Groundbreaking Research: Are Male Birth Control Pills Coming Soon?

An experimental contraceptive developed by researchers at Weill Cornell Medicine temporarily stops sperm and prevents pregnancy in preclinical models. The study, published Feb. 14 in Nature Communications, shows that a men’s on-demand contraceptive is possible. The discovery, according to study co-authors Dr. Jochen Buck and Dr. Lonny Levin, who are professors of pharmacology at Weill Cornell Medicine, could be a game changer for birth control and lead to male birth control pills.

When it comes to male contraceptives, we’re still at the beginning. In fact, for men only the proven condom that has existed for 2000 years is available, and a vasectomy, which is not an option for couples who want to have children. Research on male oral contraceptives has stalled, in part because potential male contraceptives face a much higher bar in terms of safety and side effects. Since men do not bear the risks associated with pregnancy, the department assumes that men have a low tolerance for possible side effects of contraceptives.

sAC Inhibitors Immobilize Sperm

The researchers did not initially look for a male contraceptive. But as Dr. Levin Dr. Prompt Buck to isolate an important cellular signaling protein called soluble adenylyl cyclase (sAC) that had long eluded biochemists, he set to work. Buck and Levin then shifted their research focus to the study of sAC and eventually merged their labs. The team discovered that genetically engineered mice lacking sAC are infertile. In 2018, Dr. Melanie Balbach, a postdoc in her lab, made an exciting discovery while working on sAC inhibitors as a potential treatment for an eye disease. She found that mice given a drug that inactivates sAC produce sperm that cannot move forward. The team was reassured that sAC inhibition could be a safe contraceptive option when another team reported that men lacking the gene coding for sAC were infertile but otherwise healthy.

Effect Already After 30 Minutes

The new study from Nature Communications shows that a single dose of an sAC inhibitor called TDI-11861 immobilizes 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 become motile again; after 24 hours, almost all sperm have regained their normal movement. Male mice treated with TDI-11861 mated with female mice exhibited normal mating behavior but failed to fertilize females despite 52 different mating attempts. In contrast, male mice treated with an inactive control substance fertilized almost a third of their partners. The inhibitor that the researchers developed works within half an hour to an hour. Other experimental hormonal or non-hormonal male contraceptives take weeks to reduce sperm counts or render them unable to fertilize eggs, the researchers said.

In addition, Dr. Balbach states that it takes weeks to reverse the effects of other hormonal and non-hormonal contraceptives for developing men. She said that since sAC inhibitors wear off within hours and men only take it when and as often as needed, they could allow men to make day-to-day decisions about their fertility.

Male Birth Control Pills May Soon be a Reality

Balbach and Levin noted that the development of TDI-11861 required significant medicinal chemistry work, conducted in collaboration with the Tri-Institutional Therapeutics Discovery Institute (TDI). TDI works with researchers from Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center and Rockefeller University to accelerate early-stage drug discovery.

The team is already working to make sAC inhibitors more suitable for human use. The next step is to repeat the experiments in another preclinical model. These experiments would lay the foundation for human clinical trials testing the effect of sAC inhibition on sperm motility in healthy males. If drug development and clinical trials are successful, the pill for men may eventually be available in the future.