Looking Beyond Condoms for Male Contraception
Are we getting closer to a pill for male contraception? Last week, a clinical trial of injectable, reversible hormonal birth control for men reported very high efficacy rates, but the trial was stopped early because participants experienced side effects. These side effects, including acne, mood swings, and depression, were deemed unacceptable by an independent panel.
The good news? Most of the trial participants said they would have been interested in continuing anyway. And researchers are praising the trial itself as evidence that sperm-suppressing hormonal treatment can work better than condoms for men.
Diana Blithe, the program director for the NIH National Institute of Child Health and Human Development, talks about the progress being made on male contraceptive methods, the unique challenges for developing and testing male contraception, and why even the most promising options could still be a decade away from consumers.
Hey male-identifying Twitter: would you take hormonal birth control if a pill/shot/etc were available for you? Polling for @scifri.
— Were-Christie Taylor (@ctaylsaurus) November 3, 2016
— Terra Bad (@Gebraheel) November 3, 2016
— Butros (@ButrosButrosK) November 3, 2016
— Dylan Lane (@DylanTGLane) November 3, 2016
— Ritchie (@RitchieReview) November 3, 2016
— messengerflats (@messengerflats) November 3, 2016
— Eddy Waterhouse (@EddyWateehouse) November 3, 2016
Diana Blithe is program director for contraception development at the NIH National Institute of Child Health and Human Development in Bethesda, Maryland.
IRA FLATOW: This is Science Friday. I’m Ira Flatow. It’s been more than 50 years since the FDA approved the first birth control pill for women wanting to prevent unwanted pregnancies. And since then, options for women have proliferated– more kinds of pills, implants, shots, IUDs, and more. What about the guys? The only truly 100% reversible option for men right now is condoms, which have a 12% failure rate at typical use.
But research published last week on an injection of testosterone and another hormone had very good results. It suppressed sperm production below fertile levels for nearly 96% of the men in the study. Unfortunately, the trial was halted early by an independent board because many of the men reported side effects like acne and mood swings and depression. We asked men on Twitter whether they’d take a hormonal shot, a pill, or other option.
This is highly unscientific, but a bit more than half said yes, they would. Another 20% were unsure, and the rest said no. More scientific surveys have also found men wanting more reversible ways to reduce their fertility and help their partners avoid pregnancy. So what’s taking so long? What are the promising projects? How soon could we have the pill for men?
My next guest is Diana Blithe, an endocrinologist and program director of contraception development at the National Institute of Child Health and Human Development at the NIH. Welcome to Science Friday.
DIANA BLITHE: Thank you. It’s a pleasure to be here.
IRA FLATOW: You’re welcome. A study co-sponsored by the World Health Organization published its findings last week looking at a hormone shot that suppresses sperm production in men, and we’re talking about that. 96% is pretty good, is it not?
DIANA BLITHE: It’s excellent, and that’s one of the high points of the study.
IRA FLATOW: So what’s the compound? What did they put together? I said testosterone. What else was in there?
DIANA BLITHE: Well, it’s actually a combination of two hormones, and I could take a moment to explain how that works a little bit, but the hormones include a progestin– and that was one injection– and a long-acting testosterone that’s called testosterone undecanoate, that is also a second injection. So there were actually two hormones involved and two injections.
IRA FLATOW: And now–
DIANA BLITHE: The two hormones involved is very similar to the female method.
IRA FLATOW: So it’s the same two hormones?
DIANA BLITHE: Well, it’s similar. So if you– in the female pill, you have a progestin and you have a synthetic estrogen. And we’re building on the interplay of those hormones to design something that will work in men. In this case, the men had a progestin and a testosterone. So the way this works is that in the ovary and in the testis, there has to be a high concentration of one of those hormones, which would be testosterone or estrogen, in order to have the production of an egg or sperm.
And the other hormone, progestin, shuts down the production of the first hormone, reducing the levels throughout the body so that you don’t get the production of either the egg in the female method or the sperm in the male method. But by shutting down the production of those hormones to a very low level, that means that circulating hormones are also very low, and those hormones have other functions.
So in the male in particular, it helps with maintenance of muscle mass, the ability to have an ejaculation, libido, and some other side effects that you wouldn’t want to have as a side effect of this method. So we have to replace the testosterone. And that’s what the second hormone does. It replaces it to the normal level in the blood, but it doesn’t re-establish a very high amount in the testis, so sperm production remains turned off.
However, the challenge has been that we don’t have a testosterone that is orally active. And so there isn’t going to be a male pill until we can overcome that challenge, because we can give the progestin orally, but we can’t give the testosterone orally. So in the US, you have transdermal methods where you give it through a gel, and that works very well.
In Europe, they have this injection which replaces it in the blood, and that works very well for them. But we don’t have an oral form. That’s been the challenge, and it remains a challenge even for men who have a condition known as low testosterone where they need testosterone replacement. Again, we don’t have an oral form that we know is going to not have any bad side effects for them.
IRA FLATOW: Yeah. Is there any connection, possibly, between a long-term dosages if you’re taking– if this pill does work out or the injection site does work out, of testosterone and possibly elevating the risk of prostate cancer?
DIANA BLITHE: Well, the reason we want to keep the testosterone levels in the normal range and not in an elevated range, there is another way of reducing that testicular testosterone through feedback, which is to give very high amounts of testosterone. And that study was done in a large number of men in China, and it was very effective, again, but it required large amounts of testosterone injections.
So our goal is to try to avoid having the serum levels that would circulate to the prostate to be higher than the normal range. We don’t want to have a situation that would cause something long term. But again, when you ask, why has it taken so long? It’s the challenge of trying to develop a drug for a healthy population that is going to be taking it for a very long period of time. And often times, an untoward side effect doesn’t show up until you have a very large population who have taken something for a very long time.
IRA FLATOW: In this study, I understand that the men, after this study was concluded, the men, many of them wanted to continue with it. They didn’t mind the side effects.
DIANA BLITHE: So that was the other, I think, very positive thing that came out of the study is they had a very high percentage of men who found the method to be acceptable. And remember, these were two fairly large-volume injections every two months. So it’s not as easy as taking a pill once a day. But they found it to be acceptable, and a very high percentage said they would use it if it was available, which is encouraging.
IRA FLATOW: And so why would you not make it available? Why not continue testing it if there are a lot of men who would take it?
DIANA BLITHE: Well, in our program in the US, we are continuing a method. We’re at a similar stage, maybe a bit behind this study, in that we are beginning an efficacy trial with, again, two hormones. One of them is a progestin. The other is testosterone. But they’re delivered through a gel, through a transdermal method.
And we’ve shown that in a six-month study we can effectively suppress sperm production in the men who use it. And again, they find it to be an acceptable method. So our plan is to go out into a larger trial in which couples would use this as their primary method of birth control the same way they did with the injection study. And we are very hopeful that we can overcome perhaps some of the effects that may have been caused by fluctuating hormone levels that one gets when one is taking an injection every eight weeks.
Because initially you have a fairly high amount, and then it trails off until your next injection. And that may have been– it’s not clear, but we speculate that that may have been one of the things that led to more mood issues or potentially greater side effects.
IRA FLATOW: Our number, 844-724-8255– lots of callers. Let’s head out to Denver and Jessica. Welcome to Science Friday.
JESSICA: Hi. So I wanted to comment real quickly on the double standard between men and women and the side effects we experience. I have tried about six different birth controls. Depo-Provera made me manic and suicidal, yet that is still on the market and considered acceptable for women to take. I had to go to the emergency room when I got my first IUD. I had false contractions. I was heavily medicated in order to stop internal bleeding.
Yet I’m on another IUD. It is still a great form of birth control but still accepted. Again, we all know women talk about emotions and acne, but there was– it wasn’t the men that stopped the study, and I’m aware of that, but the committee that stopped it. And it’s really upsetting to think, oh, men can’t be physically inconvenienced when it comes to birth control, but that’s OK if women are.
It’s OK that I was suicidal and that that form of birth control is still on the market. So I don’t know. I’m just– it’s just kind of a comment about how upsetting that is to women in society that what happened with the men in the birth– but then Viagra has way more side effects and way more serious side effects than the birth control had. But–
IRA FLATOW: I hear you. I hear you, Jessica. Let me get a– good comment. Let me get a reaction. Thanks for calling. Dr. Blithe?
DIANA BLITHE: Well, I would say that we have a number of alternatives for women, and we don’t want them to be taking a method that would potentially make them suicidal. And it doesn’t work– it doesn’t affect every woman that way in terms of an individual product. However, the first methods that did come along for women actually had a much lower safety profile than the ones that we have now.
And we are working– we have worked and we continue to work to make methods more safe, with fewer side effects, and more acceptable. So we’re at a much earlier stage with men, and I don’t think that the committee– there were two committees that reviewed the data. One of them said go forward. The other said stop. So they erred on the side of caution, and they stopped.
But I don’t think it was the side effects of acne and mild mood swings that caused them to make that decision. I think they were concerned because there were three serious side effects, that one was a suicide and an attempted suicide. And that was felt to be a potential risk that they weren’t sure was worth taking if they continued that study.
However, as I said, there are other studies that are going forward that we hope would be safer and potentially not cause those side effects. The important thing here is to learn from what they found and to move forward with the knowledge and try to improve the products, improve the method, and come up with something that will not have an adverse effect that could be serious.
IRA FLATOW: And–
DIANA BLITHE: And we’re doing the same thing for female. I mean, I don’t want to leave that aside. We are trying to replace some of the molecules in female methods to make it more safe for a greater population of women. But with every method, the woman should certainly consult her physician. And if that method is causing side effects that she finds to be unacceptable, then she should definitely look at a different method. Because not all methods affect all women the same way.
IRA FLATOW: So you think that the new gel, that’s what you’re studying now. You think–
DIANA BLITHE: Yes.
IRA FLATOW: –that may have fewer side effects or less–
DIANA BLITHE: Well, so the gel– the gel is applied to the skin, and it forms a reservoir, if you will, in the skin. And so the release of the hormones is fairly constant. You’re not getting fluctuations that are very high or very low, and the ratio of the hormones remains pretty constant. So we’re hoping– because we know that if you have an imbalance of hormones, that can cause a problem.
So in a situation where you were injecting every eight weeks, and the hormones have a somewhat different disappearance rate, then it’s a possibility for irregular or a fluctuating hormone level that is not optimal. In this case, if you’re applying the gel every day, then we expect the hormone amounts to be about the same and to not have that fluctuation.
Of course, it would be a user-controlled method, the first one since the condom. But that requires men to be willing to use it every day, to not forget to use it for more than a couple days, because the potential for losing effectiveness, the same with methods that require a woman to take a pill every day. The failure rate is higher when it’s not automatic, not there all the time.
IRA FLATOW: Talking with Diana Blithe of NIH on Science Friday from PRI– Public Radio International.
DIANA BLITHE: [GULP]
IRA FLATOW: Give you a chance to catch your breath and take a little sip of water. You know, this is– how long have we been talking about– 50 years about contraceptive. It’s still very much a topic of discussion and male versus female. How much more difficult is it to develop a male hormonal contraception than female? What’s going on in our bodies that make this so much more difficult?
DIANA BLITHE: Well, as I mentioned earlier, I think part of the problem is the challenge of getting the testosterone to be in a form that would be conducive to a daily method, such as a pill, which would make it easy to use. Injections are harder to regulate and have to be done by a service provider, whereas a pill you can do at home.
So we’re working very hard to try to find a method that will be convenient, that will produce the kinds of effects we expect. We know it can work, and we’re really excited that it did work so well in the population that used it. So that’s encouraging, and that the men liked it and didn’t– for the most part didn’t experience side effects that they felt–
IRA FLATOW: Right.
DIANA BLITHE: –would have caused them to want to continue. So I think it’s the men– I don’t want to be hard on the men. I don’t think it was their choice that they couldn’t continue with the method. So they were willing to tolerate whatever side effects they were experiencing.
IRA FLATOW: You know what I found interesting in the research on this is that the lead authors on last week’s research said that there’s no more funding at the World Health Organization for the male contraception. And industry is not interested in this. I find that really interesting. You know, you would think that this is something they could sell to everybody.
DIANA BLITHE: Well, that’s a question that one needs to ask industry. They used to be more involved in trying to develop a method. There were two companies in Europe, one Schering AG and Organon. Both of those companies have merged with another company, not the same company. And after the merger in each case, a decision was made to shut down their male contraceptive development program. So for whatever reason–
IRA FLATOW: Yeah.
DIANA BLITHE: But the thing that happens–
IRA FLATOW: Are they just waiting– are they waiting for public money to do it, so then they come in and just then make the profits on making the product?
DIANA BLITHE: Well, I think there are a number of issues. And again, you’d have to ask them what their position is. But I think the challenge that everyone asks, especially when something comes out, is, how long is it going to take to get a method? If you look at this particular method that they were working on in Europe, it was a four-year study.
And the study we’re about to begin, which is a Phase 2, is also designed to be a four-year study. If we complete that and everything goes really well, then we have to go to the FDA and have permission to do what they right now would say are two Phase 3 studies, which are large and long.
IRA FLATOW: Yeah, I’m getting it–
DIANA BLITHE: And so–
IRA FLATOW: –getting the picture.
DIANA BLITHE: –I would say it’s a lot of money, and it’s a long time, and it’s a lot of men who have to be exposed to the product because they’re healthy.
IRA FLATOW: Yeah, and we don’t know what the long-term effect of that is going to be yet. Diana Blithe, contraception program director at the National Institute of Child Health and Human Development at NIH. Thank you for taking time to be with us today. Have a good weekend.
DIANA BLITHE: Thank you.