Could this trial be bringing male contraceptive pills one step closer?

by · euronews

Scientists in the United States say they have developed a male birth control pill that is 99 per cent effective in mice without causing side effects, and that could begin human trials by the end of this year.

The findings, unveiled at the American Chemical Society's spring meeting, mark a key step in efforts to expand contraceptive options for men and better share the burden of birth control with women.

While there are scores of options for women to control their menstrual cycle, there have been only two effective options available so far in terms of male contraception: condoms or vasectomies.

But condoms are single-use only, and vasectomies aren’t easy to reverse, so researchers have been working on developing a male contraceptive that’s effective, long-lasting and reversible - similar to the birth control pill for women.

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

Most compounds currently undergoing clinical trials target the male sex hormone testosterone, which could lead to side effects such as weight gain, depression and increased low-density lipoprotein (known as LDL) cholesterol levels.

“We wanted to develop a non-hormonal male contraceptive to avoid these side effects,” said Noman, who works in the lab of Professor Gunda Georg at the University of Minnesota.

Non-hormonal birth control

To develop a non-hormonal drug, his team targeted a protein called retinoic acid receptor (RAR) alpha.

Inside the body, vitamin A is converted into different forms, including retinoic acid, which plays important roles in cell growth, sperm formation, and embryo development.

Retinoic acid needs to interact with RAR-alpha to perform these functions, and knocking out the RAR-α gene in male mice makes them sterile, without any obvious side effects, the team said.

So, the scientists developed a compound that blocks the action of RAR-alpha. They identified the best molecular structure with the help of a computer model.

The mice could father pups again 4 to 6 weeks after they stopped receiving the pill

Their chemical, known as YCT529, was designed to interact specifically with RAR-alpha, and not two other related receptors, in order to minimise potential side effects.

Given orally to male mice for 4 weeks, the drug dramatically reduced sperm counts and was 99 per cent effective in preventing pregnancy, without any observed adverse events.

The mice could father pups again 4 to 6 weeks after they stopped receiving the compound.

Beyond condoms and vasectomy: a pill ready in five years?

The results on mice are no guarantee that the drug could be safe and effective in humans.

The team has partnered with a private company, YourChoice Therapeutics, which aims to start human trials in the country by the third or fourth quarter of 2022, said Georg.

"I'm optimistic this will move forward quickly," she told the news agency AFP, suggesting a possible timeline to market in five years or under.

"There is no guarantee that it will work...but I would really be surprised if we didn't see an effect in humans as well," she added.

The research received funding from the National Institutes of Health and the Male Contraceptive Initiative, a nonprofit advocating a broader range of birth control options.