Preclinical Study findings show promising results of On-Demand Male Contraceptive

An experimental contraceptive drug candidate developed by Weill Cornell Medicine investigators temporarily stops sperm in their tracks and prevents pregnancies in preclinical models. The study, published in Nature Communications on Feb. 14, demonstrates that an on-demand male contraceptive is possible.

The discovery could be a "game-changer" for contraception, according to the study authors.

The team discovered that mice genetically engineered to lack sAC are infertile. Then in 2018, an exciting discovery was made while working on sAC inhibitors as a possible treatment for an eye condition. It was found that mice that were given a drug that inactivates sAC produce sperm that cannot propel themselves forward. The team was reassured that sAC inhibition might be a safe contraceptive option by another team’s report that men who lacked the gene encoding sAC were infertile but otherwise healthy.

The new Nature Communications study demonstrates that a single dose of a sAC inhibitor called TDI-11861 immobilizes mice sperm for up to two and half hours and that the effects persist in the female reproductive tract after mating. After three hours, some sperm begin regaining motility; by 24 hours, nearly all sperm have recovered normal movement.

TDI-11861-treated male mice paired with female mice exhibited normal mating behavior but did not impregnate females despite 52 different mating attempts. Male mice treated with an inactive control substance, by contrast, impregnated almost one-third of their mates.

Additionally, the authors noted that it takes weeks to reverse the effects of other hormonal and nonhormonal male contraceptives in development.Also since sAC inhibitors wear off within hours, and men would take it only when, and as often, as needed, they could allow men to make day-to-day decisions about their fertility.

Reference:

Balbach, M., Rossetti, T., Ferreira, J. et al. On-demand male contraception via acute inhibition of soluble adenylyl cyclase. Nat Commun 14, 637 (2023). https://doi.org/10.1038/s41467-023-36119-6