Male contraceptives

Current research into male contraceptives will potentially increase the equitability of family planning between males and females. This shift will also have the potential to address issues of population growth and its related detrimental effects on the environment .

While prophylactic condoms provide good barrier protection from unwanted pregnancies, they are not as effective as oral contraceptives for women. Likewise, vasectomies are very effective, but few men are willing to undergo the surgery. There are three general categories of male contraceptives that are being explored. The first category functionally mimics a vasectomy by physically blocking the vas deferens, the channel that carries sperm from the seminiferous tubules to the ejaculatory duct. The second uses heat to induce temporary sterility. The third involves medications to halt sperm production. In essence, this third category concerns the development of "The Pill" for men.

Despite its near 100% effectiveness, there are two major disadvantages to vasectomy that make it unattractive to many men as an option for contraception. The first is the psychological component relating to surgery. Although vasectomies are relatively non-invasive, when compared to taking a pill the procedure seems drastic. Second, although vasectomies are reversible, the rate of return to normal fertility is only about 40%. Therefore, newer "vas occlusive" methods offer alternatives to vasectomy with completely reversible effects. Vas occlusive devices block the flow of or render dysfunctional the sperm in the vas deferens. The most recent form of vas occlusive male contraception, called Reversible Inhibition of Sperm Under Guidance (RISUG), involves the use of a styrene that is combined with the chemical DMSO (dimethyl sulfoxide). The complex is injected into the vas deferens. The complex then partially occludes passage of sperm and also causes disruption of sperm cell membranes. As sperm cells contact the RISUG complex, they rupture. It is believed that a single injection of RISUG may provide contraception for up to 10 years. Large safety and efficacy trials examining RISUG are being conducted in India.

Two additional vas occlusive methods of male contraception involve the injection of polymers into the vas deferens. Both methods involve injection of a liquid form of polymer, microcellular polyurethane (MPU) or medical-grade silicon rubber (MSR), into the vas deferens where it hardens within 20 minutes. The resulting plug provides a barrier to sperm. The technique was developed in China, and since 1983 some 300,000 men have reportedly undergone this method of contraception. Reversal of MPU and MSR plugs requires surgical removal of the polymers. Another method involving silicon plugs (called the Shug for short) offers an alternative to injectable plugs. This double-plug design offers a back-up plug should sperm make their way past the first.

Human sperm is optimally produced at a temperature that is a few degrees below body temperature. Infertility is induced if the temperature of the testes is elevated. For this reason, men trying to conceive are often encouraged to avoid wearing snugly-fitting undergarments. The thermal suspensory method of male contraception utilizes specially designed suspensory briefs to use natural body heat or externally applied heat to suppress spermatogenesis. Such briefs hold the testes close to the body during the day, ideally near the inguinal canal where local body heat is greatest. Sometimes this method is also called artificial cryptorchidism since is simulates the infertility seen in men with undescended testicles. When worn all day, suspensory briefs lead to a gradual decline in sperm production. The safety of briefs that contain heating elements to warm the testes is being evaluated. Externally applied heat in such briefs would provide results in a fraction of the time required using body heat. Other forms of thermal suppression of sperm production utilize simple hot water heated to about 116°F(46.7°C). Immersion of the testicles in the warm water for 45 minutes daily for three weeks is said to result in six months of sterility followed by a return to normal fertility. A newer, but essentially identical, method of thermal male contraception uses ultrasound. This simple, painless, and convenient method using ultrasonic waves to heat water results in six-month, reversible sterility within only 10 minutes.

Drug therapy is also being evaluated as a potential form of male contraception. Many drugs have been investigated in male contraception. An intriguing possibility is the observation that a particular class of blood pressure medications, called calcium channel blockers, induces reversible sterility in many men. One such drug, nifedipine, is thought to induce sterility by blocking calcium channels of sperm cell membranes. This reportedly results in cholesterol deposition and membrane instability of the sperm, rendering them incapable of fertilization. Herbal preparations have also been used as male contraceptives. Gossypol, a constituent of cottonseed oil, was found to be an effective and reliable male contraceptive in very large-scale experiments conducted in China. Unfortunately, an unacceptable number of men experienced persistent sterility when gossypol therapy was discontinued. Additionally, up to 10% of men treated with gossypol experienced kidney problems in the studies conducted in China. Because of the potential toxicity of gossypol, the World Health Organization concluded that research on this form of male contraception should be abandoned. Most recently, a form of sugar that sperm interact with in the fertilization process has been isolated from the outer coating of human eggs. An enzyme in sperm, called N-acetyl-beta-D-hexosaminidase (HEX-B) cuts through the protective outer sugar layer of the egg during fertilization. A decoy sugar molecule that mimics the natural egg coating is being investigated. The synthetic sugar would bind specifically to sperm HEX-B enzyme, curtailing the sperm's ability to penetrate the egg's outer coating. Related experiments in male rats have shown effective and reversible contraceptive properties.

Perhaps one of the most researched methods of male contraception using drugs involves the use of hormones. Like female contraceptive pills, Male Hormone Contraceptives (MHCs) seek to stop the production of sperm by stopping the production of hormones that direct the development of sperm. Many hormones in the human body work by feedback mechanisms. When levels of one hormone are low, another hormone is released that results in an increase in the first. The goal of MHCs is to artificially raise the levels of hormone that would result in suppression of hormone release required for sperm production. The best MHC produced only provides about 90% sperm suppression, which is not enough to reliably prevent conception. Also, for poorly understood reasons, some men do not respond to the MHC preparations under investigation. Despite initial promise, more research is needed to make MHCs competitive with female contraception. Response failure rates for current MHC drugs range from 5–20%.

[Terry Watkins ]

RESOURCES

ORGANIZATIONS

Contraceptive Research and Development Program (CONRAD), Eastern Virginia Medical School, 1611 North Kent Street, Suite 806, Arlington, VA USA 22209 (703) 524-4744, Fax: (703) 524-4770, Email: [email protected], <http://www.conrad.org>