Male contraceptive disables sperm
For years, people have tried to create birth control for men. The World Health Organization commissioned what sounded like a promising trial, a two-hormone injection designed to lower sperm count. Initial results looked like it would be 96 percent effective in preventing pregnancy in the participants’ partners. But the Stage II trial was stopped after an independent review panel found that the drug had too many side effects. The results were published last week in The Journal of Clinical Endocrinology and Metabolism.
Male Birth Control Study Killed After Men Report Side Effects
A birth control pill for men remains an elusive dream.
Whether it’s an IUD, a shot, an implant, or a daily pill, birth control is a regular part of many adult women’s lives. It has left a lot of women asking: Why not men?
For years, people have tried to create birth control for men. The World Health Organization commissioned what sounded like a promising trial, a two-hormone injection designed to lower sperm count. Initial results looked like it would be 96 percent effective in preventing pregnancy in the participants’ partners. But the Stage II trial was stopped after an independent review panel found that the drug had too many side effects. The results were published last week in The Journal of Clinical Endocrinology and Metabolism.
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All Things Considered‘s Audie Cornish sat down with NPR science correspondent Rob Stein to discuss the trial and the reason it was canceled. Here are excerpts of their conversation, edited for length and clarity.
How did this latest study work?
It was a pretty big study; they gave shots to 320 men every eight weeks, in different countries around the world. The shot contained two hormones, and it worked pretty well. It knocked down their sperm counts significantly, and there were only a handful of pregnancies among partners of men in the trial.
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But two committees were paying close attention to the study, and they realized that a lot of guys were dropping out because they were experiencing side effects. The most common side effect was acne, and sometimes that acne was pretty severe. Some men also developed mood swings and in some cases those mood swings got pretty bad. One man developed severe depression, and another tried to commit suicide. Because of that, they cut the study short.
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But when they spoke with guys in the study who didn’t drop out, most said that if this product was available, they would use it.
There’s been a lot of eye rolling on the Internet about these side effects, because women have been experiencing things like mood swings and weight gain for decades with hormonal birth control.
No birth control is perfect. Almost everything has some sort of side effect. And the side effects they saw in this study were not that different from those you see with other kinds of birth control — except for the severe emotional problems. That was definitely more than we see with the birth control pill.
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But there’s a little bit of a different risk-benefit analysis when it comes to men using a contraceptive. When women use a contraceptive, they’re balancing the risks of the drug against the risks of getting pregnant. And pregnancy itself carries risks. But these are healthy men — they’re not going to suffer any risks if they get somebody else pregnant.
Why is it harder to develop birth control for men than women?
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That’s the a big question. There are a couple of reasons. One is that it’s harder from a biological point of view. If you think about it, it’s a numbers game: Women produce one egg a month, while men are producing millions of sperm constantly. With women, you can take advantage of their normal monthly cycle with the birth control pill. There’s nothing equivalent to that in men.
What does this mean for male birth control in general? Is this particular study a big setback, or is it no big deal?
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It’s a setback and it’s definitely a disappointment. People had a lot of optimism about this study. But I’ve talked to a bunch of scientists about this, and they say they’re not giving up yet. They’re going to tinker with the doses of the hormones to see if they can come up with safer levels. They’re also going to try different kinds of hormones and maybe administer them differently, like in a gel or an implant. They could also target how a sperm works by making it not swim as well, making it worse at fertilizing the egg.
There’s a lot of research still going on, but most of it is at a fairly early level. Scientists are saying, “We’re gonna keep trying,” but they’re still a decade away from coming up with something for men.
- Men’s Health
- Birth Control
- contraception
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Male contraceptive disables sperm
Studies suggest that about half of all pregnancies worldwide are unintended. Most modern contraceptive methods are for women. Men generally have two options: condoms or vasectomies.
The challenge with creating new contraceptives for men is the high rate of sperm production. Men produce several million sperm per day—about 1,000 per second. To prevent pregnancy, all of these need to be stopped from reaching an egg.
Both hormonal and non-hormonal approaches to stop sperm have been in development. But many of these methods need about two months to become effective, and require continuous treatment to remain fully effective. Reversing their effects takes a similarly long time. Thus, there is an unfulfilled need for an on-demand, reversible approach.
Following ejaculation, sperm begin to vigorously beat their tails. This enables them to swim through the female reproductive tract and fertilize the egg. An enzyme called soluble adenylyl cyclase (sAC) is needed to trigger this behavior. Male mice engineered to lack sAC are infertile but have few other differences from normal mice. Men who have naturally occurring mutations that inactivate sAC are also infertile.
An experimental male contraceptive drug candidate, called an sAC inhibitor, prevents sperm from beating. Dr. Melanie Balbach
An NIH-funded team of researchers, led by Drs. Jochen Buck and Lonny Levin at Weill Cornell Medicine, developed a compound called TDI-11861 that binds and inhibits sAC. They tested its effects on sperm function and fertility. Their findings appeared in Nature Communications on February 14, 2023.
A variety of tests in mice didn’t identify any potential safety issues with TDI-11861. The team then treated male mice with a single dose of TDI-11861 before allowing them to mate with females. The treated mice showed no differences in mating behavior from untreated mice. But the sperm from treated mice lost the ability to move on their own. Sperm remained immobile after being deposited in the female reproductive tract.
When male mice treated with TDI-11861 were paired with females, none of the females became pregnant. This contraceptive effect was observed for up to two and a half hours after treatment. In contrast, male mice treated with a control compound impregnated females 30% of the time. The effect of the treatment wore off with time, and by 24 hours after treatment, fertility had recovered completely.
These findings suggest that an sAC inhibitor could be developed into a safe, temporary contraceptive drug for men. “The team is already working on making sAC inhibitors better suited for use in humans,” Levin says.
However, more work is still needed before human clinical trials could begin. Several challenges remain before a drug could get approved for people to use.
*Editor’s Note: The first paragraph was modified on August 15, 2023, to remove statistics that may no longer have been accurate.
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References: On-demand male contraception via acute inhibition of soluble adenylyl cyclase. Balbach M, Rossetti T, Ferreira J, Ghanem L, Ritagliati C, Myers RW, Huggins DJ, Steegborn C, Miranda IC, Meinke PT, Buck J, Levin LR. Nat Commun. 2023 Feb 14;14(1):637. doi: 10.1038/s41467-023-36119-6. PMID: 36788210.
Funding: NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute on Aging (NIA), and National Cancer Institute (NCI); Male Contraceptive Initiative; Tri-Institutional Therapeutics Discovery Institute.
