Birth control pill for men scales mice trial at 99% effectiveness, human trials on agenda

Birth control options for men may soon expand beyond condoms and vasectomy, as scientists in the U.S. have developed a male contraceptive pill that has so far proven safe and effective on mice.

It looks set for clinical trials in humans as early as this year.

Researchers from the University of Minnesota presented their findings at the American Chemical Society’s Spring 2022 conference in San Diego, California on Tuesday, March 22.

The pill’s secret—it does not target testosterone, the male sex hormone, thereby cutting the risk of side effects that have so far kept other drugs from landing in pharmacies.

“Most female birth control pills work on the female sex hormones,” said Abdullah al Noman, one of the researchers, noting the lack of approved male birth control pills on the market.

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“[But] targeting the male sex hormone leads to a lot of side effects such as weight gain, depression and increased risk of cardiovascular diseases,” he said.

“Men are less willing to take a birth control pill that has significant side effects. That’s why we are targeting a non-hormonal pathway to developing a male birth control pill.”

This non-hormonal contraceptive targets a protein called the retinoic acid receptor alpha (RAR-α), one of a family of three nuclear receptors that bind retinoic acid—a form of vitamin A that plays an important role in sperm formation, among other things. 

The researchers found that knocking out the RAR-α gene in male mice made them infertile. Although another study had formulated an oral compound that inhibits all three nuclear receptors, the University of Minnesota team wanted to produce a drug specific to RAR-α to minimise side effects.

The researchers, led by Gunda Georg, Ph.D., found that a compound called YCT529 could inhibit RAR-α alone. The researchers then gave YCT529 orally to male mice over a period of four weeks, and found it dramatically reduced their sperm counts and prevented pregnancy by 99 percent without causing any observable side effects.

Crucially, the male mice became fertile again after four to six weeks of being taken off YCT529.

The next question, of course, is whether the birth control pill will work in humans without causing side effects. Clinical trials on humans may begin in the second half of the year, Georg said.

Because there’s no way to ensure that a drug that works well in animals would be as safe and effective in humans, Georg said her team is continuing to explore other compounds that could lead to a viable male birth control pill.