Male contraception: what's next?

All about options

"We believe in increasing the options available for couples," says Christina Horzepa of the Population Council, an international, nonprofit organization committed to improving reproductive health. "If there was a male method, it would provide couples with one more option. Part of our mission is to expand contraceptive availability."

What's in the works?

Interrupting male machinery has proven much more difficult than blocking production of an egg during a woman's monthly cycle.

"It's only been recently that we have [seen] basic physiological research in the function of testes and sperm formation, and that's providing a lot of results," says Population Council Vice President Elof Johansson, MD. "If I look back 15 years or so, there were few leads in the area of male contraception, but now it's all over. It's a new era."

Hormonal methods of male contraception may be the first new male contraceptive out of the gate, but research targeting several different non-hormonal male birth-control methods could give it stiff competition. The National Institutes of Health (NIH) recently offered scientists grants to create and test new non-hormonal agents.

"We are focusing on all three aspects?hormonal contraception, immunocontraception, and drugs that affect sperm after their formation in the testes to avoid any affect on testosterone production," says Dr. Johansson. "I think all three leads are very important."

Hormones: hard to control

Although they were expected to reach the market first, hormonal methods have been fraught with challenges such as preserving libido and potency while avoiding testosterone-related side effects. Population Council scientists have developed a synthetic male hormone, MENT?, which decreases prostate cancer risk and requires less frequent administration than other hormonal methods. Three forms of MENT? are being developed for contraception and hormone replacement therapy: an implant, a transdermal gel and a patch .

Calcium-channel blockers

Susan Benoff, PhD, at the North Shore University Hospital in Manhasset, New York, hopes to receive one of the NIH grants. Several years ago, she discovered quite by accident that a drug used to treat high blood pressure caused sterility in a patient at the hospital's fertility clinic. Delving deeper, she found many clinic patients taking the drug had sperm that appeared normal, but were ineffective. Taking men off the drug restored fertility.

The cases intrigued Dr. Benoff, who decided to investigate why this was happening. She recognized that the drug in question controls blood pressure by blocking calcium movement and that calcium is important to sperm function. She reasoned that this might be the mechanism for causing infertility, but further study disclosed that the drug stimulates sperm to make cholesterol, causing the little swimmers to develop hard membranes that cannot join with an egg.

"With that knowledge in hand, we can now start to design drugs that have the same action?with a mechanism that can be targeted to the testes," says Dr. Benoff. "It's going to be a nice little pill, easy to swallow. It's not going to affect male libido. It's not going to affect sperm production, and it's reversible."

The medication doesn't cause impotence and should work equally well in all ethnic groups. But Dr. Benoff says commercial use of the drugs for male contraception may be five to 10 years away, depending on how much funding she receives.

Genetic possibilities

Researchers at the Salk Institute in La Jolla, California, have also made a serendipitous discovery. While investigating cellular activity, professor Tony Hunter changed one single gene receptor and developed a mouse that produced no sperm. The mutation does not appear to alter mating behavior or produce feminizing side effects.

Salk researchers are now investigating whether they can switch the gene on and off in hopes of confirming its contraceptive potential. The discovery also may provide a method for protecting male fertility during chemotherapy cancer treatments.

Vaccines

An antisperm vaccine would inhibit sperms' ability to develop or function. The immunization would stimulate the body's antibodies to suppress sperm production or their ability to function properly. Population Council scientists say the reversible method could provide continuous contraception that would last for a whole year. The research, however, is not conclusive.

"It's very difficult to get a uniform response in men," says Dr. Johansson. "We have the same thing in all vaccine products. Some people [simply] respond poorly."

A Canadian firm is working on development of a monthly immunizing pill that could be available by 2005.

Other possibilities

Derived from the cottonseed, gossypol may offer men seeking a permanent contraceptive an alternative to a surgical vasectomy. Research in China during the 1970s proved the plant-based pill's effectiveness at reducing fertility, but side effects, which include an irregular heartbeat and irreversible infertility, limit its potential.

Like the calcium-channel blockers, many drugs can interfere with male fertility, including compounds related to the Chinese medicinal plant Tripterygium wilfordii, the abortion pill mifepristone (RU 486), and derivatives of two chemotherapy drugs under study by the Population Council.

With so many researchers in pursuit of a male contraceptive, options for men are gaining ground. Before any male contraceptive drug reaches the market in the U.S., studies will have to prove the medication's effectiveness and safety to the U.S. Food and Drug Administration. But experts agree, couples are ready for a male contraceptive.

"It's clear from the kind of response I've gotten from the public," concludes Dr. Benoff. "We're getting this from all over the world. It means there is a great interest."