Indian Journal of Experimental Biology Vol. 43. November 2005. pp. 1032-1041 Review Article Male contraception: Expanding reproductive choice M RajaJakshmi" Department of Reproductive Biology. All India Institute of Medical Sciences. New Delhi 110 029. India The development of steroid-based oral contraceptives had revolutionized the availability of contraceptive choice for women. In order to expand the contraceptive options for couples by developing an acceptable. safe and effective male contraceptive. scientists have been experimenting with various steroidal/non-steroidal regimens to suppress testicular sperm production. The non-availability of a long-acting androgen was a limiting factor in the development of a male contraceptive regimen since all currently tested anti-spermatogenic agents also concurrently decrease circulating testosterone levels. A combination regimen of long-acting progestogen and androgen would have advantage over an androgen-alone modality since the dose of androgen required would be much smaller in the combination regimen. thereby decreasing the adverse effects of high steroid load. The progestogen in the combination regimen would act as the primary anti-spermatogenic agent. Currently. a number of combination regimens using progestogen or GnRH analogues combined with androgen are undergoing trials. The side effects of long-term use of androgens and progestogens have also undergone evaluation in primate models and the results of these studies need to be kept in view. while considering steroidal regimens for contraceptive use in men. Efforts are also being made to popularize non-scalpel vasectomy and to develop condoms of greater acceptability. The development of contraceptive vaccines for men. using sperm surface epitopes not expressed in female reproductive tract as source. still requires considerable research efforts. Keywords: Androgens. Condom. Male contraception. Progestogens. Spermatogenesis The steadily expanding population in developing article reviews the recent developments in the area of countries is now of global concern due to its impact male contraception and highlights the research done on health and societal dynamics. The development of by Indian scientists. oral contraceptives for women initiated a revolution in It may be argued that research efforts for contraceptive options. While this was a major developing male oriented methods are not a priority landmark in expanding contraceptive choice for since men are reluctant to opt for contraception, but women, a similar breakthrough ha~ not taken place in published data show that men form 26% and 11 % of the field of male contraception. contraceptive users (adopting vasectomy, and condom New contraceptive options for men, both hormonal use, respectively) in developed and developing and non-hormonal, are required urgently since regions of the world I. Even in a setting like India vasectomy, withdrawal and condom use are where the contraceptive use of condom and inadequate and have many limitations, which are well vasectomy by men is a dismal 5% (ref. 2), it was known. Attempts to use unique sperm surface found possible to enhance male involvement by using 3 epitopes that are not expressed in the female appropriate intervention strategies . It is also likely reproductive tract as source to develop contraceptive that the contraceptive choice of men from different vaccines for men have not yielded any major socio-cultural environments and age groups may be successful lead. Increasingly, t-fforts are being different, thus requiring a wider spectrum of options. focused on the development of hormonal agents that Major attempts to develop an effective male would induce adequate level of spermatogenic contraceptive have focused on different aspects of suppression that is not compatible with fertility. This sperm development, maturation and transport. The present review will focus on research efforts towards *Presebt address-National Academy of Mecical Sciences. Ansari (1) prevention of sperm deposition, (2) prevention of Nagar, New Dellhi 110 029. India sperm transport and, (3) inhibition of Phone: 26589289; 26589326; Fax: 26588992 E-mail: [email protected] spermatogenesis. RAJALAKSHMI: MALE CONTRACEPTION 1033 Prevention of spenn deposition insertion techniques were tested. A high level of Condoms contraceptive efficacy was obtained with two SHUG 9 Condoms have been in use as a barrier method to devices . In Indonesia, removable vas occlusion has prevent sperm deposition in the female tract since been achieved by injection of Medical Grade Silicone lO 1564 when Pallopio used a sheath for "use against Rubber (MSR) which cures-in-place to form plugs . venereal disease and numerous bastard offspring". The rate of azoospermia, six months after MSR vas The history of condom use and research on the occlusion was 98.27% compared to 100% in the development of new generation of condoms have vasectomy series. 4 been reviewed earlier ,5. The partial blocking of vasal lumen by injection of The coating of condoms with microbic ides was copper resulted in loss in functional capacity of the presumed to reduce HIV transmission in women. The spermatozoa. Insertion of copper wire into the vas nonionic detergent nonoxynol-9 (N 9), which was caused decapitation of spermatozoa and resulted in considered a spermicide, has been in use for coating infertilityll but the effectiveness decreased with time, condoms. But, the use of vaginal sponges containing probably due to erosion of the copper wire12 The N 9 was found to increase the risk of HIV infection in polymer, Styrene Maleic Anhydride (SMA), when 6 female sex workers in Kenya . This was attributed to injected into the lumen of the vas deferens in dimethyl the cell membrane disrupting action of N 9, which sulphoxide is reported to be an effective method of acts as an irritant in the epithelium of penis and male contraception 13. Phase I and II clinical trials vagina in approximately 56% of women who were using the RISUG (trade name of SMA) have been using N 9 suppositories four times per day for two completed. Mishra et aZ 14 have reported focal weeks? It is clear that the use of spermicides­ degeneration of seminiferous epithelium in testis of microbicides would have a significant impact on the langur monkeys following long-term (540 days) vas role of male and female condoms in contraception and occlusion with SMA. prevention of transmission of se.'ually transmitted diseases. Inhibition of spennatogenesis Hormone-based approach to male contraception Prevention of sperm transport The development of hormone-based male Contraceptive options for men which are currently contraceptive is based on the premise that the available are vasectomy and condom use. Of these, suppression of gonadotrophin production will result in vasectomy or male sterilization is a cheap and an the inhibition of spermatogenesis. Gonadotrophin effective method of preventing sperm transport production can be suppressed by the use ctf (1) through the vas deferens. Improvement to the method . steroidal agents like androgen, progestogen, estrogen of traditional vasectomy is the "non-scalpel" or combination of these, and (2) by the use of non­ technique. Various aspects of post-vasectomy steroidal agent/>. Among the non-steroidal agents, complications, vasectomy reversal (vasovasostomy) GnRH agonists and antagonists have been evaluated and pregnancy rate, and long-term health extensively. Suppression of gonadotrophins results in consequences of vasectomy and safety have been decrease in androgen production leading to clinical 8 reviewed earlier . manifestations of androgen deficiency. To offset such In attempts to interfere with sperm passage through androgen insufficiency, external androgen the vas deferens, sclerosing agents like quinacrine, supplementation is required. Combination regimens ethanol, and silver nitrate have bt;~n introduced into using androgen supplementation need careful the vasal lumen resulting in . sclero<;is, inflammation, monitoring of the dose of androgen since higher doses and fibrosis. The occlusion thus induced was may directly sti'mulate spermatogenesis. In irreversible and in some cases, retrugrade flow of the combination reg~mens, a relatively smaller dose of agent resulted in testicular atrophy. Intra-vasal androgen is required compared to the androgen-only injection of polyurethane or silicone rubber resulted in modality since the anti-spermatogenic action is plug formation by polymerization in situ. Since in situ achieved mainly by the non-androgen component of polymerization may be accompanied with the release the combination regimen, which suppresses of potentially toxic compounds, Zaneveld and gonadotrophin se.::retion by interfering with negative associates used preformed soft hollow silicone plug feedback control at the pituitary and hypothalamus called SHUG. Several different SHUG devices and (eg. exogenous steroids) or directly by inhibiting the 1034 INDIAN J EXP BIOL, NOVEMBER 2005 effect of GnRH on the pituitary ,ego use of GnRH men with sperm count between 0.1 to 3 million/~'. analogues). None of the c:z )ospermic men in 230.4 persons years of efficacy phase reported the occurrence of Androgen-alone regimen pregnancy. Testosterone enanthate These landmark multicenter trials carried out by Clinical trials using an androgen alone for male WHO established the fact that hormonally induced contraception, though carried out f-:Jr the first time by azoospermia is compatible with effective contraception. Indian