Male birth control pill passes early safety test, with more trials underway

An experimental, hormone-free male birth control pill has just passed its first safety test in humans.

The trial included 16 people and was only intended to test whether the drug reached adequate levels in the body, as well as whether it triggered any serious side effects, such as concerning changes in heart rate, hormone function, inflammation, mood or sexual function.

Across the doses tested, no significant side effects were observed. That result tees up the pill to be tested in larger trials that will now look at both safety and efficacy.

The results of the early safety trial, published Tuesday (July 22) in the journal Communications Medicine, are a critical first step toward getting the pill approved, Dr. Stephanie Page, an endocrinologist at the University of Washington School of Medicine who wasn't involved in the study, told Scientific American. "We really need more reversible contraceptive methods for men," she added.

For the moment, the only male birth control options are condoms and vasectomies. The latter can be reversed, but the actual success rate of the reversal procedure varies widely in terms of how likely a person is to conceive a child afterward. If approved, the new pill would be the first drug in its class.

"A safe and effective male pill will provide more options to couples for birth control," Gunda Georg, a professor in the University of Minnesota College of Pharmacy, where the drug molecule was developed, said in a statement released earlier this year following promising preclinical testing of the pill. Columbia University was also involved in the drug's development, along with the company YourChoice Therapeutics, which is overseeing the trials.

Related: Why is there still no male birth control pill?

"It will allow a more equitable sharing of responsibility for family planning and provide reproductive autonomy for men," Georg said.

How the male birth control pill works

The experimental pill, called YCT-529, is designed to pause sperm production by interrupting specific signals in the body.

Specifically, the drug works by blocking a protein called "retinoic acid receptor alpha," which is known to play a key role in the formation and maturation of sperm. In the testes, the receptor would usually be activated by the insertion of a "key" — a vitamin A metabolite — but the drug stops this key from clicking into place. That, in turn, prevents the chain reaction that ends with sperm being made.

Finding a compound with this effect required the scientists to closely examine the structure of the receptor when it's bound to its key, as well as test dozens of molecules to see which could block the interaction.

In preclinical tests with male lab mice, the drug "elicited profound effects" on sperm production. It triggered reversible infertility within four weeks of use, showing 99% effectiveness at preventing pregnancy in the female mice the treated males mated with. When taken off the drug, the male mice's fertility was restored within about four to six weeks.

Further tests in nonhuman primates returned similar results, with sperm counts falling dramatically within two weeks of starting the drug and fully recovering within 10 to 15 weeks of stopping the drug. These preclinical tests set the stage for the recent clinical trial in people.

The trial included 16 males ages 32 to 59, all of whom had previously undergone vasectomies. This was done out of an abundance of caution, in case the experimental drug was to have any lasting impacts on fertility, Nadja Mannowetz, co-founder and chief science officer of YourChoice Therapeutics, told Scientific American.

The participants were split into groups who received either placebo pills or a low or high dose of the drug. Most of the participants took the pill only after a period of fasting, but a subset were also given doses after a large meal, to see if that affected levels of the drug in the body.

Across all of the doses and conditions tested, the levels of the drug in the body reached decent levels, but Mannowetz anticipates that, if approved, the final dose would be closest to the highest one tested: 180 milligrams.

Both the animal study and the human trial results suggest that the approved pill would likely be taken once a day, but further trials will confirm that dosing. And although no notable side effects emerged in this small trial, future trials with larger study cohorts will still need to monitor for these effects.

"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. That trial is already underway and again is looking at males who have already had vasectomies or who have made a firm decision not to father children.