The Status of Male Birth Control, Its Impact on Reproductive Health

February 12, 2024 - Globally, nearly half of all pregnancies are unintended. While some unintended pregnancies result in a successful and safe birth for both the infant and the mother, many unintended pregnancies result in complicated and potentially fatal outcomes. The rate of unintended pregnancies and their risks underscores the critical importance of contraceptives. To date, most of the pregnancy prevention burden has fallen on the shoulders of those who have been assigned female at birth.  

Stephanie Page, MD, PhD, Co-Director of the University of Washington Medicine Diabetes Institute, Robert B. McMillen Professor of Medicine in Lipid Research and head of the Division of Metabolism, Endocrinology, and Nutrition, and other reproductive health researchers are exploring male birth control options to minimize the rates of unplanned pregnancy following federal decisions that restrict access to abortion care. 

Veronica Salib 

Hello, everyone and welcome back to Healthcare Strategies.

My name is Veronica Salib, and I'm the associate site editor for LifeSciencesIntelligence and PharmaNewsIntelligence. We're here today with Dr. Stephanie Page, head of the division of metabolism, endocrinology and nutrition, and co-director of the University of Washington Medicine Diabetes Institute. Dr. Page is also a professor of lipid research at the University of Washington School of Medicine. She works on male birth control research and has previously provided insight on hormonal male birth control gels, with LifeSciencesIntelligence.

Dr. Page, welcome, and thank you so much for being on this episode.

Stephanie Page 

Thanks so much for having me. And I'm really excited that your listeners are interested in this field since I think it's really important.

Veronica Salib 

Last time, like I said, we spoke, we had a really informational conversation on birth control, and I wanted to bring you back so we can have something a little bit broader because we talked about one specific type last time. And so my first question is, why is there a need for more male birth control research? And have you seen an increase in the demand for male birth control options?

Stephanie Page 

Absolutely. So we forget sometimes that we continue to have a global epidemic of unplanned pregnancy, more than 40 percent--and really closer to 50 percent--of all pregnancies globally, are unplanned. And that is a statistic that is very similar in the United States. The goal of contraceptives is really to allow all pregnancies to be planned, and to be both planned and wanted.

Since the reversal of Roe and the Dobbs decision a couple of years ago--and I think that maybe what you're alluding to--we don't have a lot of academic research yet. But there's been a number of surveys and data points that have suggested that interest in contraception has really gone up. There was a CNN survey that suggested a 300 percent increase in requests for prescriptions for Plan B, or emergency contraception. And there have been a number of other studies that have shown increases in vasectomy interest and younger men wanting to have vasectomies. So even on the male side, we're seeing increases. And in addition, many younger women are looking for longer acting contraceptive methods.

So lots of data to suggest that since the restriction on female reproductive agency, there has been an increased interest in uptake in contraception.

Veronica Salib 

Yeah. So that's definitely something that comes into play. And I think we've been seeing that conversation looks different every day, the policy conversation, we're never quite sure where it's going. And so, you alluded to a lot of men looking at a vasectomy as a potential birth control option. I know we discussed that last time. But can you provide maybe a list of what birth control options are available to men today and how they compare with female birth control options?

Stephanie Page 

Absolutely, it's a pretty straightforward answer because there's only two methods of birth control available to men and one of them is not reversible

The vasectomy is very important, but we consider that a permanent method. There is some ability to reverse some of vasectomies, but in general, we think of that as a non-reversible method.

Condoms are super important. They actually are used by many couples. And they're very important for all aspects of sexual health. And we consider those a male method. The biggest downside of condoms is that they have a high failure rate at about 14 percent and really a high discontinuation rate. And that's really important, because if people stop their method and they don't take up a new one, we're back in the same non-contraceptive space.

Men do participate in contraception. Between vasectomy and condoms, that's about 25 percent of all contraception, that's done. But they really don't have the menu of options that women do. Women have many different methods available. There are problems with some of them for some women. So it's really important that people find a method that works for them. We in the male contraceptive development community are firm believers--and there's a lot of data about this--that if we gave men more options, there would be more uptake. And so that's really the goal of the field.

Veronica Salib 

Yeah, and I think that's really critical. And I want to go back to your point about vasectomies not being considered a reversible birth control method, because I think a lot of the rhetoric, especially after the Dobbs decision, has been that this is a reversible alternative. And I think it's important to clarify that it's not always reversible. So if you can touch a little bit more on the statistics of what is and how often it is reversed, if you have those on hand.

Stephanie Page 

I don't have those on hand, but I can tell you that it's a very small number.

First of all, it's a very ineffective in and of itself is not particularly invasive, but a vasectomy reversal is a much bigger deal in terms of the surgical approach and the recovery and so forth. Secondly, the secondary reversal is rarely covered by insurance. And so that is also an issue. And thirdly, it's not always successful. I don't have those numbers right offhand. But certainly the recovery of normal fertility is not that high. And again, that's because there can be a lot of scar tissue. There can be problems with reconnecting the tubes, so to speak.

So it is absolutely not straightforward and the health care costs associated with vasectomy reversal are enormous.

Veronica Salib 

Thank you for that insight. And now I want to pivot a little bit and discuss all this exciting ongoing research, we've seen a lot of different ideas enter the research space for male birth control, including hormonal and non-hormonal options, if you can just discuss some of the options, maybe the stuff that you're working on. I know you're working on a pill gel. So if we can just start by describing those, that'd be awesome.

Stephanie Page 

Sure. So I do work in the development of hormonal and male contraceptive methods. A pillar of the work we do is based upon the success of female hormonal contraceptives, which, while some women do have some side effects, overall have been an enormous breakthrough for women and are enormously effective.

So in the basic concept there is--instead of using estrogen and progestin, which is what women use in the female birth control pill, for example--we are using testosterone and a progestin to block the production of sperm in men. And ,without going into all the gory details, when we give men testosterone and progestin, it blocks the signals in the brain to the testicle, in this case, to make sperm and the sperm production is stopped. And the man receives plenty of testosterone from the hormonal contraceptive that they're using. So the goal is that they really feel nothing. They feel all the normal testosterone characteristics, they have normal male facial hair, and they have a low voice and so forth, then the only thing that's really touched is the production of sperm. So we and others are working on doing that with delivery methods that include long-acting injections, a daily gel that's rubbed on the skin by the man, and, hopefully, a pill.

So, hormonal contraceptives for men have been in development for about 50 years. And there's been reasons that it's been so slow compared to the introduction of the female pill about 60 years ago, but we do feel like we're making some progress. So then there's a whole other field. We talked about vasectomy already. There are groups that are trying to work on a truly reversible vasectomy, meaning instead of cutting the tubes that the sperm travel out on or burning them, using newfangled kinds of chemicals to inject that then could either dissolve or be dissolved with something that is reinjected to make the vasectomy reversible. So that's another method. And there's actually a company that's launching clinical trials in that space in the next year.

And then there's a whole nother field of developers that are trying to interfere with the production of sperm or the sperm getting to the egg in different ways. For example, for sperm to get to the egg and the female reproductive track, they have to do this like highly specialized, highly fast kind of swimming. And so there are investigators trying to interfere with that, the molecular processes that are required for that really fast swimming. The goal there is to not use hormones, but to target parts of sperm function that are very unique to the sperm, that you could give a man like a pill or a drug and it would just interfere with those sperm processes or with sperm development. Those lines of investigation and those trials are behind the hormonal methods because they don't have the years of female hormonal contraceptive work for foundational purposes. But I believe there are some new agents coming out. And we're hoping that there'll be clinical trials of some of those non-hormonal methods for men, even in 2024.

Veronica Salib 

So it sounds like researchers are trying to hit it from all angles, which is exciting, because that means there'll be a lot of options as there are for women right now. And maybe it will alleviate some of that burden of birth control on women and female partners. So that's really interesting.

I want to discuss--so, the hormonal birth control gel versus an oral pill that's in in development, what is the difference between those two? And you discussed the mechanism of action, but you know, if you can weigh the pros and cons of each against one another, that would be incredible.

Stephanie Page 

So we're further along with the gel in terms of it getting potentially to the market. And one of the reasons is that it's been really tricky to get testosterone into men via an oral route because, just giving men testosterone in contrast to just giving women estrogen by mouth, that testosterone is really quickly broken down in the man's system and early modifications of testosterone to get over that problem are associated with liver toxicity.

The development of a male pill is behind. It turns out when we give men the gel, they can absorb that testosterone through their skin really well. Some of you may know about products that are actually already on the market for men who have low testosterone to replace their testosterone with these gels. So the hormonal gel is really based upon that technology, and we just add the progestin. So it's a little bit ahead because of the delivery system. You might think that men wouldn't be very excited about a gel every day, because it might be messy, it might transfer their partner and so forth. And it turns out, that's actually not true. We were a little surprised at how the men actually find it acceptable. They can work it into their routine with showering pretty easily. And actually, internationally, when you ask men about their preferred method of contraceptive delivery, there's actually a lot of interest in Africa, for example, because there's a lot of familiarity with using lotions or other sorts of things. I think we have a mindset that a pill is what everybody wants. But in fact, we're learning, as we always do when we do clinical studies, that our preconceived notions about what people want may be wrong. And actually the people, the users may be wrong about themselves. They may have thought "I wanted a pill," but actually then prefer something else. So that's one of the things that's always interesting about drug development.

Veronica Salib 

Yeah. And I think it's really funny because I feel like I would also assume that a pill is the preferred method. But thinking of it based on what you said, it's so easy to put that into your daily hygiene routine. A gel is easier than having to remember to take a pill because you're already doing all the other hygiene stuff.

Stephanie Page 

Yeah.

Veronica Salib 

So that's a really interesting commentary.

Earlier, you mentioned that male birth control has been researched for about 50 years, but there's been a lot of challenges with the development of research and commercialization and all those things. Can you discuss some of those challenges, maybe a couple of the biggest ones?

Stephanie Page 

You bet, I think it's really important to remember that--I think, at least, appropriately--initial development of contraceptives was really focused on women. And that's because women need reproductive agency. They are the person to bear the burden of an unplanned or planned pregnancy and pregnancy is a life threatening condition. So hindsight is 20/20. We'd love for them to have all come up at the same time. But you can only do so many things at once.

And so, I think it's really important to remember that it is true that male hormonal contraceptive development has been puttering along for about 50 years, and there was a lot of interest in the '80s and early '90s, from WHO--the World Health Organization, sorry--and some governments in advancing male contraception, partly, I think, because of issues of concern regarding population growth there. And there was also some significant interest from the pharmaceutical industry, I think, recognizing that there's potentially a huge market. That interest has somewhat waned, or really has waned.

And I think, a big hurdle, there has been a lot of uncertainty, partly about the market--would men really do this? And I think we have a lot of survey data now from the last 20 years that men are very interested. But that didn't really exist, then in the same way it does now.

But more importantly, perhaps, that there really hasn't been guidance from the regulatory agencies--so agencies like the Food and Drug Administration here and the European equivalent--about what the bar will be for male contraceptives. Do they just have to be as good as condoms? Do they have to be as good as the best female method out there? What is the standard? And also, since the man is not actually having a part of their health, their personal health protected by the contraceptive, what is the bar for side effects or possible side effects? And so I think when there's that much uncertainty, pharmaceutical companies are really hesitant to take risk. It's risky to develop drugs in any environment. And if you don't really know what the the endpoints are, I think that becomes a trickier investment.

So I think there's a few things, but I have hope because I do think that the social norms are changing and the discussions about contraception, the interest in contraception, are really exploding for a variety of reasons. Not all of them good. And men are engaged in those conversations and also have really significant interest in controlling their own reproduction. So that's the history. There's always some nuances, but....

Veronica Salib 

Yeah, so you discuss a little bit about the regulatory landscape and how it's difficult to figure out how the FDA and other regulatory bodies will gauge the approval of these drugs. And so I'm wondering, based on that and the current pace of research, when do you anticipate these products will reach the market or will be accessible to patients? And I know the FDA recently approved an over-the-counter form of female birth control--do you anticipate these will be prescription, over-the-counter and a little bit of an explanation on that end would be great.

Stephanie Page 

Yeah, I do think, initially, it will be a whole new drug class. So it's hard to imagine they will not be by prescription at the beginning. And I think hormonal methods have the greatest chance of becoming our prescription sooner, but they first have to get to the marketplace. There is hope, I think, that the gel, the hormonal contraceptive gel for men will reach a Phase 3--which is the last big clinical trial that needs to be done--in the next couple of years. And so if those results were positive, we could see that as a product in the next six to seven years.

The pathway for these non-hormonal methods that I mentioned, they're further behind. But they could actually be accepted faster if they really show a high degree of efficacy quickly and the low side effect profile. Sometimes the development is actually slowed because of the length of time it takes a product to work. So if for example, some people are trying to develop like an on-demand contraceptive for men that you could use the day before, and so forth, so that's further behind in development. But you can imagine that those studies, once they got into the clinic, could happen a lot more quickly.

So I am optimistic that we'll find that something will get in the market in the next decade or before I'm out of this business. But we've been saying that for a long time. Lots of hurdles ahead. But I think it's great that there's more interest and more questions being asked about why we don't have this yet.

Veronica Salib 

And I guess my final question touches a little bit on that as well. I know you said that you anticipate, hopefully, something reaches patients within the next decade. So up until this point, what research gaps are there that still exist that we need more research to go into or more funding to go into, especially by federal organizations and big government organizations that sponsor a lot of this research?

Stephanie Page 

Yeah, I think that there's a couple of places. I think there is some funding for the basic research trying to identify these non-hormonal targets because I think companies and investors, they see the potential market. We have gaps, though, in trying to fund the clinical trial work, which is pretty expensive, and has historically been done by the pharmaceutical industry. So in my mind, one of the biggest gaps is bringing things that are looking good in the sort of small clinic clinical trials to those big trials that are really required for us to know--what's the failure rate? What are the issues with use? And how do we translate that into the real world? And that is expensive.

But if our government or other governments would see that the cost of unplanned pregnancy in terms of economics is enormous--and, not to mention, the pregnancies that are continued that perhaps were unwanted, and the economic burden and environmental burden that those play. I think what we're hoping is that people, that government agencies will connect the dots and realize that contraception is our best investment in preventing unplanned pregnancy and preventing the need for abortion. It doesn't replace the need for safe abortion, but it is absolutely our best tool in terms of preventing that need. So the hope--with the political climate right now, who knows?--but I really...that's the gap that we somehow as researchers and advocates need to get together to advocate for.

Veronica Salib 

Yeah, it sounds seems like that's the way all of our political climate has been going recently is "who knows?" especially with the reproductive rights stuff. But hopefully people can see that chain reaction of not having access to contraceptive from the beginning can lead to a lot more challenges down the line.

So thank you so much, Dr. Page, for joining us today. Thank you for answering all our questions.

Stephanie Page 

Thanks so much for having me.

Veronica Salib 

For our listeners. We would love to hear from you. Feel free to reach out with any healthcare-related questions or subjects that you think we should cover by emailing me at v-s-a-l-i-b@techtarget.com. And if you liked this episode, please consider rating and reviewing us on Apple podcasts, Spotify, or wherever you're listening. Thank you for listening.