American researchers have announced that an experimental pill for men that works by blocking sperm production has just passed its first safety test in humans – the hormone–free contraceptive tablet, called YCT–529, having already been found to prevent 99% of pregnancies during experiments in mice.
Daily Mail reports that it works by blocking access to vitamin A in the testes, preventing sperm production without affecting testosterone levels – meaning libido is not affected.
The male pill, which experts hope will be available this decade, is the only one currently being tested in humans.
For the trial, researchers recruited 16 men who were put on different doses of the pill across several days: the aim being to discover if there were any adverse side effects.
Analysis revealed there were no concerning changes in heart rate, hormone function, inflammation, mood or sexual function.
In upcoming larger trials, the researchers will look at how effective it is in preventing sperm production in humans.
The results of the safety trial, published in the journal Communications Medicine, are a critical first step toward getting the pill approved, experts said.
Earlier tests in male primates also found the drug lowered sperm counts within just two weeks. Crucially, both mice and non–human primates fully regained fertility after stopping the drug and no side effects were detected in either species.
Mice regained fertility within six weeks, while non-human primates fully recovered their sperm count in 10 to 15 weeks.
YCT–529 is being worked on as a collaboration between University of Minnesota College of Pharmacy, Columbia University in New York and San Francisco–based firm YourChoice Therapeutics.
Both the animal studies and the human trial results suggest that the approved pill would probably be taken once a day, but further trials will confirm that dosing.
“The positive results from this first clinical trial laid the groundwork for a second trial, where men receive YCT–529 for 28 days and 90 days, to study safety and changes in sperm parameters,” the study authors wrote in their paper.
Study details
Safety and pharmacokinetics of the non-hormonal male contraceptive YCT-529
Nadja Mannowetz, Stewart W. McCallum, Sharan Sidhu et al.
Published in Communications Medicine on 22 July 2025
Abstract
Background
Since nearly half of all pregnancies in the US and worldwide are unintended, there is a critical need for additional contraceptive options for men and women. After a hiatus in non-hormonal male contraceptive development of about half a century, the new chemical entity YCT-529 – a retinoic acid receptor-α antagonist – is being developed as a non-hormonal oral male contraceptive to decrease sperm count by impairing retinoic acid signalling in the testes.
Methods
Here, we report the results of the first in human Phase 1a clinical trial with YCT-529 to assess its safety, tolerability, pharmacokinetics and pharmacodynamics, and its potential effects on heart rate, inflammatory biomarkers, sexual desire and mood. Sixteen male volunteers were enrolled to receive single oral doses of 10, 30, 90 or 180 mg of YCT-529 in the fasted state. Volunteers also received 30 mg in the fed state to study the effect of food on the pharmacokinetics of YCT-529.
Results
Single doses of up to 180 mg of YCT-529 had no effects on heart rate, hormone (follicle-stimulating hormone, luteinizing hormone, and testosterone), sex hormone-binding globulin or inflammatory biomarker levels, sexual desire or mood. Further, there was no clear food effect on the pharmacokinetics of YCT-529.
Conclusions
Overall, YCT-529 was well tolerated in this single ascending dose study which is a substantial requirement in contraceptive development.
See more from MedicalBrief archives:
Time for change in the world of contraception?
Most promising study to date on male contraceptive pill
Second potential male birth control pill passes human safety tests