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.
In 2002, researchers fed extracts from the seeds of papaya fruits (Carica papaya) to monkeys. Subsequently, the monkeys had no sperm in their ejaculate. 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.
In 2002, tests were performed on male rats using oleanolic acid, extracted from Eugenia jambolana, a tree in the southern part of Africa. The tests demonstrated that the chemical was found to reversibly lower the rats' sperm motility without affecting the sperm count.
Heat-based contraception, dating in concept to the writings of Hippocrates, involves heating the testicles to prevent the formation of sperm. Requiring the maintenance of testes at 116 °F(47 °C) (just below the threshold of pain) for 45 minutes, it is not a widely appealing technique, but a variant employing ultrasound has been under investigation.
Methods in development
RISUG/VasalGel consists of injecting a polymer gel, styrene maleic anhydride in dimethyl sulfoxide, into the vas deferens. The polymer has a positive charge, and when negatively charged sperm pass through the vas deferens, the charge differential severely damages the sperm. A second injection washes out the substance and restores fertility. As of 2011[update], RISUG is in Phase III of human testing in India and has been patented in India, China, Bangladesh and the United States.
Inhibition of chromatin remodeling by binding to a pocket on BRDT has been shown to produce reversible sterility in male mice.JQ1, a selective BRDT inhibitor which acts in this manner, is currently under development as a non-hormonal male contraceptive drug. It effectively blocks the production of sperm by the testes, and lacks the adverse effects of previously researched hormonal contraceptives for men.
One goal of research is to develop a male oral contraceptive, a male contraceptive that can be taken in pill form by mouth, similar to the existing oral contraceptive pill for women.
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. Recent 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.
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. 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. Another way is blocking retionic receptors themselves, although it can also have serious side effects.
Adjudin, a non-toxic analog of lonidamine has been shown to cause reversible infertility in rats. 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.
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.
Research has been performed on interference with the maturation of sperm in the epididymis.
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.
Silodosin, an α1-adrenoceptor antagonist with high uroselectivity, has been shown to completely block ejaculation in human males while permitting the sensation of orgasm.
Trestolone is an anabolic steroid that has been shown to significantly reduce sperm count.
Vasectomy is a surgical procedure for male sterilization and/or permanent birth control. During the procedure, the vasa deferentia of a man are severed, and then tied/sealed in a manner such to prevent sperm from entering into the seminal stream (ejaculate). Vasectomies are usually performed in a physician's office or medical clinic. CDC research has estimated there is a probability of 11 failures per 1,000 procedures over 2 years; half of the failures occurred in the first three months after the vasectomy, and no failures occurred after 72 weeks. Due to the presence of sperm retained beyond the blocked vasa deferentia, vasectomies only become effective about three months following the operation.
Research on the safety and effectiveness of using ultrasound treatments to kill sperm has undergone since the idea originally came about following experiments in the 1970s by Mostafa S. Fahim which noticed ultrasound killed microbes and decreased fertility. As of 2012 a study conducted on rats found that two 15-minute treatments of ultrasound delivered 2 days apart in a warm salt bath effectively lowered their sperm count to below fertile levels. Another small study involved dogs, and found that after three ultrasound applications the dogs' ejaculate contained no sperm. Further experiments on its effectiveness on humans, the longevity of the results, and its safety have yet to be conducted.
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.
^Guha, Sujoy; Singh G, Ansari S, Kumar S, Srivastava A, Koul V, Das HC, Malhotra RL, Das SK. (Oct 1997). "Phase II clinical trial of a vas deferens injectable contraceptive for the male.". Contraception56 (4): 245–50. PMID9408706.|accessdate= requires |url= (help)
^ abc Expanding Options for Male Contraception. Planned Parenthood Advocates of Arizona. August 8, 2011. Retrieved April 1, 2012.
^Dioscorides (ca. 40 A.D.). De Materia Medica. (translated by Goodyer (1655), modified and published 1933 by Robert Gunther). The herbs are said to "extinguish conception".
^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 Urology23 (3): 257–60. doi:10.4103/0970-1591.33720. PMC2721602. PMID19718326.
^Hadley MA, Lin YC, Dym M. (1981). "Effects of gossypol on the reproductive system of male rats". J Androl. (2): 190–9.
^Khaleghi Ghadiri M, Gorji A (February 2004). "Natural remedies for impotence in medieval Persia". International Journal of Impotence Research16 (1): 80–3. doi:10.1038/sj.ijir.3901153. PMID14963476.
^Lohiya NK, Manivannan B, Mishra PK et al. (Mar 2002). "Chloroform extract of Carica papaya seeds induces long-term reversible azoospermia in langur monkey". Asian J Androl.4 (1): 17–26. PMID11907624.
^Goyal, S.; Manivannan, B.; Ansari, A.; Jain, S.; Lohiya, N. (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 Ethnopharmacology127 (2): 286–291. doi:10.1016/j.jep.2009.11.007. PMID19914367. edit
^O'Rand, MG; EE Widgren, P Sivashanmugam, RT Richardson, SH Hall, FS French, CA Vande Voort, SG Ramachandra, V Ramesh, A Jagannadha Roa (2004). "Reversible immunocontraception in male monkeys immunized with Eppin". Science306 (5699): 1189–90. doi:10.1126/science.1099743. PMID15539605.
^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 Reviews25 (5): 747–806. doi:10.1210/er.2003-0022. PMID15466940.
^Mruk DD, Wong CH, Silvestrini B, Cheng CY (November 2006). "A male contraceptive targeting germ cell adhesion". Nature Medicine12 (11): 1323–8. doi:10.1038/nm1420. PMID17072312.
^Tash, Joseph; Attardi, B; Hild, SA; Chakrasali, R; Jakkaraj, SR; Georg, GI (July 2008). "A Novel Potent Indazole Carboxylic Acid Derivative Blocks Spermatogenesis and Is Contraceptive in Rats after a Single Oral Dose". Biology of Reproduction78 (6): 1127–1138. doi:10.1095/biolreprod.106.057810. PMID18218612.
^Gu YQ, Wang XH, Xu D et al. (February 2003). "A multicenter contraceptive efficacy study of injectable testosterone undecanoate in healthy Chinese men". The Journal of Clinical Endocrinology and Metabolism88 (2): 562–8. doi:10.1210/jc.2002-020447. PMID12574181.
^Gu Y, Liang X, Wu W et al. (June 2009). "Multicenter contraceptive efficacy trial of injectable testosterone undecanoate in Chinese men". The Journal of Clinical Endocrinology and Metabolism94 (6): 1910–5. doi:10.1210/jc.2008-1846. PMID19293262.
^Turner TT, Johnston DS, Jelinsky SA (May 2006). "Epididymal genomics and the search for a male contraceptive". Molecular and Cellular Endocrinology250 (1–2): 178–83. doi:10.1016/j.mce.2005.12.042. PMID16458420.
^Gottwald U, Davies B, Fritsch M, Habenicht UF (May 2006). "New approaches for male fertility control: HE6 as an example of a putative target". Molecular and Cellular Endocrinology250 (1–2): 49–57. doi:10.1016/j.mce.2005.12.024. PMID16442214.
^Amory JK, Muller CH, Page ST et al. (March 2007). "Miglustat has no apparent effect on spermatogenesis in normal men". Human Reproduction (Oxford, England)22 (3): 702–7. doi:10.1093/humrep/del414. PMID17067996.