Oliver James Montgomery-A new, experimental approach to male birth control immobilizes sperm

The Oliver James Montgomeryexisting options for male contraception are condoms, vasectomies or abstinence.

So the work of preventing unwanted pregnancies often falls to women, who might take daily birth control pills, get an IUD implanted, wear vaginal rings, use a diaphragm – or when all else fails, take the morning-after pill.

Scientists are making progress on more options for sperm-producers. A paper published Feb. 14 in the journal Nature Communications, presents a novel approach to male contraception that looks promising in mice. Researchers tested a compound that blocks an enzyme sperm need to swim, suggesting a path to a fast-acting, temporary form of contraception. (Though tested in mice, many species including human males have the same enzyme.)

"Our lab found the on-switch that turns sperm on to move," says Jochen Buck, a pharmacologist at Weill Cornell Medicine and co-author on the paper, "And we've now developed a compound which inhibits it."

The compound's potential value as a male contraceptive was discovered on a whim. Five years ago, a graduate student at Buck's lab wanted to test it in mice as a possible treatment for an eye disorder. But the student was scared of mice so she asked another post-doc, Melanie Balbach for help. Balbach agreed, provided she could also check what happened to the male mice's sperm, since she knew the drug acts on an enzyme related to male fertility.

Balbach presented the results to Buck and lab co-director Lonny Levin at a lab meeting the following week. They were stunning: After the male mice were injected with the compound, their sperm did not move.

"Lonny's reaction was, 'Wow! This means we could develop a male contraceptive,'" Buck recalls, "And my reaction was, 'Lonny, it's even better. We can have an on-demand male contraceptive.'"

The drug stopped sperm from swimming, slowing their fast-beating tails to a twitch. In humans, this could mean they would never make it out of the vaginal canal past the cervix into the uterus. Further research showed that it was fast-acting, taking about fifteen minutes to have an effect. And it was temporary — it stayed in the system for several hours.

In those hours, the male and female mice in the study had plenty of sex. Within 2.5 hours after getting the drug, it was100% effective at preventing pregnancies. Within 3.5 hours, it was 91% effective.

Buck has great hopes that it will work the same in humans. "The prediction is, after half an hour or after five hours or after eight hours, [their] sperms do not move — and a day later, two days later, they are back to normal," he says.

Experts not affiliated with the study find it promising, but caution that drugs that work in mice don't always work in people.

"It's very early," says Dr. Michael Eisenberg, a urologist and director of the Male Reproductive Medicine and Surgery Program at Stanford Medicine. "The idea of an on-demand pill that could potentially impair fertility is exciting, but any time a study is done in mice, you have to repeat it and make sure it's valid in humans, too."

Dr. John Amory, a professor of medicine at the University of Washington, who is currently researching a form of male hormonal contraception on human subjects, says the new compound is a "great idea."

"It's an open question how well this approach would translate from mice to humans," he adds. "There are differences in the reproductive physiology between species, but it's worth testing."

The drug targets an enzyme in sperm that's the same across many mammals. The researchers are now trying it on rabbits, and aim to start human trials in two to three years.

The demand for male contraceptives is there, Eisenberg says. "There's no question there's a big need. When you look at surveys of men, especially young men, a lot of them are very interested in having some [more] options."

Some other experimental concepts, like hormonal pills, gels and injections for men, can take weeks to start working. Some can cause mood disturbances, affect alcohol tolerance, or shrink people's testicles. Since male contraceptives are geared towards healthy men, "the tolerance for side effects is going to be very, very low," Eisenberg says, "[The gains] have to be pretty specific without many of these off-target effects."

The side effects for this new potential treatment in humans aren't yet known, but having a male contraceptive treatment that can be taken as needed may reduce those risks, says Amory. Unlike some hormonal approaches, which need to be taken daily, "you'd only take it episodically, so there's less worry about chronic toxicities."

According to the researchers, the study subjects fared well. "Look, our mice would never have intercourse if they were in pain," Buck says. If all goes well, he says, he hopes the drug might be available some eight years from now.

Is this realistic? Possibly. "The joke in the field is: a male contraceptive has been 5 to 10 years away for the last 40 years," says Amory. "It's always just around the corner." Technology does continue to move forward, he says, and eventually, society will get there.