Getting your Trinity Audio player ready...
For the first time ever, a non-hormonal male birth control pill has entered the second phase of human clinical trials. This breakthrough has the potential to shift the balance of responsibility in contraception, which has traditionally fallen almost entirely on women.
“This is the holy grail of contraception research, and it has been for many years,” says Prof. Ido Sholt, head of the Maternal-Fetal Medicine Unit at Rambam Health Care Campus. “The entire burden has been placed on women, who take hormonal treatments with all the consequences that come with it. This issue spans social, medical, historical and political dimensions.”
The study was recently published in the scientific journal Nature Communications. Initial clinical trials (Phase 1) have concluded, demonstrating that the drug is safe for use in men. Safety and efficacy tests involving a small group of volunteers (Phase 2) have now begun in New Zealand. The research team expects to complete this phase and publish results later in 2025.
“It’s still too early to predict how successful the drug will be in humans, but based on the results in primates, things are heading in a good direction,” says Prof. Sholt. “The experimental drug blocks sperm production in males, with almost no side effects.”
The new drug, known as YCT-529, showed auspicious results in trials involving mice and macaque monkeys, with minimal side effects. In male mice, the contraceptive became effective within a month, reducing pregnancy rates in female partners to nearly zero. Male macaques required a higher dosage of the drug, but they also experienced a rapid and significant drop in sperm count, without any severe side effects.
How the drug works
The study examined the effectiveness, safety and reversibility of the non-hormonal contraceptive pill for men, YCT-529, which works by blocking the RARα retinoic acid receptor. This receptor is involved in sperm production. The research was conducted on dozens of male mice and six macaque monkeys, divided into two groups. The mice received daily doses of 10 or 20 milligrams per kilogram for two or four weeks, while the monkeys were given gradually increasing doses of up to 7.5 milligrams per kilogram per day.
Researchers analyzed sperm count, mating fertility, testicular biopsies, histological examinations and hormone levels, including testosterone, FSH and inhibin B. Among the mice that received 10 milligrams per kilogram for four weeks, the contraception success rate was 99%. In monkeys, sperm counts dropped sharply within just two weeks. Fertility was fully restored within 6–12 weeks in mice and 73–148 days in monkeys, depending on the dosage. No serious side effects were observed, hormone levels remained stable and no permanent damage to testicular tissue was found—supporting the continued evaluation of the drug in human trials.
A fully reversible option
The key advantage of this development is that the drug’s effects are completely reversible. Once treatment was stopped, the animals regained full fertility. Additionally, the drug did not alter the levels of the three main hormones involved in sperm production: testosterone, FSH and inhibin B.
According to Prof. Sholt, this reversibility makes the new pill particularly appealing compared to existing male contraceptive methods. “As soon as the treatment stops, fertility returns. This provides a reversible solution without side effects or the need for surgical procedures. Over the years, all male contraceptive methods developed involved significant side effects, such as weight gain, depression, increased levels of ‘bad’ cholesterol and loss of libido, among others.”
YCT-529 works by specifically targeting the RARα receptor, a protein involved in cell growth, sperm production and embryonic development. By exclusively blocking this receptor, the drug minimizes the risk of side effects in other systems.
“There are many receptors in the body, but this one is particular to the testes,” explains Prof. Sholt. “The brilliance of this development is that the drug targets only this specific receptor, avoiding side effects in other systems.”
A collaborative effort
The lab led by Prof. Gunda Georg at the University of Minnesota is heading the research, in collaboration with scientists from Columbia University and the pharmaceutical company YourChoice Therapeutics. The project, funded by the U.S. National Institutes of Health (NIH), has been ongoing since 2022, though its progress has been slower than expected.
Get the Ynetnews app on your smartphone: Google Play: https://bit.ly/4eJ37pE | Apple App Store: https://bit.ly/3ZL7iNv
“A safe and effective male contraceptive will provide additional options for couples looking to prevent pregnancy,” said Prof. Georg. “It will allow for a more equitable distribution of family planning responsibility and give men greater reproductive autonomy.”
Public response and future potential
The public response to the idea of male contraceptive pills appears encouraging. A 2023 survey of over 2,000 men found that more than three-quarters were willing to use a new contraceptive method. Dr. Nadja Mannowetz, chief scientist and founder of YourChoice Therapeutics, emphasized the potential for social change: “Women have carried the burden of contraception for far too long. The data shows that men want to share the responsibility and are open to trying new options—and women trust them to do so.”
Prof. Ido SholtPhoto: Rambam Health Care CampusProf. Sholt also sees the pill as having the potential to change relationship dynamics. “In a good relationship, where there’s trust between partners, it’s natural for a man to take on responsibility just as a woman does,” he says. “There are women who cannot use hormonal contraceptives for medical reasons or who suffer from significant side effects. This gives couples the option to choose who takes responsibility—or to alternate that responsibility over time. It’s also a great option for single men who want to engage in regular sexual activity without worry.”
Looking ahead
YCT-529 is not the only non-hormonal contraceptive option being studied. In 2024, a study at Baylor College of Medicine tested a different compound, CDD-2807, which successfully prevented reproduction in male mice after an injection. However, this method has not yet entered clinical trials. The last male contraceptive method to be approved was in the 1980s, when a minimally invasive vasectomy technique was introduced. This method, however, is nearly irreversible and requires complex surgery to restore fertility.
“In Israel, for example, vasectomy hasn’t gained popularity like it has in the United States,” says Prof. Sholt. “That’s why there’s growing interest in a pill—especially a non-hormonal option.”
Although widespread approval of YCT-529 is still a long way off, the findings so far have sparked significant interest in the scientific and public health communities. The ultimate goal is to expand contraceptive options and promote a more equitable distribution of responsibility between men and women.