Minnesota mice made news recently when researchers at the University of Minnesota shared promising findings from animal trials of a novel non hormonal oral contraceptive billed as “the Pill for men.” According to the researchers, the pill was “99% effective in preventing pregnancy, without any observable side effects” and furthermore, its effects were reversible within 4-6 weeks of discontinuing the drug. But will the pill work in humans?
Even though every few years there’s media buzz about one or more potentially forthcoming innovative male contraceptive(s), decades’ worth of experiments have amounted to exactly nothing new on the market to date, leaving, so far as most men know, the same-old, same-old options of vasectomies or condoms. The former, of course, are not easily reversible, and can have serious side effects, and the latter are single-use and less effective than most female contraceptives.
Why is it so difficult to develop effective, reversible male contraceptives? What options are currently being studied, and what are the pros and cons of each? Here we’ll explore the answers to all the above, and, most importantly, highlight a holistic option for family planning that’s built on a couple’s shared responsibility for the gift of their fertility.
Why is it so difficult to develop effective, reversible male contraceptives?
There are several reasons effective, reversible male contraceptives don’t already exist. The first reason is biological. Whereas female contraceptives seek to prevent a once-a-cycle event (ovulation), male contraceptives have to continually inhibit the production of, or otherwise render ineffective, millions of sperm at a time, with millions more being produced every day.
Double standards concerning side effects
Another reason male contraception hasn’t meaningfully materialized is due to a disconcerting double standard when it comes to acceptable side effects of birth control for men vs. women. Hormonal birth control comes with a whole host of side effects regardless of whether its consumers are male or female, but, as Natural Womanhood previously noted, tolerance for side effects in men has been notoriously low. As an example, one 2016 male hormonal contraceptive study was terminated early by an external safety review committee due to “acne, injection site pain, increased libido, and mood disorders” in the (all male) study subjects.
In contrast, a few women enrolled in the Puerto Rican trials for the original birth control pill (Enovid) died, and yet the trial continued, and the Pill was approved by the FDA a few years later. Sadly, over 60 years later, nothing has changed; as recently as 2020, pharmaceutical giant Bayer was made to pay out $1.6 billion to settle 39,000 lawsuits alleging harm due to Essure, its now-defunct permanent birth control device.
In an interview with The Washington Post, Heather Vahdat, executive director of the Male Contraceptive Institute (MCI), summarized the reasons effective, reversible male contraceptives do not exist, citing “limited funding, lengthy regulatory procedures, biological challenges and societal issues such as the long-standing belief that the people who can get pregnant should bear the responsibility for preventing pregnancies.” University of Minnesota graduate student Md Abdullah al-Noman, who presented the research team’s findings from the mice trials mentioned above, underscored Vahdat’s last point, opining bluntly that “since men do not have to suffer the consequences of pregnancy, the threshold for side effects from birth control pills is rather low.”
Male birth control pills and contraceptive gels: The latest birth control options being studied for men
MCI keeps a running tally of ongoing research into various forms of male contraception, mostly funded by the Eunice Kennedy Shriver National Institute of Child and Health Development. Here we’ll cover the three male contraceptives garnering the most media attention in recent months.
The Pill for men
In March 2022, researchers at the University of Minnesota presented their findings from animal trials of a reversible non hormonal oral contraceptive at the American Chemical Society spring meeting. The pill specifically inhibits the action of Vitamin A, which is vital for sperm production. Md Abdullah al-Noman explained, “men produce around 1,500 sperm per heartbeat. This massive production of sperm needs vitamin A in different stages. But we need vitamin A for many essential physiological processes as well. So, we specifically blocked the action of vitamin A in such a way that it (YCT529) reduces sperm production without interfering with other functions of vitamin A to preclude side effects.”
According to the U of M press release, “When given orally to male mice for 4 weeks, YCT529 dramatically reduced sperm counts and was 99% effective in preventing pregnancy, without any observable side effects. The mice could father pups again 4-6 weeks after they stopped receiving the compound.”
In an interview with Medical News Today, al-Noman acknowledged that researchers have no idea whether the resounding success in mice will translate to human subjects. He commented, “it’s hard to predict how the human clinical trial will go since that’s the most significant barrier for a drug candidate to prove its safety and efficacy. We licensed this candidate to YourChoice Therapeutics, and they are planning to take it to clinical trial by the end of this year.”
NES/T contraceptive gel
The National Institutes of Health (NIH) is funding research on a reversible hormonal contraceptive gel called NES/T. NES/T has two active ingredients: Nestorone (the NES in NES/T), a synthetic form of progesterone, and Testosterone (the T in NES/T). The synthetic progesterone blocks the body’s own production of testosterone, and the supplemental testosterone replaces what the body isn’t making in order to reduce the side effects (think weight gain, depression, and high cholesterol) that would otherwise occur due to low testosterone.
Currently, NES/T is in Phase II testing, which began in 2018 and is expected to wrap up in 2023 at 15 sites in the United States and abroad. A Phase III trial will presumably follow, with an expected duration of 5 years. Researchers told Cosmo that the gel, applied once daily to the shoulders and upper arms, is perhaps 10 years from becoming commercially available.
One potential barrier to widespread uptake is the lengthy time for total absorption of the gel into the user’s skin. Participants in the Phase II trial have to wait four hours every single day after application before their bare shoulders can touch anyone else’s skin.
The primary proof of the gel’s effectiveness is the complete absence of unintended pregnancies amongst trial participants to date, and the secondary proof is measurably low sperm counts. And despite what Vahdat (of MCI) called the “biological challenge” of dramatically reducing sperm counts via medication, NES/T researcher Dr. Brian Nguyen reassured The Los Angeles Times that the goal isn’t to get sperm counts to zero.
He commented, “Your normal semen contains about 40 million to 300 million sperm per milliliter, which is huge, right? And if you ask yourself, why evolutionarily does a man need that much sperm per milliliter of semen in order to impregnate women?…The process of getting that sperm and egg is extremely perilous. So even at 10 [million] to 20 million, you’re expecting this man is going to have difficulty achieving a pregnancy.”
But while the researchers celebrated the lack of unintended pregnancies in particular, it’s difficult to say just how generalizable these results would be in the real world since the study required just one act of sexual intercourse without a condom or other barrier method each month.
ADAM implanted contraceptive hydrogel
Researchers are calling a non hormonal, implanted male contraceptive hydrogel named ADAM the “IUD for men,” and say it’s “the first major development in male contraception since the vasectomy.” Like IUDs and other forms of long-acting reversible contraception (LARC), ADAM is intended to be a set-it-and-forget-it contraceptive. Normally, when a man is sexually aroused, sperm travels from the testes through the vas deferens for ejaculation from the urethra. But the implanted ADAM gel effectively blocks the way, preventing sperm’s exit from the vas deferens.
Keven Eisenfrats, co-founder and CEO of Contraline, the medical device company that invented ADAM, noted in a video interview with MCI that ADAM lasts reliably for several years, after which time it “degrades” or liquefies on its own. ADAM is explained in greater detail here. Eisenfrats acknowledged that a similar concept has been unsuccessfully tested in India, Indonesia, and China in decades past. Without going into detail, Eisenfrats insisted that Contraline’s approach takes the problems observed in previous research on occlusive gels and seeks to solve them “from scratch.” While IUDs can be physically removed in a doctor’s office, Eisenfrats did not describe how the ADAM gel could be removed for contraceptive reversibility. Eisenfrats told The Washington Post that some 2,000 men have “expressed interest” in participating in a clinical trial.
Towards a more equitable future: shared responsibility for family planning
A Medical News Today article on the University of Minnesota mice research quoted the British Pregnancy Advisory Service saying, “This isn’t just a question of benefits for men—it’s a matter of working toward ensuring that fertility and contraception are a shared burden and that women are no longer expected to spend the bulk of their fertile years avoiding pregnancy without an active contribution from their partners.”
While ADAM and NES/T and the Vitamin A inhibitor (YCT529) are just the latest iterations of maybe-someday-effective reversible male contraceptives, couples who use evidence-based fertility awareness methods are already utilizing the science of male and female fertility to responsibly plan their families without side effects. Rather than suppressing his or her fertility, couples work with their bodies’ natural design to achieve or avoid pregnancy. These couples understand that fertility is a shared gift and responsibility and furthermore a sign of health in both persons.