EXECUTIVE SUMMARY
Researchers across the world are studying hormonal and nonhormonal male contraceptive products in hopes of being the first to bring a new, reversible contraceptive for men to market within the next 10 to 20 years.
- Funding and finding the right administration are two of the biggest challenges in bringing a male contraceptive to market.
- The Male Contraceptive Initiative in Durham, NC, is a major funder of nonhormonal male contraceptive research, providing around $3 million in grants since 2017.
- Societal changes regarding gender dynamics and male participation in family planning have contributed to changes in how people think about gender responsibility, which makes a male contraceptive a more appealing prospect than it was several decades ago.
The persistent joke among male contraceptive researchers is that a male contraceptive has been 10 years away for the last 50 years.
There have been exciting leads and thudding dead-ends since the 1970s. But contraceptive researchers and experts tell Contraceptive Technology Update that the end goal may finally be in sight.
“This is the analogy of eating an elephant one bite at a time,” says Logan Nickels, PhD, research director with Male Contraceptive Initiative in Durham, NC. “A core group of people have been working on this one for decades. Multiple candidates come to surface, and we’re hopeful we’ll see multiple products come to the market with diverse characteristics.”
The groundwork is ready for a hormonal contraceptive method to emerge over the next decade.1 “Some of the data look good,” says Daniel S. Johnston, PhD, chief of the Contraception Research Branch at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, MD.
The big question is whether researchers will find an adequately safe method. “I’m confident they’ll get efficacy,” Johnston says. “I’m optimistic. I think we have spent a lot of time working on hormonal contraceptives.” He also is hopeful there will be nonhormonal methods within two decades.
The male contraceptive technology field is much more enticing today than it was a decade ago, says Anita L. Nelson, MD, professor and chair of obstetrics and gynecology at Western University of Health Sciences in Pomona, CA. Some exciting progress has occurred in Phase II trials, but some obstacles remain.
“I wouldn’t be surprised if something happened, but also wouldn’t be surprised with slow progress,” Nelson adds.
Administration, Funding Are Issues
The main difficulty of developing a male contraceptive is the challenge of finding the right administration, says Brian T. Nguyen, MD, MSc, assistant program director in the section of family planning and assistant professor in the department of obstetrics and gynecology at Keck School of Medicine at the University of Southern California.
Funding also is a major issue. Most research into male contraceptives comes from federal funding. “No pharmaceutical company is funding production of these drugs,” he says.
The problem related to funding is that it has been episodic. “It will get moving in a direction, and then get cut off,” Nelson laments. “This is an important social issue because there are women you can’t just give an effective contraceptive to, and they don’t want to get pregnant.”
The Male Contraceptive Initiative has been granted more than $3 million for nonhormonal male contraceptive research since receiving its first grant in 2017, says Heather Vahdat, MPH, executive director.
“The contraceptive space is a small space, and the number of people funding in the space is limited,” Vahdat says.
The total funding for male, nonhormonal, reversible contraception research and development was $3.2 million in 2018. The Male Contraceptive Initiative was a main funder, along with the National Institutes of Health (NIH). The organization funds fellowships, seed grants, and vas occlusion research grants. (More information is available at: https://www.malecontraceptive.org/history.html.)
“We are a small fish,” Nickels says. “We’re doing everything we can in terms of an advocacy angle to increase awareness and bring male contraceptives to the forefront of the conversation. The time is right.”
Gender Dynamics Are Changing
Massive societal changes in terms of gender dynamics and male participation in family planning have contributed to changes in how people think of gender responsibility. “People are finally asking the questions of ‘Why is that?’ and ‘Why has it always been that way?’” Nickels explains. “Men want to help their partners in family planning, or they might think, ‘I’m an autonomous man, and I’m not finding the options out there to fit my needs.’”
Men are limited to just two contraceptive options, neither of which is as convenient as a pill, patch, or injection: Condoms or vasectomy. Other than those, they could use the withdrawal method. “Men want something like an IUD for men, which is effective, but reversible,” Nelson explains.
“My hypothesis is there needs to be a huge culture change where men are demanding it and wanting to take it,” Nguyen adds.
Men have control over much of the pharmaceutical company leadership. Until they recognize their role in preventing unplanned pregnancy, they will prioritize women taking drugs and implants before they focus on men, Nguyen explains.
Men absolutely would like some control over contraception, says Susan Wysocki, WHNP, FAANP, medical director for the Partnership for Male Youths (PMY) in Washington, DC, a not-for-profit organization that focuses on medical issues for males.
“What I hear from guys is ‘What if I don’t know that my partner has been inconsistent with contraception?’” Wysocki says. “Pregnancy potentially throws a wrench in their own personal plans. Men want to have a method that works for them, and that they have some control over potentially becoming a father.” Women also would welcome male contraception so they can ask their male partners to take turns with the responsibility of preventing pregnancy, Wysocki adds.
“We’re not providing an effective range of options for half the population of the world,” Vahdat says. “It’s frustrating to think that one of the challenges is the chicken and the egg [conundrum]. You’ve got people who want to demonstrate the demand, but you can’t do that with the existing products, and anything else you are doing is speculative work.”
Scientists working in the male contraceptive field have endured decades of disappointments. “I hope the [current male contraceptive projects] are successful, and we’re not far from a male contraceptive. We’ve been there before, and they tend to fail at the late stage,” Johnston says.
Over the years, researchers and clinicians have dramatically reduced hormones in the female contraceptive pill. They also created contraceptive rings and patches, Johnston notes.
“But with men, we haven’t found that window between where something is effective and where it is safe,” he adds. “The first goal is safety, and we have to have both safety and efficacy. A lot of male products fail because if they’re safe, they’re not effective — or if they’re effective, they’re not safe.”
After 40 years of research and more than 30 clinical trials, there hopefully will be a breakthrough in male contraceptive research, Johnston says.
Nearly two decades into their research involving the male reproductive tract, a pair of researchers from Weill Cornell Medicine in New York City had an epiphany moment. “The enzyme we worked on was known to make sperm inactive if inhibited in a certain way,” says Lonny Levin, PhD. “We’ve known that for 17 years.”
Initially, the researchers were developing inhibitors for this enzyme — but not for contraception, says Jochen Buck, MD, PhD, professor at Weill Cornell.
When they injected the inhibitor into a male mouse, sperm could not be activated for six hours. The next day, the sperm were normal again, Buck explains.
“Essentially, 30 minutes after it’s given, sperm doesn’t work anymore,” he adds. “The next day, it’s working again.”
They developed the inhibitors as research tools, Levin says. (See story about a possible new, nonhormonal contraceptive in this issue.)
Robert A. Hatcher, MD, chairman of the Contraceptive Technology Update editorial board, agrees with the male contraceptive researchers who suggest that male contraceptives have been 10 years away for the last 50 years. He suggests that “it will be significantly more than 10 years before a hormonal or nonhormonal method for men that would be highly effective will be available in this country.”
REFERENCE
- Gava G, Meriggiola MC. Update on male hormonal contraception. Ther Adv Endocrinol Metab 2019;10:2042018819834846.
