Analysis Contraception

Biology, Funding, and Ego Slow Quest for Male Birth Control

Sarah Ellis

In a field packed with methods for women, researchers are still struggling to close this persistent contraception gap.

It’s the pill that changed history for women, opening up unprecedented opportunities to build a life unrestricted to marriage and motherhood.

Since its launch in the early 1960s, the birth control pill has expanded our understanding of what is possible in modern relationships. It has ushered in the rise of women in the workplace and the era of casual sex. Contraceptive technology has made it possible for a woman to protect herself almost infallibly from the risk of unintended pregnancy. Options have increased beyond the traditional once-a-day pill—long-acting methods such as intrauterine devices (IUDs) and implants are becoming safer and more attractive to a broad demographic, with an effectiveness rate of more than 99 percent. Some 62 percent of women between 15 and 44 years old are currently using some form of contraception.

But what about options for men? Rubber condoms have been around since the 19th century, and they remain one of the most effective ways to protect against sexually transmitted infections. For pregnancy prevention, however, the condom has a failure rate of about 15 percent. The only other options for men are the vasectomy—which is often irreversible—and the “pullout” or withdrawal method, which is famously unreliable. Despite advancements in the field of women’s contraceptives, not a single long-acting reversible option for men has hit the market.

Male contraception could fundamentally shift the burden of family planning, bringing equal responsibility to both sexual partners. Talk of a male birth control pill has been around for decades. Every few months, a news headline will appear about a promising clinical trial. But due to a combination of scientific hurdles, financial barriers, and a lukewarm reception from the public, nothing has reached the consumer.

Biology and Barriers

Scientifically, a male birth control pill poses a greater challenge than its female counterpart. Women undergo hormone shifts constantly throughout each 28-day cycle, and an effective birth control need only block the one monthly spike in hormones that signals ovulation. The pill works by “tricking” the body into thinking it is already pregnant, thus blocking ovulation and preventing an egg from being released.

In men, sperm are produced by the tens of millions, and it’s impossible to stop the body from creating them altogether. To reach a level of sperm suppression that makes for a reliable birth control, men have to reach what is known as near-azoospermia, which equates to less than one million sperm per one milliliter of ejaculate.

Hormonally, the best way to do this is by lowering the body’s natural testosterone levels and replacing them with a synthetic version (called an androgen) that mimics the same functions testosterone plays in a man’s body: increasing muscle mass, controlling mood, and boosting metabolism.

As most women know all too well, hormone replacement comes with side effects. Ideally the androgen is meant to be interchangeable with testosterone in the body. However, in the case of hormonal contraception for men, they would likely notice subtle physical and emotional changes similar to the side effects women experience on the pill. Early trials of any new method are intended primarily to assess both efficacy and tolerability. In other words, does this work, and are side effects minimal enough that men will take it?

Societal beliefs about testosterone make it a touchy subject for many men. The hormone is linked to muscle growth and assertive behavior—characteristics commonly associated with masculinity. Whereas female contraceptives promise enticing effects like clearer skin and regular or fewer menstrual cycles, potential male methods do not promise favorable physical results. A vast decrease in sperm could cause the testes to shrink dramatically, which is not a consequence most men will take lightly.

One man (who preferred to remain anonymous) interviewed for this story mentioned the psychological effects he fears such changes could cause: “Guys have high performance pressure when it comes to sex, so I think taking something that affects our testosterone could really get into our heads. We’re worried we might notice the difference.”

Promising Studies—but Slow Progress

Though some men may express hesitation, possible future options are in development. The latest possible male birth control method to make the news is dimethandrolone undecanoate (DMAU), a daily pill that has shown early promise in a 28-day human study. It works by suppressing the brain’s luteinizing- and follicle-stimulating hormones that typically signal the testes to initiate sperm production. Without these hormones, the body stops producing testosterone on its own, and sperm count is drastically reduced after the first few months.

The DMAU study was completed by 83 healthy men between the ages of 18 and 50, and it tested three different doses of the drug, along with a placebo. At the highest dose, participants experienced a marked decline in their naturally circulating testosterone levels, which should translate to sperm suppression in subsequent longer-term studies. Side effects included moderate weight gain, though it is unclear as to whether this was muscle mass or fat.

Dr. Arthi Thirumalai, one of the study’s collaborators at the University of Washington, said in an interview with Rewire.News that when it comes to side effects, there are different incentives at play for men and women.

“Pregnancy is in itself a health risk for women. So you could argue that women are trading one risk for another, and men are not.” Thirumalai believes, however, that if side effects can be minimized, this technology will be marketable to the public. “It’s nice to see the interest this is generating,” she said. “Because at the end of the day, for this to actually be used and be marketed, we need people to be interested in it.”

The study’s findings are especially encouraging for scientists like Dr. Christina Wang at UCLA and LA BioMed, one of the lead researchers for the DMAU trial. Wang has worked on male contraceptive development since the 1990s. “We are seeing progress,” she said. “Obviously you have progress, you have setbacks, you have progress. But we are excited.” The next steps with DMAU will be longer clinical trials, in which researchers will evaluate the drug’s effectiveness at suppressing sperm counts.

With enough financial support and successful subsequent trials, this product could hit the market in five to ten years, according to Thirumalai. DMAU is funded by the National Institute of Child Health and Human Development (NICHD), a government institution that supports a variety of research related to human health. That solid financial backing increases its chances of moving forward.

To reach the general public, however, it will need support from major pharmaceutical companies. “We want to stimulate the pharmaceutical industry because they are much more efficient than the government,” Wang said regarding funding. And for Big Pharma to back its development, popular interest will need to be evident.

Another project in development is the Nestorone-testosterone combination gel, a joint venture by the Population Council and the NICHD. Like DMAU, this method is hormonally based; it uses a synthetic progestin to signal the testes to stop producing sperm, combined with a testosterone replacement to minimize physical side effects. The gel is applied daily to the upper arms and shoulders. This fall, more than 400 couples will start human trials, committing to use the gel as their primary form of contraception for one full year. If successful, this will be a significant development in a field that has faced decades of slow momentum.

“It doesn’t require many sperm to produce a pregnancy,” said John Townsend, director of country strategy at the Population Council. “So making sure they’re eliminated is a very difficult biological task, whereas if there is a single ovum coming down once a month, there are many more options for interfering with that successful pregnancy.”

Townsend has spent decades working in the development and global supply of contraceptive products (he is not working on any of the methods in progress cited in this article), and he understands the scientific challenges inherent in developing a male pill. “It isn’t a clear market that the pharmaceutical industry is comfortable with. So one of the challenges we will have is: How do you get this stuff to people?”

Where Drug Companies Fear to Tread

The Population Council offices, tucked away in a research building at Rockefeller University on New York’s Upper East Side, bring to mind a cross between a mad scientist’s workshop and a high school chemistry lab. Gadgets and vials are stacked from floor to ceiling, and a walk through the rooms requires skilled maneuvering around refrigerators and filing cabinets. Narender Kumar, a senior scientist at the Center for Biological Research, is a soft-spoken man with kind eyes and a rapt dedication to his life’s passion: the study and development of new contraceptive methods.

Kumar has worked for 29 years at the Population Council, where he is the lead investigator on one of the older male contraceptive projects—a one-year arm implant called 7 alpha-methyl-19-nortestosterone (MENT) that releases a form of synthetic testosterone into the body. It has undergone several small human trials since its inception in 1986, but the loss of significant funding in the early 2000s slowed research progress.

“This was my baby,” Kumar said. “I started working on it at the beginning.” He spoke about the challenges of developing a completely new and reliable form of birth control. “There’s potential. We just have to come up with something great.”

In the early years of contraceptive development, scientists had fewer hoops to jump through to get new medications to human trials. Now the FDA requires an extensive combination of laboratory and animal experiments before testing can occur in humans. And any kind of clinical research requires an extensive financial commitment. The Population Council’s work is funded primarily by NICHD, but money is not plentiful, which explains why projects can take decades to come to fruition.

“We keep saying, five years, five years. I’ve stopped saying that,” Kumar remarked. “When somebody gives ten million dollars, we might make it closer.”

The money in birth control lives with big pharmaceutical companies, who draw huge profits from the sale of oral contraceptives and IUDs. In 2016, the U.S. market for hormonal methods topped $6 billion, and sales are on the rise across the world. Female methods provide a clear and growing revenue stream, but the potential success of male alternatives is more nebulous. “Male contraceptives won’t bring them money,” mused Kumar, further noting that new drugs carry the risk of lawsuits for the companies that sell them.

When users experience health scares, fertility issues, or birth defects in children, it can be difficult to prove whether the contraceptive is at fault. One notable example is the $100 million lawsuit in 2014 against NuvaRing, a hormonal contraceptive for women that has been linked to blood clots and heart attacks. Merck, the drug’s manufacturer, settled claims with more than 3,000 users who raised concerns. NuvaRing remains on the market, just with clearer warnings about potential dangerous side effects.

Representatives from Bayer, the pharma giant behind the Yaz pill and the Mirena, Kyleena and Skyla IUDs, told Rewire.News in a statement that the company has supported male contraceptive research in the past. Ultimately, it was suspended as the manufacturer focused on products “that would bring the greatest benefits to patients while ensuring the company was operating in a financially responsible manner.” Bayer has no plans to invest in male contraceptive research in the future.

However, some advocates believe there is interest among men who want a greater share in the responsibility of pregnancy prevention. “Couples are interested in making family planning a more equitable two-way process,” said Logan Nickels, director of operations and programs at the Male Contraception Initiative (MCI). “People want more options.” Based in Durham, North Carolina, the nonprofit promotes male contraceptive development through a combination of research grants and public education.

“I think that people knowing about them at all is one of the biggest hurdles,” Nickels said of the research projects currently under way. “I think people are really fixated on, ‘This is what we have and this is what the status quo has been.’”

According to MCI, its unpublished research suggests that more than half of men say they would be willing to use a new male contraceptive once it hits the market. That’s in line with other research that has concluded men aren’t hostile to the idea. And this likely wouldn’t discourage women from continuing to use their current methods.

“Most couples could use this to increase protection, to double up on methods and really protect themselves instead of swapping the contraceptive burden,” Nickels noted. “Once we establish a want, a demand, a need from the public, that kind of brings a mandate around it.”

MCI is focused primarily on supporting research into nonhormonal options, which Nickels believes will be more successful once they hit the market. These contraceptives would ideally have no side effects and begin to work in the body almost immediately.

One of these projects, the recipient of a $500,000 research grant from MCI in 2017, is a small company based in Bozeman, Montana, called Vibliome Therapeutics. Researchers have discovered a kinase inhibitor, a molecule that blocks a natural enzyme reaction, that shows potential for preventing sperm production. It has yet to be developed into a method of birth control, but the MCI grant will help the research through its pre-clinical phase.

“This is how getting a new male contraceptive to market must start,” said former MCI Executive Director Aaron Hamlin in a statement. “We have the patience and will continue offering support wherever we can.”

Robert Goodwin, chief executive officer of Vibliome, told Rewire.News that with any new contraceptive, the bar for success is set very high. “If you have a vaccine that’s 70 or 80 percent effective, you can prevent a lot of disease,” Goodwin said. “When you get into contraception, you want something that’s 100 percent effective and 100 percent safe. It is the highest bar of any potential drug to work on.”

This may be a factor in why Big Pharma has kept its distance. “That’s a big part of how drug companies look at investing resources,” Goodwin said, adding that taking on projects with a near-perfect success requirement can be risky.

Another reason that research has been slow-moving at best is that men and women see pregnancy risk through different lenses. Men, though they may bear financial responsibility for a child, rarely face the same social consequences from an unexpected pregnancy.

In terms of the market, contraceptives are one of the few areas of medical research that have focused primarily on the female body. “A lot more money and time has been invested in products for women,” said Townsend of the Population Council, “in much the same way that a lot of the work on therapeutics has been on men.”

In addition, few men are accustomed to dealing routinely with their reproductive health. They do not have specialized health-care providers to give them access to contraception, which adds an additional hurdle to drug distribution.

In Townsend’s mind, the solution likely lies in web-based physician networks. “Men could get on their cell phones, they could have an interview with somebody. They could pay the co-pay and get a prescription for this product.”

No matter which method hits the market first, advocates hope that talking more about male birth control will prompt a shift in public perspective. “It makes you think, ‘That’s what women have to deal with,’” one man said in an interview. “It makes me realize that I’m very willing for other people—women—to take care of this, and do things I don’t want to do because it might affect my body or my autonomy.”

But the “male pill” is still years away, reliant on scientific advances, funding, and the premise that today’s man will take a drug to suspend his fertility. It has a chance to radically alter the conversation around sexual health—yet its greatest challenge may be reaching the public at all.

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