Male contraception could be on its way after an experimental drug that may temporarily stop sperm in its tracks in just 30 minutes has been given the go ahead for further clinical investigation. Experts at Weill Cornell Medicine have received a multimillion dollar grant from the National Institute of Child Health and Human Development (NICHD) to test a pill they developed that would provide men with a six to eight hour window of protection from initiating a pregnancy. After that window, fertility would return to normal.
The four-year grant will enable them to test whether the pill is safe in humans, and is the third grant since 2020 that pharmacologists Dr Jochen Buck and Dr Lonny Levin have received for their work in developing a male contraceptive pill. The two pharmacologists told Newsweek that it is "extremely gratifying" to receive the grant because they said few like it are awarded nationwide, and the decision about who gets a grant is dependent on peer review by a panel of experts in the field, so they said "it is rewarding to learn that our work is valued so highly by the experts who know this field the best." Around 40 percent of pregnancies in the U.S. are unplanned, according to data from the Centers for Disease Control and Prevention (CDC), and contraceptive options for men are currently limited to condoms and vasectomies. Contraception is therefore largely a burden placed on women, who rely on long-term use of hormonal contraceptives which can have a range of side effects.
"About a third of women stop a hormonal method within the first year, most often because of side effects, and stopping while still wanting to avoid pregnancy is a leading route to unintended pregnancy, about 121 million a year worldwide and 2.6 million in the U.S., close to half of all pregnancies in both," Jean-Ju Chung, an associate professor of cellular and molecular physiology at Yale University, told Newsweek. "We need options that act before fertilization, that do not ask a healthy person to take hormones continuously, and that let men share the responsibility rather than only comply with it," she said. How the pill works all comes down to an enzyme called soluble adenylyl cyclase (sAC).
The enzyme is inside a sperm cell and "is essential for the sperm to swim and continue maturing after they are ejaculated from the man into the woman’s reproductive tract," Buck told Newsweek. Levin explained that "if this enzyme is missing, men are infertile because while they ejaculate normally, their sperm do not travel through the female reproductive tract from the vagina to deep inside the female reproductive tract where they need to get to meet and fertilize the egg." What the two pharmacologists discovered was that they could "turn off" the enzyme temporarily. "We found that if you give a man an inhibitor of the enzyme as a pill, it will get into the man’s sperm which are awaiting ejaculation, and because we found inhibitors that have a unique ability to stay stuck to the enzyme for a very long time, the inhibitor keeps the enzyme off even after the sperm are ejaculated into the woman," Buck said.
This means that, because the enzyme remains "off," those sperm cannot swim deep into a woman's reproductive tract to fertilize an egg, Levin said. But, just like all drugs taken as pills, the "level of the drug in the body peaks shortly after taking the pill and then those levels decrease over time," Buck said. "After that time window, the levels of the drug in the man’s body would fall to be below the level where it can turn off sperm," Levin said, meaning fertility remains back to normal.
Chung said that "almost every male contraceptive so far targets sperm production, and since human spermatogenesis takes about two and a half months, those methods take weeks to work and weeks to reverse," but sAC inhibitors, like this drug, act on sperm that already exist, blocking the switch the cell needs to turn on its motor after ejaculation, enabling the effect to "be fast, brief and fully reversible." Buck and Levin said that they are often asked "whether women would trust men to be the ones responsible for birth control," but said that this drug could solve that problem because of its "on-demand" nature. So far, in the animal studies conducted, "no side effects" have been noted, the two pharmacologists said. This was even the case when "we give our inhibitor to animals at very high doses for extended periods of time suggesting there should not be side effects in men who take the eventual drug." However, this still needs to be tested in humans.
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