Hormonal contraceptive gel for men suppresses sperm production by week 8
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Key takeaways:
- A progestin/testosterone gel for contraceptive use by men is effective by 8 weeks of daily use.
- Men and women reported favorable experiences using the gel as their only contraceptive method.
BOSTON — In a phase 2b trial, a hormonal contraceptive gel for use by men worked faster than expected, suppressing sperm count to effective levels by week 8 of use, making it an “attractive” product, according to a speaker at ENDO 2024.
The gel combines the progestin segesterone acetate (Nestorone) with testosterone to suppress endogenous testosterone production and replace just enough testosterone to reach physiologic levels to maintain normal functions that depend on androgens, according to senior researcher Diana Blithe, PhD, chief of the Contraceptive Development Program at NIH.
Men in the ongoing trial apply about 2.5 mL of the gel daily to their shoulders, similar to the instructions for the testosterone gel used by men for hormone replacement, Blithe said during a press briefing.
For the trial, which is projected to end by the end of the year, Blithe and colleagues enrolled 222 couples worldwide in which the male partner has two consecutive normal sperm counts of more than 5 million per mL/semen. The primary endpoint is pregnancy prevention, and secondary endpoints are safety, adverse effects and acceptability to both partners.
The men apply the segesterone acetate 8 mg/testosterone 74 mg combination gel daily. Sperm counts are assessed every 4 weeks. At the beginning of the trial, when two consecutive counts indicate a sperm concentration of 1 million per mL or less — with a goal of zero — a couple enters the 1-year efficacy phase of the trial, in which they use no other contraceptive method. At 1 year, the man discontinues the gel and enters the recovery phase of the trial.
Of the cohort, 192 of the men achieved sperm suppression with median time to suppression of 8 weeks.
“Our initial thought, based on previously published data, was that it would take about 12 to 15 weeks for suppression to occur ... but what we were seeing actually was less than 8 [weeks to sperm suppression],” Blithe said. “In fact, we may be able to even show a faster suppression. ... We weren’t expecting this, so we didn’t measure at 4, 5 or 6 weeks on everybody, and we don’t know how many of them actually might have been suppressed prior to 8 weeks.”
Reported adverse effects of the gel were those generally associated with androgen therapy, and “better than we projected. It might be similar to effects that women may experience on hormones, so we’re pretty encouraged by that,” Blithe said.
Overall, the couples reviewed their experiences favorably, Blithe said.
“This is a 2-year study, and this is a long time, a lot of visits. The fact that the men want to continue, and they want to remain in the study, I think it is an endorsement for the product that’s stronger than anything I could convey,” Blithe said.
The women in the study also commented that they wish they could continue using the method.
“This is actually a women’s health issue in addition to being a male health issue,” Blithe said.
After discontinuing the gel, the men appear to recover their pre-trial sperm counts, and several of the couples have had babies.
“It’s not part of the protocol to have return to fertility, but we don’t anticipate any problem because in order to exit the study, they need to have a normal sperm count that’s similar to what they had when they came in,” Blithe said.
The next step in the trial program is a phase 3 study. Because this is the first men’s hormonal contraceptive to reach this stage of development, the FDA has no guidance for approval.
“We hope to finish by the end of the year and present the data to the FDA and then get their guidance on the path to approval,” Blithe said.
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Gross D, et al. OR24-01. Presented at: ENDO annual meeting; June 1-4, 2024; Boston.
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