Experimental Male Birth Control Pill Works ‘On-Demand’
A number of less-than PG jokes can be made about the state of male contraceptive drugs, but what’s certainly true is that none of them have come prematurely. To date, vasectomy, condom use, and withdrawal (aka the “pull-out method”) remain the only options for sperm producers to lower the odds of a pregnancy—leaving much to be desired.
Withdrawal fails about 20 percent of the time, while vasectomies require a (minimally invasive) surgery and a second one for a reversal. And though effective, condoms aren’t a one-size-fits-all solution.
“I’ve never met a man or a woman who likes a condom,” Jochen Buck, a pharmacology researcher at Weill Cornell Medicine, told The Daily Beast. Buck and Weill Cornell Medicine collaborator Lonny Levin are behind a new approach to male contraception that, quite literally, stops sperm in their tracks.
Here’s how it works: Imagine a NASCAR race, with sperm cells in the drivers’ seats. Upon ejaculation, an enzyme present in semen called soluble adenylyl cyclase gives sperm the cue to “go” much like a starter waving a green flag, and they start swimming forward. Buck and Levin found that if you block this enzyme, the effect is akin to removing the flagman from his post—the sperm won’t receive the signal to begin swimming. Crucially, when the drug wears off hours later, the race resumes as if nothing happened.
Results of their method in mice were published on Feb. 14 in the journal Nature Communications. But the technique is just one among a handful that researchers are testing as possible male contraception. The decades-old field has received renewed interest from the American public in light of the Supreme Court’s decision on Dobbs v. Jackson Women's Health Organization last year, prompting many to ask: It’s 2023. Why are the options for male contraceptives so lackluster?
And researchers mostly agree with this assessment. Stephanie Page, an endocrinologist at the University of Washington School of Medicine who has been working on developing male hormonal contraceptives for two decades and wasn’t involved in the study, told The Daily Beast that society is long overdue for reevaluating who bears the burden of contraception.
“Unintended pregnancy is an enormous public health problem that is stagnant with 45 percent of global pregnancies being unintended, and yet, we're not really investing in research that would potentially change that,” she said.
Long Time Coming
The truth is that preventing pregnancy from the side of a sperm-producing partner has been a tough nut to crack for a slew of reasons—some practical, others more arbitrary. For one thing, Page said, men make millions of sperm every day, while a woman releases a single egg over the course of a menstrual cycle.
“It's been a bit of a conundrum to sort out if all the sperm need to be blocked, and if not what that threshold is,” she said. Still, several efforts have focused on hormonal solutions, like those available for women. Of the methods tested, which include pills, injectables, and implants, a hormonal gel is perhaps the closest to the clinic: NES/T gel, named for its two hormonal components, is being tested in a Phase II clinical trial scheduled to start wrapping up later this year.
So far, at least, the trial seems to be going well. Diana Blithe, the chief of the National Institute of Child Health and Human Development’s Contraceptive Development Program, said in a news release last August that the efficacy of the gel seemed to be a cut above oral birth control pills. Societal factors—and a healthy dose of gender roles—have contributed to international foot-dragging, Christina Wang, a male reproductive biology researcher at The Lundquist Institute who wasn’t involved in the study, told The Daily Beast.
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Wang explained that China’s equivalent of the Food and Drug Administration tabled a monthly hormonal injection, even after a 2009 study showed it to be highly effective as a male contraceptive. Regulators, she added, said they didn’t see the purpose of new contraceptive methods when many already existed for women.
And when it comes to side effects, Wang said that the bar has been higher for recent trials in men compared to the process of approving hormonal birth control for women. Take, for instance, the controversial decision to stop a Phase II trial for a two-hormone injection in 2016 because male participants experienced acne and mood changes—despite the fact that hormonal contraception for women can result in equally severe symptoms.
National debates over reproductive care have further frustrated efforts to bring a contraceptive to market. Even though contraceptives have remained legal after the Dobbs decision, experts have worried that states restricting abortion access may consider limiting birth control options and emergency contraceptives like Plan B. “It's become very politicized, so contraception is neglected, as is caring for unintended pregnancies,” Page said.
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Finally, despite survey data suggesting otherwise, Page said that pharmaceutical companies have been apprehensive about backing male contraceptives because of their politicized nature and out of fear that there would not be enough demand for them. Changing these perceptions, she said, will require a drug making it to the finish line.
“If we can somehow get something to the market that demonstrates that there's demand and that men are actually interested in reversible contraceptives, I think it will open up the field and show that men are actually interested in sharing the burden of contraception with their partners,” she said.
Just Keep Swimming
Though Buck and Levin have been working on the enzyme at the core of their new study, blocking it wasn’t on their mind until a recent experiment. In fact, Levin said the field was afraid of tinkering with the enzyme’s levels since it is made throughout the body, and researchers worried about off-target effects.
Then, a postdoctoral researcher in his lab announced that she had experimented with blocking the enzyme, which caused mouse sperm to stop moving.“In the lab meeting when she presented that, I went, ‘Oh my God, that's a holy grail. That's a contraceptive,’” Levin said. Then, he recalled, Buck added, “It's not just that—it's better. It's an on-demand contraceptive.”
In following experiments, the pair’s labs injected the body cavities of mice with a drug to temporarily block the enzyme that caused sperm to move, then allowed the male mice to mate with females after different time spans. Between 30 minutes and two and a half hours, the drug prevented pregnancy in 52 different pairings; in contrast, 24 hours after receiving the drug, all but two of 15 mice impregnated the female.
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Page called it “really exciting work” on non-hormonal birth control. “An on-demand pill that would work within four to six hours of taking it when you wanted to have sex would be a wonderful addition to the contraceptive menu,” she said.
Even so, she cautioned that the research is still in its early stages—future work will have to test whether the drug is as effective in humans, let alone if it works in pill form. Additionally, researchers will have to pay close attention to any side effects caused by this method, since the mice treated with the drug were found to develop more kidney stones and a higher eye pressure than the control mice.
One day, Buck said that he hopes to see his and Levin’s nonhormonal method augment other options for male contraception. A method like the NES/T gel, which has to be continuously applied for months and takes still longer for its effects to fully wear off, might be a better fit for someone in a long-term relationship. A pill that a person could take around the time of intercourse could complement or even replace emergency contraception—and, Buck said, could change how society views protection and contraception.
“A blue and a pink pill you take together when you’re dating,” he said. “Imagine how that partner pill would change the social structure of [contraception].”
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