A Bitter Pill: Slow Progress Toward a Male Contraceptive

The CruxBy Carrie ArnoldDec 27, 2013 1:30 AM


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Scientists have called the contraceptive pill one of the most important inventions of the twentieth century. Now, more than fifty years after the Pill was first released, contraception remains a woman’s world. Sure, men can use condoms or have a vasectomy, but women have a much more dizzying array of options from which to choose. From pills to contraceptive vaginal rings to intrauterine devices and more, most scientists and pharmaceutical companies have focused their contraception efforts on women. This isn’t necessarily a bad thing. Many reproductive health scientists say that we need more, not fewer, options for contraception. The problem is that virtually all contraception is being geared toward women. That’s largely because, historically, contraception was grouped in with the traditional female concerns of family and childbearing. “There are a fair number of women who are dissatisfied with their current method of contraception,” said Michael O’Rand, a biologist and male contraception expert at the University of North Carolina at Chapel Hill. In recent years, however, attitudes have been shifting. Men are expressing more and more willingness and even desire to take on some of the responsibilities of contraception. Cross-cultural surveys reveal that men are willing to take contraception

and, at least in committed relationships, females would trust their partner to take the drug

. The problem is that they have no new options. Even as new breakthroughs in male contraception in animal models are being published to great fanfare—the latest

came out earlier this month in the journal PNAS—they haven’t translated into products men can use to prevent pregnancy. “The forces that should drive pharmaceutical research and development spending are somehow not working. They’re leaving promising opportunities untapped because they have an emotional bias that men won’t buy it. As far as we can tell, that’s just not true,” says David Bishai

, a public health economist at the Johns Hopkins School of Public Health in Baltimore.

Contraceptive Checklist

The requirements of good birth control, whether for men or women, seem almost ridiculously simple on the surface. It needs to be very effective, have low levels of side effects, be easy to use, and also be reversible, so fertility can return after the contraception is stopped. Neither condoms nor vasectomies meet these criteria. Although condoms are very effective at preventing the spread of sexually transmitted infections, they are less so at preventing pregnancy. The Centers for Disease Control estimates that condoms have an 18% failure rate. This means that 18 of 100 women who typically use condoms during intercourse will have an unintended pregnancy in the first year of use. Vasectomies are more than 99% effective, but they are not considered reversible. When trying to create a male contraceptive that fulfills these four criteria, researchers have focused primarily on the testes. Just as hormonal contraception for women works partly by preventing ovulation, scientists have tried to design a hormonal contraceptive for men by preventing the creation or development of sperm.

Trying Testosterone

They first turned to testosterone. Ironically, high doses of the hormone most closely associated with male virility and fertility can render a man effectively sterile. The problems for researchers have been balancing potential side effects of the drug (which can include mood swings and acne) as well as finding a way to administer it. O’Rand said that pharmaceutical companies invested lots of time and money to develop a formulation of testosterone that would survive a swim in the acid bath of the stomach. They couldn’t do it. Patches, gel, or injections could avoid the oral route, though injections are unlikely to be practical since most men would find them too inconvenient to have on a regular basis. Thus drug developers are down to a testosterone patch or gel should they elect to go the testosterone route. Several testosterone-containing male contraceptives are currently in Phase II trials, but even harder trials may lie ahead for them. It’s currently not clear whether the side effects of these compounds will be tolerable over the long term. Clinical trials are better at detecting acute side effects than potential problems after years of use. Nor do scientists know if using these drugs for months or years could permanently alter a man’s future fertility. “A number of these drugs may be okay if you give them in a low dose for a short time, but over the long term, they may be toxic. It’s a problem, and we just don’t know,” O’Rand said. Although this is true for any number of compounds, male contraceptives will be given to an otherwise healthy population and researchers expect that regulatory agencies and males alike will have a lower tolerance for potential harms that may arise.

An Untapped Market

Testosterone isn’t the only player in the male fertility market, although it is currently the best-researched idea. O’Rand and his colleagues at UNC have successfully tested ultrasound as a way to disrupt sperm development. His lab has also spent more than a decade developing a way to freeze sperm in their tracks. The method relies on a protein known as Eppin

. Eppin is found on the outside of sperm and acts as a brake by binding to another protein known as semenogelin. When Eppin and semenogelin are bound together, sperm can’t swim and thus can’t move up the female reproductive tract to fertilize the egg. But this brake is released after ejaculation, when semenogelin breaks down and the sperm start swimming. When O’Rand and colleagues immunized male monkeys against Eppin, he found that he could render the monkeys temporarily infertile. The work has been slow going, in part due to a lack of good animal models to use. The reproductive systems of rats and mice are nothing like human ones, O’Rand says, which leaves only primates as potential animal models. This can get expensive quickly, and is one more barrier for investors and pharmaceutical companies to take a chance on a male contraceptive. Still, though, the rewards are great. “Male contraception is a drug that you would have to take every day for years and years. This is what pharmaceutical companies love. This is the big prize in pharmaceutical research,” Bishai said. The market, Bishai and O’Rand say, is there and waiting. The contraceptive market as a whole

is estimated to be worth $16 billion and to reach $23.3 billion by 2018. In the past year, however, only 37 of the 13,500 studies on contraception focused on males. Until Big Pharma and scientists alike can shift their thinking that contraception isn’t just for women, that market will remain untapped.

Image by Danil Nevsky / Shutterstock

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