A team of scientists has said they have developed a male oral contraceptive that is 99 percent effective in mice and has caused zero observable side effects. The drug is expected to enter human trials by the end of 2022.
The findings are set to be presented at the American Chemical Society’s spring meeting, and mark a defining step towards expanding birth control options and responsibilities for men.
The female birth control pill was first approved in the 1960s and since then, researchers have been interested in a male equivalent, Md Abdullah Al Noman, a graduate student at the University of Minnesota who will present the work, told AFP.
“Multiple studies showed that men are interested in sharing the responsibility of birth control with their partners,” he said — but until now, there have been only two effective options available: condoms or vasectomies.
For vasectomy, reversal surgery is expensive and not always successful.
Since its inception, the female pill uses hormones to disrupt the menstrual cycle. Historic efforts to develop a male equivalent has always targeted the male sex hormone testosterone.
Analysts indicate that the problem with this approach was that it sparked side effects including weight gain, depression and rising levels of a cholesterol known as low-density lipoprotein, which increases risks of heart diseases.
The female pill also carries side effects, among them blood-clotting risks — but since women face becoming pregnant in the absence of contraception, the risk calculation differs.
Aiming at a non-hormonal drug, Noman, who works in the lab of Professor Gunda Georg, 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 lab experiments have shown mice without the gene that creates RAR-alpha are sterile.
For this particular work, Noman and Georg developed a compound that blocks the action of RAR-alpha. They identified the best molecular structure with the help of a computer model.
“If we know what the keyhole looks like, then we can make a better key — that’s where the computational model comes in,” said Noman.
Their chemical, known as YCT529, was also designed to interact specifically with RAR-alpha, and not two other related receptors RAR-beta and RAR-gamma, in order to minimize potential side effects.
DROPPING SPERM COUNT
When administered orally to male mice for four weeks, YCT529 drastically shrunk sperm counts and was 99 percent effective in preventing pregnancy in a mating trial.
The researchers monitored weight, appetite and overall activity, finding no apparent adverse impacts, although mice of course can’t report side effects like headaches or mood changes.
Four to six weeks after they were taken off the drug, the mice could once more sire pups.
The team, which received funding from the National Institutes of Health and the Male Contraceptive Initiative, is working with a company dubbed YourChoice Therapeutics to start human trials by the third or fourth quarter of 2022, said Georg.
“I’m optimistic this will move forward quickly,” she said, envisioning 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.
A persistent question about future male contraceptive pills has been whether women will trust men to use them.
But surveys have shown that most women would in fact have faith in their partners, and significant numbers of men have indicated they would be open to the medication.
“Male contraceptives will add to the method mix, providing new options that allow men and women to contribute in whatever way they deem appropriate to contraceptive use,” argues the nonprofit Male Contraceptive Initiative, which engages in fundraising and advocacy.