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New Contraceptives for Him -- May 10, 1998

RESEARCH TRIANGLE PARK, NC -- Despite years of research, no modern contraceptive drug currently exists for men, whose most effective choices are limited to condoms or vasectomy. Nevertheless, a number of intriguing research projects are seeking new contraceptives that men, instead of women, would use.

These experimental prototypes typically rely on one of two mechanisms of action. One approach is aimed at suppressing the production of sperm, either by hormonal or non-hormonal means. Another approach seeks to inhibit the fertilizing ability of sperm, usually by disrupting a key step in the complex process of conception.

Even the more promising experimental male methods are at least a decade away from general use, experts say in the current issue of Network, the bulletin of Family Health International, a nonprofit research organization that specializes in reproductive health. Experts say a lack of commercial interest and funding have held back research. Progress also has been slow because of the challenging physiological task of controlling the male reproductive system. A woman's ovulation is easier to interrupt than a man's sperm production because a woman produces only one egg a month, while a man produces hundreds of millions of sperm daily.

Most research is focusing on ways to suppress sperm production by inhibiting hormones that control sperm production. A variety of testosterone derivatives have already demonstrated that this approach can result in effective contraception among men, but some of these early prototypes have drawbacks that make them unsuitable for general use.

Among these and other promising candidates for a male contraceptive drug are the following:

• An experimental injection may stimulate an immune response to gonadotropin hormone-releasing hormone (GnRH), which is essential to sperm production. A single injection may produce effective contraception for up to one year and, when discontinued, should allow a return to fertility. The experimental injectable is combined with tetanus toxoid, widely used as a tetanus immunization. If successful, this approach would combine a male contraceptive with protection from tetanus infections.

• A hormone called 7-alpha methyl-19-nortestosterone, or MENT, may also provide successful sperm suppression. Under this approach, MENT would probably be delivered by using implants under a man's skin. Toxicology testing in animals has not been completed.

• Another derivative, testosterone buciclate (TB), has been studied among men in Germany, but an appropriate dosage to achieve adequate sperm suppression in all men has not yet been identified. Further studies are planned for TB, which could be given by injection, probably at three-month intervals.

• A non-hormonal substance called gossypol, an extract from natural cottonseed oil, has achieved reliable contraception in Chinese men. However, doses given in early studies depleted potassium levels, which can led to dangerous heartbeat irregularities, and some men appeared to become permanently sterile. More recent studies are focusing on smaller doses of daily pills, which may be safer.

• A few researchers are seeking ways to impede the ability of sperm to fertilize eggs using drugs taken as daily pills. Research in the U.S. shows that nifedipine, routinely used to treat high blood pressure and migraine headaches, blocks enzymes in sperm cells needed to penetrate an egg's protein coating. In France, mifepristone has disabled sperm by acting on the sperm's membrane. While both drugs prevent sperm from fertilizing an egg, they have undesirable side effects. Researchers are examining chemically similar compounds that may produce effective, safe contraception without these disadvantages. Very early research for a vaccine to block a sperm's ability to fertilize is also under way.

Other articles in the current issue of Network, which focuses on men and reproductive health, review aspects of the existing male methods of vasectomy (male sterilization) and condom use. Articles also discuss a variety of reproductive health risks men face and the responsibilities men should take for family planning and other reproductive health concerns.