Male contraceptive

Male contraceptives, also known as male birth control, are methods of preventing pregnancy by leveraging male physiology.[1] Globally, the most common forms of male contraceptives include condoms, vasectomy, and withdrawal. Men are largely limited to these forms of contraception, and combined, male contraceptives make up less than one-third of total contraceptive use.[2][3][4]

Novel forms of male contraception are in clinical and nonclinical stages of research and development, however, none have reached regulatory approval for widespread use.[5][6][7] Studies of men indicate that around half of survey populations are interested using a novel contraceptive method, and they display interest in a wide variety of contraceptive methods including hormonal and non-hormonal pills, gels, and implants.[8][9][10]

Currently available methods

Vasectomy
Main article: Vasectomy

Vasectomy is surgical procedure for permanent male sterilization usually performed in a physician's office in an outpatient procedure.[11] During the procedure, the vasa deferentia of a patient are severed, and then tied or sealed to prevent the transport of sperm through the reproductive tract and thereby causing a pregnancy. Vasectomy is an effective procedure, with less than 0.15% of partners becoming pregnant within the first 12 months after the procedure.[12] Vasectomy is also a widely reliable and safe method of contraception, and complications are both rare and minor.[13] However, due to the presence of sperm retained beyond the blocked vasa deferentia, vasectomies are not initially effective and the remaining sperm must be cleared through ejaculation and / or time.[14] Vasectomies can be reversed, though rates of successful reversal are variable, and the procedure is often costly.[11]

Condoms
Main article: Condom
Male contraceptive
A rolled-up condom

A condom is a sheathed barrier device that is rolled onto an erect penis before intercourse and retains ejaculated semen, thereby preventing pregnancy.[15] Condoms are marginally effective when compared to vasectomy or modern methods of contraception for women, and have a typical-use failure rate of 18%.[12] However, condoms have the advantage of providing protection against some sexually transmitted infections such as HIV/AIDS.[16][17] Condoms may be combined with other forms of contraception (such as spermicide) for greater protection.[18]

Withdrawal
Main article: Coitus interruptus

The withdrawal method, or 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.[19][20] Withdrawal is considered an ineffective contraceptive method, with typical use failure rates of around 22%.[11][12]

Chance of pregnancy during first year of use - Pearl Index
Method Typical use Perfect use
Vasectomy 0.15% 0.1%
Condoms 18% 2%
Withdrawal 22% 4%

Other currently available methods for men include abstinence, outercourse, and other non-vaginal means of ejaculation.

Research into new methods

Research is ongoing to generate novel male contraceptive products based on drugs and medical devices. Products in development currently include long-acting reversible contraceptives (LARCs), daily transdermal gels, daily oral pills, injectables, implants, and oral on-demand contraceptives.[21][22][23] Development of novel male contraceptive methods has ongoing for many decades, but progress been stymied by a lack of industry involvement. Most funding for male contraceptive research is derived from government or philanthropic sources.[24][25][26][27]

Because of the nature of the male reproductive system, many stages of sperm development, and complex regulatory and signaling pathways involved in maturation steps such as capacitation and fertilization, a contraceptive effect in men can be elicited through multiple mechanisms of action.[28] For example, a potential drug product leveraging a mechanism that targets spermatogenesis will likely also result in a reduction in sperm count and testis weight for the user, as well as some measure of an onset time, similar to a vasectomy, where the product is not effective immediately after administration.[29] Other mechanisms that target later steps of the sperm life cycle could have unique characteristics such as near on-demand contraceptive efficacy through oral administration or topical administration in a female user.[30] Many research programs are also early in development and have yet to consider delivery modality. Application of diverse dosage forms and innovative drug delivery platforms such as controlled release formulations and microneedles could generate further diversity in male contraceptive products.[31]

Sperm targets can also be leveraged in the female reproductive system, potentially generating new female or unisex contraceptives.[32][3]

Hormonal Contraceptives

Hormonal contraceptives for men, similar to hormonal female methods, use exogenous steroids to interrupt physiologic hypothalamic-pituitary-gonadal pathways. These exogenous steroids suppress secretion of the gonadotropins LH and FSH, which further impairs testosterone production and sperm generation in the testes. This reduced sperm output manifests 4–12 weeks following initiation of the contraceptive method.[33]

Multiple methods of male hormonal contraception have been tested in clinical trials and found to be effective and reversible.[34][35][36][37][38][39] Currently, there are contraceptive products in development through the NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Contraceptive Clinical Trials Network (CCTN).[40]

  • Nestorone®/Testosterone (Nes/T) Gel is a transdermal gel that users apply to the upper arms and shoulders once daily.[41][42] Developed as a collaboration between the NICHD and Population Council, Nes/T is currently in clinical trials (ClinicalTrials.gov ID NCT03452111) being evaluated for safety and efficacy.[43][44][45][46]
  • Dimethandrolone undecanoate (DMAU) is a novel progestogenic androgen which contains both androgenic and progestational activities that facilitate contraceptive activity while maintaining libido and other androgen-dependent functions. DMAU is currently being tested in clinical trials in both oral (NCT01382069 & NCT03455075) and injectable (NCT02927210) forms.
  • 11β -Methyl Nortestosterone Dodecylcarbonate (11β-MNTDC) is another progestogenic androgen in clinical development (NCT03298373) as an oral contraceptive for men.[47]
  • 7-Alpha-methyl-19-nortestosterone (MENT) has been formulated as a contraceptive implant.[48]

Some hormonal contraceptives for men such as testosterone undecanoate have faced criticism for their side effect profiles and the perceived tolerability of users.[49][50]

Some anabolic steroids may exhibit suppressive effects on spermatogenesis, but none are currently approved for use as a male contraceptive.[51]

Non-hormonal Contraceptives
  • Non-hormonal oral medications based on extracts and derivatives of Tripterygium wilfordii (雷公籐, lei gong teng), a plant used in Traditional Chinese Medicine, were studied clinically from the mid-1980s to mid-1990s.[52] In 2021, a trial published in Nature Communications showed that one derivative, triptonide, was safe, effective, and reversible in laboratory mice and monkeys.[53]
  • Pharmacological inhibition of chromatin remodeling by the pan-inhibitor JQ1 on the target BRDT has been shown to produce reversible sterility in male mice.[54][55][56]
  • Immunocontraception targeting sperm antigens has been found to be effective in male primates.[57]
  • Calcium channel blockers such as nifedipine may cause reversible infertility by altering the lipid metabolism of sperm so that they are not able to fertilize an egg.[58] Research at Israel's Bar-Ilan University show that as of June 2010, such a pill may be five years away. Testing it on mice has been found to be effective, with no side effects.[59]
  • BMS-189453, a compound that interferes with the vitamin A pathway has been shown to render male mice sterile for the course of the treatment without affecting libido. Once taken off the compound, the mice continued to make sperm. The mechanism of action includes blocking the conversion of vitamin A into its active form retinoic acid which binds to retinoic receptors which is needed to initiate sperm production.[60][61] This can be done, for instance, by blocking an aldehyde dehydrogenase called RALDH3 (ALDH1A2), which converts retinaldehyde into retionic acid in testes. Past attempts to do this failed because the blocking compounds were not sufficiently specific and also blocked other aldehyde dehydrogenases, such as those responsible for the alcohol metabolism, causing serious side effects.[62] Another way is blocking retionic receptors themselves, although it can also have serious side effects.[60]
  • Phenoxybenzamine has been found to block ejaculation, which gives it the potential to be an effective contraceptive. Studies have found that the quality of the semen is unaffected and the results are reversible by simply discontinuing the treatment.[63]
  • A male birth control pill based on ouabain, a plant extract used by traditional African hunters to stop the hearts of game, has been shown to reduce sperm motility sufficiently for effective contraception in rats.[64]
  • YCT529, a Vitamin A receptor antagonist, is in development by the startup YourChoice Pharmaceuticals as a male contraceptive.[65]
  • Soluble adenylyl cyclase inhibition has been demonstrated to temporarily reduce male fertility in mice.[66][67][68][69][70]
  • EP055[71][72]

Vas-occlusive male contraceptive approaches

Vas-occlusive contraception provides a contraceptive effect through physical blockage of the vas deferens, the portion of the male reproductive system 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 tissue, reversible vas-occlusive methods provide partial or total blockage of the tissue while leaving it intact. In vasectomy, fascial interposition, electrocautery, clips, and sutures are often used to occlude the open ends of the vas deferentia after excision, but these methods are still used for permanent sterilization.[73][74] Novel surgical methods for vas-occlusive male contraception are largely focused on creating long-acting reversible options, and reversibility of most vas-occlusive devices consist of a second procedure that removes the blockage.[75]

  • ADAM is a hydrogel-based male contraceptive implant in clinical development (NCT05134428) by Contraline, Inc.[76] Previously known as Echo-VR, 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.[77] Results from an exploratory trial in humans were published in 2023.[78]
  • Reversible inhibition of sperm under guidance (RISUG) is an injectable male contraceptive implant composed of the polymer styrene maleic anhydride (SMA) and is proposed to provide protection from pregnancy for more than ten years.[79][80] RISUG has been in development in India since the 1970s and has been studied in rats, rabbits, non-human primates, and most recently, men.[81][82] To reverse RISUG, a second injection of bicarbonate is proposed to dissolve the substance and be fully flushed from the tissue to restore fertility, though reversibility has not yet been demonstrated in humans.[83] RISUG may act through both chemical and occlusive mechanisms. RISUG is in human testing in India and has been patented in India, China, Bangladesh and the United States.
  • Plan A, formerly known as Vasalgel, is a brand name of polymer gel injection based on the same SMA platform as RISUG. Licensed by the Parsemus Foundation and developed by NEXT Life Sciences, Plan A is currently in preclinical studies.[84][85][86][87][88][89][90]

Other methods have been proposed that use ultrasound treatment to reverse the blockage, though these methods are largely in basic science studies.[91]

Thermal male contraceptive approaches
Silicone rings, worn by users for male contraceptive purposes.

Heat-based contraception causes thermal dysregulation of spermatogenesis and is a well-established means of producing a contraceptive effect in men.[92][93][94][95] Normally, the testis are held at a temperature approximately 2°C below that of basal body temperature, and are thermoregulated by smooth muscle tissue in the scrotum. Increases in testicular temperature of as little as 2°C are associated with decreased sperm count and decreased sperm quality, and the effect has been shown to be directly related to heat intensity and frequency.

Various approaches have been taken to induce hyperthermia in the testes, including the application of simple heat via exogenous “wet” means, such as a heated water bath, and “dry” means such as insulated or externally-heated underwear.[96][97] Other thermal methods utilize endogenous body temperature to halt spermatogenesis, usually by holding the testes in the inguinal canal for an extended period through the use of a wearable device such as underwear or a silicone ring.[98] Currently, no thermal male methods of contraception have been approved by a regulatory agency for use as a contraceptive method.

The mechanism by which hyperthermia disrupts spermatogenesis is still not fully understood, though generally, these methods are thought of as safe.[99] In the many human studies, no severe consequences or side effects have been reported, though there are some safety concerns, generally related to genetic risks of increasing testicular temperature, either from a testicular cancer risk, drawing a parallel to the increased cancer rates seen in cryptorchidism, or from alteration of sperm DNA, resulting in reproductive harm to potential offspring.[97]

Another approach to heat the testes involves conducting electromagnetic energy via ultrasound to the testes through immersion in liquid baths or direct application of a transducer probe.[100] Ultrasonic methods may also have a non-thermal component to their mechanism.[101]

In 2021, a design of a water bath based ultrasonic male contraceptive product called COSO was a finalist for the James Dyson Award.[102]

Other methods in basic science studies include magnetic targeting and magnetic hyperthermia.[103]

Other approaches
  • In 2002, researchers fed extracts from the seeds of papaya fruits (Carica papaya) to monkeys. Subsequently, the monkeys had no sperm in their ejaculate.[40] Traditionally used for contraception, papaya seeds had no apparent ill effects on the testes or other organs of rats tested with a long-term treatment.[104]
  • Innovative condom approaches[105]

Abandoned research
  • Miglustat (Zavesca or NB-DNJ) is a drug approved for treatment of several rare lipid storage disorder diseases. In mice, it provided effective and fully reversible contraception. But it seems this effect was only true for several genetically related strains of laboratory mice. Miglustat showed no contraceptive effect in other mammals.[106]
  • Silodosin, an α1-adrenoceptor antagonist with high uroselectivity, approved by the FDA to treat Benign Prostatic Hyperplasia (BPH), has been shown to decrease sperm count when taken in at 5 times normal doses.[107]
  • Gossypol, an extract of cotton, has been studied as a male contraceptive pill. It decreased sperm production; however this is permanent in 20% of people.[108]
  • Gamendazole, a derivative of lonidamine, shows semi-reversible infertility in rats. The mechanism of action is thought to be disruption of Sertoli cell function, resulting in decreased levels of inhibin B.[109]
  • Adjudin, a non-toxic analog of lonidamine has been shown to cause reversible infertility in rats.[110] The drug disrupts the junctions between nurse cells (Sertoli cells) in the testes and forming spermatids. The sperm are released prematurely and never become functional gametes. A new targeted delivery mechanism has made Adjudin much more effective.[111]
  • The intra-vas device (IVD) is a rod-shaped device intended to be inserted into the vasal lumen via a small incision. The outer shell of the intra‐vas device (IVD) is mainly urethane, and filled with medical grade nylon thread.[112][113] Two grooves near the head and tail are intended to fix the device within the vas and to prevent sperm transport between the device and the vas wall.
  • The “Shug” is a noninjectable device consisting of 2 silicone plugs with nylon tails to help anchor the plug to the vas, and is inserted via the no-scalpel method.[114]
  • Injectable medical polyurethane (MPU)

Impact

It is predicted that introduction of a long-acting reversible contraception for males could decrease the rate of unintended pregnancy.[115][23]

Acceptability

Men consistently report high levels of interest in novel forms of male contraception. Men's willingness to use novel male contraception is linked to gender-equitable attitudes in an online survey.[116][8][45]

Multiple small-scale acceptability questionnaires also indicate high levels of interest in male contraception.[117][118]

Acceptability of some thermal methods has been reported in the literature.[119][120]

History

Contraceptives for use by men have been described in the writings of Antiqiuty. Dioscorides, ca. 40 A.D., described the contraceptive property of hemp seeds (Cannabis sativa) and rue (Ruta graveolens) in De Materia Medica, a text widely used into medieval times.[121] One test in rats (20 milligrams of the 80% ethanol extract) found that these reduced sperm count by more than half.[122] In medieval Persia (and in other traditions as cited) these herbs were used for male contraception, as well as Gossypium herbaceum (Malvaceae),[123] Cyperus longus (Cyperaceae), Vitex pseudonegundo (Verbenaceae), Chenopodium ambrosioides (Chenopodiaceae),[78][124] Aristolochia indica (Aristolochiaceae),[5] Punica granatum (Punicaceae),[47] and Sarcostemma acidum (Asclepiadaceae).[102] However, the compound isolated from Gossypium, as well as other cotton seeds and okra (gossypol) has been abandoned for contraceptive use because it was found to cause permanent infertility in ten to twenty percent of users.[125]

[126]

In Indian traditional medicine, uses of the neem tree were described in Ayurvedic medicine, by Sushruta and in the Rasarathasamucchaya, Sarangadhara, Bhavaprakasha and Bhisagya Ratnavali. Held traditionally to have antifertility effects, its leaves were demonstrated to reduce pregnancy rate and litter size in a test of male rats.[33]

References
  1. http://www.plannedparenthood.org/health-topics/birth-control-4211.htm >.
  2. United Nations. "Contraceptive Use by Method 2019" (PDF).
  3. Guttmacher Institute (7 April 2021). "Contraceptive Use in the United States by Method".
  4. Haakenstad A, Angelino O, Irvine CM, Bhutta ZA, Bienhoff K, Bintz C, et al. (July 2022). "Measuring contraceptive method mix, prevalence, and demand satisfied by age and marital status in 204 countries and territories, 1970-2019: a systematic analysis for the Global Burden of Disease Study 2019". Lancet. 400 (10348): 295–327. doi:10.1016/s0140-6736(22)00936-9. PMC 9304984. PMID 35871816.
  5. Gorvett Z. "The weird reasons there still isn't a male contraceptive pill". BBC Future.
  6. Gibbens S (2023-03-03). "Birth control options for men are advancing. Here's how they work". National Geographic Magazine. Retrieved 2023-10-12.
  7. Barber R (Dec 4, 2022). "In the hunt for a male contraceptive, scientists look to stop sperm in their tracks". National Public Radio. Retrieved Oct 12, 2023.
  8. Glasier A (November 2010). "Acceptability of contraception for men: a review". Contraception. 82 (5): 453–456. doi:10.1016/j.contraception.2010.03.016. PMID 20933119.
  9. Heinemann K, Saad F, Wiesemes M, White S, Heinemann L (February 2005). "Attitudes toward male fertility control: results of a multinational survey on four continents". Human Reproduction. 20 (2): 549–556. doi:10.1093/humrep/deh574. PMID 15608042.
  10. Friedman M (2019). "Interest Among U.S. Men for New Male Contraceptive Options" (PDF). Male Contraceptive Initiative. Retrieved Oct 12, 2023.
  11. Hatcher RA (2023). Contraceptive Technology (22rd ed.). Managing Contraception LLC. ISBN 9781284299267.
  12. "Contraceptive Effectiveness in the United States". Guttmacher Institute. 2020-01-23. Retrieved 2023-10-12.
  13. Yang F, Li J, Dong L, Tan K, Huang X, Zhang P, et al. (July 2021). "Review of Vasectomy Complications and Safety Concerns". The World Journal of Men's Health. 39 (3): 406–418. doi:10.5534/wjmh.200073. PMC 8255399. PMID 32777870.
  14. "How effective is vasectomy? | NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development". www.nichd.nih.gov. 2022-02-18. Retrieved 2023-10-12.
  15. "Condom | Definition of Condom by Merriam-Webster". Merriam-webster.com. Retrieved 2016-05-14.
  16. "What are the Benefits and Advantages of Using Condoms?". www.plannedparenthood.org. Retrieved 2023-10-12.
  17. Hatcher RA, Trussel J, Nelson AL, et al. (2007). "Contraceptive Technology" (19th ed.). Archived from the original on 2008-05-31. Retrieved 2016-10-10.
  18. Kestelman P, Trussell J (1991). "Efficacy of the simultaneous use of condoms and spermicides". Family Planning Perspectives. 23 (5): 226–7, 232. doi:10.2307/2135759. JSTOR 2135759. PMID 1743276.
  19. "Withdrawal". Student Health and Counseling Services. University of California - Davis. Retrieved 2019-11-08.
  20. Carroll JL (2012). Sexuality Now: Embracing Diversity. Cengage Learning. ISBN 978-1-111-83581-1.
  21. "What Is In Development". Male Contraceptive Initiative. Retrieved 2023-10-12.
  22. Abbe CR, Page ST, Thirumalai A (September 2020). "Male Contraception". The Yale Journal of Biology and Medicine. 93 (4): 603–613. PMC 7513428. PMID 33005125.
  23. Anderson DJ, Johnston DS (April 2023). "A brief history and future prospects of contraception". Science. 380 (6641): 154–158. Bibcode:2023Sci...380..154A. doi:10.1126/science.adf9341. PMID 37053322. S2CID 258112296.
  24. Wang CC. "Male Birth Control Is in Development, but Barriers Still Stand in the Way". Scientific American. Retrieved 2023-10-12.
  25. "Birth control for men". Chemical & Engineering News. Retrieved 2023-10-12.
  26. Sitruk-Ware R (2018-05-11). "Getting contraceptives for men to the market will take pharma's help". STAT. Retrieved 2023-10-12.
  27. "G-FINDER data portal". Policy Cures Research. Retrieved Oct 12, 2023.
  28. "Mechanisms of Male Contraception". Male Contraceptive Initiative. Retrieved 2023-10-12.
  29. "Spermatogenesis – Mechanisms of Male Contraception". Male Contraceptive Initiative. Retrieved 2023-10-12.
  30. "Sperm Motility – Mechanisms of Male Contraception". Male Contraceptive Initiative. Retrieved 2023-10-12.
  31. Kim YC, Park JH, Prausnitz MR (November 2012). "Microneedles for drug and vaccine delivery". Advanced Drug Delivery Reviews. 64 (14): 1547–1568. doi:10.1016/j.addr.2012.04.005. PMC 3419303. PMID 22575858.
  32. "Finally, the promise of male birth control in a pill: Compound makes mice reversibly infertile". ScienceDaily. Retrieved 2018-03-09.
  33. Page ST, Blithe D, Wang C (2022). "Hormonal Male Contraception: Getting to Market". Frontiers in Endocrinology. 13: 891589. doi:10.3389/fendo.2022.891589. PMC 9203677. PMID 35721718.
  34. "Contraceptive efficacy of testosterone-induced azoospermia in normal men". The Lancet. 336 (8721): 955–959. October 1990. doi:10.1016/0140-6736(90)92416-F. S2CID 25825354.
  35. World Health Organization Task Force on Methods for the Regulation of Male Fertility (April 1996). "Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men". Fertility and Sterility. 65 (4): 821–829. doi:10.1016/S0015-0282(16)58221-1. PMID 8654646.
  36. McLachlan RI, McDonald J, Rushford D, Robertson DM, Garrett C, Baker HW (August 2000). "Efficacy and acceptability of testosterone implants, alone or in combination with a 5alpha-reductase inhibitor, for male hormonal contraception". Contraception. 62 (2): 73–78. doi:10.1016/S0010-7824(00)00139-6. PMID 11102590.
  37. Turner L, Conway AJ, Jimenez M, Liu PY, Forbes E, McLachlan RI, Handelsman DJ (October 2003). "Contraceptive efficacy of a depot progestin and androgen combination in men". The Journal of Clinical Endocrinology and Metabolism. 88 (10): 4659–4667. doi:10.1210/jc.2003-030107. PMID 14557437.
  38. Gu Y, Liang X, Wu W, Liu M, Song S, Cheng L, et al. (June 2009). "Multicenter contraceptive efficacy trial of injectable testosterone undecanoate in Chinese men". The Journal of Clinical Endocrinology and Metabolism. 94 (6): 1910–1915. doi:10.1210/jc.2008-1846. PMID 19293262.
  39. Gu YQ, Wang XH, Xu D, Peng L, Cheng LF, Huang MK, et al. (February 2003). "A multicenter contraceptive efficacy study of injectable testosterone undecanoate in healthy Chinese men". The Journal of Clinical Endocrinology and Metabolism. 88 (2): 562–568. doi:10.1210/jc.2002-020447. PMID 12574181.
  40. "CDP Research: Developing Hormonal Contraception Methods for Men | NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development". www.nichd.nih.gov. 2022-02-16. Retrieved 2023-10-10.
  41. "With a New Gel, the Future of Male Birth Control Looks Bright". Yahoo News. 2023-03-01. Retrieved 2023-10-09.
  42. "What Happens When Men Take Hormonal Birth Control?". Cosmopolitan. 2022-02-22. Retrieved 2023-10-12.
  43. Amory JK, Blithe DL, Sitruk-Ware R, Swerdloff RS, Bremner WJ, Dart C, et al. (August 2023). "Design of an international male contraceptive efficacy trial using a self-administered daily transdermal gel containing testosterone and segesterone acetate (Nestorone)". Contraception. 124: 110064. doi:10.1016/j.contraception.2023.110064. PMID 37210024. S2CID 258800752.
  44. Ilani N, Roth MY, Amory JK, Swerdloff RS, Dart C, Page ST, et al. (October 2012). "A new combination of testosterone and nestorone transdermal gels for male hormonal contraception". The Journal of Clinical Endocrinology and Metabolism. 97 (10): 3476–3486. doi:10.1210/jc.2012-1384. PMC 3462927. PMID 22791756.
  45. Roth MY, Shih G, Ilani N, Wang C, Page ST, Bremner WJ, et al. (October 2014). "Acceptability of a transdermal gel-based male hormonal contraceptive in a randomized controlled trial". Contraception. 90 (4): 407–412. doi:10.1016/j.contraception.2014.05.013. PMC 4269220. PMID 24981149.
  46. Anawalt BD, Roth MY, Ceponis J, Surampudi V, Amory JK, Swerdloff RS, et al. (November 2019). "Combined nestorone-testosterone gel suppresses serum gonadotropins to concentrations associated with effective hormonal contraception in men". Andrology. 7 (6): 878–887. doi:10.1111/andr.12603. PMC 6768743. PMID 30969032.
  47. Nguyen BT, Yuen F, Farrant M, Thirumalai A, Fernando F, Amory JK, et al. (November 2021). "Acceptability of the oral hormonal male contraceptive prototype, 11β-methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC), in a 28-day placebo-controlled trial". Contraception. 104 (5): 531–537. doi:10.1016/j.contraception.2021.06.009. PMC 8995005. PMID 34153318.
  48. Nieschlag E, Kumar N, Sitruk-Ware R (March 2013). "7α-methyl-19-nortestosterone (MENTR): the population council's contribution to research on male contraception and treatment of hypogonadism". Contraception. 87 (3): 288–295. doi:10.1016/j.contraception.2012.08.036. PMID 23063338.
  49. Behre HM, Zitzmann M, Anderson RA, Handelsman DJ, Lestari SW, McLachlan RI, et al. (December 2016). "Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men". The Journal of Clinical Endocrinology and Metabolism. 101 (12): 4779–4788. doi:10.1210/jc.2016-2141. PMID 27788052.
  50. Abbe C, Roxby AC (April 2020). "Assessing safety in hormonal male contraception: a critical appraisal of adverse events reported in a male contraceptive trial". BMJ Sexual & Reproductive Health. 46 (2): 139–146. doi:10.1136/bmjsrh-2018-200206. PMC 8029306. PMID 31754066.
  51. El Osta R, Almont T, Diligent C, Hubert N, Eschwège P, Hubert J (2016). "Anabolic steroids abuse and male infertility". Basic and Clinical Andrology. 26: 2. doi:10.1186/s12610-016-0029-4. PMC 4744441. PMID 26855782.
  52. Zhen QS, Ye X, Wei ZJ (February 1995). "Recent progress in research on Tripterygium: a male antifertility plant". Contraception. 51 (2): 121–129. doi:10.1016/0010-7824(94)00018-R. PMID 7750290.
  53. Chang Z, Qin W, Zheng H, Schegg K, Han L, Liu X, et al. (February 2021). "Triptonide is a reversible non-hormonal male contraceptive agent in mice and non-human primates". Nature Communications. 12 (1): 1253. Bibcode:2021NatCo..12.1253C. doi:10.1038/s41467-021-21517-5. PMC 7902613. PMID 33623031.
  54. "A male contraceptive pill in the making?". Retrieved 17 August 2012.
  55. Matzuk MM, McKeown MR, Filippakopoulos P, Li Q, Ma L, Agno JE, et al. (August 2012). "Small-molecule inhibition of BRDT for male contraception". Cell. 150 (4): 673–684. doi:10.1016/j.cell.2012.06.045. PMC 3420011. PMID 22901802.
  56. Wisniewski, Andrea; Georg, Gunda I. (2020-03-15). "BET proteins: Investigating BRDT as a potential target for male contraception". Bioorganic & Medicinal Chemistry Letters. 30 (6): 126958. doi:10.1016/j.bmcl.2020.126958. ISSN 1464-3405. PMC 7023680. PMID 32019712.
  57. O'rand MG, Widgren EE, Sivashanmugam P, Richardson RT, Hall SH, French FS, et al. (November 2004). "Reversible immunocontraception in male monkeys immunized with eppin" (PDF). Science. 306 (5699): 1189–1190. Bibcode:2004Sci...306.1189O. doi:10.1126/science.1099743. PMID 15539605. S2CID 34816491.
  58. Hershlag A, Cooper GW, Benoff S (March 1995). "Pregnancy following discontinuation of a calcium channel blocker in the male partner". Human Reproduction. 10 (3): 599–606. doi:10.1093/oxfordjournals.humrep.a135996. PMID 7782439.
  59. Kissling E (2 July 2010). "A Pill for Men-Still Five Years Away". Ms. Magazine.
  60. Parry W (4 June 2011). "New Male Birth Control Concept Shows Promise". LiveScience.
  61. Chung SS, Wang X, Roberts SS, Griffey SM, Reczek PR, Wolgemuth DJ (June 2011). "Oral administration of a retinoic Acid receptor antagonist reversibly inhibits spermatogenesis in mice". Endocrinology. 152 (6): 2492–2502. doi:10.1210/en.2010-0941. PMC 3100616. PMID 21505053.
  62. Kean S (October 2012). "Contraception research. Reinventing the pill: male birth control". Science. 338 (6105): 318–320. Bibcode:2012Sci...338..318K. doi:10.1126/science.338.6105.318. PMID 23087225.
  63. Kjaergaard N, Kjaergaard B, Lauritsen JG (June 1988). "Prazosin, an adrenergic blocking agent inadequate as male contraceptive pill". Contraception. 37 (6): 621–629. doi:10.1016/0010-7824(88)90008-X. PMID 2899490.
  64. "Heart-Stopping Arrow Poison Could be Key to Male Birth Control".
  65. A non-hormonal pill could soon expand men’s birth control options. ACS News 23 March 2022
  66. Balbach M, Rossetti T, Ferreira J, Ghanem L, Ritagliati C, Myers RW, et al. (February 2023). "On-demand male contraception via acute inhibition of soluble adenylyl cyclase". Nature Communications. 14 (1): 637. Bibcode:2023NatCo..14..637B. doi:10.1038/s41467-023-36119-6. PMC 9929232. PMID 36788210.
  67. Sullivan W. "Male Birth Control Drug 'Stops Sperm in Their Tracks' in Study of Mice". Smithsonian Magazine. Retrieved 2023-10-12.
  68. "Male contraceptive pill prototype stops sperm swimming". BBC News. 2023-02-14. Retrieved 2023-10-12.
  69. Johnson CY (2023-02-14). "Quick-acting male birth control drug shows promise in the lab". Washington Post. ISSN 0190-8286. Retrieved 2023-10-12.
  70. Jarvis L (2023-02-14). "Give Him a Birth Control Pill for Valentine's Day". Bloomberg.com. Retrieved 2023-10-12.
  71. Gomes, Antoniel A. S.; Santos, Natália C. M.; Rosa, Leonardo R.; Borges, Rafael J.; Fontes, Marcos R. M.; Hamil, Katherine G.; O'Rand, Michael G.; Silva, Erick J. R. (2023-09-01). "Interactions of the male contraceptive target EPPIN with semenogelin-1 and small organic ligands". Scientific Reports. 13 (1): 14382. Bibcode:2023NatSR..1314382G. doi:10.1038/s41598-023-41365-1. ISSN 2045-2322. PMC 10474283. PMID 37658081.
  72. O'Rand, Michael G.; Hamil, Katherine G.; Adevai, Tiffany; Zelinski, Mary (2018). "Inhibition of sperm motility in male macaques with EP055, a potential non-hormonal male contraceptive". PLOS ONE. 13 (4): e0195953. Bibcode:2018PLoSO..1395953O. doi:10.1371/journal.pone.0195953. ISSN 1932-6203. PMC 5908160. PMID 29672554.
  73. Cook, Lynley A.; Van Vliet, Huib A. A. M.; Lopez, Laureen M.; Pun, Asha; Gallo, Maria F. (2014-03-30). "Vasectomy occlusion techniques for male sterilization". The Cochrane Database of Systematic Reviews. 2014 (3): CD003991. doi:10.1002/14651858.CD003991.pub4. ISSN 1469-493X. PMC 7173716. PMID 24683020.
  74. Clenney, Timothy L.; Higgins, James C. (1999-07-01). "Vasectomy Techniques". American Family Physician. 60 (1): 137–146. PMID 10414634.
  75. Thirumalai, Arthi; Amory, John K. (2021-04-27). "Emerging approaches to male contraception". Fertility and Sterility. 115 (6): 1369–1376. doi:10.1016/j.fertnstert.2021.03.047. ISSN 1556-5653. PMC 8169637. PMID 33931201.
  76. "Contraline Announces First Patients Successfully Implanted in Male Contraceptive Study". www.businesswire.com. 2022-11-10. Retrieved 2023-10-13.
  77. "Male contraceptive implanted at Epworth Freemasons in world first - Epworth HealthCare". www.epworth.org.au. Retrieved 2023-10-13.
  78. Anderson P, Bolton D, Lawrentschuk N (April 2023). "PD42-08 Preliminary Results of a First in Human Dose-Ranging Clinical Trial of Adam®, a Nonhormonal Hydrogel-Based Male Contraceptive". Journal of Urology. 209 (Supplement 4). doi:10.1097/JU.0000000000003352.08. ISSN 0022-5347. S2CID 257727789.
  79. Millikan, Arikia (2015-04-01). "The Perfect Birth Control for Men Is Here. Why Can't We Use It?". Vice. Retrieved 2023-10-13.
  80. "Will the world's 'first male birth control shot' work?". BBC News. 2019-12-06. Retrieved 2023-10-13.
  81. Khilwani, Barkha; Badar, Ayesha; Ansari, Abdul S.; Lohiya, Nirmal K. (2020). "RISUG® as a male contraceptive: journey from bench to bedside". Basic and Clinical Andrology. 30: 2. doi:10.1186/s12610-020-0099-1. ISSN 2051-4190. PMC 7017607. PMID 32082579.
  82. Guha SK, Singh G, Ansari S, Kumar S, Srivastava A, Koul V, et al. (October 1997). "Phase II clinical trial of a vas deferens injectable contraceptive for the male". Contraception. 56 (4): 245–250. doi:10.1016/s0010-7824(97)00142-x. PMID 9408706.
  83. Ansari, Abdul S.; Badar, Ayesha; Balasubramanian, Krithika; Lohiya, Nirmal K. (2017). "Contraception with RISUG® and functional reversal through DMSO and NaHCO3 in male rabbits". Asian Journal of Andrology. 19 (4): 389–395. doi:10.4103/1008-682X.185000. ISSN 1745-7262. PMC 5507081. PMID 27586026.
  84. "Home". NEXT Life Sciences. Retrieved 2023-10-13.
  85. "Vasalgel, a Multi-year Contraceptive". Retrieved 19 February 2018.
  86. Altstedter A (2017-04-04). "Male contraceptive is being blocked by drug companies who make billions from the female pill". The Independent. Retrieved 2023-10-12.
  87. "$1.55M Raised for Plan A™ Male Birth Control Product, Seeking Clinical Trials in 2023". Yahoo Finance. 2023-06-02. Retrieved 2023-10-12.
  88. Waller, Donald; Bolick, David; Lissner, Elaine; Premanandan, Christopher; Gamerman, Gary (2017). "Reversibility of Vasalgel™ male contraceptive in a rabbit model". Basic and Clinical Andrology. 27: 8. doi:10.1186/s12610-017-0051-1. ISSN 2051-4190. PMC 5381074. PMID 28417005.
  89. Colagross-Schouten, Angela; Lemoy, Marie-Josee; Keesler, Rebekah I.; Lissner, Elaine; VandeVoort, Catherine A. (2017). "The contraceptive efficacy of intravas injection of Vasalgel™ for adult male rhesus monkeys". Basic and Clinical Andrology. 27: 4. doi:10.1186/s12610-017-0048-9. ISSN 2051-4190. PMC 5294830. PMID 28191316.
  90. Waller, Donald; Bolick, David; Lissner, Elaine; Premanandan, Christopher; Gamerman, Gary (2016). "Azoospermia in rabbits following an intravas injection of Vasalgel ™". Basic and Clinical Andrology. 26: 6. doi:10.1186/s12610-016-0033-8. ISSN 2051-4190. PMC 4812607. PMID 27030808.
  91. Wang, Zi-Qi; Liu, Zhong-Qing; Zhao, Chang-Hao; Zhang, Kuo; Kang, Zhi-Jian; Qu, Tian-Rui; Zeng, Fan-Shu; Guo, Peng-Yu; Tong, Zhi-Chao; Wang, Chang-Lin; Wang, Ke-Liang; Wang, Hong-Lei; Xu, Yin-Sheng; Wang, Wan-Hui; Chu, Mao-lin (2022-04-26). "An Ultrasound-Induced Self-Clearance Hydrogel for Male Reversible Contraception". ACS Nano. 16 (4): 5515–5528. doi:10.1021/acsnano.1c09959. ISSN 1936-0851. PMID 35352555. S2CID 247791477.
  92. Macleod, John; Hotchkiss, Robert S. (1941-05-01). "The Effect of Hyperpyrexia Upon Spermatozoa Counts in Men". Endocrinology. 28 (5): 780–784. doi:10.1210/endo-28-5-780. ISSN 0013-7227.
  93. Wallach, Edward E.; Kandeel, Fouad R.; Swerdloff, Ronald S. (1988-01-01). "Role of temperature in regulation of spermatogenesis and the use of heating as a method for contraception". Fertility and Sterility. 49 (1): 1–23. doi:10.1016/S0015-0282(16)59640-X. ISSN 0015-0282. PMID 3275550.
  94. Robinson, Derek (1968-04-22). "Control of Human Spermatogenesis Intrascrotal Temperature". JAMA: The Journal of the American Medical Association. 204 (4): 290. doi:10.1001/jama.1968.03140170006002. ISSN 0098-7484.
  95. Fahim, M. S.; Fahim, Z.; Harman, J.; Thompson, I.; Montie, J.; Hall, D. G. (August 1977). "Ultrasound as a new method of male contraception". Fertility and Sterility. 28 (8): 823–831. doi:10.1016/S0015-0282(16)42735-4. ISSN 0015-0282. PMID 407106.
  96. Fahim, M. S.; Fahim, Z.; Der, R.; Hall, D. G.; Harman, J. (May 1975). "Heat in male contraception (hot water 60 degrees C, infrared, microwave, and ultrasound)". Contraception. 11 (5): 549–562. doi:10.1016/0010-7824(75)90109-2. ISSN 0010-7824. PMID 1139942.
  97. Soufir, Jean-Claude (2017). "Hormonal, chemical and thermal inhibition of spermatogenesis: contribution of French teams to international data with the aim of developing male contraception in France". Basic and Clinical Andrology. 27: 3. doi:10.1186/s12610-016-0047-2. ISSN 2051-4190. PMC 5237323. PMID 28101363.
  98. Labourie, Paul; Ferrari, Bianca (2023-08-30). "I Made My Own DIY Birth Control By Pushing My Balls Into My Body". Vice. Retrieved 2023-10-13.
  99. Durairajanayagam, Damayanthi; Agarwal, Ashok; Ong, Chloe (2015-01-01). "Causes, effects and molecular mechanisms of testicular heat stress". Reproductive Biomedicine Online. 30 (1): 14–27. doi:10.1016/j.rbmo.2014.09.018. ISSN 1472-6491. PMID 25456164.
  100. Tsuruta, James K.; Dayton, Paul A.; Gallippi, Caterina M.; O'Rand, Michael G.; Streicker, Michael A.; Gessner, Ryan C.; Gregory, Thomas S.; Silva, Erick J. R.; Hamil, Katherine G.; Moser, Glenda J.; Sokal, David C. (2012-01-30). "Therapeutic ultrasound as a potential male contraceptive: power, frequency and temperature required to deplete rat testes of meiotic cells and epididymides of sperm determined using a commercially available system". Reproductive Biology and Endocrinology: RB&E. 10: 7. doi:10.1186/1477-7827-10-7. ISSN 1477-7827. PMC 3340307. PMID 22289508.
  101. Sewak, Robert; Teng, Bettina; Learman, Lee A.; Hennekens, Charles H. (September 2017). "Male contraception: Prospects for sound and ultrasound". Medical Hypotheses. 107: 1–4. doi:10.1016/j.mehy.2017.06.010. ISSN 1532-2777. PMID 28915951.
  102. "COSO – The new way of male contraception". James Dyson Award. Retrieved 2023-10-10.
  103. Ding, Weihua; Chen, Zhichuan; Gu, Yayun; Chen, Zhengru; Zheng, Yanqiong; Sun, Fei (2021-07-28). "Magnetic Testis Targeting and Magnetic Hyperthermia for Noninvasive, Controllable Male Contraception via Intravenous Administration". Nano Letters. 21 (14): 6289–6297. Bibcode:2021NanoL..21.6289D. doi:10.1021/acs.nanolett.1c02181. ISSN 1530-6992. PMID 34232048. S2CID 235756835.
  104. Goyal S, Manivannan B, Ansari AS, Jain SC, Lohiya NK (February 2010). "Safety evaluation of long term oral treatment of methanol sub-fraction of the seeds of Carica papaya as a male contraceptive in albino rats". Journal of Ethnopharmacology. 127 (2): 286–291. doi:10.1016/j.jep.2009.11.007. PMID 19914367.
  105. Lee C. "The search to make a perfect condom". www.bbc.com. Retrieved 2023-10-12.
  106. Amory JK, Muller CH, Page ST, Leifke E, Pagel ER, Bhandari A, et al. (March 2007). "Miglustat has no apparent effect on spermatogenesis in normal men". Human Reproduction. 22 (3): 702–707. doi:10.1093/humrep/del414. PMID 17067996.
  107. "CHMP Assessment Report for Silodyx (International Nonproprietary Name: silodosin)" (PDF). Europeans Medicine Agency. 10 January 2010.
  108. Coutinho EM (April 2002). "Gossypol: a contraceptive for men". Contraception. 65 (4): 259–263. doi:10.1016/s0010-7824(02)00294-9. PMID 12020773.
  109. Tash JS, Attardi B, Hild SA, Chakrasali R, Jakkaraj SR, Georg GI (June 2008). "A novel potent indazole carboxylic acid derivative blocks spermatogenesis and is contraceptive in rats after a single oral dose". Biology of Reproduction. 78 (6): 1127–1138. doi:10.1095/biolreprod.106.057810. PMID 18218612.
  110. Mruk DD, Cheng CY (October 2004). "Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis". Endocrine Reviews. 25 (5): 747–806. doi:10.1210/er.2003-0022. PMID 15466940.
  111. Mruk DD, Wong CH, Silvestrini B, Cheng CY (November 2006). "A male contraceptive targeting germ cell adhesion". Nature Medicine. 12 (11): 1323–1328. doi:10.1038/nm1420. PMID 17072312. S2CID 19460327.
  112. Cook, Lynley A.; Van Vliet, Huib A. A. M.; Lopez, Laureen M.; Pun, Asha; Gallo, Maria F. (2014-03-30). "Vasectomy occlusion techniques for male sterilization". The Cochrane Database of Systematic Reviews. 2014 (3): CD003991. doi:10.1002/14651858.CD003991.pub4. ISSN 1469-493X. PMC 7173716. PMID 24683020.
  113. Song, L.; Gu, Y.; Lu, W.; Liang, X.; Chen, Z. (2006-03-27). "A phase II randomized controlled trial of a novel male contraception, an intra‐vas device". International Journal of Andrology. 29 (4): 489–495. doi:10.1111/j.1365-2605.2006.00686.x. ISSN 0105-6263. PMID 16573708. Retrieved Oct 13, 2023.
  114. Zaneveld, L. J.; Burns, J. W.; Beyler, S.; Depel, W.; Shapiro, S. (1988-03-01). "Development of a potentially reversible vas deferens occlusion device and evaluation in primates". Fertility and Sterility. 49 (3): 527–533. doi:10.1016/s0015-0282(16)59785-4. ISSN 0015-0282. PMID 3342906.
  115. Dorman E, Perry B, Polis CB, Campo-Engelstein L, Shattuck D, Hamlin A, et al. (January 2018). "Modeling the impact of novel male contraceptive methods on reductions in unintended pregnancies in Nigeria, South Africa, and the United States". Contraception. 97 (1): 62–69. doi:10.1016/j.contraception.2017.08.015. PMC 5732079. PMID 28887053.
  116. "La CMT" [archive] (consulter on 7 February 2019)
  117. Buck, Kirstin A.; Stadick, Jessica L.; Frazier, Marian L. (2020-09-01). "Preparing for sperm-targeted contraception: College students' perceptions and intentions related to non-hormonal intravas injectable gel". Public Health Nursing (Boston, Mass.). 37 (5): 639–646. doi:10.1111/phn.12761. ISSN 1525-1446. PMID 32627239. S2CID 220367503.
  118. Giacometti, A.; Huyghe, E.; Ferretti, L.; Moreau, D. (2023-10-06). "[Acceptability of innovative male contraceptive methods among major of age heterosexual adult men in France in 2021]". Progres en Urologie: Journal de l'Association Francaise d'Urologie et de la Societe Francaise d'Urologie: S1166–7087(23)00225–7. doi:10.1016/j.purol.2023.09.022. ISSN 1166-7087. PMID 37806909. S2CID 263750193.
  119. Joubert, Samuel; Tcherdukian, Jessica; Mieusset, Roger; Perrin, Jeanne (2022-11-01). "Thermal male contraception: A study of users' motivation, experience, and satisfaction". Andrology. 10 (8): 1500–1510. doi:10.1111/andr.13264. ISSN 2047-2927. PMID 35934916. S2CID 250199471.
  120. Amouroux, Marie; Mieusset, Roger; Desbriere, Raoul; Opinel, Pierre; Karsenty, Gilles; Paci, Marine; Fernandes, Sara; Courbiere, Blandine; Perrin, Jeanne (2018). "Are men ready to use thermal male contraception? Acceptability in two French populations: New fathers and new providers". PLOS ONE. 13 (5): e0195824. Bibcode:2018PLoSO..1395824A. doi:10.1371/journal.pone.0195824. ISSN 1932-6203. PMC 5973589. PMID 29813095.
  121. Dioscorides. De Materia Medica. Archived from the original on 2011-07-28. (translated by Goodyer (1655), modified and published 1933 by Robert Gunther). The herbs are said to "extinguish conception".
  122. Sailani MR, Moeini H (July 2007). "Effect of Ruta graveolens and Cannabis sativa alcoholic extract on spermatogenesis in the adult wistar male rats". Indian Journal of Urology. 23 (3): 257–260. doi:10.4103/0970-1591.33720. PMC 2721602. PMID 19718326.
  123. Hadley MA, Lin YC, Dym M (8 July 1981). "Effects of Gossypol on the Reproductive System of Male Rats". Journal of Andrology. 2 (4): 190–199. doi:10.1002/j.1939-4640.1981.tb00615.x.
  124. Conway GA, Slocumb JC (October 1979). "Plants used as abortifacients and emmenagogues by Spanish New Mexicans". Journal of Ethnopharmacology. 1 (3): 241–261. doi:10.1016/s0378-8741(79)80014-8. PMID 232204.
  125. Coutinho EM (April 2002). "Gossypol: a contraceptive for men". Contraception. 65 (4): 259–263. doi:10.1016/S0010-7824(02)00294-9. PMID 12020773.
  126. Kolata, Gina (1994-03-08). "In Ancient Times, Flowers and Fennel For Family Planning". The New York Times. ISSN 0362-4331. Retrieved 2023-10-13.
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