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Two women may have a solution to a question that’s vexed women ever since the birth control pill was approved for use by everyone in 1972: Why isn’t there a hormonal contraceptive for men?

The challenge has been both biological and sociological.

Men make millions and millions of sperm every day, whereas women only release one or two eggs per month, making it an easier reproductive process to target. But scientists figured out how to stem sperm production in the 1990s, and two clinical trials from that time showed that the method was as effective as the pill.

Drug companies, however, didn’t trust that men would use the method — despite surveys suggesting otherwise — so they wouldn’t invest in the large-scale clinical trials needed to show the Food and Drug Administration that the method is safe and effective.

“People say ‘Oh the man will never take the contraception and the female will never trust them.’ But all the studies that were done … showed that in fact over 50 percent of the men will accept a new method,” says Christina Wang, lead researcher at LA BioMed.

Wang and Stephanie Page, a professor of medicine at the University of Washington, are part of a new wave of scientists — many of them women — spearheading the latest push for a male hormonal contraceptive. And the recent launch of two major clinical trials suggests they’re getting close.

The drugs — Nestorone and Dimethandrolone (DMAU) — increase levels of both testosterone and progestin (a synthetic form of progesterone) in the blood. Combined, the two hormones suppress men’s natural production of testosterone, which in turn blocks sperm maturation. DMAU can be taken as a once-daily pill or a long-acting injection, while Nestorone comes in a gel that is applied to the man’s shoulders and upper arms every day.

Testosterone is made in the testicles, but the process is controlled by two key chemicals in the brain, luteinizing hormone (LH) and follicle stimulating hormone (FSH), the same chemicals that regulate the female menstrual cycle. By increasing levels of testosterone in the blood, the drugs trick LH and FSH into thinking there’s plenty of testosterone being produced, so the two hormones turn off. That signals the testosterone factory in the testicles to shut down, and no testosterone means no sperm.

“We’re basically tricking the brain — really tricking the testicle — into not making more testosterone because there’s already plenty around,” says Page.

The drugs used in the 1990s blasted men with super high levels of testosterone, but that ended up causing some unpleasant side effects — another reason those early drugs were sidelined. In the new versions, the scientists scaled back on the testosterone and added progestin to the mix, which also blocks LH and FSH in men.

Together, the testosterone and progestin reduce sperm concentration to less than one million sperm in every milliliter of ejaculation — about the size of a quarter teaspoon. While that sounds like a lot, men can have up to 200 million sperm per milliliter. Getting a man’s sperm count down to less than a million per milliliter is 98 percent effective at preventing pregnancy, according to Page.

Because the men still have high amounts of testosterone in their blood stream, they don’t experience any negative side effects typically associated with low testosterone production. However, there are concerns about side effects from the progestin. In 2016, a clinical trial for an injectable form of birth control — also made up of testosterone and progestin —was cut short because some men experienced depression, most likely caused by the type of progestin used.

Nestorone (the gel) and DMAU (the pill) use different forms of progestin, and so far they don’t appear to be linked to any of the negative mood effects that plagued the earlier trial, although some participants in preliminary studies have experienced weight gain and changes in sex drive, symptoms that women often experience on hormonal birth control. Page and Wang are currently enrolling 100 men in a 12-week test of the DMAU pill and 84 men for an initial study of the injection. Nestorone is further along and is currently being tested in 420 couples around the world for two years.

Julia Mora and Michael Medrano are one of those couples. Both in their late 20s, they had been using condoms for protection after their son was born eight years ago. She says that if male contraceptive had been available back then, they would have been less likely to get pregnant because “at least there’d be two of us more on top of it.”

Mora says being enrolled in the study gives her a sense of more support. “It’s kind of nice to not have the full responsibility," she says. "If we do get pregnant, it’s not all my fault because I didn’t take the proper precaution.”

If the trial is a success, Wang and Page will still have to attempt a final two-year study of the Nestorone gel in 1,000 couples before they can get FDA approval. However, these types of phase 3 trials, as they’re called, are much more expensive. Page hopes that a drug company or nonprofit organization will finally see the potential promise and need for a male hormonal option.

“Men have crummy options for contraception: the condom or the vasectomy,” says Page. “If we really want to make an impact on unplanned pregnancy, further engaging 50 percent of the population would behoove everybody.”

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