Male contraceptive pills: Key findings explained as safe tests on mice pave the way for human trials

On March 23, scientists said that they had created an oral male contraceptive that is 99 percent effective in mice with no side effects. They said that developed drug could enter human trials by the end of this year.

These findings will be presented at the spring meeting of the American Chemical Society and provide a step towards expanding men's birth control options and responsibilities.

Md Abdullah Al Noman, a graduate student at the University of Minnesota who will present the work, told AFP that researchers have been interested in a male birth control pill since the female pill was approved in 1960s.

"Multiple studies showed that men are interested in sharing the responsibility of birth control with their partners."

However, he said that there have been only two effective options available: vasectomies and condoms. In some cases, vasectomy reversal surgery is unsuccessful.

The female pill disrupts the menstrual cycle with hormones, while historic efforts to develop a male equivalent focus on the hormone testosterone.

However, this approach contributes to weight gain, depression, and increased cholesterol levels called low-density lipoprotein, which increases the probability of heart disease.

Additionally, the female pill has side effects, such as blood-clotting risk, but since women are at risk of becoming pregnant without contraception, the risk calculation differs.

---

Male contraceptive pills are non-hormonal

To create a non-hormonal contraceptive drug, Noman, who works in Gunda Georg's lab, focused on a protein called "retinoic acid receptor (RAR) alpha."

As vitamin A is converted inside the body, it becomes retinoic acid, which plays a key role in sperm formation, cell growth, and embryo development.

For these functions to occur, retinoic acid must interact with RAR-alpha. Lab experiments have shown that mice lacking the gene that creates RAR-alpha are sterile.

In their research, Noman and Georg developed a compound that blocks the action of RAR-alpha. Using a computer model, the researchers identified the best molecular structure. Noman said:

"If we know what the keyhole looks like, then we can make a better key -- that's where the computational model comes in."

The chemical, YCT529, was also developed to interact with only RAR-alpha rather than two other related receptors, RAR-beta and RAR-gamma, to minimize side effects.

YCT529 significantly reduced male mice's sperm counts over four weeks and was 99 percent effective in preventing pregnancy, without any observed side effects.

The mice could conceive for a second time four to six weeks after being taken off the drug.

Georg said his team will begin human trials in the third or fourth quarter of 2022 with the help of a company called YourChoice Therapeutics, which has received funds from the National Institutes of Health and the Male Contraceptive Initiative.