When it comes to birth control, there’s a bit of an imbalance between products targeted at women and those assigned female at birth, and products targeted at men. And when we say “imbalance”, we mean that nearly all the effective, reversible methods are designed around the female reproductive system. There’s long been a drive to try and redress this with the development of a male contraceptive pill, and a new study has found a promising option that’s already seen success in animals.

“Although researchers have been investigating several strategies to develop male contraceptives, we still do not have a birth control pill for men,” said corresponding author Dr Martin Matzuk of Baylor College of Medicine in a statement.

“In this study we focused on a novel approach – identifying a small molecule that would inhibit serine/threonine kinase 33 (STK33), a protein that is specifically required for fertility in both men and mice.”

This new approach does not rely on manipulating hormone levels, like many existing contraceptives. Instead, like some other male contraceptives that are being explored, it has been born out of genetic research.

The drug targets the STK33 protein, which is expressed at high levels in the testes and has been shown to be essential for proper sperm development. Natural mutations in the STK33 gene are a known cause of infertility in men; but, while the quality of the sperm is affected, there is no change in the external appearance of the testes, or any other identifiable issues.

“STK33 is therefore considered a viable target with minimal safety concerns for contraception in men,” Matzuk explained.

The team set about screening billions of compounds, trying to find one that might work to inhibit STK33 – an effort aided by the fact they also managed to elucidate the crystal structure of the protein for the first time.

Several candidates were taken forward for further modifications and experiments, and one emerged at the head of the pack. “Among these modified versions, compound CDD-2807 turned out to be the most effective,” said staff scientist and first author Dr Angela Ku.

Previous work in a mouse model had shown that knocking out their matching Stk33 gene has the same effect as it would in human males – it causes infertility by negatively affecting sperm quality. The team therefore tested out their CDD-2807 compound in mice to assess its potential as a contraceptive.

The drug was able to successfully migrate into the testes, reducing sperm count and motility. Testis size was not impacted, and there were no toxic side effects.

“Importantly,” explained co-author Dr Courtney M. Sutton, “the contraceptive effect was reversible. After a period without compound CDD-2807, the mice recovered sperm motility and numbers and were fertile again.”

The achievement was hailed as a “tour de force” by co-author Dr Mingxing Teng, and Matzuk explained that the next step will be to test out the compound in primates.

This is not the first hormone-free male contraceptive that’s shown promise in the lab. Another compound, YCT-529, is already in early clinical trials. Other approaches being explored put a temporary block on sperm production itself, render sperm unable to swim, or act as a reversible alternative to a vasectomy.

But the process of drug development is long and, given the desert of contraceptive options for men up to now, there would certainly be no downside to additional choices. Which birth control method you opt for is a very personal decision, so in an ideal situation, we’d have a range of options to suit different people.

Perhaps this time, the promise of a male contraceptive is finally coming closer to fulfillment.

The study is published in the journal Science.