First hormone-free male birth control pill enters human trials
128 comments
·April 20, 2025thecupisblue
ein0p
[flagged]
loeg
I was curious about the mechanism.
https://www.nature.com/articles/s43856-025-00752-7
> YCT-529 works by interfering with vitamin A signaling necessary for sperm production and fertility.
> The importance of dietary vitamin A and retinoid signaling for male germ cell development and differentiation has been recognized for many years6. All trans-retinoic acid (Fig. 1a) is an active metabolite of vitamin A that exerts its function, at least partly, by binding to retinoic acid receptors (RARs). The RARs α, β, and γ, are encoded by the Rara, Rarb, and Rarg genes in mice, and Rarα and Rarγ have been validated as contraceptive targets by genetic knockouts resulting in male sterility7,8. Notably, the effects on spermatogenesis in the absence of RARα most resemble the loss of RAR signaling in vitamin A deficiency, and the mice are otherwise normal7,8. Further, the effects on spermatogenesis in animals treated orally with the dual RARα/RARγ antagonist BMS-189453 (Fig. 1a, b) closely phenocopied the absence of RARα function. Importantly, the resulting male sterility is reversible9,10,11. We, therefore, wished to identify RARα−selective inhibitors for potential male non-hormonal contraception. Our study describes the development of YCT-529, a highly selective RARα antagonist that reduces sperm counts in mice and non-human primates. Mating studies with male mice treated with 10 mg/kg/day for 4 weeks show that YCT-529 is 99% effective in preventing pregnancies and that the mice fully regain fertility after drug cessation.
johnisgood
We had alpha-blockers for a long time now, which prevents ejaculation but not orgasm; read: it can completely block the emission phase of ejaculation, while orgasmic function is retained.
Example: Silodosin.
You need to experiment with it. Sensitive clinical trials measured rates as high as 90-99%.
It is entirely non-hormonal. It does not affect libido (rarely), while hormonal male contraceptives do, and it is reversible upon cessation, without any delay, unlike hormonal male contraceptives.
AstralStorm
Closer to 90%, and generally the side effects are a bit annoying too. Circulatory ones. Sometimes even to floppy. (Like 1% dosage dependent)
Plus the thing does not stop the drip so you do have to pull out sooner rather than later or else. It does not stop sperm production.
Also dry ones tend to result. They're sometimes uncomfortable.
Tamsulosin is I believe the modern one but all of them are for long term. Probably least side effects.
Otherwise if taken as a single dose fresh, side effects like orthostatic hypotension are vastly increased.
johnisgood
Circulatory side effects like dizziness or orthostatic hypotension do occur, though they tend to be mild and dose-dependent.
You're right that it doesn't stop sperm production, just emission. As for "the drip"; that's pre-ejaculate, which doesn't contain sperm inherently, but can pick up residual sperm in the urethra from a prior ejaculation.
And that's true, anejaculatory orgasms can feel strange or less satisfying for some, but it is not universal.
> Otherwise if taken as a single dose fresh, side effects like orthostatic hypotension are vastly increased.
That is true.
Edit: I / We will have to research the side-effect profile and mechanisms of the mentioned pill (in the submission). I have not yet done so. They mention no side-effects but it might be too early to tell.
cstrahan
> You're right that it doesn't stop sperm production, just emission. As for "the drip"; that's pre-ejaculate, which doesn't contain sperm inherently, but can pick up residual sperm in the urethra from a prior ejaculation.
I’d like to stress that point a bit.
I had a vasectomy about a year ago, and being the weirdo that I am, I figured I’d see how much sperm remained in my ejaculate (and for how long) after the procedure.
I waited maybe two or three days after the procedure, and then for the next three days, I’d collect three samples per day and take a look under my microscope. In the first four or five samples, the swimmers were swimming hard. Told my brother (who had been trying for a kid for a couple years, and had observed his own samples trying correlate diet and other factors to improved motility) about the straight laser beams I was seeing in the scope — he nearly had a fit when I described how long it took them to go from one side of the slide to the other under the given magnification.
It was the ninth sample when there were very few observable sperm, and what remained looked kinda drunk and unmotivated.
All of that to say: if you’re going to get a vasectomy, when your doctor tells you to abstain from condom-less/birthcontrol-less sex until you come back for a sperm count, take that seriously. It’s amazing how motile they are even when kinda old, and also amazing how many hang around downstream of the vas deferens after many ejaculations. And, while rare, sometimes the vas deferens do manage to reconnect.
And a bonus tip along these lines: testosterone replacement, even without hCG, is not a reliable form of birth control. I’m on (and was on) TRT, without hCG, and the concentration of sperm under the scope looked higher than any YouTube video I could find at the same magnification (meanwhile my bro is taking silly amounts of hCG and struggling). I hear a lot of people joke about TRT having the beneficial side effect of infertility, but that’s far from a certainty.
johnisgood
> Both mice and non-human primates fully regained fertility after stopping the drug. Mice regained fertility within six weeks, and non-human primates fully recovered their sperm count in 10-15 weeks.
Hard pass on messing with my fertility like that, too, TBH.
loeg
> clinical trials measured rates as high as 90-99%.
This is in the same range as, like, pulling out, for what it's worth.
johnisgood
The similarity is not the same.
If no semen is emitted, the chance of pregnancy is null (more about it in my other comments).
Plus 90–99% suppression of ejaculation has been recorded and suggested that it has a potentially high contraceptive efficacy, so that is way better than withdrawal.
Experiment, maybe it affects you in a way that you get 99%, which would make it a very efficient hormone-free male birth control pill.
Side-note: personally I prefer IUDs, and/or a medication that has been extensively studied, so this pill can wait.
loeg
The "as typically used" quoted figure for pulling out ("withdrawal") is 80% success, but the ideal use figure is 96-98%. If you know a little bit about yourself and also aren't going back to back without peeing, you can do a lot better than the 80% figure. (Also yeah, it's amusing that both of these figures are more or less identical to male condoms.)
(Meta-comment: probably best to keep everything in "success" percentage figures for direct comparison, instead of switching to failure percentages for some figures.)
__turbobrew__
Yea similar with tracking ovulation dates. Seems like pretty bad EV for messing with my nervous system.
BurningFrog
If it's never ejaculated, what happens to the fluid?
johnisgood
The body has several well-regulated mechanisms for handling it.
If semen isn't ejaculated, the body reabsorbs the sperm in the epididymis and recycles the cellular material. Seminal fluids, which are produced during arousal, are either reabsorbed or, in cases like retrograde ejaculation (e.g., with alpha-blockers), pass into the bladder and are later urinated out. The system self-regulates; there's no harmful buildup to worry about. :)
So, TL;DR: You will just urinate it out in our case.
chneu
What do you think happens with a vasectomy? It gets reabsorbed.
steanne
it's been a few decades, but i don't recall sperm in seminal fluids being entirely limited to the grand finale, only mostly.
loeg
Sperm is virtually entirely absent from pre-ejaculation fluids if you've peed since the last time you ejaculated. Almost all of the "sperm can be in pre-ejaculate" effect is from having sex a second time in a row without anything flushing out the tubes.
johnisgood
Fair, and it needs clarification to avoid conflating pre-ejaculate, seminal plasma, and sperm emission.
It may be confusing, so to clarify: "seminal fluids" is a term typically used to refer to the fluid released during ejaculation, not throughout the arousal phase. The idea that sperm would be in the mix before the emission phase goes against standard reproductive physiology.
Sperm are only actively introduced into seminal fluid during the emission phase of ejaculation; the so-called "grand finale." :D. Before that, in the arousal phase, the fluids released (like pre-ejaculate) typically contain no sperm unless there's residual contamination from a previous ejaculation.
yard2010
It's funny that residual contamination, in the right context, might lead to the world's best magic - life.
throwaway743
Retrograde ejaculation is a weird thing to experience. It's the physical manifestation of the sound of a slide whistle both ways.
Alpha blockers also give one hell of a stuffy nose. Worst sleep ever after taking one.
Mountain_Skies
Take it a step further into 'Demolition Man' territory to get the orgasm without any physical contact. Certainly would be good for reducing STDs though no doubt would come with a whole range of societal impacts.
johnisgood
In all honesty, orgasm without physical contact is entirely possible already (mental orgasm / psychological stimulation), but it is not common and not easy.
Fantasy, meditation, hypnosis, Kegel exercises... They could lead to orgasms and sometimes even ejaculation (which would be bad in this case).
Some medications rarely may cause spontaneous orgasms, even, without physical contact, arousal or stimulation.
giantg2
We're basically there with VR porn and ever more realistic toys.
johnisgood
Not parent but made a comment to parent, and damn, completely forgot about that! You are right.
hwpythonner
Do their stats include the guy who forgets to take it every third day, or is that part of the 1%?
askonomm
I know plenty women who also forget to take it every day.
Loughla
Like Richard Hammond said, if I was a woman, I'd be pregnant a lot.
I'm terrible at remembering to take pills. Maybe it's because they're pretty low stakes?
patall
It's a mouse and NHP (non-human primate) study
badgersnake
This is why it won’t succeed. The person getting pregnant is going to want some proof that the contraception is being used properly. And that means something that they can see or something that they do themselves.
JumpCrisscross
> person getting pregnant is going to want some proof that the contraception is being used properly
Plenty of couples aren’t in distrustful relationships?
Cthulhu_
Exactly. I'm confident women worry a lot more about getting pregnant than men worry about getting someone pregnant.
crazygringo
Really? You don't think men worry about having a kid with someone they don't want to, being responsible for 18 years of child support, making hard decisions about whether they want to be involved in the kid's life, etc.?
Men are terrified of getting someone pregnant. At least women have a choice as to what to do about it. Men don't.
w10-1
RARα pathway operates in cell development eg of blood cells and in apoptosis, implicated in some cancers.
Long-term safety seems doubtful. Offspring could be affected. In a rational world there would be no volunteers for the trials.
patall
Could also positively affect offspring if spermatogenesis is blocked at the right step, stopping the gamete progenitors from accumulating somatic mutation. The majority of rare genetic diseases arising from de-novo mutations has its origin in the fathers gamete formation (with increasing risk (i.e accumulation of mutations) at older paternal age). Maybe this could block/slow down this process (i.e cell division) and in 20 years all males that still may want to have kids will take a RARα blocker.
Traubenfuchs
This is important, as women coercing men or ignoring their consent regarding pregnancy is not uncommon.
1024core
> Both mice and non-human primates fully regained fertility after stopping the drug. Mice regained fertility within six weeks, and non-human primates fully recovered their sperm count in 10-15 weeks.
Great recurring source of revenue for the drug company!
Though I'm more interested in feral animals like dogs. It looks like this drug may work on dogs too? If so, it would be a huge boon for cities and villages in India.
Someone1234
Why would Cities and Villages in India want a reversible dog contraceptive? They want a cheap, easily deployable, indefinite one.
Retric
Seems like neutering them would be cheaper and there’s no risk of the dogs missing a drug cycle.
astura
Wtf? This is ridiculous. Who the fuck is going to be giving feral dogs a pill everyday? And why would you want a reversible contraceptive for feral dogs? You want a one-and-done irreversible one, which neutering is.
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khazhoux
Whoever invents a drug to eliminate male refractory period, will make all the money. All of it.
matheusmoreira
Cabergoline. Lowers prolactin and can get rid of the refractory period. Problem is there is risk of significant cardiovascular side effects and they appear to be cumulative.
vachina
This is like removing the rev limiter on your engine. Your engine can now go beyond redline, but not for long because it melted itself.
giantg2
Meh, there are people with low to no refactory period already and they don't seem to have any real issues.
MarcelOlsz
Offset it with a restrictor plate.
m000
restrictor + microtransactions -> profit!
"Insert coin to continue"
glacier5674
[dead]
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panny
I can't wait until this stuff hits the water supply /s
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mr90210
I got the /s
Europe is struggling with low birth rates. They wouldn’t do it here, as is right now it’s already a calamity.
Mountain_Skies
What would that look like? Women complain it's unfair they have to be responsible for birth control in relationships. Now there's the ability for men to shoulder the responsibility too. Will voters, male and female, be ok with not taking the egalitarian path? Obviously governments are concerned about falling birthrates but they already have shown a willingness to continue policies that get them re-elected, even at the expense of birthrates.
jocaal
I hope you replied to the wrong comment, I don't think women complaining about paying for birth control is a valid reason for sterilizing a population. Also condoms exist.
steele
TL;DR: red pill
First off, this thread seems to bring out the most "reddit-like" posts on HN. If you've come here to shoot a funny one-liner comment, please reconsider - the point is discussion, not karma farming.
Now, on the topic itself - I really wonder about the safety profile of these. While this selectively inhibits only RARα and is thus "biased" towards mostly acting on testes, it could also have side-effects - and while the effect might not be pronounced yet, with long term use it definitely could be, especially if all the RARα receptors get inhibited (will beta and gamma pick up the slack? what is it going to cause?).
Considering the 99% effectiveness claim and the method of action, I wonder if the embryos in that 1% case can even survive.