The Daily Populous Monday July 28th, 2025 morning edition
Authored by scientificamerican.com and submitted by Aralknight

When it comes to birth control, the market has long been skewed: female contraception comes in a variety of pills, implants, injections and devices, all approved by U.S. regulators. Condoms and vasectomies are the only male contraceptives available. Researchers have been chipping away at this problem for decades, and progress is finally ramping up. Now a male birth control pill with an entirely new kind of contraceptive mechanism has been tested for the first time in humans.

In the first clinical trial of its kind, a nonhormonal oral contraceptive that reversibly stops sperm production has just been deemed safe for human use. The daily pill, called YCT-529, blocks a vitamin A metabolite from binding to its receptor in the testes; this prevents the chain of gene-expression changes that are required to start the sperm-making process. Safety results from the early phase 1 clinical trial were published on Tuesday in Communications Medicine.

The trial did not assess the pill’s efficacy in reducing sperm, and the drug’s developer, YourChoice Therapeutics, is currently running trials to collect that data. But the safety finding is a crucial milestone, says Stephanie Page, an endocrinologist at the University of Washington School of Medicine, who wasn’t involved in the study and has worked on other male hormonal contraceptives for more than 20 years. “We really need more reversible contraceptive methods for men,” she says.

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The small trial included 16 healthy men aged 32 to 59, all of whom had undergone a vasectomy—a common surgery to prevent the release of sperm by snipping the vas deferens ducts in the scrotum. Enrolling only such participants was an extra precaution to avoid the risk of permanently affecting participants’ fertility; no one has clinically trialed a nonhormonal male contraceptive pill before, says Nadja Mannowetz, co-founder and chief science officer of YourChoice Therapeutics, who oversaw the new trial. Using nonfertile participants worked for the trial because the team wasn’t yet evaluating the drug’s effectiveness but rather its tolerability and bioavailability (active levels that build up in the body), Mannowetz says.

Participants were split into two groups. In the first, people either received an initial dose of 10 milligrams (mg) of YCT-529 and then a second, 30-mg dose two weeks later or got a placebo each time. Participants in the second cohort either received a first dose of 90 mg and then a second dose of 180 mg two weeks later or always received a placebo. All participants took the pills after fasting. Four from each cohort were selected to return and take a third, 30-mg dose after a high-fat, high-calorie breakfast to see whether food might affect the drug’s tolerability.

Across dosages “we saw good and quick bioavailability,” meaning the drug didn’t rapidly break down in the body, Mannowetz says. On average, it took two to three days for the drug availability levels in the blood to reduce by half—a promising result that suggests the pill might only be needed once daily if it later proves effective at reducing sperm. Mannowetz anticipates the final dosage that will hit stores if the drug is eventually approved by the U.S. Food and Drug Administration will probably be closer to the higher amount tested, 180 mg, though follow-up trials will help discern the exact optimal dose.

The research team didn’t note any adverse side effects related to the drug. An advantage of a nonhormonal contraceptive medication is that, in theory, there’s a smaller chance of certain side effects such as changes to sexual function, libido or mood, Mannowetz says.

The results are exciting and important, Page says—but she points out that this was just one small trial. “I think it would be overstating the data to say they know much about side effects yet,” she says. “Every medication on the market has side effects.”

Several other reversible male birth control methods are now in the clinical trial pipeline as well. The furthest along is NES/T, a combination of the progestin Nestorone and testosterone. Applied daily as a gel to the shoulders and upper arms, it is absorbed into the bloodstream through the skin. Like the YCT-529 pill, the gel targets sperm production, but it does so by circulating testosterone and progestin—hormones that tell the brain to halt the production process. Researchers have just completed a larger, longer phase 2 clinical trial of NES/T to show effectiveness and will hopefully start a phase 3 trial soon, says Page, who has been involved in the gel’s clinical research.

Users of a male contraceptive that targeted sperm production, such as NES/T or YCT-529, would need to take it for about three months daily before it would take effect because that’s how long it takes the body to produce mature sperm cells. Sperm production would resume about three months after a user stopped taking the medication.

A couple of other candidates for hormonally acting daily male contraceptive pills are in early development. A hydrogel implant called ADAM is also being tested in early clinical trials. ADAM acts as a reversible vasectomy, physically blocking off the vas deferens to prevent sperm release until the implant is removed.

And studies show growing interest. One paper published in 2023 found that 75 percent of more than 2,000 men surveyed in the U.S. and Canada were willing to try novel contraceptives. And a report in 2019 found nearly 50 percent of U.S. men aged 18 to 49 who had sex with women, did not have a vascectomy or beliefs that prevented the use of contraception and did not wish to parent a pregnancy were “very interested.” These stats line up with Page’s experience in the field: “Men are very eager to have more reproductive agency and to participate in contraception,” she says, and all these contraceptives in the pipeline could elevate individuals’ and couples’ agency over their sexual and reproductive lifestyles.

clovisx on July 27th, 2025 at 11:21 UTC »

I hope this is real and that something is developed and comes to market. After decades of waiting and hoping for something I finally had a vasectomy because it was clear that nothing substantial was on the horizon.

biaggio on July 27th, 2025 at 10:54 UTC »

Really interesting article. Liked seeing how they set up the trials only with men who had undergone vasectomies in case there were any permanent effects on fertility.

hunkydorey-- on July 27th, 2025 at 10:48 UTC »

I have seen "male birth control pills" headlines for years and nothing ever comes of it.

A little more pinch of salt if you please.