Scientists Work on Male Version of Pill

Monday, April 19th 2004, 12:00 am

By: News On 6

More than 40 years after The Pill hit the market for women, scientists are still trying to come up with a version for men, who account for nearly a third of all contraceptive use in the United States and worldwide. Right now, they're basically limited to condoms and vasectomies.

So experts see a market for a male Pill, even if it's not actually a pill, and some large studies to develop one are in progress. In China, for example, hundreds of men are getting injections once a month. In Europe, more than 300 men are signing up to get 2-inch rods implanted in their arms and take injections every three months.

The research quest is hardly new _ about 3,000 men have participated in such studies over the past two decades _ but it could get its own shot in the arm later this year. The federal government plans to gather researchers, representatives of drug companies and federal regulators to figure out where the research should be going.

``We're pushing to move it forward,'' said Robert Spirtas, chief of the contraception and reproductive health branch of the National Institute of Child Health and Human Development (NICHD).

New contraceptives for men would be welcome, experts say.

``The more options that are available, the more likely a couple will find an option that fits very neatly into their particular lifestyle,'' said Dr. Vanessa Cullins, vice president for medical affairs of the Planned Parenthood Federation of America.

The focus for developing contraceptives has been on women for some time, she noted, but ``men are partners in heterosexual sexual activity, and in heterosexual attempts to prevent pregnancy. So it's only right that there be more options that men can consider.''

In fact, ``the shocker for most people is that men are interested in contraception, are actually using a lot of contraception,'' said researcher Dr. John Amory of the University of Washington in Seattle.

Noting that men provide nearly a third of all contraceptive use despite ``pretty limited options,'' Amory said, ``I think there's a market there.''

Besides condoms and vasectomy, men recently gained another contraceptive option: the ``Vasclip,'' a device about the size of a grain of rice that a physician can install in the testes to block the flow of sperm. It's considered permanent. Of course, there is also abstinence.

Researchers generally envision a male version of the Pill being used by men in committed relationships. Other couples should be using a condom anyway to prevent sexually transmitted diseases, the experts say.

Besides, the hormonal approach that has attracted the most research so far takes about three months to shut off fertility, hardly fast enough for a man who's just landed a hot date.

The male Pill might not really be a pill at all, at least at first. It might instead require a long-lasting injection or a small implant given under local anesthesia, or both. That's mostly a result of the biology, but experts say it's not entirely a bad thing.

An injection that lasts for, say, three months or more would take away the pressure of remembering to take a pill regularly, notes Diana Blithe, director of a male contraceptive development program at the NICHD. And an implant in a man's arm that a woman could feel would ``provide ready proof that he is taking the contraceptive,'' said Bernard Robaire of McGill University.

Apparently that's no drawback for men. Amory recalls that in a study some time ago, ``the guys were proud of their implants. They were conversation starters at cocktail parties. They would have a woman feel their arm.''

Scientists have known for 50 years that it should be possible to fiddle with a man's hormones and make him sterile for a while. But that hasn't produced a marketed product yet for lots of reasons, like sporadic research funding, cultural concerns and limited interest by drug companies, a recent report from the Institute of Medicine noted.

``I think there may have been a social feeling that men would be less willing to do this (practice contraception), that they aren't the ones who end up with the responsibility of the pregnancy if it occurs,'' Blithe said. ``So the women needed at least initially to be able to control their own bodies, since they're the ones who ultimately end up with the consequences.

``I think that's why drug companies initially at least didn't have as much of an interest. The feeling was it was already taken care of, more or less. They didn't see a big profit margin in it.''

Then there's the biology.

Consider the challenge a contraceptive drug faces. If you block one egg a month in a woman, you've done your job. But a man produces about 100 million sperm a day. ``Probably, as little as 5 percent of those sperm are enough to maintain fertility,'' Robaire said. If so, a drug that blocks even 95 percent of sperm production wouldn't help.

In addition, men wouldn't be willing to accept much in the way of side effects. So you want an extremely high degree of effectiveness with very little if any side effects, Robaire said. ``You couldn't ask more of a drug,'' he said. ``It's really the ultimate challenge.''

But some researchers have responded.

In the most advanced work, scientists are trying to block the chemical signal from the brain that orders production of testosterone and sperm. One way is simply to inject a man with testosterone; the brain senses the dose and figures the testes are working overtime, so it shuts off the signal and sperm production eventually stops. At least in theory.

In practice, it doesn't work in all men, and it can include side effects like oily skin, acne and shrunken testicles. So scientists are experimenting with testosterone-like substances and hormonal mixes.

The big Chinese study, for example, is injecting an altered version of testosterone called TU, for testosterone undecanoate. While results may not be available until early 2006, an earlier trial of TU found that monthly injections dropped sperm counts to zero or close to it in 296 of 308 men. But six of these men began making sperm again during the treatment. There were no serious side effects.

The current Chinese study, sponsored by the World Health Organization in collaboration with the Chinese government and Xianju Pharmaceutical Co., recruited more than 1,000 couples, although some have left the project. The goal is to see how well TU prevents pregnancy over two years in the sexual partners of men who respond to the drug.

Taking another tack, the nonprofit Population Council, based in New York, is working with a synthetic hormone called MENT. It's almost 10 times as powerful as testosterone, said council researcher Narender Kumar. The council is studying the idea of combining MENT implants with implants of a hormone used in female contraceptives, because they can act together to suppress sperm production.

The combination approach is also being pursued in the European study, which started putting implants in men in January and is still recruiting toward its goal of 350 participants. Men will carry implants of the hormone etonogestrel, which suppresses production of both sperm and testosterone. The rod-like implants are placed under the skin of an upper arm for 42 or 44 weeks.

The men will also get injections of TU every three months to replace the testosterone their bodies are no longer producing. Researchers will monitor sperm counts in the men, who are being studied in Denmark, Finland, Germany, Great Britain, Italy and the Netherlands.

The drug companies sponsoring the project, Schering AG and Organon, say the study will conclude by December 2005, but no product is expected for at least five years.

Experts say the involvement of drug companies in the field is important because it's the pharmaceutical industry, not researchers, who can actually bring a product to market.

Hopes for hormonal contraception got a boost recently from a study in Australia, where researchers said it did well at preventing pregnancy in a study of 55 couples. No serious side effects appeared in men who got testosterone implants every four or six months plus shots of a different hormone every three months, the researchers reported.

That result is ``a good step along the way'' to a workable male contraceptive, said Douglas Colvard of CONRAD, the Virginia-based reproductive health organization that helped pay for the work. One goal is longer-lasting implants and injections, he said, because surveys show men would prefer they last for six months or a year.

Researchers are also exploring non-hormonal approaches. Some are taking their lead from existing drugs that impair fertility as a side effect. For example, Oxford University researchers recently reported that a drug used to treat a condition called Gaucher's disease makes male mice sterile by rendering their sperm abnormal. The effect disappeared several weeks after the drug was withdrawn.

Robaire, meanwhile, is using genetic studies in rats to explore ways to keep sperm from maturing.

Such non-hormonal approaches might really lead to a male pill, without need for the shots or implants.

But the hormonal strategy could turn out to provide a different bonus.

Because of testosterone's various effects in the body, said contraceptive researcher Dr. William Bremner of the University of Washington, a treatment that essentially replaces it with a chemical cousin might lower a man's risk for enlarged prostate, prostate cancer and even baldness.

And that, Bremner said, ``might well have considerable appeal.''