Male contraception: a hormonal gel in trials, a non-hormonal pill past first safety

After roughly half a century with almost nothing new, two male contraceptives are now in human trials: a daily hormonal gel that is being tested for its ability to actually prevent pregnancy, and a non-hormonal pill that has cleared only its first safety study [s2][s3]. Neither is approved, and the non-hormonal pill has not yet been shown to lower sperm counts in people, let alone prevent a pregnancy [s2].

The gap this is meant to fill is real. The developers of both candidates note that nearly half of all pregnancies worldwide are unintended, and the reversible options available to men have not changed in generations: condoms and withdrawal, both with high typical-use failure rates, and vasectomy, which is effective but not easily reversed [s2][s3]. That leaves the burden of reversible contraception almost entirely with women. For a fuller account of how the existing methods compare, see our explainers on vasectomy and on typical versus perfect-use failure rates.

The hormonal gel

The most advanced candidate is a combination hormonal gel, applied daily to the shoulders, containing testosterone and the progestin segesterone acetate, better known by its research name Nestorone [s1][s3]. The mechanism is well established: a progestin plus an androgen suppresses the pituitary hormones that drive the testes, which in turn suppresses sperm production, and because the gel also supplies testosterone, it replaces the body's own suppressed testosterone and limits side effects [s3][s4]. Suppression is reversible, with sperm production returning within a few months of stopping [s3].

What has been missing is proof that this prevents pregnancy in real couples. An international, multicentre trial was designed to answer exactly that, and it finished enrolling on 1 November 2022 with 462 couples in committed relationships, in which the man had normal baseline sperm production and the woman was at risk of unintended pregnancy [s1]. The primary outcome is the pregnancy rate over a 52-week efficacy phase; secondary outcomes include how many men suppress sperm production enough to enter that phase, side effects, and the possibility of the gel transferring to a partner through skin contact [s1]. The results have not yet been published [s1]. Earlier hormonal approaches, including injections, have suppressed sperm effectively in trials, so the open questions for the gel are less about whether it can work than about how reliably men adhere to a daily gel and how acceptable it proves in practice [s1][s4].

The non-hormonal pill

The second candidate takes a different route. YCT-529 is a first-in-class non-hormonal drug, an antagonist of the retinoic acid receptor alpha, designed to interrupt the retinoic-acid signalling that the testes need to make sperm [s2]. Because it does not touch the hormonal axis, the hope is that it avoids the mood, libido and metabolic effects that have complicated hormonal methods [s2].

The evidence so far is early and should be read as such. The first-in-human trial was a single-ascending-dose safety study: 16 male volunteers took one oral dose of 10, 30, 90 or 180 milligrams, with one group also taking 30 milligrams with food [s2]. At doses up to 180 milligrams, the drug had no effect on heart rate, on the reproductive hormones follicle-stimulating hormone, luteinising hormone and testosterone, on sex-hormone-binding globulin, on inflammatory markers, or on sexual desire and mood, and it was well tolerated [s2]. That is a genuine milestone for a class of drug that has stalled for decades, but it is important to be precise about what it does and does not show. A single-dose safety study tests whether the drug is tolerable; it does not test whether it lowers sperm counts, and it certainly does not test whether it prevents pregnancy [s2]. Those questions require multiple-dose and efficacy trials that have not yet reported.

What it means for a reader

The honest headline is progress, not arrival. One method is being tested against the outcome that matters most, pregnancy, and the other has only demonstrated that a single dose is safe. Male hormonal contraception has a long history of trials that suppressed sperm well but were slowed by side effects, adherence and the commercial reluctance to develop a product for healthy men [s4]. That history is the reason to treat announcements of an imminent "male pill" with caution: candidates have looked promising at this stage before.

What to watch next is concrete. For the gel, it is the published pregnancy-rate result from the 462-couple trial [s1]. For the pill, it is whether repeated dosing actually reduces sperm counts in men and, later, whether that translates into contraceptive efficacy and full reversibility [s2]. Until those readouts exist, the accurate summary is that the male contraceptive pipeline is the healthiest it has been in fifty years, and that nothing in it is ready for a pharmacy shelf.