Developing Contraceptives for Men Is Really Hard

When the contraceptive pill was approved in the 1960s, it was hailed as a major breakthrough. It enabled women to take control of their fertility more than ever before, and was even credite​d for a rise in women attending and graduating from college.

However, there's still no equivalent for men. Part of that is because male fertility works very differently to female fertility on a purely mechanical level; part of it is a ​business problem. For now, men are pretty much left with a choice of using condoms every time or going the whole hog and getting a vasectomy.

But some researchers are pursuing potential alternatives. ​Male Contraception Initiative is one organisation dedicated to pushing forward new contraceptives for men through education, advocacy, and help with funding. I spoke to Chair and Director David Sokal and Executive Director Aaron Hamlin about why there's no male pill yet, and what options men might have in the future.

MOTHERBOARD: Why do we not yet have a male pill? The female version's been around for a while.
​David Sokal: Right after the female pill was marketed, people got enthusiastic about the idea of a male hormonal pill and so that developed a lot of momentum and funding, and most of the effort since really the 1960s went into developing a male hormonal pill. Unfortunately, there's a basic physiological difference, and that is that it's easy to fool the ovaries with a very low dose of hormones to make the ovaries think a woman is pregnant, and so the ovaries will stop ovulation. However, there's no similar situation for male sperm production; there's no normal state where sperm production stops.

So using hormones to stop sperm production requires very high doses and causes side effects. There have been a number of trials which ​were halted—they did show effectiveness in 90, 95 percent of men, but they were considered unsuccessful or halted because of either low effectiveness or side effects.

Our approach is to focus on new opportunities that haven't been explored. There's a lot of new biotech stuff; there are many more ways to control male fertility than stopping sperm production. And sperm production is a 90-day process, so a disadvantage of stopping sperm production is that once you stop it, you're still fertile for three months—unlike ovulation, within a week you can fool the ovary and it won't ovulate. So there is now some promising work being started to look at: How do you stop sperm from swimming? Or, how do you interfere with fertilisation? But the general field has not gotten the support it needs.

The other thing is sociological—there was initially a lot of skepticism that men would be responsible enough, or women would trust them to take a pill. And of course the pharmaceutical companies are very happy making money on female pills, and the liability issues have been worked out pretty well, and they're a little afraid of a new male pill. Any time you give something to a large number of healthy people there are liability issues. Someone's going to get sick after taking the pill, and he's going to blame it on the pill, whether that's a true connection or just a coincidence. We hope to find something that's quite safe that would not have any significant side effects.

Even given these difficulties, there are still people researching in this area. So the demand is there?
​Aaron Hamlin: For one, we know the demand is there. There are surveys that show, in the US at least, one out of every two men would use a new male contraceptive. The need is also there: Men's only option for reversible contraception is the condom. We're talking about the same kind of 16th ce​ntury idea here, and it doesn't particularly fare well in the real world with pregnancy rates either. You've got factors like inconsistent use, slippage, breakage—among couples that use the condom as their primary method, 18 perc​ent experience a pregnancy in their first year. That's more than one in six. Who in their right mind would be comfortable with a dice roll when it comes to planned parenthood? It's just not acceptable.

Unplanned pregnancy has consequences that obviously affect women and men: their careers, education, finances—we're basically talking about their whole future, particularly when they're younger. We have to remember that it affects children as well; you can imagine that if you choose to put a child with parents where a contraceptive failed versus where a child was planned, anybody is going to put that child with the couple where the child was planned.

Sokal: I'll throw in another item. You're talking to two men, however quite a few women have been strong advocates in this field. There are a number of articles in the field about social justice—and men should be sharing the side effects. We'd hope to have something with no side effects, but that's rare, and the best way to avoid the side effects for the pill for women is to have the man have a good option.

More specifically, what are some of the difficulties that are specific to male contraceptives?
​Sokal: The hormonal machinations and different varieties of testosterone and progesterone that have been used are very difficult to calibrate, to try to reduce the side effects by using different hormones. The hormonal approach has tried many different candidates and combinations. One issue is that, for example, you can't take testosterone orally, because the things you eat go through the liver and testosterone taken orally is toxic to the liver. The current best regimen is a testosterone implant plus oral progesterone, or some form of progesterone—so that gets complicated.

If you get out of the hormonal field, there are quite a few interesting leads. There's a fellow just down the road from where I am at UMC Chapel Hill who's got a very promising lead compound he's been working on that prevents sperm from swimming. The onset of action from that would be a few days or maybe a week. It hasn't gotten to human trials yet but it seems very promising; he's got primate data suggesting that it'll work.

At this point we have contact with a couple other folks, two outside the US—one has a concept, another has something that's been in trials in Indonesia but hasn't been confirmed by other researchers, because it's relatively little-known. But the difficulty is that there have not been a lot of resources devoted to this area. There's a lot of new biotech technology. We've had one person contact us (I can't tell you who or what he's doing because it's confidential) who is using an approach that would have been unimaginable five or ten years ago. If there were some more funding, I think there are a lot of possibilities using current biotech methods to look at non-hormonal methods.

What do you mean by non-hormonal methods, what kind of biotech are we talking here?
​Sokal: The one I can tell you about is a target called Eppin, which is a protein that's essential to let sperm swim after ejaculation. Michael O'Rand at UMC Chapel Hill showed that interfering wit​h Eppin in primates prevents conception. It stops the sperm from swimming. He's got some grant applications in to NIH and he's hoping to continue work, but to me that's one more promising area.

Another, the Indonesian group working on an herbal medicine called Genda​russa, has something that'll interfere with fertilisation. They show normal sperm count, normal motility, but no babies. They're up to phase two human trials. This work is based on a lead from ethnographic research where a tribe in Papua found that this tea made from Gendarussa stopped men's fertility—it's a fascinating story.

And what's next for this field of research—what can we hope to see in the future, and what timescale are we looking at?
​Hamlin: David pointed out that a lot of the promising research looks to be in non-hormonal methods, and he pointed out Gendarussa, which may be sooner than we think in upcoming years, at least with the Indonesian FDA. Some things in science are unpredictable, with funding concerns. He also pointed out Eppin, looking at motility. That one still needs to go through human trials, so that's a little bit further away.

The other method that really comes to mind is ​Vasalgel​, and that's probably closest to US FDA approval. It will be going through as a medical device rather than a drug. Vasalgel is a gel polymer that's injected into the vas deferens. The vas deferens is a tube that goes from the epididymis of each testicle [tubes that carry sperm] and connects up to the urethra. So what they're doing is taking advantage of a bottleneck the sperm has to pass through; the gel blocks the sperm from getting through while still allowing some sperm-free fluid to get by. Vasalgel is designed to be reversible, by using a second injection to dissolve the gel polymer.

The cool thing about this is what we're talking about is basically a long-acting reversible contraceptive. That means on the user end there's nothing to mess up. We know from female methods that long-acting reversible methods tend to result in a very low real-world pregnancy rate. So Vasalgel is finishing up its primate study in baboons and it's looking to start human trials this year. So if the funding is good and the research pans out, it wouldn't be surprising to see this hit the market within five years, assuming the best-case scenario.

This story is part of Motherboard's Sex Ed Week, a series of sex-focused science and technology stories. Check out more stories here: http://motherboard.tv/sex-ed