Quest for "male pill" brings scientists of the world here

By Warren King
Seattle Times medical reporter

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Whatever the approach, 150 scientists gathered in Seattle this week have one goal in common: Thwarting human sperm in its mission to fertilize human eggs.

As the 40-year quest for a new male contraceptive appears more promising, a groundbreaking international conference on the technology got under way last night at the Edgewater Hotel in Seattle.

"There has never been a symposium of this size and this breadth on this topic," said Dr. Diana Blithe, conference chairwoman and director of male-contraceptive development at the federal National Institute of Child Health and Human Development.

Researchers at the conference are learning about the latest efforts to develop a hormone-based male contraceptive, along with other approaches. The work has gained considerable momentum during the past decade, according to veteran scientists participating in the conference, sponsored by the National Institutes of Health (NIH) and the University of Washington, among others.

"There is substantial progress, especially since pharmaceutical companies have taken an interest. I think they see a potential market, that they can make some money," said Dr. William Bremner, a UW professor of medicine who for nearly 30 years has helped keep the university in the forefront of the search for a "male pill."

Could synthetic hormones and drugs be used to stop sperm production in a temporary way so that when the man wanted to father a child he still could? That will be the question behind a good deal of discussion this week.

Contraception and population The world population is now more than 6 billion and increases about 8 million a year. In the United States, about 20 percent of couples use condoms. In about 11 percent of couples, the male has had a vasectomy. Research on a new type of male contraception has been under way for nearly 40 years. UW seeks test subjects The UW is seeking volunteers for tests of a new, hormone-based male contraception method. The tests will evaluate sperm counts, not pregnancy rate. Participants should continue to practice other means of birth control during the test. The research project will last for about one year and will require one or two clinic visits a month. Each participant will be paid $1,000 for completion of the project. Call 206-616-1818 for more information.

A large-scale test of a hormone-based contraceptive recently was started in Europe. And the UW is beginning a smaller trial of a different hormonal approach to temporarily stop sperm production.

Other nonhormonal techniques being discussed are far less advanced. They include interfering with the sperm's maturation or impairing its ability to move toward an egg and fertilize it. Others would inhibit the sperm's ability to bind to an egg or impair its ability to penetrate the egg.

Bremner was hard-pressed to predict when a male-contraceptive method might be widely available. "I would guess," he said, "in the five- to seven-year range."

Several large surveys in Europe and the United States have indicated that a majority of men would be willing to take a long-acting injection for contraception. Many are tired of the alternatives: condoms, which decrease sensation and sometimes break, and vasectomy, a surgical procedure that is difficult to reverse.

The new enthusiasm and multiple approaches to the technology have been a long time coming. The obstacles have been considerable, said Bremner and Dr. John Amory, another scientist working in the UW's Center for Research in Reproduction and Contraception. The center was established two years ago with a $9.5 million, five-year grant from the NIH.

Past hurdles

Figuring out how to stop sperm production — which the testicles make at the rate of 1,000 per second — is a lot more difficult than stopping the release of one female egg per month, which is the job of women's birth-control pills, the scientists said.

In addition, society has usually assigned the responsibility of birth control to women. Strong objections to contraception have come from some organized religions. And drug companies have worried about litigation if sexual function were impaired by the use of hormones in contraception.

But times are changing. The male's role in birth control has become more accepted in many countries. And the popularity of drugs for erectile dysfunction has opened discussion of male sexuality to the extent that drug companies may feel male contraception could have a market.

"It's just more acceptable now to deal with men's reproductive health," said Bremner, chairman of the UW Department of Medicine.

The international conference in Seattle is the first to be attended by drug-company representatives, which reflects the unprecedented interest in the technology for commercial production, Bremner and Amory said.

For years, researchers have focused on a long-lasting, injectable contraceptive for men. Pills did not achieve an adequate blood level of testosterone, the male hormone commonly used in such tests. But recent efforts by drug companies and universities are looking at new ways to deliver the hormone in pill form.

The large-scale trial under way in Europe involves about 350 volunteers. Each man's upper arm is implanted with a 1.6-inch plastic rod containing etonogestrel, a synthetic hormone that lowers the body's testosterone production and stops the testicles' production of sperm.

To maintain some testosterone in the body, which is needed for other purposes, the men will receive injections of a testosterone derivative every three months.

The UW and the University of California, Los Angeles, originally were scheduled to participate as the U.S. centers in the trial, but they canceled after the Food and Drug Administration was not satisfied that testosterone levels reached high enough levels with the injections. More studies are under way, and the universities hope to participate in a later extension of the trial.

In the smaller UW trial, 60 volunteers will receive injections of a drug that essentially short-circuits the complex chain of hormonal events leading to sperm production.

The drug blocks production in the pituitary gland — at the base of the brain — of the initial hormone needed to start the cascade of events. The patients also will rub a testosterone gel on their shoulders to maintain adequate levels of the hormone; it easily migrates into the bloodstream.

As with other administrations of testosterone, side effects of the approach can include temporary increases in muscle mass and acne and temporary decreases in body fat, testes size and HDL, the good cholesterol that helps remove bad cholesterol from arteries.

Blithe, the conference chairwoman, is excited about the increased attention to male contraception and the many approaches being considered.

Scientists from around the world, including the United States, Europe, Australia and India, will be presenting reports at the meeting through Saturday. A smaller World Health Organization conference on contraception will follow Sunday and Monday.

"We will really have a spectrum of [approaches] to be discussed" Blithe said. "It is an intense program."

Warren King: 206-464-2247 or wking@seattletimes.com

Copyright © 2004 The Seattle Times Company

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