | volume = 10 | issue = 1 | pages = 29–42 | date = 2020-12-30 | pmid = 33442490 | doi = 10.21106/ijma.444 | pmc = 7792749 }}  Since unintended pregnancies can have negative effects on an individual's physical and mental health, educational attainment, and economic prospects, these higher unintended pregnancy rates likely contribute to the persistent socioeconomic gaps within and between societies.   It's therefore possible that the introduction of new male contraceptives would not only mitigate gender inequities, as discussed above, but racial and income inequities as well, by providing more ways for individuals to avoid unintended pregnancies.

In addition to the personal financial savings of avoiding unintended pregnancy mentioned above, on a societal level, contraceptives are a public health intervention with a high return on investment: for every dollar the United States government spends on family planning programs, it saves $7.09, for a total of over $13 billion per year.{{cite journal | vauthors = Frost JJ, Sonfield A, Zolna MR, Finer LB | title = Return on investment: a fuller assessment of the benefits and cost savings of the US publicly funded family planning program | journal = The Milbank Quarterly | volume = 92 | issue = 4 | pages = 696–749 | date = December 2014 | pmid = 25314928 | pmc = 4266172 | doi = 10.1111/1468-0009.12080 }} Unintended pregnancies in the United States are estimated to cause $4.5 billion in direct medical costs. New male contraceptives are likely to prevent some unintended pregnancies and therefore reduce these costs.

61% of unintended pregnancies end in abortion,{{Cite web |date=2020-06-10 |title=Unintended Pregnancy and Abortion Worldwide | work = Guttmacher Institute |url=https://www.guttmacher.org/fact-sheet/induced-abortion-worldwide |access-date=2024-02-10 |language=en}} whereas only 20% of all pregnancies end in abortion.{{cite journal | vauthors = Jones RK, Kirstein M, Philbin J | title = Abortion incidence and service availability in the United States, 2020 | journal = Perspectives on Sexual and Reproductive Health | volume = 54 | issue = 4 | pages = 128–141 | date = December 2022 | pmid = 36404279 | pmc = 10099841 | doi = 10.1363/psrh.12215 }} Interestingly, unintended pregnancy rates are higher in countries where abortion is illegal than those where abortion is legal, yet the incidence of abortion is similar between these groups of countries.{{cite journal | vauthors = Bearak J, Popinchalk A, Ganatra B, Moller AB, Tunçalp Ö, Beavin C, Kwok L, Alkema L | title = Unintended pregnancy and abortion by income, region, and the legal status of abortion: estimates from a comprehensive model for 1990-2019 | journal = The Lancet. Global Health | volume = 8 | issue = 9 | pages = e1152–e1161 | date = September 2020 | pmid = 32710833 | doi = 10.1016/s2214-109x(20)30315-6 | doi-access = free | hdl = 20.500.14005/1317 | hdl-access = free }} Illegal abortions are more likely to be unsafe, and there are an estimated 25 million unsafe abortions globally each year, leading to 50,000 - 70,000 yearly deaths and 5 million people with long-term health consequences.{{Cite web |date=2011-06-06 |title=Unsafe Abortion: The Missing Link in Global Efforts to Improve Maternal Health {{!}} Guttmacher Institute |url=https://www.guttmacher.org/gpr/2011/06/unsafe-abortion-missing-link-global-efforts-improve-maternal-health |access-date=2024-02-23 |website=www.guttmacher.org |language=en}}{{Cite web |date=2017-09-25 |title=Worldwide, an Estimated 25 Million Unsafe Abortions Occur Each Year {{!}} Guttmacher Institute |url=https://www.guttmacher.org/news-release/2017/worldwide-estimated-25-million-unsafe-abortions-occur-each-year |access-date=2024-02-23 |website=www.guttmacher.org |language=en}}{{cite journal | vauthors = Haddad LB, Nour NM | title = Unsafe abortion: unnecessary maternal mortality | journal = Reviews in Obstetrics & Gynecology | volume = 2 | issue = 2 | pages = 122–126 | date = 2009 | pmid = 19609407 | pmc = 2709326 }}{{cite journal | vauthors = Ahman E, Shah IH | title = New estimates and trends regarding unsafe abortion mortality | journal = International Journal of Gynaecology and Obstetrics | volume = 115 | issue = 2 | pages = 121–126 | date = November 2011 | pmid = 21885049 | doi = 10.1016/j.ijgo.2011.05.027 }} Importantly, increases in the prevalence and uptake of modern contraceptives have been shown to decrease unintended pregnancy and abortion rates when fertility rates are constant.{{cite journal | vauthors = Gebeyehu NA, Tegegne KD | title = Intention to Use Postpartum Contraceptive and Its Determinants in Sub-Saharan Africa: Systematic Review and Meta-Analysis | journal = Women's Health Reports | volume = 4 | issue = 1 | pages = 627–641 | date = 2003 | pmid = 38155871 | doi = 10.2307/3180995 | jstor = 3180995 | pmc = 10754424 }}{{cite journal | vauthors = Bongaarts J, Westoff CF | title = The potential role of contraception in reducing abortion | journal = Studies in Family Planning | volume = 31 | issue = 3 | pages = 193–202 | date = September 2000 | pmid = 11020931 | doi = 10.1111/j.1728-4465.2000.00193.x }}{{cite journal | vauthors = Bajos N, Le Guen M, Bohet A, Panjo H, Moreau C | title = Effectiveness of family planning policies: the abortion paradox | journal = PLOS ONE | volume = 9 | issue = 3 | pages = e91539 | date = 2014-03-26 | pmid = 24670784 | doi = 10.1371/journal.pone.0091539 | doi-access = free | pmc = 3966771 | bibcode = 2014PLoSO...991539B }} This suggests that the introduction of new forms of male contraception could prevent a significant number of abortions, save lives, and avoid unnecessary suffering.

{{Main|History of birth control|History of condoms|Vasectomy#History}}

A variety of plant extracts have been used throughout history in attempts to prevent pregnancy, though most were used by women, and the efficacy and safety of these methods is questionable.{{cite book |author=Dioscorides |url=http://www.therenaissanceman.org/images/DIOSCORIDES-Books_2_-_4.doc |title=De Materia Medica |archive-url=https://web.archive.org/web/20110728100517/http://www.therenaissanceman.org/images/DIOSCORIDES-Books_2_-_4.doc |archive-date=2011-07-28 |url-status=dead |orig-year=ca. 40 A.D}} (translated by Goodyer (1655), modified and published 1933 by Robert Gunther). The herbs are said to "extinguish conception".{{Cite news |date=1994-03-08 |title=In Ancient Times, Flowers and Fennel For Family Planning |url=https://www.nytimes.com/1994/03/08/science/in-ancient-times-flowers-and-fennel-for-family-planning.html |work=The New York Times |language=en-US |vauthors=Kolata G}}{{cite journal | vauthors = Sailani MR, Moeini H | title = Effect of Ruta graveolens and Cannabis sativa alcoholic extract on spermatogenesis in the adult wistar male rats | journal = Indian Journal of Urology | volume = 23 | issue = 3 | pages = 257–260 | date = July 2007 | pmid = 19718326 | pmc = 2721602 | doi = 10.4103/0970-1591.33720 | doi-access = free }}

Condoms made of animal organs or fabric have been in documented use since at least the 16th century,{{cite journal | vauthors = Youssef H | title = The history of the condom | journal = Journal of the Royal Society of Medicine | volume = 86 | issue = 4 | pages = 226–228 | date = April 1993 | pmid = 7802734 | pmc = 1293956 | doi = 10.1177/014107689308600415 }} and various types of penile coverings have been depicted and referenced in materials from cultures around the world as early as 3000 BCE, though it is not always clear that these coverings were used for birth control or protection from sexually transmitted infections.{{Cite book | vauthors = Collier A |title=The humble little condom: a history |date=2007 |publisher=Prometheus Books |isbn=978-1-59102-556-6 |edition=1st American paperback |location=Amherst, NY}} The 1800s saw the development of thick reusable rubber condoms, and thinner disposable latex rubber condoms entered production in the 1920s.{{Cite book |url=http://archive.org/details/sim_chemical-engineering_1930-02_37_2 |title=Chemical & Metallurgical Engineering 1930-02: Vol 37 Iss 2 |date=February 1930 |publisher=Access Intelligence LLC | via = Internet Archive |language=English}}{{Cite web | vauthors = Borge J |date=2021-02-11 |title=Durex condoms: how their teenage immigrant inventor was forgotten by history |url=http://theconversation.com/durex-condoms-how-their-teenage-immigrant-inventor-was-forgotten-by-history-152497 |access-date=2024-05-06 |website=The Conversation |language=en-US}}{{Cite book | vauthors = Borge J, Hall LA |url=https://www.worldcat.org/title/on1143645992 |title=Protective practices: a history of the London Rubber Company and the condom business |date=2020 |publisher=McGill-Queen's University Press |isbn=978-0-2280-0333-5 |location=Montreal; Kingston; London; Chicago |oclc=on1143645992}}

Vasectomy was first performed in humans in the late 1800s, but not initially as a method of voluntary birth control. Instead, it was first used as an attempted treatment (later proved to be ineffective) for enlarged prostates, and within a few years, one-sided vasectomy became popular as a supposed method of sexual rejuvenation in older men.{{cite journal | vauthors = Sheynkin YR | title = History of vasectomy | journal = The Urologic Clinics of North America | volume = 36 | issue = 3 | pages = 285–294 | date = August 2009 | pmid = 19643231 | doi = 10.1016/j.ucl.2009.05.007 | series = Vasectomy and Vasectomy Reversal: Important Issues }}{{cite journal | vauthors = Drake MJ, Mills IW, Cranston D | title = On the chequered history of vasectomy | journal = BJU International | volume = 84 | issue = 4 | pages = 475–481 | date = September 1999 | pmid = 10468765 | doi = 10.1046/j.1464-410x.1999.00206.x }} Although this rejuvenation treatment was ineffective pseudoscience and any perceived effects were likely due only to the placebo effect, many prominent men, such as Sigmund Freud and W.B. Yeats, sought out the procedure.{{Cite news | vauthors = Ellmann R |date=1985-05-09 |title=Yeats's Second Puberty |url=https://www.nybooks.com/articles/1985/05/09/yeatss-second-puberty/ |access-date=2024-05-06 |work=The New York Review of Books |language=en |volume=32 |issue=8 |issn=0028-7504}} In the early 1900s, the use of vasectomy took a darker turn, and it became widely promoted and practiced as a means of eugenic involuntary sterilization. It was not until the 1950s that vasectomy became widely used as a method for voluntary sterilization and family planning. Since then, vasectomy has undergone extensive technical improvements and innovations, such that it is no longer a single procedure, but a family of related procedures.{{cite journal | vauthors = Rogers MD, Kolettis PN | title = Vasectomy | journal = The Urologic Clinics of North America | volume = 40 | issue = 4 | pages = 559–568 | date = November 2013 | pmid = 24182975 | doi = 10.1016/j.ucl.2013.07.009 | series = Office Procedures in Urology }}

In the 1990s, and into the early 2000s, major pharmaceutical companies Organon, Wyeth, and Schering were pursuing preclinical and clinical development of various male contraceptive products, but in 2006, all three companies ceased development of these products within a short time of each other, for reasons that have not been publicly released.{{Cite magazine | vauthors = Goodman A |date=2008-08-03 |title= The Long Wait for Male Birth Control |url=https://content.time.com/time/health/article/0,8599,1829107,00.html |access-date=2024-05-07 |magazine=Time |language=en-US |issn=0040-781X}}

In 2013, the Male Contraceptive Initiative was founded with the goal of funding and supporting the development of new male contraceptives.{{Cite web |title=History |url=https://www.malecontraceptive.org/history.html |access-date=2024-05-07 |website=Male Contraceptive Initiative |language=en}}{{Cite web |title=Vision and Mission |url=https://www.malecontraceptive.org/vision-and-mission.html |access-date=2024-05-07 |website=Male Contraceptive Initiative |language=en}}

In 2020, Dr. Polina Lishko was awarded the MacArthur "Genius" Fellowship for her contributions to the understanding of sperm physiology, with the award specifically noting her work on "opening up new avenues in ... the development of male-specific or unisex contraceptives."{{Cite web |title=Polina V. Lishko |url=https://www.macfound.org/fellows/class-of-2020/polina-v-lishko |access-date=2024-05-07 |website=www.macfound.org |language=en}}

Many researchers have attempted to develop male contraceptive products over the last hundred years. A selection of these efforts (that are no longer in development as of 2024) are listed below.

• Hormonal
• Trestolone (MENT) was investigated as a contraceptive implant in the 1990s and early 2000s by the Population Council, but this molecule was never approved for contraceptive use.{{cite journal | vauthors = Nieschlag E, Kumar N, Sitruk-Ware R | title = 7α-methyl-19-nortestosterone (MENTR): the population council's contribution to research on male contraception and treatment of hypogonadism | journal = Contraception | volume = 87 | issue = 3 | pages = 288–295 | date = March 2013 | pmid = 23063338 | doi = 10.1016/j.contraception.2012.08.036 }}{{cite journal | vauthors = Sundaram K, Kumar N, Bardin CW | title = 7 alpha-methyl-nortestosterone (MENT): the optimal androgen for male contraception | journal = Annals of Medicine | volume = 25 | issue = 2 | pages = 199–205 | date = April 1993 | pmid = 8489761 | doi = 10.3109/07853899309164168 }}
• An injectable male contraceptive consisting of Testosterone undecanoate and Norethisterone enanthate reached Phase II clinical trials in 2008.{{Cite journal |title=Sperm suppression and contraceptive protection provided by norethisterone enantate (NET-EN) combined with testosterone undecanoate (TU) in healthy men |url=https://www.isrctn.com/holding |access-date=2024-05-08 |website=www.isrctn.com |doi=10.1186/isrctn07760234|doi-access=free | vauthors = Vogelsong K |url-access=subscription }} The injection was administered every 8 weeks, and it effectively and reversibly suppressed sperm production in at least 95% of the participants. However, in 2011 the trial was halted early on the recommendation of a World Health Organization Research Project Review Panel, based on their evaluation of adverse events, specifically noting "mood changes, depression, pain at the injection site, and increased libido". This decision generated significant controversy amongst scientists and in public media.
• Non-Hormonal
• WIN 18446 is a molecule initially developed by a pharmaceutical company called Sterling Drug that was shown to produce reversible infertility in rats. In the late 1950s, it was tested in male prisoners at the Oregon State Penitentiary, and while it showed effective and reversible suppression of sperm production with limited adverse effects, if men drank alcohol while taking WIN 18446, they experienced a severe Disulfiram-alcohol reaction, including nausea, vomiting, and heart palpitations, and so the molecule was not developed further at that time.{{cite journal | vauthors = Heller CG, Moore DJ, Paulsen CA | title = Suppression of spermatogenesis and chronic toxicity in men by a new series of bis(dichloroacetyl) diamines | journal = Toxicology and Applied Pharmacology | volume = 3 | issue = 1 | pages = 1–11 | date = January 1961 | pmid = 13713106 | doi = 10.1016/0041-008X(61)90002-3 | bibcode = 1961ToxAP...3....1H }} However, research on this class of compounds was renewed in 2006 by a team at University of Washington, who uncovered the mechanism of action for the contraceptive effect and the alcohol reaction (inhibition of Aldehyde dehydrogenase (ALDH) enzymes), and are attempting to produce molecules that selectively inhibit the sperm-specific isoform of the enzyme (ALDH1A2).{{cite journal | vauthors = Paik J, Haenisch M, Kim A, Snyder JM, Amory JK | title = Return to fertility, toxicology, and transgenerational impact of treatment with WIN 18,446, a potential male contraceptive, in mice | journal = Contraception | volume = 129 | pages = 110306 | date = January 2024 | pmid = 37813273 | pmc = 10959076 | doi = 10.1016/j.contraception.2023.110306 }}{{cite journal | vauthors = Amory JK | title = Male contraception | journal = Fertility and Sterility | volume = 106 | issue = 6 | pages = 1303–1309 | date = November 2016 | pmid = 27678037 | pmc = 5159259 | doi = 10.1016/j.fertnstert.2016.08.036 }}
• Gossypol, an extract of cotton, has been studied as a male contraceptive pill, and was given to thousands of men in China in the 1970s.{{Cite news |date=25 September 1979 |title=Thousands Try Male 'Pill' In China |url=https://www.nytimes.com/1979/09/25/archives/thousands-try-male-pill-in-china-in-china-thousands-try-a-male-pill.html |access-date=18 December 2023 |work=The New York Times |vauthors=Sullivan W}} It successfully decreased sperm production, leading to infertility without significant adverse effects, but this effect was permanent in a substantial percentage of the users, and so it was not pursued for widespread approval.{{cite journal | vauthors = Coutinho EM | title = Gossypol: a contraceptive for men | journal = Contraception | volume = 65 | issue = 4 | pages = 259–263 | date = April 2002 | pmid = 12020773 | doi = 10.1016/s0010-7824(02)00294-9 }} However, synthetic derivatives of gossypol that work through a similar mechanism of action, but more selectively target the sperm-specific Lactate Dehydrogenase C enzyme, are still in development as potential male contraceptives.{{cite journal | vauthors = Yu Y, Deck JA, Hunsaker LA, Deck LM, Royer RE, Goldberg E, Vander Jagt DL | title = Selective active site inhibitors of human lactate dehydrogenases A4, B4, and C4 | journal = Biochemical Pharmacology | volume = 62 | issue = 1 | pages = 81–89 | date = July 2001 | pmid = 11377399 | doi = 10.1016/S0006-2952(01)00636-0 }}
• Miglustat (Zavesca or NB-DNJ) is a drug approved for treatment of several rare lipid storage disorders. In several genetically-related strains of laboratory mice, it provided effective and fully reversible contraception,{{cite journal | vauthors = van der Spoel AC, Jeyakumar M, Butters TD, Charlton HM, Moore HD, Dwek RA, Platt FM | title = Reversible infertility in male mice after oral administration of alkylated imino sugars: a nonhormonal approach to male contraception | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 26 | pages = 17173–17178 | date = December 2002 | pmid = 12477936 | pmc = 139288 | doi = 10.1073/pnas.262586099 | doi-access = free | bibcode = 2002PNAS...9917173V }}{{cite journal | vauthors = Bone W, Walden CM, Fritsch M, Voigtmann U, Leifke E, Gottwald U, Boomkamp S, Platt FM, van der Spoel AC | title = The sensitivity of murine spermiogenesis to miglustat is a quantitative trait: a pharmacogenetic study | journal = Reproductive Biology and Endocrinology | volume = 5 | issue = 1 | pages = 1 | date = January 2007 | pmid = 17241468 | pmc = 1794412 | doi = 10.1186/1477-7827-5-1 | doi-access = free }} but later studies of showed no contraceptive effect in rabbits or humans.{{cite journal | vauthors = Amory JK, Muller CH, Page ST, Leifke E, Pagel ER, Bhandari A, Subramanyam B, Bone W, Radlmaier A, Bremner WJ | title = Miglustat has no apparent effect on spermatogenesis in normal men | journal = Human Reproduction | volume = 22 | issue = 3 | pages = 702–707 | date = March 2007 | pmid = 17067996 | doi = 10.1093/humrep/del414 | doi-access = free }}
• Various small molecules have been shown to cause infertility in rodents and other species by disrupting the junctions between Sertoli cells and elongating spermatids, leading to premature release of immature, nonfunctional sperm.{{cite journal | vauthors = Kim J, So B, Heo Y, So H, Jo JK | title = Advances in Male Contraception: When Will the Novel Male Contraception be Available? | language = English | journal = The World Journal of Men's Health | volume = 42 | issue = 3 | pages = 487–501 | date = January 2024 | pmid = 38164023 | doi = 10.5534/wjmh.230118 | doi-access = free | pmc = 11216971 }} These fertility-disrupting molecules include derivatives of lonidamine, such as Adjudin{{cite journal | vauthors = Mruk DD, Cheng CY | title = Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis | journal = Endocrine Reviews | volume = 25 | issue = 5 | pages = 747–806 | date = October 2004 | pmid = 15466940 | doi = 10.1210/er.2003-0022 }} and Gamendazole,{{cite journal | vauthors = Tash JS, Attardi B, Hild SA, Chakrasali R, Jakkaraj SR, Georg GI | title = A novel potent indazole carboxylic acid derivative blocks spermatogenesis and is contraceptive in rats after a single oral dose | journal = Biology of Reproduction | volume = 78 | issue = 6 | pages = 1127–1138 | date = June 2008 | pmid = 18218612 | doi = 10.1095/biolreprod.106.057810 }} and indenopyridine derivatives such as RTI-4587-073(l) (also known as CDB-4022).{{cite journal | vauthors = Service CA, Puri D, Hsieh TC, Patel DP | title = Emerging concepts in male contraception: a narrative review of novel, hormonal and non-hormonal options | journal = Therapeutic Advances in Reproductive Health | volume = 17 | pages = 26334941221138323 | date = 2023 | pmid = 36909934 | pmc = 9996746 | doi = 10.1177/26334941221138323 }} Toxicity, reversibility, and bioavailability challenges limited the development of lonidamide derivatives, though efforts to create more specific delivery vehicles partially ameliorated these problems.{{cite journal | vauthors = Mruk DD, Wong CH, Silvestrini B, Cheng CY | title = A male contraceptive targeting germ cell adhesion | journal = Nature Medicine | volume = 12 | issue = 11 | pages = 1323–1328 | date = November 2006 | pmid = 17072312 | doi = 10.1038/nm1420 }} A new lonidamide derivative called BHD that showed contraceptive effects in rodents was developed in 2023, but further characterization is needed.{{cite journal | vauthors = Gong S, Zhu S, Zhou P, Cheng CY, Li W, Yao W, Sun F | title = Discovering a Reversible Male Contraceptive Agent Derived from Lonidamine | journal = ACS Omega | volume = 8 | issue = 20 | pages = 18245–18254 | date = May 2023 | pmid = 37251173 | pmc = 10210193 | doi = 10.1021/acsomega.3c01840 }} Indenopyridine derivatives have not been fully evaluated for effects on fertility and toxicity, and as of 2024, it is unclear if work on these compounds is ongoing.{{cite journal | vauthors = Kim J, So B, Heo Y, So H, Jo JK | title = Advances in Male Contraception: When Will the Novel Male Contraception be Available? | language = English | journal = The World Journal of Men's Health | volume = 42 | issue = 3 | pages = 7–8 | date = January 2024 | pmid = 38164023 | doi = 10.5534/wjmh.230118 | doi-access = free | pmc = 11216971 }}
• In the 20th century, various small molecules such as α-chlorohydrin and 6-chloro-6-deoxy-glucose were shown to cause infertility in rodents, but these molecules also caused unacceptable systemic toxicity, and were not developed further.{{Cite book | vauthors = Plant TM, Zeleznik AJ |title=Knobil and Neill's physiology of reproduction |date=2015 |publisher=Elsevier/Academic Press |isbn=978-0-12-397175-3 |edition=4th |location=Amsterdam |pages=740–741}}
• Contraceptive immunization with sperm antigens has been found to be partially effective and reversible in male primates.{{cite journal | vauthors = O'rand MG, Widgren EE, Sivashanmugam P, Richardson RT, Hall SH, French FS, VandeVoort CA, Ramachandra SG, Ramesh V, Jagannadha Rao A | title = Reversible immunocontraception in male monkeys immunized with eppin | journal = Science | volume = 306 | issue = 5699 | pages = 1189–1190 | date = November 2004 | pmid = 15539605 | doi = 10.1126/science.1099743 | bibcode = 2004Sci...306.1189O | s2cid = 34816491 | url = http://eprints.iisc.ac.in/2456/1/reversible_immunocontraception.pdf }}
• Numerous plant extracts and naturally-derived molecules have been preliminarily evaluated for use as male contraceptives or spermicides. While some of these extracts have become the basis of more specific molecular drug development campaigns mentioned earlier in this article, others require more work to clarify the active ingredient, or further research into efficacy, toxicity, and reversibility.{{Cite journal |last1=Shunnarah |first1=Alana |last2=Tumlinson |first2=Robin |last3=Calderón |first3=Angela I. |date=2021-10-22 |title=Natural Products with Potential for Nonhormonal Male Contraception |url=https://pubs.acs.org/doi/10.1021/acs.jnatprod.1c00565 |journal=Journal of Natural Products |language=en |volume=84 |issue=10 |pages=2762–2774 |doi=10.1021/acs.jnatprod.1c00565 |pmid=34633803 |bibcode=2021JNAtP..84.2762S |issn=0163-3864|url-access=subscription }}{{Cite journal |last1=Hifnawy |first1=Mohammed S. |last2=Aboseada |first2=Mahmoud A. |last3=Hassan |first3=Hossam M. |last4=Tohamy |first4=Adel F. |last5=El Naggar |first5=El Moataz B. |last6=Abdelmohsen |first6=Usama Ramadan |date=2021 |title=Nature-inspired male contraceptive and spermicidal products |url=https://link.springer.com/10.1007/s11101-020-09721-5 |journal=Phytochemistry Reviews |language=en |volume=20 |issue=4 |pages=797–843 |doi=10.1007/s11101-020-09721-5 |bibcode=2021PChRv..20..797H |issn=1568-7767|url-access=subscription }}{{Cite journal |last1=Dias |first1=Tania R. |last2=Alves |first2=Marco G. |last3=Oliveira |first3=Pedro F. |last4=Silva |first4=Branca M. |title=Natural Products as Modulators of Spermatogenesis: The Search for a Male Contraceptive |url=https://www.eurekaselect.com/article/64840 |journal=Current Molecular Pharmacology |date=2015 |language=en |volume=7 |issue=2 |pages=154–166 |doi=10.2174/1874467208666150126155912|pmid=25620230 |url-access=subscription }} These molecules face an additional financial challenge in drug development, since unaltered natural products cannot be patented in the United States and many other countries, which reduces the interest of for-profit pharmaceutical companies in these compounds.{{Cite web |last=Lowe |first=Derek |date=8 Apr 2014 |title=Can You Patent A Natural Product? Prepare For a Different Answer |url=https://www.science.org/content/blog-post/can-you-patent-natural-product-prepare-different-answer |website=Science}}{{Cite web |last=christina.reilly@829llc.com |date=2016-05-12 |title=New USPTO Guidance On Patent Eligibility Of Natural Products |url=https://www.foley.com/insights/publications/2016/05/new-uspto-guidance-on-patent-eligibility-of-natura/ |access-date=2024-07-23 |website=Foley & Lardner LLP |language=en-US}}
• Vas-Occlusive
• The following vas-occusive device prototypes were developed in the late 20th and early 21st centuries, but are no longer in development.
• The intra-vas device (IVD) was a rod-shaped device intended to be inserted into the lumen of the vas deferens via a small incision.{{cite journal | vauthors = Cook LA, Van Vliet HA, Lopez LM, Pun A, Gallo MF | title = Vasectomy occlusion techniques for male sterilization | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 3 | pages = CD003991 | date = March 2014 | pmid = 24683020 | pmc = 7173716 | doi = 10.1002/14651858.CD003991.pub4 }}{{cite journal | vauthors = Song L, Gu Y, Lu W, Liang X, Chen Z | title = A phase II randomized controlled trial of a novel male contraception, an intra-vas device | journal = International Journal of Andrology | volume = 29 | issue = 4 | pages = 489–495 | date = August 2006 | pmid = 16573708 | doi = 10.1111/j.1365-2605.2006.00686.x | doi-access = free }}
• The “Shug” was a noninjectable device consisting of 2 silicone plugs with nylon tails to help anchor the plug to the vas deferens, and was inserted via the no-scalpel scrotal puncture method.{{cite journal | vauthors = Zaneveld LJ, Burns JW, Beyler S, Depel W, Shapiro S | title = Development of a potentially reversible vas deferens occlusion device and evaluation in primates | journal = Fertility and Sterility | volume = 49 | issue = 3 | pages = 527–533 | date = March 1988 | pmid = 3342906 | doi = 10.1016/s0015-0282(16)59785-4 | doi-access = free }}
• Injectable medical polyurethane was used as a vas-occlusive contraceptive for several hundred thousand men in China in the 1980s.{{cite journal | vauthors = Zhao SC | title = Vas deferens occlusion by percutaneous injection of polyurethane elastomer plugs: clinical experience and reversibility | journal = Contraception | volume = 41 | issue = 5 | pages = 453–459 | date = May 1990 | pmid = 2347193 | doi = 10.1016/0010-7824(90)90055-z }}

{{Notelist|group=note}}

{{Reflist}}

{{Commons category|Contraception for males}}

• [http://www.malecontraceptive.org/ Male Contraceptive Initiative]
• [https://www.nichd.nih.gov/about/org/dir/dph/officebranch/cdp National Institute of Child Health and Human Development]

• [https://www.ic-mc.info/ International Congress on Male Contraception]
• [https://andrologysociety.org/annual-meeting/ American Society for Andrology Meeting]
• [https://andrologysociety.org/testis-workshop/ North American Testis Workshop]
• {{usurped|1=[https://web.archive.org/web/20230402141013/https://etw2023.org/index.php/about-european-testis-workshops/ European Testis Workshop]}}
• [https://www.eshre.eu/ European Society of Human Reproduction and Embryology Annual Meeting]
• [http://ssr.org/ Society for the Study of Reproduction Annual Meeting]
• [https://www.grc.org/fertilization-and-activation-of-development-conference/2023/ Gordon Research Conference on Fertilization and Activation of Development]
• [https://www.grc.org/mammalian-reproduction-conference/2024/ Gordon Research Conference on Mammalian Reproduction]
• [https://www.bcm.edu/research/faculty-labs/martin-matzuk-lab/2023-national-contraception-meeting NICHD Contraceptive Development Meeting]
• [https://www.mbl.edu/education/advanced-research-training-courses/course-offerings/frontiers-reproduction Frontiers in Reproduction Summer Course]

• [https://theicfp.org/about International Conference on Family Planning]
• [https://www.nationalfamilyplanning.org/national-conference-2024-home National Family Planning and Reproduction Health Association Meeting]
• [https://ctcsrh.org/nrhc/ National Reproductive Health Conference]
• [https://societyfp.org/learning/annual-meeting/ Society of Family Planning Annual Meeting]

{{Birth control methods}}

{{Hormonal contraceptives}}

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