Medical Science

Is the “pill” coming for men?

Fast and reversible contraceptive blocks sperm movement

“Game changer” in contraception? A new active substance could in future also enable men to use short-term, effective contraception. In initial tests with mice, the non-hormonal agent stopped sperm movement shortly after ingestion and prevented any fertilization. Because the effect sets in quickly and lasts for several hours, the active ingredient called TDI-11861 could also be used spontaneously for contraception. But first it has to prove itself in further tests.

So far, if men want to prevent unwanted conception, their only options are condoms or sterilization. Because an effective and spontaneously usable drug contraception for men does not yet exist. One of the reasons for this: Such a contraceptive must completely and reliably block the production or function of millions of sperm. However, hormonal agents tested so far only worked after weeks of ingestion and sometimes had significant side effects.

The inhibitor TDI-11861 (grey) binds to a pocket of the sAC enzyme (green) and blocks its function.© Clemens Steegborn

Enzyme blockade makes sperm immobile

But now there is a new approach. This does not interfere with sperm production and the testosterone balance in men like previous drug candidates. Instead, it works on an enzyme that regulates sperm motility. Under normal conditions, the soluble adenylyl cyclase (sAC) produces a messenger substance that is crucial for cellular signal transmission – and also for the maturation and movement of sperm.

This is where the newly discovered active ingredient comes into play. For their study, the team led by Melanie Balbach from Weill Cornell Medicine in New York looked for inhibitors that selectively and temporarily only switch off the adenylyl cyclase that is active in the testes and sperm. “However, such an inhibitor must still be effective when the ejaculate and sperm are in transit in the female reproductive tract,” the researchers explain.

100% effectiveness in mice

Balbach and her team have now found such an inhibitor. In experiments with male mice, the inhibitor known as TDI-11861 proved to be effective quickly and reliably: when male mice were given this active ingredient, their sperm remained immobile and infertile for at least two and a half hours. In 52 matings with receptive female mice, not a single fertilization and pregnancy occurred within this period. In the male mice of the control group, one-third of their mating partners were pregnant after the test.

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