The “pill” for men enables non-hormonal contraception

enzyme blockade

So far, men can only prevent condoms or sterilization. A new inhibitor makes sperm immobile and enables spontaneous, drug-based contraception that lasts for several hours.


New York (United States). So far, men have only been able to prevent unwanted conception by using condoms or permanent sterilization. A drug-based contraceptive like the pill for women has not yet been developed for men. Hormone-based contraceptive pills for men have already been tried, but they caused severe side effects and only worked after several weeks. A recently presented contraceptive pill for men from the University of Minnesota, which achieved an effectiveness of 99 percent in animal tests, does not require hormones and causes no side effects, is only partially practical because the desired effect only occurs after several weeks.

A team from Weill Cornell Medical College has now presented a new approach in the journal Nature Communications that does not interfere with testosterone levels or sperm production. Instead, non-hormonal contraception starts with the production of the enzyme adenylyl cyclase (sAC), which controls sperm motility. Normally, the enzyme releases a messenger substance that is essential for cellular signal transmission, including sperm movement.


Sperm adenylyl cyclase deactivated

The researchers working with Melanie Balbach were therefore looking for an inhibitor that would selectively and temporarily deactivate the active adenylyl cyclase in the testicles and sperm. Crucially, the inhibitor remains active even after the ejaculate and sperm are already in the female reproductive tract.

Inhibitor makes sperm immobile and infertile

In their experiments, the scientists discovered the inhibitor called TDI-11861, which acts spontaneously and reliably. In animal studies with mice, the inhibitor was able to immobilize and infertile sperm for at least two and a half hours. As a result, no fertilization occurred in more than 50 matings with receptive female mice. In the control group mice, whose males did not receive the inhibitor, fertilization occurred in a third of the matings.

Inhibitor acts quickly and reversibly

Further investigations showed that the effect of the inhibitor sets in after 30 to 60 minutes and is completely reversible. Eight to 24 hours after taking the drug contraceptive, the mice were fertile again. Malformations or behavioral abnormalities in the sperm or other side effects could not be observed. Mating behavior, potency and ejaculation were also not affected by the inhibitor.

Spontaneous, non-hormonal contraception for men

The study thus shows that the inhibitor could enable spontaneous, non-hormonal contraception in men.


“Our study demonstrates the feasibility of two pioneering paradigms of human contraception: non-hormonal male contraception and spontaneously ingested medical contraception. Our strategy has the potential to create more gender equality and could revolutionize family planning, much like the birth control pill did back then.”

Sperm live for several days

However, as the researchers explain, it must be remembered that human sperm can survive in the uterus for several days. However, the proven sAC inhibitor only works for a few hours. In order to be able to prevent fertilization in humans, it is therefore also necessary to prevent the sperm from penetrating the cervix. If they only remain in the vagina, they die quickly due to the acidic vaginal environment.

However, the researchers are confident that the inhibitor will also work in humans.

“The sperm must be actively motile in order to cross the cervix and exit the vagina. They should not be able to do this under the influence of the sAC inhibitor.”

The scientists are currently preparing further animal experiments. If these are also successful, a phase 1 clinical trial with humans could take place.

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