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Though they didn't look like much, the white specks squirming under a microscope in researcher Debra Wolgemuth's lab could have a big impact in the high stakes world of controlling fertility, not for women but for men. 

The specks were sperm from mice that had been treated with a new contraceptive. The healthy, swimming cells showed that the new drug did not have a permanent effect once the mice had gone off it. For Wolgemuth, this was an important first step toward one day testing the drug in human men.

Professor Wolgemuth and other researchers at Columbia University Medical Center were using the drug, called BMS-189453, to block retinoid receptors -- proteins that bond with vitamin A to turn on certain genes. The drug prevented sperm from developing normally, making the male mice unable to impregnate females.

"We demonstrated that the mice are infertile," explained Wolgemuth "We take them off the drug, and then after a certain period of time they're fertile again."

If the method works as well in humans, it could become a true contraceptive option for men. Maybe one day, biologist Sanny Chung said as she weighed mouse testes, "males can play a bigger role" in family planning.

NEW OPTIONS

Men, on the other hand, still have only two options for controlling their fertility.

"You have condoms, which are in the moment, and vasectomies, which are permanent, and nothing in between," said Elaine Lissner, founder of the nonprofit Male Contraceptive Information Project.

But researchers around the world are working on new options for male birth control, including retinoid blocking, implants that could be removed when a man decides to become a father, and even special underwear that prevent sperm production. A new analysis of 30 studies done between 1990 and 2006 shows that male hormonal contraception might not be that far away. One day, there could be two dial packs of birth control pills on the nightstand, one for her and one for him.

"The initial work toward producing contraceptives focused on women, because women get pregnant," explained Ronald Swerdloff, head of the endocrinology department at the University of California, Los Angeles, Harbor Medical Center. "That attitude has changed with the changing attitudes of partners. Women, in multiple surveys, have said they would like to share responsibility with a partner, just like we have come to believe that men and women should share economic and childcare roles."

Because of the commercial success of the female birth control pill, many researchers are trying to develop a men's pill, which would block sperm production using the body's chemical signals, just as the women's pill blocks ovulation.

Normally, a man's pituitary gland produces chemicals that tell the testes to make sperm and testosterone. A male hormonal contraceptive would consist of testosterone, along with the female hormone progestin. Once in the bloodstream, these hormones would tell the pituitary that the testes already had done their job, so the pituitary would not produce the signals.

"It's fooling the system," said Swerdloff, who worked on the new analysis. "The signals that normally regulate the system are used to turn it off." He uses the analogy of an air conditioner, which produces cool air until it gets the signal that the air is cool enough. "We want to turn off the thermostat, if you will."

NOT FOR EVERYONE

Swerdloff's analysis showed that this method works very well in about 86 percent of men. Unfortunately, it does not work for all men, and scientists do not yet understand why.

"That's what's kept it off the market," said John Amory, who studies male contraception at the University of Washington Medical Center. "After three months, you'd have to test them and tell one out of six people it didn't work. Hormones are still worth pursuing, but it's going to be a while."

Amory is working on an effective pill form of testosterone, which currently is administered as a gel or an injection. This could be helpful for contraception, as well as for men who have testosterone deficiency. Like Wolgemuth, at Columbia, Amory also is beginning to study retinoid blocking.

Wolgemuth thinks this method is promising, but she said that there still are questions she and her team would like to answer. They want to understand retinoids' role in sperm production more fully, and they need to determine how long the drug can be used before it damages the testes permanently. The next goal is to test the drug in monkeys, a step toward eventually testing it in humans.

Are men ready for this? Definitely, say researchers. In a 2002 survey of 9,000 men on four continents, more than half said they would use male hormonal birth control. Male hormonal birth control methods appear to have lower risks of side effects than female methods, which can be dangerous for some women, according to Swerdloff.

Methods such as the Intra-Vas Device, an implant that blocks the flow of sperm, and an injectable gel called RISUG would be ideal in developing countries, where access to pills or condoms is not always guaranteed, said Lissner.