Non-hormonal reversible male contraceptive shows promise in mice

Scientists at Weill Cornell Medical College (WCM) have successfully tested a compound in mice that can serve as a non-hormonal and reversible male contraceptive for males and revolutionize family planning, according to a press release.

For men, there are currently only two methods of contraception available; vasectomy and condoms. According to the researchers, the former is hard to reverse, and the latter has a failure rate of up to 15 percent. 

"Men require more options, especially on-demand and readily reversible ones so that they can more actively participate in family planning. Enriching the contraceptive landscape will also benefit females, who have more options right now, but most of them are based on hormones and suffer from heavy side effects," lead researcher Melanie Balbach told Interesting Engineering.

Testing the male-contraceptive on mice

The researchers identified a compound named TDI-11861 that inhibits soluble adenylyl cyclase (sAC), an enzyme that controls the mobility and maturity of sperm cells in mammals. They tested the compound on mice to observe its effect on their fertility and sexual activity.

They injected and orally fed TDI-11861 to a group of male mice and then allowed the subjects to copulate with female mice. About 30 minutes post-copulation, they examined the sperm cells in mice bodies and those that were released in females' genital tracts during copulation.

They noticed that TDI-11861 made the sperm cells almost immotile and prevented them from maturing. The enzyme was successful in preventing sperm activity. 

When about two and a half hours passed since the sAC inhibitor was injected into the mice, the sperm cells started showing some motility. However, it took the cells 24 hours to completely regain their motility. 

None of the female mice who mated with the male mice within 2.5 hours of the latter receiving the sAC inhibitor got pregnant. About 50 different matings were studied during the experiment, and not a single pregnancy was reported.  

However, when the male mice mated with another group of female mice after 24 hours, the females became pregnant. This confirmed that the sAC inhibitor (TDI-11861) was now completely metabolized by the body, and the mice regained their fertility. 

Moreover, no side effects on the sexual activity and functions of the mice were observed due to the use of TDI-11861. "We do not have any indications from our mouse studies that the on-demand treatment with sAC inhibitor causes toxicity or any other side effects," said Balbach.

A short and sweet male contraceptive

The researchers suggest that previous efforts in developing a male contraceptive focused mainly on hormonal methods blocking sperm production (spermatogenesis). Such chronic treatments are prone to side effects and don't work for every man.

"For our sAC inhibitors, we chose an on-demand approach blocking the motility of mature sperm instead of sperm development. We envision that men will take the compound about 30 min before sexual intercourse to block the sperm's motility, and within 24 to 48 hours, their fertility will be restored once the inhibitor is metabolized by the body," Balbach told IE.

Balbach and her team will now further test the sAC inhibitor on rabbits as their reproductive system is quite similar to humans. However, based on the current findings, TDI-11861 surely seems promising for developing a revolutionary male contraceptive pill.

The study is published in the journal Nature Communications.

Study Abstract:

Nearly half of all pregnancies are unintended; thus, existing family planning options are inadequate. For men, the only choices are condoms and vasectomy, and most current efforts to develop new contraceptives for men impact sperm development, meaning that contraception requires months of continuous pretreatment. Here, we provide proof-of-concept for an innovative strategy for on-demand contraception, where a man would take a birth control pill shortly before sex, only as needed. Soluble adenylyl cyclase (sAC) is essential for sperm motility and maturation. We show a single dose of a safe, acutely-acting sAC inhibitor with a long residence time renders male mice temporarily infertile. Mice exhibit normal mating behavior, and full fertility returns the next day. These studies define sAC inhibitors as leads for on-demand contraceptives for men, and they provide in vivo proof-of-concept for previously untested paradigms in contraception; on-demand contraception after just a single dose and pharmacological contraception for men.