A Phase 2 trial into the efficacy of a male contraceptive gel is about to get underway bringing modern medicine closer than it ever has before to finally developing a male birth control drug, decades after the female contraceptive pill hit the market.

Finding a simple male contraceptive compound that is safe, effective and reversible has been relatively elusive for scientists. Outside of condoms and vasectomies, birth control has remained well and truly in hands of women. A male contraceptive agent, some have argued, is simply a much more difficult pharmacological challenge: stopping the production of an egg or two a month seems to be much easier than limiting the efficacy of millions of constantly regenerating sperm.

However, several exciting innovations are rapidly being developed – from an injectable compound acing its early animal trials to a more traditional "pill" passing the first phase of human safety trials earlier this year. The most advanced male contraceptive prospect though is a novel gel, designed to be used once a day, and now moving into a serious phase 2b trial set to establish whether it actually stops unwanted pregnancies or not.

The gel is called NES/T and contains two hormonal compounds. The primary compound is called Nesterone, a progestin hormone formulated to lower sperm production by blocking testosterone production in the testes. The second compound is a concentration of testosterone designed to maintain blood levels of the hormone, important for general health and mood, but low enough to not kick-start sperm production.

Prior human trials into the gel, rubbed onto a man's arms and shoulders once a day, have found the contraceptive agent to be low in harmful side effects, and effective in reducing overall concentrations of sperm. This new trial is set to encompass over 400 couples worldwide and will follow use for well over a year to clearly find out if the gel actively prevents pregnancies.

The trial will run through several stages, first the men will use the gel daily for up to 16 weeks while being monitored for unexpected side effects. By that point tests should reveal whether sperm levels have declined to levels below recommended conception thresh-holds.

At this point the second phase is for the men to use the gel as their only form of birth control for 52 weeks. All men enrolled into the study must be part of a committed, monogamous couple, with both members signing onto the trial. After a year of using the gel as the only form of birth control, the men will discontinue the treatment and be observed for 24 weeks to examine any after effects and to make sure sperm levels return to normal.

"The success of a reversible contraceptive for men requires an approach that reduces the production of sperm without impacting a man's testosterone levels or ability to produce sperm at a later date," says Christina Wang, lead researcher and a study principal investigator. "The challenge is achieving the right combination of Nestorone and testosterone at the right time."

This is the first serious, real-world test into a male contraceptive for some time, and all members signing up for the trial must be aware and willing to enter into a pregnancy if the gel proves ineffective. The results from this trial won't be known until around 2022, and if positive, the treatment will move into an even larger, final phase 3 trial before it can ultimately reach the market. So all up, despite this being the most advanced male contraceptive currently in development, it still may be close to ten years before it reaches the general public – and that is if all goes to plan.

"Expanding male contraceptive options could help make family planning more of a shared responsibility between women and men," says Regine Sitruk-Ware, co-director of the trial, explaining the urgent need to develop an effective male contraceptive treatment. "Safe, effective, and reversible tools for men to control their own fertility gives new meaning and significance to the term 'family planning.' No matter the challenge, we must continue to innovate and develop new products to improve lives."

The trial is currently recruiting subjects in California, Kansas and Washington, before expanding to a number of other locations worldwide. Interested participants can look at the selection criteria here.

Source: UW Medicine