FUTURE OF CONTRACEPTION? ON-DEMAND MALE CONTRACEPTIVE PILL STOPS SPERM IN THEIR TRACKS

Drs. Buck and Levin noted that condoms and vasectomies have been men's only options to date. Research on male oral contraceptives has stalled, partly because potential contraceptives for men must clear a much higher bar for safety and side effects, Dr. Levin said. Because men don't bear the risks associated with carrying a pregnancy, he explained, the field assumes men will have a low tolerance for potential contraceptive side effects.

The team, including the study's co-senior authors Lonny Levin and Jochen Buck, discovered that mice genetically engineered to lack an important cellular signaling protein called soluble adenylyl cyclase (sAC) are infertile.

The study, published in the journal Nature Communications, demonstrates that a single dose of an 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 and by 24 hours, nearly all sperm have recovered normal movement, the researchers said. 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.

"Our inhibitor works within 30 minutes to an hour. Every other experimental hormonal or nonhormonal male contraceptive takes weeks to bring sperm count down or render them unable to fertilize eggs," Balbach said.

The researchers noted that it takes weeks to reverse the effects of other hormonal and nonhormonal male contraceptives in development. 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, they said. "The team is already working on making sAC inhibitors better suited for use in humans," Levin said.

The next step is repeating the experiments in a different preclinical model. These experiments would lay the groundwork for human clinical trials that would test the effect of sAC inhibition on sperm motility in healthy human males, Buck said. If the drug development and clinical trials are successful, Levin said it could lead to the development of "the male pill."

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