A pill for him promises a new era for contraception

For decades, conversations about birth control have mostly centered on women’s options: pills, patches, injections, implants, and intrauterine devices. Men, on the other hand, have had to choose between two extremes: condoms, which can fail more often than we’d like, and vasectomy, a surgical step that’s meant to be permanent. Now, a new contender is stepping onto the stage, and it’s not hormonal. In early 2025, researchers led by Nadja Mannowetz and Akash Bakshi from YourChoice Therapeutics in San Francisco, in collaboration with scientists from Quotient Sciences in the UK and Incyte in the US, published results in [Communications Medicine] from the first human trial of YCT-529, a once-a-day, non-hormonal male contraceptive pill. The trial might mark the start of a long-awaited shift in reproductive responsibility: one where men can take an active, reversible role in preventing pregnancy without hormones. ### What’s different about YCT-529? Most male birth control research over the past half-century has revolved around hormones, altering testosterone levels to suppress sperm production. While these approaches can work, they tend to bring along side effects like acne, weight gain, and mood changes. YCT-529 takes a different route. It targets retinoic acid receptor-alpha (RAR-α), a key player in how the body uses vitamin A to produce and mature sperm. If you block this receptor in the testes, sperm production halts, but the rest of the body’s functions stay largely unaffected. Animal studies with mice and monkeys showed that this effect was both highly effective and reversible, which is crucial for a contraceptive. ### The first test in humans The Phase 1a trial enrolled 16 healthy men, all of whom had already undergone vasectomy. This allowed scientists to focus on safety without worrying about unplanned pregnancies just yet. Participants received single doses of YCT-529 ranging from 10 to 180 milligrams, either on an empty stomach or after a high-fat breakfast, while some got a placebo. For two weeks after taking the pill, researchers monitored everything they could think of: heart function, hormone levels, markers of inflammation, mood, sexual desire, and any adverse effects. The results? No significant safety issues. Vital signs, testosterone and other hormone levels, and mood scores stayed steady. Most side effects—like mild headaches or temporary colds—were random and not tied to the drug. One participant had a brief, irregular heart rhythm detected by continuous ECG monitoring, but it was mild, symptom-free, and cleared up on its own. YCT-529 reached peak blood levels between 4 and 10 hours after swallowing, and it stuck around for more than two days, with a half-life of about 51–76 hours. Food slightly increased absorption, but not in a way that raised safety concerns. Even the smallest tested dose brought blood concentrations into the range that had proven effective in animal studies. That means that, at least in theory, a daily pill could maintain the drug at steady, sperm-blocking levels. ### What it didn’t do (on purpose) Because YCT-529 is non-hormonal, it didn’t affect testosterone, follicle-stimulating hormone, luteinizing hormone, or sex hormone-binding globulin. That’s important: these hormones control much more than reproduction, and avoiding their disruption could mean fewer side effects than traditional hormone-based male contraception. The pill also didn’t mess with sexual desire or function, a crucial detail for a drug intended to be taken long-term by healthy people. ### Why this matters Nearly half of pregnancies in the US and worldwide are unintended. That’s not just a statistic; it’s a reflection of a gap in reproductive responsibility and choice. Many men say they want to share that responsibility, but their options have been stuck in the 20th century. The last big push for non-hormonal male birth control (for instance, compounds like gossypol or WIN 18,446) fizzled out decades ago due to safety problems. YCT-529 may be the first in a new generation of candidates to pass the first, most critical test: showing that it’s safe enough to keep studying. ### What’s next? The team is already running a Phase 1b/2a trial, where men will take YCT-529 daily for either 28 or 90 days. This time, sperm counts will be measured to see if the drug delivers on its main promise: temporarily shutting down sperm production while keeping everything else running smoothly. If all goes well, YCT-529 could one day sit on pharmacy shelves next to the female pill, a small capsule representing a big cultural shift. For the first time, men could have a reliable, reversible, hormone-free way to take control of their fertility. Of course, there’s a long road between a promising Phase 1 trial and a product you can pick up at your local drugstore. But as this research shows, that road might finally be open for travel. And who knows? A decade from now, couples might be sharing birth control in the most literal sense, by each taking their own pill. If you want to learn more, the original article titled "Safety and pharmacokinetics of the non-hormonal male contraceptive YCT-529" on [Communications Medicine] at [https://www.nature.com/articles/s43856-025-01004-4](https://www.nature.com/articles/s43856-025-01004-4). [Communications Medicine]: https://www.nature.com/articles/s43856-025-01004-4

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