‘Stopping sperm in its tracks’: US researchers report promising development in ‘male pill’ research

Dr. Jochen Buck and Dr. Lonny Levin, professors of pharmacology at Weill Cornell Medicine, said the discovery could be a game-changer for contraception. In the abstract of their study (“On-demand male contraception via acute inhibition of soluble adenylyl cyclase”), published in Nature Communications on February 14, they write: “Almost half of all pregnancies are unintended ; thus, existing family planning options are inadequate.

What does the study say?

Basically, this study was an attempt to show proof of concept and whether the idea of ​​such a pill could practically work. The aim here was to work on slowing down the mobility or movement of sperm or the male gamete, which fertilizes the gamete or the female ovum during human reproduction.

According to the Weill Cornell Medicine Newsroom, the study came about thanks to work on a single protein. “Dr. Levin challenged Dr. Buck to isolate an important cell signaling protein called soluble adenylyl cyclase (sAC) that had long eluded biochemists,” he says. Later, the two started working together as part of a team.

They found that mice genetically engineered to lack sAC are sterile. In 2018, Dr. Melanie Balbach, a postdoctoral associate in their lab, discovered mice that had been given a drug that inactivates sACs leading to sperm unable to propel themselves forward. Therefore, sAC inhibition was considered a possible safe contraceptive option, as another team’s report indicated that men lacking the gene encoding sAC were infertile but otherwise healthy.

How was the study carried out?

A single dose of an sAC inhibitor, called TDI-11861, has been shown to immobilize mouse sperm for up to two and a half hours, and the effects persist in the female reproductive tract after mating. After three hours, some sperm begin to regain their motility; within 24 hours, almost all sperm recovered normal movement.

“Our inhibitor works in 30 minutes to an hour,” Dr. Balbach said. “All other hormonal and non-hormonal experimental male contraceptives take weeks to reduce sperm count or render them unable to fertilize eggs.”

The team now plans to conduct these experiments in a different preclinical model, eventually hoping to move into human clinical trials.

Why was the male contraceptive pill difficult to develop?

Contraception, in general, has focused on women. In 1960, the oral contraceptive pill was approved for release. Although the pill has also not been totally controversial, often resulting in side effects such as the risk of blood clots and even the risk of cancer according to some studies, there was also a great benefit. This allowed women to have more power in procreation.

The operation of the pill was done by the regulation of progestin and estrogen hormones, preventing the fertilization of the egg by the sperm. Christina Wang, a contraceptive researcher in the United States, said The Washington Post that biology may be at play in explaining why the same did not happen for men. Women produce one egg per month while men produce sperm in much greater numbers. Therefore, developing a method is more difficult.

Sometimes studies have been dropped after finding even mildly mild side effects, such as acne or mood swings in a 2016 study, even though women have dealt with them over the years. But it also has to do with changing norms about what is now acceptable in such trials, compared to when female contraception was developed in Western countries in the mid-twentieth century.