Male birth control options could expand with non-hormonal pill

Unlike women, contraceptive options for men have been limited to condoms or a vasectomy. But a third option could eventually become available: researchers at the University of Minnesota have developed a non-hormonal male contraceptive they say is 99 per cent effective on mice and comes with no obvious side effects.

The results were presented at a meeting of the American Chemical Society this week. The project, funded by the National Institutes of Health and the Male Contraceptive Initiative, is set to begin human clinical trials in the third or fourth quarter of this year, according to Gunda Georg, the lead scientist in this drug development.

“Scientists have been trying for decades to develop an effective male oral contraceptive, but there are still no approved pills on the market,” Md Abdullah Al Noman, a graduate student who works under Georg and presented at the meeting, said in a statement.

Male options like the condom can fail, while a vasectomy is a surgical procedure that is often permanent. While reversal surgery is possible, it is costly and success is not guaranteed. The limited options can mean the burden and responsibility often fall on women to prevent pregnancies.

Other male birth control drugs under development target testosterone, which can cause side effects like weight gain, depression, and higher levels of low-density lipoprotein (LDL) cholesterol, known as the “bad” cholesterol.

The contraceptive developed by Georg’s team targets a protein called the retinoic acid receptor alpha (RAR-α), one of three such nuclear receptors. Retinoic acid is a form of vitamin A that is key to cell growth, differentiation like sperm formation, and embryonic development. Scientists were able to make male mice temporarily sterile by “knocking out” the RAR-α gene, without any observable side effects.

Other oral compounds that target the nuclear receptors have also been developed by other scientists, but those usually target all three. This particular drug is different because only the RAR-α is targeted, and as such, researchers say it is less likely to result in side effects.

The team designed and synthesized roughly 100 compounds when they found YCT529, which inhibited RAR-α nearly 500 times more effectively than the other two protein receptors.

When researchers gave the compound to male mice for four weeks, sperm count in the mice fell dramatically and was 99 per cent effective at preventing pregnancy. The effects were also reversible, with the mice able to sire babies four to six weeks after the drug was no longer administered.

“Because it can be difficult to predict if a compound that looks good in animal studies will also pan out in human trials, we’re currently exploring other compounds, as well,” says Georg, who is a consultant with YourChoice Therapeutics.