Researchers have developed a non-hormonal male contraceptive, YCT529, which effectively and reversibly prevents conception in mice without side effects. The contraceptive targets a specific protein involved in sperm formation. Human trials are planned for late 2022.
Women have a variety of birth control options, ranging from pills to patches to intrauterine implants, and they carry the brunt of the responsibility for avoiding conception. However, men’s birth control choices — and hence responsibilities — may be growing shortly. Scientists have developed a non-hormonal male contraception that efficiently prevents conception in mice while having no noticeable adverse effects.
The researchers presented their findings at the American Chemical Society’s (ACS) spring conference this week. ACS Spring 2022 was a hybrid conference that took place March 20-24, both remotely and in-person, with on-demand access accessible from March 21 through April 8. More than 12,000 presentations on a broad variety of scientific subjects were featured during the gathering.
Male condoms and vasectomy are currently the only two effective birth control options available to men. However, condoms are only good for one use and are prone to failure. A vasectomy, on the other hand, is a surgical treatment that is considered a permanent method of male sterilization. Although vasectomies may be reversed in rare cases, the procedure is costly and not always effective. As a result, males need a contraceptive that is effective, long-lasting, and reversible, comparable to the birth control pill for women.
“Scientists have been trying for decades to develop an effective male oral contraceptive, but there are still no approved pills on the market,” says Md Abdullah Al Noman, who is presenting the work at the meeting. Most compounds currently undergoing clinical trials target the male sex hormone testosterone, which could lead to side effects such as weight gain, depression and increased low-density lipoprotein (known as LDL) cholesterol levels. “We wanted to develop a non-hormonal male contraceptive to avoid these side effects,” says Noman, a graduate student in the lab of Gunda Georg, Ph.D., at the University of Minnesota.
To develop their non-hormonal male contraceptive, the researchers targeted a protein called the retinoic acid receptor alpha (RAR-a). This protein is one of a family of three nuclear receptors that bind retinoic acid, a form of vitamin A that plays important roles in cell growth, differentiation (including sperm formation) and embryonic development. Knocking out the RAR-a gene in male mice makes them sterile, without any obvious side effects. Other scientists have developed an oral compound that inhibits all three members of the RAR family (RAR-a, -ß and -?) and causes reversible sterility in male mice, but Georg’s team and their reproductive biology collaborators wanted to find a drug that was specific for RAR-a and therefore less likely to cause side effects.
So the researchers closely examined crystal structures of RAR-a, -ß and -? bound to retinoic acid, identifying structural differences in the ways the three receptors bind to their common ligand. With this information, they designed and synthesized approximately 100 compounds and evaluated their ability to selectively inhibit RAR-a in cells. They identified a compound, which was named YCT529, that inhibited RAR-a almost 500 times more potently than it did RAR-ß and -?. When given orally to male mice for 4 weeks, YCT529 dramatically reduced sperm counts and was 99% effective in preventing pregnancy, without any observable side effects. The mice could father pups again 4-6 weeks after they stopped receiving the compound.
According to Georg, YCT529 will begin testing in human clinical trials in the third or fourth quarter of 2022. “Because it can be difficult to predict if a compound that looks good in animal studies will also pan out in human trials, we’re currently exploring other compounds, as well,” she says. To identify these next-generation compounds, the researchers are both modifying the existing compound and testing new structural scaffolds. They hope that their efforts will finally bring the elusive oral male contraceptive to fruition.
The researchers acknowledge support and funding from the National Institutes of Health and the Male Contraceptive Initiative. Georg is a consultant with YourChoice Therapeutics.
Development of selective RARa antagonists as male contraceptive agents
The quest for an effective male contraceptive agent has begun decades ago with no approved pills to date. Compounds undergoing clinical trials are all targeted on male sex hormone testosterone which could lead to hormonal side effects such as weight gain, depression, increased low-density lipoproteins, etc. Our effort focused on developing a non-hormonal male contraceptive to avoid the hormonal side effects. Vitamin A has long been known to be essential for male fertility and vitamin-A-deficient diet causes mammalian male sterility. One particular receptor of vitamin A metabolite retinoic acid (RARa) is validated as the target for male contraception by gene knockout studies. Also, oral administration pan-RAR antagonist BMS-189453 which inhibits the activity of RAR a, ß, and ? lead to reversible sterility in male mice. Knocking out RAR alpha and treatment with a pan-RAR antagonist did not present any significant side effects in mice. We pursued to develop a selective RARa antagonist as a safe, effective, and reversible male contraceptive agent with no off-target effects on RARß and RAR?. Based on the published crystal structures of RARa-ligand complex as well as structures elucidated by us, we envisioned to exploit the structural differences between RARa, ß, and ? ligand-binding domain to achieve RARa selectivity. Also, the structural differences between RARa bound to the agonist and the antagonist facilitated the design of full antagonists. Aided by all the structural information, we designed and synthesized about 100 compounds and evaluated RARa antagonist activity and selectivity using a luciferase-reporter cell assay. We obtained several antagonists with single-digit nanomolar IC50 values for RARa with excellent selectivity over RARß and RAR?. One RARa-selective antagonist showed good oral bioavailability and desired pharmacokinetic properties in mice, and upon oral administration, it showed complete inhibition of embryo formation in mating studies. Modification of active compounds is ongoing to obtain additional potent and selective inhibitors with good pharmacodynamic and pharmacokinetic properties.
Why bother, when we are all destined to end up (of Klaus and his transhumanist chums have their way) as cyborgs restricted to having virtual sex with Metaverse avatars?
This sounds cool, but it’s a mouse study. It seems like 90% of the cool things I read about in mouse studies are never mentioned again. I never hear whether they failed at a later point for science reasons or whether the corporate entity with the ownership chose not to pursue it for other reasons. I just never hear mention again.
Quick, ship it to Africa!
Michael what the hell are you talking about? Any idea???
We need to make this work. I don’t really like the fact that they are spending money to investigate a non hormonal way to create a male contraceptive. It’s the preferred method, don’t get me wrong. But, it is messed up that, for decades, nobody seems to have tried as hard to look into the obsoletion of DNA which could create sterility in women. Instead, they fare the easier route of manipulating the women’s hormones for which there are many more functions than the 3 of men’s simple hormones.
If proven effective, put it into the water supply ASAP.
Wow they actually care that guys could have such bad side effects and are working on another version without them while women are stuck with all sorts of methods of birthcontrol that wreck our bodies.
Awesome! Men need an option besides condoms which take almost all pleasure out, are expensive, and prone to failure. Condoms are better suited for disease prevention. My girlfriend can’t do most birth control due to blood clots, and being allergic to latex means condoms are expensive, we have limited options. Men also need a way to be in control without relying on women (who can be hormone driven, or have ulterior motives) when it comes to babies. Sorry, scientifically proven, and it’s just nature. Don’t believe me? Try dating a mid 30’s woman who hasn’t had a baby yet and wants one. Their biological clock is ticking and amazing how forgetful it is to take a daily pill to prevent pregnancy when deep down that’s what they want. Those hormones conveniently help you forget… Been there. Women also have the right to choose to keep or terminate a pregnancy even if they forgot to take their pill or do it incorrectly. At this point a man doesn’t have much say but must pay alimony for 18 years. They can say they’re on the pill then stop the next day to purposely become pregnant, you’re still on the hook and still a man must be responsible and take the craziest things as a possibility. Fact! We must be careful even where we dispose of used condoms because a woman can use it to impregnate herself! Also has happened. Let’s take some of that responsibility off females. It also sounds safer than female birth control that already exists which is mostly hormonal. If this could work it would be a sexual revolution FOR MEN!!!! Sex would be more enjoyable with more orgasms, less anxiety, or risk of being trapped by someone purposely getting pregnant. Men for once could take control and have more responsibility. Teenage boys could take this until they’re ready for a family, I bet teen and unwanted pregnancy rates would drop tremendously. That is IF this can work AND be safe in humans. I’m all for MORE options!
Men would enjoy sex more if they were in charge of birth control?? Sir you are embarrassing yourself. You sound very misogynistic yikes!
There’s a number of less desirable side effects I can already think of. It probably wouldn’t be perceptible in mice of course~
So they can make a mens birth control without any side effects but not a womans… cool.
It’s a great idea for couples in monogamous relationships. However, I wouldn’t trust most high school/ college age guys to take it correctly let alone consistently.
Total idiotic thing.
90% will never recover sperm and PCT for thet dont exist.
Ship it to Israel.
Don’t let’s that 1% Get aways Boyzzz
Why keep things the way they are? . . . . . . . It is still a Women’s responsible role to control her use of her uterus & WHEN she allows the man to touch her.
Lol please take some accountability. Sex is a two way street. It is not solely the woman’s job not to get pregnant. If you don’t see it that way maybe you shouldn’t be having sex.
City Boyz Up😈😈
I doubt if any man would take this. But women will probably be dumb enough to believe it when they say they do.
Count me in. I am Divorced with 2 boys, and because I Don’t have 3 children my friken Dr. doesn’t want to perform the Vasectomy which I think is cruel. I am 56, and happy with only having 2 boys. The World is so f_cked up rite now why bring more children to suffer. I am C”A?R#L$O:S I;N&I€G?÷[email protected]£Z B+R&A*V=O on fc-book ladies in the LA Orange County area. Lets Smash…
I’m all for more contraceptive options and sure there should be more options for men. What surprises me is that there is nothing like this for women.
Almost all the options at the moment for women are hormonal based and can cause serious and fatal side effects.For example blood clots which can also cause DVT(deep vein thrombosis), heart attack,stroke. Other things that hormonal contraceptives can cause is depression and cancer and many many more.
It’s amazing that men can in the future get more options for contraception.
But it’s ridiculous that women’s contraception is riddled with risks that we just have to accept while at the same time special care is taken to ensure that men dont feel a fraction of what women can be subjected to.
Contraception should have minimal risk and be readily available for ALL genders.
Look at all the comments of people crying for the women. Guess they didn’t read the article, this is birth control for men. Got a problem about it cry to the people who market women’s birth control or sit still and listen
Since you don’t understand why women are “crying” I’ll explain. Women’s birth control is mostly hormonal. Do you know what that is? The birth control options we have give many side effects. Including several severe ones such as blood clots and heart attack. If they can make a males pill with no side effects. Why can’t they put that same energy into making it for a woman? Hope that makes sense to you.
I love how hard the scientists are trying for zero side effects that are identical to the ones women have been putting up with for years. 😑
Bettersafe is one of two things one your not working with much or two you have been with guys that are not! No loss of pleasure with condoms old wives tail! Unless they have nothing, to begin within the first place!
Also, this is new! No side effects are BS even sugar pills have side effects on people. So to say NO said effects this is a lie there is NOTHING that has no side effects! People are naive and ignorant to think that!
I’d like to see it work don’t miss understand me as I feel it’s both the male and females’ responsibility to not have a child! Be nice if there is something more than condoms or having your junk snipped as it is not much else.
Yet let’s not kid ourselves! Nothing has no side effects!
Why the f*** are you putting so much effort into making a non hormonal contraceptive for men that has no side effects yet women still dont even have one? Literally all of the side effects you said they were trying to avoid are the same damn side effects that regular a** birth control has.
I understand why everyone is upset about no one pursuing a better birth control for women, but it’s simple. Woman are born with their eggs already developed. They don’t make them everyday like men do with sperm. They just release the already developed eggs periodically every month, and that’s only controlled with hormones. Any other approach would more than likely result in permanent sterilization. The real question is, why hasn’t anyone pursued male birth control sooner?
Please bring it to the market 🙏
Asap, intercourse is a two way street , women and men are both equally responsible , for what happens after.
Although in society its sometimes really difficult to hold someone to his or her responsibility
As a man i would like to use this! to be more involved and more impowered to make such a decision
Do i want children or not its the very same decision a woman can make now. So i feel while men and women are getting slowly more equal all over the world ( mostly western countries agreed) and sex is no longer defined in male or female but more and more with a gender neutral approach i feel the world is ready for this !!
Idk who this jenn is but wauw what a negative take you have on this
It seems your pretty upset about not having this non hormonal pill as a choice for women , as said in another comment its not as simple as with men, it seems im sorry that there’s so much unfairness in your world , Still i believe this is also a very positive step forwards for the female folk , pills can be lawfully subscribed ( by a judge ) and regulated/enforced
As where a sterilization is really tuff to get a judge ruling for a permanent alterations to someone,s body think rapist ,child molesters and all other monsters we have amongst us in this world
😔 This could change a whole lot
For women and
For unmarried women who complain about current contraceptive options… Why should you suppress your own natural reproductive powers for the sake of relationship with a guy who isn’t able or willing to commit to marriage? Why should either of you sterilize yourselves?
If he can’t accept the responsibility of having a wife and possibly children, he doesn’t deserve you.
And if he can’t wait for marriage, how do you know he’ll be able to control himself once you are married?
This is the greatest news ever
There is no such thing you name “without side effects”. The side effects are determined by the individual body solely, not by the medicine. Depending on the body conditions, even water presents side effects if ingested.
I understand the effort to make a non-hormonal birth control for men but instead of wasting money on making birth-control for men that are definitely not going to take it because America has forced the country to believe that womens body’s are mens property so men assume or try to require women to be on the pill, why don’t we put money into DNA/Gene therapy modulation for men to sterilize us and prevent sperm production? Stop controlling women for once and let us men do something for the women.