For the first time and without side effects, a team of scientists has come up with the production of contraceptive pills for men, in a precedent that is the first of its kind, away from condoms or surgeries.
In recent preliminary research, the team says they developed a non-hormonal form of male contraceptive, one that kept lab mice sterile for four to six weeks without any side effects. Human trials of the pill are expected to begin by the end of the year.
According to the US website Gizmodo, 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 for fertility in mammals. For example, diets deficient in vitamin A have been linked to infertility.
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 will be sufficient to induce long-term but reversible sterility while causing little or no off-target effects elsewhere.
“There are other potential male birth control treatments that are closer to fruition in clinical trials already, although it has been a long and difficult road to get there,” said Abdullah Al-Noman, principal researcher and the post-graduate student in medicinal chemistry at the university.
Most of these suggested options work by targeting testosterone, which can come with unwanted side effects such as high cholesterol or low sex drive.” The UMN team believes their treatment can bypass these concerns, which could make it a more attractive option.
“Since men do not have to suffer the consequences of pregnancy, the threshold for side effects from contraceptive pills is rather low, which is why we are trying to develop a non-hormonal birth control pill to avoid hormonal side effects,” he told Gizmodo.
So far, the compound called GPHR-529 appears to be working as intended.
And in new data presented Wednesday at the spring meeting of the American Chemical Society, the team found that male mice given the treatment doses for four weeks consistently experienced severely reduced sperm counts 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 animal research has similarly shown that α-RAR-inhibition should be safe and effective in inducing temporary male sterility.
Noaman added: “All this looks promising so far. But clinical trials are the ultimate test of the safety of any drug candidate.”
The team has since licensed GPHR-529 to Yourchoice Therapeutics for further development, and if all goes as planned, they hope to begin early clinical trials in people by the latter half of the year.
The UMN team is also still working to identify other promising candidates, either in the absence of GPHR-529 or to improve their current concept, which could allow them to obtain the same contraceptive effect at a lower dose.
Elsewhere, the conceptual male gel, which lowers sperm and natural testosterone levels but then supplements its own testosterone to reduce side effects, is round the corner.
A larger-scale Phase 2B trial of the gel is expected to be completed in early 2023, although more trials will be needed for FDA approval.