New research reports on very promising results with the much-desired male contraceptive pill — in mice.

Birth control options for men today are quite limited: there’s condoms, and there’s vasectomies. Much ink has already been spilled about the various complaints men (and some women) have with the former. And, for all their exposure and promotion of their use, it is still quite common to see men unsure as to how to correctly apply and use them. For all these reasons and more, researchers have been quite interested for some time in developing a contraceptive pill for men, although progress has been slow.

New research led by a graduate student at the University of Minnesota reports on a promising development in this regard. The prototype pill has proven itself to be 99% effective in animal studies, and will hopefully deliver similar results during human trials later this year.

No-baby pill

“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,” says lead author Md Abdullah Al Noman.

The female birth control pill was first approved for use in the 1960s. It delivers a certain quantity of hormones that are meant to disrupt the menstrual cycle, preventing the onset of pregnancy. Since those days, an equivalent pill for males has been demanded.

The main approach up to now was to develop a pill that targeted the male sex hormone testosterone. The issue researchers have encountered, however, is that such a pill leads to side effects such as weight gain, depression, and increased levels of cholesterol which increases heart disease risks. The female pill causes its own side effects, the team explains — most notably an increased risk of blood clotting — but since women are the ones who become pregnant in the absence of contraception, the risk calculation differs between the two sexes.

The current study describes the development of a non-hormonal male contraceptive pill. It works by targeting a protein known as retinoic acid receptor (RAR) alpha. This protein plays an important role in cell growth, sperm formation, and embryo development in collaboration with retinoic acid, a compound derived from vitamin A in the body. Lab experiments have shown that mice without the gene that encodes the RAR-alpha protein are sterile.

For the pill, the team developed a compound that blocks the activity of RAR-alpha in the body. The best structure for this compound was determined using a computer model before being synthesized in the lab.

“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.

Christened YCT529, the chemical was designed specifically to interact with RAR-alpha, and leave two other related substances — RAR-beta and RAR-gamma — unaffected, in order to minimize the risk of side effects.

YCT529 was tested in a laboratory setting using mice. It was delivered orally to male mice for four weeks, after which the team recorded a very significant drop in the sperm counts of these mice. The compound was 99% effective in preventing pregnancy in the mates of these mice later during the study. No signs of changes in weight, appetite, or overall activity levels were recorded in the treated mice, although the team does note that they can’t determine the existence of side effects like headaches or mood changes until they go to human trials.

The mice involved in the study could successfully impregnate females four to six weeks after being taken off of YCT529, showing that the effects are fully reversible.

Human trials should start by the third or fourth quarter of 2022, say the researchers, who are collaborating with a company called YourChoice Therapeutics to get the pill to market for people around the world. If everything goes well, the pill could be available in the next five years or so.

That being said, the findings should be taken with a grain of salt. Just because a drug works on mice does not mean that it will work in humans too. However, the results so far give us reasonable grounds to suspect that the pill will have at least some contraceptive effect in human males.

The findings have been presented at the American Chemical Society (ACS) Spring 2022 meeting under the title “A non-hormonal pill could soon expand men’s birth control options”.