Male contraceptive


Male contraceptive

Male contraceptives include condoms, withdrawal (although medical professionals do not regard this as an effective method of contraception), and vasectomy.[1] In other animals, castration is commonly used for contraception. Other forms of male contraception are in various stages of research and development.[2]

Contents

Traditional methods

The withdrawal method has a failure rate of about 4% per year if used correctly at every act of intercourse.[3]

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.[4] One test in rats (20 milligrams of the 80% ethanol extract) found that these reduced sperm count by more than half.[5] In medieval Persia (and in other traditions as cited) these herbs were used for male contraception, as well as Gossypium herbaceum (Malvaceae),[6] Cyperus longus (Cyperaceae), Vitex pseudonegundo (Verbenaceae), Chenopodium ambrosioides (Chenopodiaceae),[7][8] Aristolochia indica (Aristolochiaceae),[9] Punica granatum (Punicaceae),[10] and Sarcostemma acidum (Asclepiadaceae).[11] However, the compound isolated from Gossypium, as well as other cotton seeds and okra (gossypol) has been abandoned as for contraceptive use because it was found to cause permanent infertility in ten to twenty percent of users.[12]

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.[13]

In 1995, researchers isolated compounds from a plant used in Chinese herbal medicine called Tripterygium wilfordii (, lei gong teng).[14]

In 2002, researchers fed extracts from the seeds of papaya fruits (Carica papaya) to monkeys. Subsequently, the monkeys had no sperm in their ejaculate.[15] 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.[16]

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.[17]

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.[18]

Methods in development

Pharmaceutical methods

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.[19] 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.[20]
  • 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.[21][22]
  • Adjudin, a non-toxic analog of lonidamine has been shown to cause reversible infertility in rats.[23] 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.[24]
  • 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.[25]
  • Multiple male hormonal contraceptive protocols have been developed. One is a combination protocol, involving injections of Depo-Provera to prevent spermatogenesis, combined with the topical application of testosterone gel to provide hormonal support.[26][27] Another is a monthly injection of testosterone undecanoate, which recently performed very well in a Phase III trial in China.[28][29]
  • Research has been performed on interference with the maturation of sperm in the epididymis.[30][31]
  • Phenoxybenzamine has been found to block ejaculation, which not only gives it the potential to be an effective contraceptive, but could also lead to much cleaner sex. Studies have found that the quality of the semen is unaffected and the results are reversible by simply discontinuing the treatment.[32]
  • 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.

Other techniques

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.[33]

Notes

  1. ^ Glasier A, Acceptability of contraception for men: a review, Contraception, 82(5):453-456, 2010, PMID 20933119
  2. ^ http://www.msnbc.msn.com/id/3543478/
  3. ^ Hatcher, RA; Trussel J, Stewart F, et al. (2000). Contraceptive Technology (18th ed.). New York: Ardent Media. ISBN 0-9664902-6-6. http://www.contraceptivetechnology.org/table.html. 
  4. ^ Dioscorides (ca. 40 A.D.). De Materia Medica. http://www.therenaissanceman.org/images/DIOSCORIDES-Books_2_-_4.doc.  (translated by Goodyer (1655), modified and published 1933 by Robert Gunther). The herbs are said to "extinguish conception".
  5. ^ 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): 257–60. doi:10.4103/0970-1591.33720. PMC 2721602. PMID 19718326. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2721602. 
  6. ^ Hadley MA, Lin YC, Dym M. (1981). "Effects of gossypol on the reproductive system of male rats". J Androl. (2): 190–9. 
  7. ^ Khaleghi Ghadiri M, Gorji A (February 2004). "Natural remedies for impotence in medieval Persia". International Journal of Impotence Research 16 (1): 80–3. doi:10.1038/sj.ijir.3901153. PMID 14963476. 
  8. ^ Conway GA, Slocumb JC (October 1979). "Plants used as abortifacients and emmenagogues by Spanish New Mexicans". Journal of Ethnopharmacology 1 (3): 241–61. doi:10.1016/S0378-8741(79)80014-8. PMID 232204. 
  9. ^ Pakrashi A, Pakrasi PL (April 1977). "Antispermatogenic effect of the extract of Aristolochia indica Linn on male mice". Indian Journal of Experimental Biology 15 (4): 256–9. PMID 914334. 
  10. ^ Prakash AO, Saxena V, Shukla S, et al. (1985). "Anti-implantation activity of some indigenous plants in rats". Acta Europaea Fertilitatis 16 (6): 441–8. PMID 3832714. 
  11. ^ Venma PK, Sharma A, Mathur A, et al. (March 2002). "Effect of Sarcostemma acidum stem extract on spermatogenesis in male albino rats". Asian Journal of Andrology 4 (1): 43–7. PMID 11907627. 
  12. ^ Coutinho EM (Apr 2002). "Gossypol: a contraceptive for men". Contraception 65 (4): 259–63. doi:10.1016/S0010-7824(02)00294-9. PMID 12020773. 
  13. ^ Deshpande VY, Mendulkar KN, Sadre NL (July 1980). "Male antifertility activity of Azadirachta Indica in mice". Journal of Postgraduate Medicine 26 (3): 167–70. PMID 7205685. http://www.jpgmonline.com/article.asp?issn=0022-3859;year=1980;volume=26;issue=3;spage=167;epage=70;aulast=Deshpande. 
  14. ^ Zhen QS, Ye X, Wei ZJ (February 1995). "Recent progress in research on Tripterygium: a male antifertility plant". Contraception 51 (2): 121–9. doi:10.1016/0010-7824(94)00018-R. PMID 7750290. 
  15. ^ 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. PMID 11907624. 
  16. ^ 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 ethnopharmacology 127 (2): 286–291. doi:10.1016/j.jep.2009.11.007. PMID 19914367.  edit
  17. ^ Mdhluli MC, van der Horst G (Oct 2002). "The effect of oleanolic acid on sperm motion characteristics and fertility of male Wistar rats". Lab Anim. 36 (4): 432–7. doi:10.1258/002367702320389107. PMID 12396287. 
  18. ^ "Heat Methods of Male Contraception". Male Conception Information Project. http://74.125.93.132/search?q=cache:46FbjlDtIg8J:www.newmalecontraception.org/heat.htm+http://www.newmalecontraception.org/heat.htm&cd=1&hl=en&ct=clnk&gl=us. 
  19. ^ 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. PMID 7782439. http://humrep.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=7782439. 
  20. ^ http://msmagazine.com/blog/blog/2010/07/02/a-pill-for-men-still-five-years-away/
  21. ^ Parry, Wynne "New Male Birth Control Concept Shows Promise", LiveScience, June 4, 2011, accessed June 6, 2011.
  22. ^ Chung, SS; Wang, X; Roberts, SS; Griffey, SM; Reczek, PR; Wolgemuth, DJ (2011). "Oral Administration of a Retinoic Acid Receptor Antagonist Reversibly Inhibits Spermatogenesis in Mice". Endocrinology 152 (6): 2492–502. doi:10.1210/en.2010-0941. PMC 3100616. PMID 21505053. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3100616. 
  23. ^ 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. 
  24. ^ Mruk DD, Wong CH, Silvestrini B, Cheng CY (November 2006). "A male contraceptive targeting germ cell adhesion". Nature Medicine 12 (11): 1323–8. doi:10.1038/nm1420. PMID 17072312. 
  25. ^ 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 Reproduction 78 (6): 1127–1138. doi:10.1095/​biolreprod.106.057810. PMID 18218612. 
  26. ^ a b Finn, Robert (May 2007). "Male Contraceptive Methods Are in the Pipeline". Ob.Gyn. News 42 (9): 8. doi:10.1016/S0029-7437(07)70395-6 (inactive 2010-01-29). http://www.obgynnews.com/article/S0029-7437%2807%2970395-6/preview. 
  27. ^ Nuzzo R (2006) Beyond condoms: male hormonal contraceptives may finally be on track. Los Angeles Times, 16 October.
  28. ^ 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 Metabolism 88 (2): 562–8. doi:10.1210/jc.2002-020447. PMID 12574181. 
  29. ^ 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 Metabolism 94 (6): 1910–5. doi:10.1210/jc.2008-1846. PMID 19293262. 
  30. ^ Turner TT, Johnston DS, Jelinsky SA (May 2006). "Epididymal genomics and the search for a male contraceptive". Molecular and Cellular Endocrinology 250 (1–2): 178–83. doi:10.1016/j.mce.2005.12.042. PMID 16458420. 
  31. ^ 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 Endocrinology 250 (1–2): 49–57. doi:10.1016/j.mce.2005.12.024. PMID 16442214. 
  32. ^ Kjaergaard N, Kjaergaard B, Lauritsen JG (June 1988). "Prazosin, an adrenergic blocking agent inadequate as male contraceptive pill". Contraception 37 (6): 621–9. doi:10.1016/0010-7824(88)90008-X. PMID 2899490. 
  33. ^ 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. PMID 17067996. 

References

Further reading


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