Science Vs - The Male Pill: When Is It Coming?

Episode Date: November 3, 2022

A male birth control pill has been this big tease for decades. And today, with the overturning of Roe v. Wade … a male pill might matter more than ever. So we’re grabbing science by the balls to find out – where is it? Will it ever get to the shelves? We talk to physicians Prof. John Amory and Dr. Brian Nguyen.  Find our transcript here: https://bit.ly/3zq9dcq This episode was produced by Michelle Dang, with help from Disha Bhagat, Rose Rimler and Meryl Horn. We’re edited by Blythe Terrell. Additional editing help on this episode from Caitlin Kenney and Jorge Just. Wendy Zukerman is our Executive Producer. Fact checking by Diane Kelly. Mix and sound design by Bumi Hidaka. Music written by Bumi Hidaka, Emma Munger, Bobby Lord, and Peter Leonard. Special thanks to Thomas Rossetti, Jacob Rimler and Jack Weinstein.  Learn more about your ad choices. Visit podcastchoices.com/adchoices

Hi, I'm Michelle Dang, filling in for Wendy Zuckerman this week. She has a tummy ache from eating too much Vegemite. And you're listening to Science Versus from Gimlet. Today on the show, we're pitting facts against fending off fertilization. We are taking on the male pill. This is a topic that you've all been asking for, and it's been making headlines for years now. We found tons of news stories that said male birth control is just around the corner. For the past 50 years, the responsibility of taking a daily birth control pill has fallen squarely on the shoulders of women.

But that may soon be changing. Scientists have announced that they've developed a male contraceptive pill that has been showing impressive results in lab mice. Researchers have spent decades trying to develop a birth control pill for men. And according to a new study, they may finally be making headway. Seems like we've been oh so close to having this male pill for years now with a big fat nothing to show for it. Is this a big tease or are we really on the edge of a breakthrough? Because now the stakes seem higher than ever in the U.S.

The Supreme Court overturned Roe versus Wade, which has got a lot of people thinking, oh crap, what do we do now? A lot of people in this country have also been looking up options when it comes to contraception and reproductive health care. With Roe v. Wade out, women will be asking more of men in the family planning department. Now, even before Roe v. Wade was overturned, it seemed like we could use more options here for spermers. Especially when you realize just how many pregnancies in the U.S. are, whoops, a surprise. One big study looking at national data found that in 2011, 45% of pregnancies were unplanned. Yeah, almost half. So, today on the show, we're going to find out where the heck

is the male pill? Will we ever get there? Because when it comes to the male pill, there's a lot of they may finally be making headway. And then there's science. Coming after the break. Bumble knows it's hard to start conversations. Hey, no, too basic. Hi there. Still no. What about hello, handsome?

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And where is Jan Eleven? I'm here, astrophysicist and co-host, ready for anything. That's right. I'm bringing in the A-team. So brace yourselves. Get ready to learn. I'm Jan Eleven. I'm Steve Strogatz.

And this is... Quantum Magazine's podcast, The Joy of Why. New episodes drop every other Thursday, starting February 1st. What does the AI revolution mean for jobs, for getting things done? Who are the people creating this technology and what do they think? I'm Rana El-Khelyoubi, an AI scientist, entrepreneur, investor, and now host of the new podcast, Pioneers of AI. Think of it as your guide for all things AI, with the most human issues at the center. Join me every Wednesday for Pioneers of AI.

And don't forget to subscribe wherever you tune in. Welcome back. Today, we're looking at male birth control. Just a note, we're using the terms male and female birth control because that's how a lot of the research talks about it. And a lot of the research is in cisgender people, but we're going to use inclusive language where we can. So people who make sperm basically have just two forms of decent birth control in their ballpark, condoms and vasectomies. We know condoms are great. They're very handy against STDs, And they're very effective in preventing pregnancy. But only if they're used perfectly. In the real world, they fail 13% of the time.

Vasectomies? They aren't cutting it either. I mean, okay, they are technically cutting it. The surgeries are very effective, but that requires going under the knife. And if you change your mind and want to reverse it, it doesn't always work. So overall, you have to be pretty sure you want to hop off the fertility train. And even though the female pill has its downsides, there's one great thing about it. You get your fertility back if you just stop taking it. So we want the same thing for spermers. A male pill. Why don't we have it?

Well, to answer this, one of the first things I had to figure out was, how are babies made? Just kidding. I may sound like I'm 12, but we can skip that part. But really, is it that hard to figure out how to stop sperm in their tracks? For sure. And you might say, why? This is John Amory.

He's a professor of internal medicine from the University of Washington. He specializes in male reproductive health. And I'd say because the physiology of men and women is so different. So women, when they go through puberty, they make an egg every month unless they're pregnant. And because then they turn off egg production. Yeah, when you get knocked up, your body ramps up certain hormones like progesterone and basically hangs up a sorry, we're closed sign. The ovaries then know to stop sending out eggs. And part of what the female birth control pill does is mimic this process by ramping up these same hormones. And that stops the egg in

the same way. Take the pill away and voila, all systems are a go. And we've known this for ages. Scientists first saw it way back in the 1930s, when they were pumping hormones into animals. And by the late 50s, scientists had figured out the female pill. And today, there's lots of options that are effective. Implants, injections, IUDs, patches, rings. So that egg-stop stopping process is pretty straightforward because we can mimic what happens during pregnancy. But when it comes to sperm, there's no stop sign. Men start making sperm when they hit puberty and they do so until they die.

And there's nothing for us to mimic. So yes, I think physiologically it's easier to make a female than a male contraceptive. Yeah, for sperm, they may look cute and innocent, but put them all together and there are beasts to tackle here. And a big reason why is that they've got strength in numbers. Men make a lot of sperm. Men make about a thousand sperm every second or every heartbeat. Yeah, basically the biggest challenge for male birth control is that we need to stop a big buttload of sperm. Big ball load? The amount of sperm in a single ball load is nuts. A healthy man puts out around 15 to 200 million sperm per milliliter of semen. Per milliliter. That's like just one-fifth of a teaspoon. And that's not even a full load. Like generally when a dude comes... Total sperm, you have around 30 to 300 million per ejaculate.

Like what? That is insane to me. When I picture this, I think of that scene in Lord of the Rings where there's a sea of orcs continuing to be born by the second. It's basically that, but multiplied thousands of times over. Yeah, that is a lot of sperm in just a spoonful of splooge. So when it comes to birth control, we need to cut that hoard way down. But the good news is, we don't have to go totally John Wick and kill all the sperm. To stop pregnancies, the target is to bring that sperm concentration from more than 15 million down to 1 million sperm per milliliter. And the wild thing

is, we almost had something that could do this decades ago. It was back around the 50s. There was this drug called Win-18466 being developed by a pharma company called Sterling Winthrop. And the way they came across it as a birth control was pretty much by accident. They were developing it to fight off parasites, amoeba infections, and they were testing this in rats. That is, until they noticed something weird. Usually, it's not hard to get rats to have babies. They can pop out a litter of pups every few weeks. But the male rats getting treated with this drug, they weren't making any babies. Couldn't get any pregnancies. So they looked at the testes and there was no sperm.

And they're like, holy cow. They also noticed that when they stopped the drug, the rats were fertile again. It was fully reversible and it seemed like the rats were fine. no side effects. The scientists thought, hey, this might be a birth control breakthrough. Would this work in humans? So they decided to do something that today seems pretty sketchy. They organized an experiment at a prison. It was at Oregon State Penitentiary, starting in the late 1950s. They got 60 men who were prisoners,

gave them the drug, and watched what happened with their sperm. About a year in, everything was going pretty darn well. Looked great. All of them had their sperm counts go down. Stopped the drugs, sperm counts come back up. Everybody's happy. They seem fine. Their sperm counts plummeted. They were infertile, just like the rats. A scientist's dream. But it didn't last too long. And then they discovered the unanticipated side effect. John's mentor was one of the people researching this drug.

And he told John that one guy in the study started getting really sick. Sweating, vomiting, nausea. At first, they weren't sure why this guy was so sick, when the other people taking the drug were fine. They examined the guy, and they said, you know what? It seems like he has alcohol poisoning. But he wasn't supposed to be drinking. He was in prison. So they asked him, have you been drinking cleaning fluid or something? It turned out that somebody had smuggled a guy in, you know, a bottle of Jim Beam or Jack Daniels or something. So he pulls this out of his coat and shows it to the investigators and says, no, it wasn't cleaning fluid. It was this. And that's when they knew they had a problem. Here's what was going on. The drug messed with the body's production of sperm by disabling an enzyme in the balls. But this same enzyme

also breaks down alcohol in the liver, meaning the enzyme wasn't working right, so the alcohol stuck around and acted like a toxin, leading to those nasty side effects. So if you were on this drug for birth control, you'd have to give up alcohol. They knew this would be a hard sell, so they halted the trial and gave up on this drug as a male contraceptive. Scientists like John are actually poking around this enzyme again, but no luck yet. And yeah, in the past 60 years, there's been a lot of other stuff tested, but basically everything has had performance issues, and no male pill has made it to the market. It's hard to say exactly why, but John told us that part of it might be that we got the female pill first. Right around the time of that prison experiment, female birth control was approved. The first contraceptive pill became available in the U.S. in the late 50s. And then the floodgates

basically opened. Within five years, it was a major player in the U.S. birth control scene. Millions of women were taking it. So it's possible that this slowed down research into the stuff for sperm. We don't know for sure, but it does look like female birth control tends to get more money. For example, one database found that in 2018, female birth control R&D got five times as much in funding than male birth control. Still, research on the male pill has been dribbling out, and it does seem like we're getting closer. After the break, we'll look at the most promising drug yet to try to stop that orc army of sperm. Welcome back. welcome back so we had one early dead end for male birth control and since then we haven't been able to crack this nut of a problem but it turns out there is a drug that has kept the ball rolling, and it's really starting to pick up speed. For this, I talked to Brian Nguyen. He's an OB-GYN from the University of Southern California,

who also specializes in family planning and male contraceptives. As a male OB-GYN provider, it always struck a chord with me that men should be doing something as well, or men should be sharing that responsibility. And so that's what made me think to myself, well, I need to do something about this. Before we jump into how this one works, we need to know that there's a very important ingredient for making sperm, a fancy dancy hormone that you may have heard of. Testosterone. The balls make testosterone, A lot of it. They send a little bit of this stuff around the body to make and do male body things. But the balls keep most of it. In fact, the

concentration of testosterone in the balls can be up to 125 times greater than in the rest of the body. And they need all of that ball testosterone to be the unbelievable sperm factory that they are. Now, the brains behind this operation is the brain. Your brain keeps track of how much testosterone is in your body. And it does that by looking at how much of it is in your blood. Based on that read, it tells your balls just how much testosterone to make. If there's too little, the brain sends signals to the balls to make more. And if there's too much, the brain says stop. Scientists have figured out they can take advantage of this.

They can trick the brain by adding more testosterone to the body in the form of a drug. The brain starts thinking, whoa, balls, you are making way too much testosterone. Please tone it down a bit. And the testicles would stop making testosterone, which in that same process would stop making sperm. So pretty, pretty easy, right? Yeah, seems easy. And we've known about this for decades. But it's actually been pretty hard to pull off. When we started getting clinical trials on testosterone for birth control, researchers saw that it didn't work across the board. Like, not everyone's sperm counts went down enough to be infertile.

So scientists knew they had to do better. And after tinkering around in rats, they realized that you could use a different hormone to suppress the sperm factory even more. Progestin. This is what you find in female birth control. And turns out, progestin works really well for shutting down sperm production. Together with testosterone, the combo drops sperm counts lower and faster than testosterone on its own. And today, there's a progestin-testosterone drug

in the works. It's called Nestea. Brian's actually part of a large team running clinical trials on it around the world. And by the way, it's not a pill. Producing a male pill has always been very challenging because at the dose that you need, it can actually be toxic to the liver. So for that reason, we've not been able to develop a male pill. So this one Brian's working with, it comes in the form of a gel that men rub onto their shoulders. Oh, is it? So is it like a lotion? Yeah, it's kind of like, I mean, it's alcohol based, right? So it's kind of like hand sanitizer in that sense. How often do they have to apply it?

You know, daily. On their shoulders, on both sides. And they kind of rub it in. Weird, right? It goes through the skin and into the bloodstream. And Brian's pretty excited about it. It's been checked for safety, and now they're looking at how well it works. The team is testing it in hundreds of couples around the world right now. They give them the gel, drop their sperm counts down,

then tell the couples to stop any other form of birth control and just use this. They check their sperm counts at the clinic once a month, restock them on gel, and see if any of these couples get pregnant over the course of a year with their regular hanky-panky. Do we know how effective it is yet? Nothing I can say on record.

But what I can tell you so far is that the preliminary results of the trial have been promising in a way that we're currently planning for phase three. And this is the furthest along that a male birth control has come? Correct. Yeah, this is the furthest. A male contraceptive like this has come in the U.S. So Brian mentioned phase three. That's the next trial they'll need to do. Another bigger one testing the drug in thousands of people to see how well it works. And that process could take years. But, you know, already, one of the top nerds from the agency funding this study says the gel stacks up well compared to what we've got for women. She said, quote, the efficacy rate appears better than the pill, and so far seems on par with

long-acting reversible contraceptives for women. It's super exciting. We're all very enthusiastic about it. I think the hard part is that as scientists, we are always prepping for the worst-case scenarios, and so we always try to stay measured. But by saying that I'm excited, you should take that to a different level. So this stuff, it's sounding pretty promising. It's probably what's most likely to reach the market before other contenders. But it could still be 10 years away. And there is a caveat here. These drugs will probably have side effects.

Brian said his team has tweaked the dosing to try to minimize them. But still, these are a thing when it comes to hormonal drugs. I mean, any hormones can have side effects, right? So, you know, some changes to their mood, skin changes like acne. These drugs can also lead to weight changes, all of which probably sounds familiar to anyone who's taken female hormonal birth control. The side effects for testosterone-based drugs can actually be pretty similar, and they raise the question of whether men will want to take this stuff. Producer Merrill Horn asked Brian about it. Overall, do you think men want this?

Absolutely. What's interesting is that we never really ask women the same question of, do you want a female contraceptive? We just assume that they do, right? Yeah. When scientists survey the people in clinical trials for male birth control, they generally find that despite any side effects, at least half of them say they were happy with the drug. But another kind of complicated piece

is that the calculus for women and men is different. If you've got a uterus and the associated bits, you're balancing side effects of birth control against the risk of pregnancy. And pregnancy is pretty much always the riskier option. But when it comes to male birth control, if you can't get pregnant, you may be less willing to take on some crappy side effects. All this is a big reason why scientists are working on other options too. And there are things in the works, drugs that don't use hormones, even physical blockers like a gel to stop sperm from coming out of the testicles. Some of this is still in animal trials, and there are a few that have made it to testing in people.

So it's worth keeping an eye on that too. So in the ideal world, we would have lots of options for both men and women. In the same way that we have more than 12 options currently that people with uteruses can choose from, I think that it's just as important to have that many or even more for male partners. Okay, so where does this leave us? Well, it turns out the road to getting a male birth control has been bumpy for all sorts of reasons. Dealing with endless amounts of sperm is just harder than dealing with one egg at a time. And there's been a bunch of fits and starts where scientists got excited, but things ended up going flaccid because of weird side effects or drugs not working well enough.

Overall, it doesn't seem to have gotten as much money or attention as the stuff for people with uteruses. Still, Brian thinks we might be at an inflection point, with his trial getting further and further, and because of how the Supreme Court decision is changing the conversation. With the overturning of Roe versus Wade, seeing my inbox kind of bubble up with messages from men saying that they want to join male

consciousness clinical trials because they feel threatened by the recent Dobbs decision has been very encouraging. It does hearten me to know that there are men out there who saw this as a threat and a call to action. That's Science Versus. Okay. Ring, ring. Ring, ring. Hello. Hey, producer. How are you? Hey, Michelle. I'm doing well. How about you? Good. So this week's episode, how many citations do we have? We have 77 citations. And where can people find these citations if they want to check them out? Yeah, they could go to our show notes and you'll find links to the transcript that has all of our citations. Cool.

Yeah. What were your thoughts on, you know, the world of sperm? I can't get over how many sperm they make. Like, so much. It's crazy. The heartbeat thing. I can't get over it. Millions.

Well, hope everyone sleeps well thinking about that tonight. All right. See you, Deesha. Thanks. Thanks. Bye. This episode was produced by me, Michelle Dang, with help from Disha Bugup, Rose Rimler, and Meryl Horn.

We're edited by Blive Terrell. Additional editing help on this episode from Caitlin Kenney and Jorge Just. Wendy Zuckerman is our executive producer. Fact-checking by Diane Kelly. Mix and sound design by Bumi Hidaka. Music written by Bumi Hidaka, Emma Munger, Bobby Lord, and Peter Leonard Special thanks to Thomas Rossetti, Jacob Rimler, and Jack Weinstein We got the term spermers from Mona Chalabi She's got a great podcast called Am I Normal?

Check it out Thanks for listening.