Scientists are still racing to create the first male contraceptive that isn’t a condom or surgery. In new preliminary research, a team says they’ve developed a non-hormonal form of male birth control, one that kept lab mice sterile for four to six weeks with seemingly no side effects. Early human trials of the pill are expected to begin by the end of the year.
The proposed contraceptive is the product of researchers at the University of Minnesota, who say it works by targeting how our bodies interact with vitamin A, known to be essential to fertility in mammals. Diets deficient in vitamin A have been linked to sterility, for instance. After a lengthy search, they found an experimental compound that blocks a protein responsible for binding to a form of vitamin A (retinoic acid) in our cells, known as retinoic acid receptor alpha (RAR-α). RAR-α is one of three proteins with a similar function, and the hope is that its selective blocking is enough to induce long-lasting but reversible sterility while causing little to no off-target effects elsewhere.
There are other potential male birth control treatments closer to fruition in clinical trials already, though it’s been a long and difficult road to get there. Most of these proposed options work by targeting testosterone, which could come with unwanted side effects like higher cholesterol or lower sex drive. The UMN team thinks their treatment could skate past these concerns, which could make it a more appealing option, according to lead researcher Md Abdullah Al Noman, a graduate student in medicinal chemistry at the university.
“Since men do not have to suffer the consequences of pregnancy, the threshold for side effects from birth control pills is rather low,” Noman told Gizmodo in an email. “That’s why we’re trying to develop nonhormonal birth control pills to avoid hormonal side effects.”
So far, the compound — dubbed GPHR-529 — seems to work as intended. In new data presented Wednesday at the spring meeting of the American Chemical Society, the team found that male mice dosed with the treatment for four weeks consistently experienced a sharp drop in sperm count and became sterile. Overall, GPHR-529 was estimated to be 99% effective in preventing pregnancy, with no noticeable side effects. And about four to six weeks after they stopped taking it, the male mice were no longer sterile. Other research of theirs in animals has similarly shown that inhibiting RAR-α should be safe and effective at inducing temporary male sterility.
“This all looks promising so far. But clinical trials are the definitive test for the safety of any drug candidate,” Noman noted.
The team has since licensed GPHR-529 to the company YourChoice Therapeutics for further development, and should things go as planned, they hope to start early-stage clinical trials in people by the later half of the year. The UMN team is also still working to identify other promising candidates, both in case GPHR529 doesn’t pan out and to improve on their existing concept, which could allow them to get the same contraceptive effect at a lower dose.
Elsewhere, the male conceptive gel NES/T, which lowers levels of sperm and natural testosterone but then supplements its own testosterone to reduce side-effects, is rounding the corner. A larger scale Phase IIb trial of the gel is expected to be completed in early 2023, though more trials will be needed for FDA approval.