“The Pill” for Guys?

More than six decades after the U.S. Food and Drug Administration approved the first birth control pill for American women in 1960, work to create a male pill may finally be coming to a climax.

Clinical trials of male hormonal contraceptives began in the 1970s, but an oral pill has never reached market. Today, men have two choices for birth control: condoms (which are single use and have an 18 percent failure rate) or a vasectomy (which is not reliably reversible). These options account for only 30 percent of contraception used, leaving the remaining 70 percent of birth-control methods to women.

Many people decry the lack of contraceptive equality and responsibility. Yet, according to the National Institutes of Health (NIH), developing contraception for men versus women is not the same — and is, in part, a numbers game: Women typically release one mature egg a month, and a pill can focus on that monthly cycle.

“The challenge with creating new contraceptives for men is the high rate of sperm production. Men produce several million sperm per day — about 1,000 per second. To prevent pregnancy, all of these need to be stopped from reaching an egg,” notes the NIH.

“The challenge with creating new contraceptives for men is the high rate of sperm production. Men produce several million sperm per day — about 1,000 per second. To prevent pregnancy, all of these need to be stopped from reaching an egg.”

In the 2010s, a male hormonal contraceptive seemed to be looming on the horizon at long last. As part of a clinical trial with backing from the World Health Organization, the procedure used injections every two months to reduce testosterone production and sperm count. It tested 96 percent effective in preventing pregnancy.

But during phase II, study participants reported myriad side effects, including acne, weight gain, and myalgia (muscle pain or tenderness), as well as depression and other mood disorders — side effects hauntingly similar to those connected with the pill for females. The trial was halted by an independent review board.

Now, trials of a new, nonhormonal male birth control pill are underway. In March 2022, the research groups of the University of Minnesota’s Gunda Georg, PhD, and Columbia University’s Debra Wolgemuth, PhD, unveiled a pill that has proven 99 percent effective in preventing pregnancy in mice; follow-up studies showed a similar efficacy in monkeys.

The contraceptive targets a protein (retinoid acid receptor alpha) that receives vitamin A, which is involved in sperm production and fertility, and no side effects have been reported in the animal studies. The pill, now called YCT529, has been licensed to the company YourChoice Therapeutics; it’s currently awaiting approval for clinical trials.

Other types of male contraception are also under development, including the following.

⋅ sAC inhibitor is an on-demand pill that “a man would take . . . shortly before sex, only as needed,” say developers Jochen Buck, MD, PhD, and Lonny R. Levin, PhD, at New York City’s Weill Cornell Medicine. The pill is based on a compound called TDI-11861 that inhibits soluble adenylyl cyclase (sAC), which is essential for sperm motility and maturation.

The pill would make men temporarily infertile; full fertility returns the next day. As of February 2023, the NIH-funded research needed more work before starting human trials.

⋅ NES/T is a gel applied to the back and shoulders and absorbed through the skin. It contains the progestin Nestorone, which suppresses sperm creation. The Nestorone/testosterone gel, funded by the NIH, is undergoing clinical trials at the Lundquist Institute at Harbor-UCLA Medical Center. The gel was developed by the Population Council research group and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

⋅ ADAM is “like the IUD, for men,” explains developing biotech company Contraline. A hydrogel is injected by needle into the vas deferens to block sperm; the sperm is then reabsorbed into the body. One injection is believed to maintain infertility for a year, after which the hydrogel liquifies and the barrier dissolves. Trials are currently underway in Australia.

⋅ RISUG is an acronym for Reversible Inhibition of Sperm Under Guidance and has been compared with a reversible vasectomy. RISUG is a copolymer of styrene and maleic anhydride that is injected into the vas deferens to block sperm. (It’s also being studied as a female contraceptive injected into the fallopian tubes.) The polymer can be flushed out to reverse the contraception. Phase III trials are currently under way in India.

⋅ IVD stands for Intra Vas Device; it’s also known as the Shug, a nickname for the silicone plugs that are surgically inserted into the vas deferens to dam sperm, which is then reabsorbed into the body.

⋅ Contraceptive vaccines (CVs), or immunocontraceptives, have so far only been tested on animals; the vaccines induce an adaptive immune response that cause the animals to become temporarily infertile. A CV is currently under development in India.

⋅ Nonhormonal pills of different types continue to be studied. At the University of Minnesota, Georg is experimenting with a contraceptive based on ouabain (pronounced wa-bay-in), a plant extract that has been used as both a poisonous dart in some parts of Africa and as a treatment for congestive heart failure.

⋅ Hormonal pills are still being researched despite failed tests. Current pills under development include dimethandrolone undecanoate (DMAU, a.k.a. CDB-4521) and 11β-methyl-19-nortestosterone (11β-MNT). Both are experimental progestogen medications that suppress testosterone, which in turn lowers sperm production. Still, as with the halted pill trials, DMAU has triggered some problematic side effects, including lowering levels of “good” HDL cholesterol, which is key to cardiovascular health.

One question remains: Will men take the pill?

Several studies say yes. A 2022 British survey reported that 58 percent of male respondents would consider using a contraceptive pill. And a 2019 survey by the U.S. Male Contraceptive Initiative found that 85 percent of participants want to prevent their partner from becoming pregnant, and 60 percent of those men said that taking responsibility for birth control is the primary reason they would like a new male option for contraception.