SignalHub-In the hunt for a male contraceptive, scientists look to stop sperm in their tracks

Condoms have SignalHubbeen used to prevent pregnancy since the Middle Ages, with the rubber version arriving in the industrial mid-1800s. Over the years, they've become more effective and comfortable to use.

But it was the invention of birth control pills, followed by IUDs in the 1960s, that created a seismic shift in humans' ability to control reproduction. A growing range of pills, patches and implants became available to women. And yet, a stretchy sheath that covers the penis remains the only medically approved form of contraception for men, short of vasectomy.

But now, researchers are looking into both hormonal and non-hormonal contraceptives for sperm bearers. The hope is that couples will begin to treat contraception more as a shared responsibility.

"We would like to create a menu of options for men similar to what women have available to them," says Stephanie Page, a researcher and endocrinologist at the University of Washington.

(Note: The studies mentioned here are typically done on cisgender males between 18 and 50, so this story refers to the medications as "male contraception," and their target demographic as "men" or "males," though people of other genders can produce sperm.)

Hormonal methods get renewed research

Page's lab is conducting a clinical trial along with researchers at 15 other sites across the globe, testing out a topical gel that a man applies to his shoulders every day. The gel contains synthetic hormones — a combination of testosterone and progestin — that signal the brain to lower testosterone levels in the body. And since testosterone is necessary for sperm to reach maturation, the testes then produce fewer and fewer sperm.

Page's study enrolls couples — nearly 450 of them worldwide. Having the woman involved too means "she's taking on consent as well as him, and they're really both participants," Page says.

The trial run in phases. In the first phase, the man applies the gel every day, but the couple still uses another form of contraception when they have intercourse. During this phase, researchers are periodically monitoring the man's sperm count. Then when the count is low enough to prevent pregnancy, the couple enters the second phase: they stop using other contraceptive methods, while the man continues to use the gel daily.

In the third and final phase, the man stops using the gel, and researchers begin to monitor his sperm count once again. Researchers hope their results will demonstrate that the effect on fertility is reversible — just as women can regain their fertility when they stop taking birth control pills.

Brian Nguyen, an OB-GYN and professor at the Keck School of Medicine at the University of Southern California who also researches male contraception, says he's encouraged by what he's hearing from some of the men in the gel trial, especially those "who really just want to support their female partners."

"I hear stories about how men are really tired of hearing about their partner suffering from hormonal side effects or in some cases, complications related to IUDs or implants," he says. "And they want to do something."

Nguyen's lab is also working on a hormonal pill that would work similarly to the gel, and Page's lab is hoping to eventually develop an injectable hormone solution.

In the 1990s, the World Health Organization sponsored trials for male hormonal contraceptive — where men were given high doses of testosterone — but those drugs never came to market. Researchers thought they weren't effective enough to sell, and side effects were serious, including toxicity for the heart, liver and kidney, and a potential increased risk of prostate cancer.

The University of Washington's Stephanie Page says the gels and pills being tested now don't come with the same risks.

"We have worked really hard to develop methods that don't impact those other physiologic parameters," says Page. "So we don't see any impacts on kidney function, liver function and the like."

As for side effects, some participants report weight gain, changes in libido, acne, or mood swings." Those, she points out, are "very similar to those that some women experience using female hormonal contraceptives."

Promising non-hormonal approaches

Another area of research targets precise points in the sperm's life cycle, including its ability to swim, or to fertilize an egg. These drugs are a bit more precise than hormonal ones, says Logan Nickels, research director at the Male Contraceptive Initiative, which supports researchers working on non-hormonal contraceptives.

"They target a very specific link in the chain of the generation or lifetime of a sperm and ... if you were to break that link, there aren't any other bodily functions or any sort of broad signals that you're interrupting." In other words, someone using these methods would likely experience few to no side effects, he says.

"The male reproductive system is really cool in that there's hundreds and hundreds of links in this chain, [so] that if you take out any one of them, you end up with effectively an infertile man," Logan says.

Another non-hormonal method undergoing trials in Australia is a gel that's injected into the vas deferens — the tube that carries sperm to the urethra in preparation for ejaculation — and blocks the transport of sperm. Logan says it could be like a reversible alternative to a vasectomy.

Why is it taking so long?

Page estimates it will be another seven to 10 years before any of these new methods can be sold. So why have women had to shoulder so much of the responsibility for contraception for so long?

"Women bear the life-threatening burden of pregnancy," Page says. "And so the initial energy went into ensuring that women had control of their own reproduction."

And, she says, developing male contraception is more complicated. Women typically release an egg or two a month. Men produce millions of sperm a day — a single ejaculation contains roughly 15 million to 200 million sperm per milliliter of semen. Researchers had to figure out how low the count should be to reliably prevent pregnancy. They've now determined it needs to be less than 1 million sperm per milliliter of semen, Page says.

And the Food and Drug Administration criteria for approving male contraceptives is vague.

The pharmaceutical industry and the FDA use data from trials to weigh benefits and risks to the patient. But Page says in this case, the risk calculation should be different.

"When we think about risks, what are we protecting the man from? In the case of female contraception, the woman is being protected from the risk of pregnancy and of potentially unsafe abortion. But with men, they're really using a contraceptive to protect their partner. If we just think about the man as a single unit, there should be obviously no side effects and no risk. But I think we really need to move to thinking about couples as a dyad and this is a shared risk," she says.

Another barrier to bringing male contraceptives to market is the rate of efficacy. Female contraceptive implants and IUDs are 99% effective, and birth control pills are 93% effective, according to Planned Parenthood. Male contraceptives may have to be just as good at preventing pregnancy in order to sell.

"Drug companies invest millions and millions and millions of dollars into a drug before they ever see a dime of profit," says Nickels. "And so when they take those calculated risks, those calculated investments, they try to make sure that they're going to see their money at the end of it," he says.

Nickels, Page and Nguyen all expressed optimism that a male contraceptive will come to market in the next decade, though funding could be a limiting factor.

Logan predicts that either the injectable non-hormonal gel or the topical hormonal gel will be the first to reach the market.

For male contraception drugs to succeed on the market, says Brian Nguyen, it's important for men to become better educated on what women go through.

"Men are often shielded from discussions about menstruation, pregnancy, labor, infertility. There's somewhat of a feeling of invulnerability among most men because they don't have to think about the need for contraception. And the only way to remedy that is by having more and more open conversations with men about reproduction, and their responsibility in a process that is not just a women's issue."

Women have been waiting for that mindset shift for a long time. But even if it doesn't happen right away for most heterosexual men, perhaps the freedom to skip the sheath will be motivation enough.

The audio of this episode was produced by Rebecca Ramirez, edited by Gisèle Grayson and fact-checked by Abē Levine. Tre Watson was the audio engineer.