In 2018, a handful of couples ditched their birth control to embark on a one-year trial of a hormonal topical gel as their only contraceptive. This gel, however, was for men to use in order to suppress their sperm levels enough that they wouldn’t impregnate their partner. Over the next 6 years, 200 monogamous couples at 15 sites worldwide completed this experiment as part of a phase 2 clinical trial for the gel, which may become the first available hormonal male birth control.
Now, the last of the participants have come off the gel, entering the recovery phase for their sperm count as the trial winds down. The trial’s director presented the preliminary findings of the phase 2 trial at the endocrinology conference ENDO in Boston on June 2. According to Diana Blithe, the study director of the Contraceptive Development Program at the National Institute for Child Health and Human Development (NICHD), a division of the National Institutes of Health, the initial findings look promising.
“I'm usually not a glass half full person, but this trial has really been amazing.”
“I'm usually not a glass half full person, but this trial has really been amazing,” she tells Inverse. Throughout this trial, she and her team have tested for product safety, effectiveness, dose, and side effects. “We feel like we have a very good safety profile,” she says. “We haven't had any adverse events that would be unexpected or serious.” The most common side effects that participants reported during the trials were acne, increased libido, and mood swings.
The trial won’t officially conclude until the end of the year, at which point researchers predict that all participants should have recovered their sperm counts and Blithe’s team will analyze their data.
Some participants had a profoundly positive experience, evidenced in their attachment to the gel. At the endocrinology conference, Blithe shared some of the participants’ comments as they exited the trial. One male participant called the regimen easy while another wished the product was already on the market.
“My favorite comment from the guys is, ‘Can I re-enroll?’” Blithe says.
The gel positively impacted the women in these couples, too. Some of their comments expressed their wishes to stay off female birth control, and how much they enjoyed this gel option.
To Blithe and her team’s surprise, the gel took effect more quickly than they thought. They expected sperm suppression, on average, to occur around the 12-week mark and no earlier than the 8-week mark. However, they saw sperm suppression as early as 4 weeks in one participant, and by 8 weeks more than half reached suppression.
Some participants had a profoundly positive experience, evidenced in their attachment to the gel.
This welcome surprise, according to Blithe, means users won’t have to wait as long for their new birth control to be fully effective. “Two months is better than three months,” she says. She foresees that once her team processes and analyzes the data from the trial, they’ll find that the average time to suppression is between 7 and 8 weeks.
The gel is a combination of testosterone and segesterone acetate (a.k.a. nestorone), which is a synthetic progesterone. It functions by absorption through the skin. Participants rub about half a teaspoon’s worth on their shoulders once a day. Once absorbed, the hormones target the production of another set of hormones called gonadotropins, which come from the brain’s tiny pituitary gland. The nestorone suppresses the creation of two gonadotropins that promote sperm and testosterone creation in the testes, resulting in a steep dropoff of both. The testosterone, on the other hand, replenishes the supply diminished by the nestorone. Once the gel has taken full effect, the user has gone from producing about 20 million to 30 million sperm per day to fewer than 1 million sperm per milliliter of semen, at which point unprotected sex is theoretically free of pregnancy risk for the couple. This trial demonstrates that this gel works in practice.
The team also continued to fine-tune the product throughout this trial. The initial ratio of testosterone to nestorone was 62 milligrams to 8 milligrams. The goal was for the gel to boost testosterone levels enough that it resembled a normal range, but the team observed low levels and symptoms of low testosterone. They decided to increase testosterone from 62 mg to 74 mg, while keeping the nestorone the same. With this change, Blithe says they expected to see incidences of high testosterone, but that didn’t happen.
A few hurdles still keep the team from a phase 3 trial. For one, no male contraceptive has ever made it this far in the pharmaceutical pipeline, so the Food and Drug Administration (FDA) has no guidelines for what such a trial would look like. Typically, a phase 3 trial’s goal is to test the new treatment against other treatments already on the market; currently there’s no male birth control available to test it against. This trial would also need to be considerably larger than the most recent one, which would require much more money from an investor. This trial received over $7.5 million in 2023, and over $20 million since its initial funding in 2014.
Next steps are on everyone’s mind. “Our hope is to meet with the FDA early next year once the data are available for them to review,” Blithe says. It’s difficult for Blithe to estimate when a phase 3 trial will start, let alone when the product will be commercially available. Funding will make all the difference. With a significant investment, “it could be four or five years” until the end of a phase 3 trial “instead of 7 or 8.” Without investors, Blithe says the next leg could take as long as 15 years.
“We hope the results, once they're published, will be exciting to not just the general public but to industry,” Blithe says, “and that someone will see this opportunity and say, ‘We’ve got to be part of this.’”
