Finally, researchers are closing in on an oral male contraceptive pill that works without hormones, offers full reversibility and – most strikingly – has caused zero side effects. The pill, called YCT-529, which has an entirely new kind of contraceptive mechanism, has passed a critical human safety benchmark and will now advance to efficacy trials, and it could potentially be widely available within a few years.
In the first human safety trial – the Phase Ia randomized, double-blind, placebo-controlled, single ascending dose study – 16 healthy men between the ages of 32 and 59 years were enlisted to test the tolerability and safety of YCT-529, which had already undergone stringent animal research. Participants received a single oral dose of YCT-529, from 10 mg to 180 mg (or a placebo) under both fasted and fed conditions, in order to assess absorption variables. The men were then monitored for 14 days.
What the researchers found was there were no serious side effects at any dose level, and hormones remained stable and libido was unchanged. There were also no changes in inflammatory markers, mood or key blood chemistry measures. Overall, this points to YCT-529 being essentially without adverse outcomes – something that can't be said for female contraceptive pills or devices.
And based on pharmacokinetic data, the drug has a long half-life of 51–76 hours – which means that YCT-529 would remain active and effective in the body for several days. Basically, the pill could potentially be taken every three days, rather than daily (upcoming 28- and 90-day studies will test dosing in regards to sperm count).
While this is an outstanding outcome for the most promising male contraceptive candidate we have, news coverage of it drew plenty of ire from women who have had to endure a host of side-effects and serious health risks associated with their hormonal birth control methods. As well as mood changes, weight gain, increased stroke and clot risks, just to name a few side effects, a 2023 study found for the first time that these medications affect women’s responses to stress and their risk for inflammation-related illnesses.
And while hormonal contraceptives are safely used by more than 300 million women worldwide, the researchers behind this study noted that there has been little research on their downstream physiological and behavioral effects of the drugs. Earlier research had identified that hormonal contraceptive pills can increase the risk of chronically elevated inflammation, which then carries the long-term risk of developing illnesses such as cancer, cardiovascular disease, and autoimmune disorders, as well as potential mood disorders, including depression. Once again, the mechanisms behind this association has remained understudied.
While YCT-529 is not at all comparable to hormonal contraception – it's nonetheless sparked the wider debate of the lack of research into how these widely used contraceptive methods impact women's health. Meanwhile, there's been plenty of work in the quest for a male equivalent – albeit, until now, something that's eluded scientists.
Why this new drug from young pharmaceutical startup YourChoice Therapeutics is so promising, however, is that unlike hormonal male contraceptive candidates – which typically lower testosterone and can cause side effects – YCT-529 targets a specific protein: retinoic acid receptor alpha (RARα). This receptor is part of the vitamin A signaling pathway needed for sperm production. Blocking it halts sperm development without affecting sex hormones or broader vitamin A functions elsewhere in the body.
“A peer-reviewed publication for our first-in-human study reinforces YCT-529’s strong safety profile," said lead author Nadja Mannowetz, Chief Science Officer at YourChoice Therapeutics. "It also shows ‘the Pill for men’ had no effect on sexual desire or mood. Two back-to-back publications demonstrate our commitment to conducting rigorous studies, which strengthens our ability to develop the first hormone-free birth control pill for men efficiently and as expeditiously as possible to meet the growing demand.”
Mannowetz is a sperm biologist and she's now leading the way in creating the first male contraceptive pill, which if it delivers in the next trial stages, could be widely available before the end of the decade.
In primate and mouse studies, the drug suppressed sperm production and was fully reversible once treatment had ceased. In May, the team published the data of this latest animal research in Communications Medicine, backing up the promise the drug showed when we first reported on the startup's early testing in 2022. In mice, oral YCT-529 caused near-complete infertility, but fertility was fully restored within six-to-12 weeks of stopping treatment. In cynomolgus macaques, sperm counts fell sharply within two-to-five weeks and returned to normal within around three months. Again, there were no hormone disruption or adverse effects.
YCT-529 is the most promising male contraceptive candidate to date, and if successful, it could transform not just family planning, but go some way to rebalancing contraceptive responsibility that has so far been significantly one-sided.
And if you want to hear more about the company and Mannowetz background, in her plight to deliver the first therapeutic of its kind, she appeared on the excellent health IT podcast HIT Like A Girl in 2024.
The study was published in the journal Communications Medicine.
Source: YourChoice Therapeutics via Business Wire
