Indian Jouma1 of Experimental Biology Vol. 43, November 2005, pp. 1042-1047 Review Article Perspectives of contraceptive choices for men N K Lohiya*, B Manivannan, S S Bhande, S Panneerdoss & Shipra Garg Reproductive Pbysiology Section, Department of Zoology, University of Rajasthan, Jaipur 302 004, India Apart from condoms and vasectomy, which have several limitations of their own, no other methods of contraception are available to men. Various chemical, honnonal, vas based and herbal contraceptives have been examined and few of them have reached the stage of clinica1 testing. Promising leads have been obtained from testosterone bucic1atelundecanoate, alone or in combination with levonorgestrel butanoate or cyproterone acetate, RlSUG, an injectable intra vasal contraceptive and a few herba1 products, particularly the seed products of Carica papaya. It is feasible that an ideal male contraceptive. that meets out all the essential criteria will be made available to the community in the near future. Keywords: Carica papaya, Herbal methods, Honnonal methods. Male contraception, RISUG. Vas based methods In the new millennium, India has crossed the one lead from sperm production in the testis to sperm egg billion mark. sharing 16% of the world population on interactions and fertilization in the female genital tract 2.4% of the global land area. More than 18 million need to be considered. Accordingly, the biomedical people are added every year, which is almost the options available in control of male fertility are entire population of Australia With the current trend, limited to (1) inhibition of spermatogenesis at the it is projected that India may overtake China in the level of testis, (2) inhibition of sperm maturation at year 2045 to become the most populous country in the the level of epididymis, (3) inhibition of sperm world, the distinction which no Indian would be proud transport at the level of vas deferens, (4) inhibition of of. Although India was the first to launch National sperm deposition in the female genitalia, and (5) Family Planning Programme as early as 1952 in order inhibition of sperm egg interaction at the level of to curtain the population menace, 16% of currently female reproductive traer. The options available to married women in the country have an unmet need for men are limited to condoms, periodic abstinence, family planning; 8% women want child spacing withdrawal and male sterilization. Survey among without contraceptive use, while the other 8% do not married men in developing countries indicate that want any more child but without the use of only 4% of men use condoms, 4% undergo l contraceptive . As per the National Family Planning vasectomy, 3% use periodic abstinence and 4% use Survey (1998-1999), 25% of total family planning withdrawal in which periodic abstinence and programme had an uomet need, and the contraceptive withdrawal have higher failure rates and are often 3 prevalence rate in the country is only a moderate practiced with other contraceptive measures . 48.2%, with female sterilization accounting for 34.2% Current Trials and the currently available male methods accounting It is speculated that men's participation in family negligible. planning would increase, if there are wider choices of Currently men's involvement in regulating family contraception available to them, which should be safe, size is negligible, as there is an argument that they do effective, and economical and that it should provide not have sufficient contraceptive choices to adopt, long term and completely reversible contraception, compared to their female counterparts. For regulation preferably free of surgery with greater acceptability of male fertility, the various steps in reproduction that rate. One of the main problems encountered in development of a male contraceptive is the fact that it *Corresponding Author" is necessary to achieve azoospermia or make all the Phone 0141-2701809; 2703552 (0) sperm nonfunctional, since it is believed that even a 0141-2710071 (R) Fax: 0141-2710880; 2701809 single functional spermatozoon is adequate for e-mail: lohiyank~boImaiI,(;()m fertilization. Azoospermia could be easily achieved by LOHIY A et al.: CONTRACEPTIVE CHOICE FOR MEN 1043 interfering with production of testosterone which is surgical vas occlusion. The latter is considered more indispensable for spermatogenesis, but the same could advantageous because it causes minimal honnonal interfere with libido which is unacceptable4. and systemic side-effects and offers a better scope for A number of approaches including the use of reversal. Currently, testosterone undecanoate alone or hormones or non-hormones involving androgens, in combination with depotmedroxy progesterone anti androgens or GnRH analogs with sites of action in acetate or norethisterone enanthate are also under the testis and epididymis, and non occlusive devices clinical trial to identify more priority leads for male that have either a chemical or mechanical effect on contraception 12,13. spermatozoa as they pass along the vas deferens, are being investigated; these approaches may interfere Vas based methods with sperm function either in the testis, epididymis or Vasectomy is a simple, safe, effective and an in other parts of the male reproductive tract, and are inexpensive method of male contraception; the intended mainly to affect sperm production directly or operation can be easily performed in 10-15 min on an out-patient basis with minimal training for most render the spermatozoa infertile without affecting the 28 30 circulating testosterone level. Most of these appro­ surgeons - • It is perceived in some cultures that aches have reached the stage of clinical testing, but vasectomy reduces physical strength and has been none of them has so far reached the stage of accepta­ claimed by some men who had undergone the bility or commercialization for public utility5. operation and also by their partners that it reduces sexual potency31. In addition, vasectomy is considered Hormonal methods as a permanent method and even if reanastomosis of The hormonal approach to male contraception is the vas is successful, the resulting fertility is poor. based on the suppression of gonadotrophin secretion An ideal intravasal device for male contraception with secondary suppression of spermatogenesis to should be easy to inse~ and be flexible; it should achieve azoospermia, the ultimate goal in male contr­ prevent sperm passage and be capable of being easily aceptive studies. Androgen alone in the form of removed for restoration of vas patency and return of 9 testosterone esters6-8, testosterone enanthate , testo­ fertility32. Initial attempts have been made to solve the lO ll 15 sterone buciclate , testosterone undecanoate - , 7 problems associated with the reversal of vasectomy. alpha methyl 19 nor testosterone [MENT] 16-18, Several mini biomedical devices, viz., intravasal androgen in combination with progestogen i.e., depot­ thread, copper wire, biogalvanic cells, and tantalum medroxy progesterone acetate and testosterone clips have been tried. but they failed to meet out the 19 enanthate , medroxy progesterone and testosterone ideal requirements]3. Injectable plugs, employing emmthate, levonorgestrel and testosterone unde­ percutaneous injection of polyurethane elastomer to 20 canoate , levonorgestrel and testosterone enanthatel form plugs34-J6 and non injectable silicon plugs, called 21 22 testosterone buciclate . , desogestrel and testo­ the 'shug,37 have also been tried up to the level of sterone23,24 , and androgen in combination with clinical trial in over lO,OOO men. However, the progestogenic anti androgens viz., cyproterone acetate surgical intervention for implantation of devices into 25 and testosterone enanthate .26, cyproterone acetate the vas deferens and their reversal limits further and testosterone buciclate27, norethisterone enanthate consideration in use of intravasal devices for mass I2 13 and testosterone undecanoate . and norethisterone family planning programme. Hence, from the delivery enanthate and testosterone enanthatell have been point of view, injection of a polymer into the vas investigated up to clinical trial for many years but lumen, by a minimal invasive procedure that provides without identifying a suitable regimen which would a safe and effective contraception and offers reversal, result in suppression of spermatogenesis to achieve would appear to be more advantageous, convenient contraception, without adverse metabolic effects. and globally acceptable. The WHO consultative meeting on "Setting the Styrene maleic anhydride (SMA), currently Agenda for Fertility Regulation Technology Research renamed as RISUG®, is a co-polymer of styrene and in Reproductive Health for the Next Decade" (held at maleic anhydride and offers fertility control through Geneva, Switzerland, 1996) identified two leads in the multiple modes viz., it blo.;;~ the vas deferens and field of male contraception viz., (i) a tri-monthly prevents forward flow of sperm, induces pH lowering injectable levonorgestrel butanoate plus testosterone effect and causes charge disturbances to the buciclate or testosterone buciclate alone and (ii) non- membrane of the spermatozoa, resulting into the 1044 INDIAN J EXP BIOL, NOVEMBER 2005 acrosome damageJ8 . Further, SMA has no teratogemc• particular are those which are orally effective, non­ 39 40 effect and is toxicologically safe in animal models • • steroidal, non-estrogenic, safe and effective in Clinical trials at Phase tl