Behind the scenes: Creating a hormone-free male birth control pill

Around the world, roughly 121 million unintended pregnancies occurred each year between 2015 and 2019. Of those unintended pregnancies, about 61 percent—or 73 million—ended in abortion each year.

“In the United States and other continents, it’s the same,” says Gunda Georg, a Regents Professor in the College of Pharmacy. “Women are mostly responsible for birth control. Men have only condoms and vasectomies, which are hard to reverse.”

But after 10 years of research, Georg and her team at the Institute for Therapeutics Discovery & Development have produced a non-hormonal birth control pill for men that is now undergoing a second round of clinical tests. Its performance so far makes it a leading candidate to reduce unplanned pregnancies and their consequences. 

The non-hormonal nature of the new drug, called YCT-529, is key. 

“There are side effects with hormones,” Georg explains. “For example, heart problems, weight gain, and low libido.” She notes that people will tolerate side effects in order to get rid of a disease, but “tolerance is low when it’s about something like fertility, which isn’t a disease.”

Inventing a new drug from scratch

Georg, who received bachelor’s and doctoral degrees from Philipps University in Marburg, Germany, says she was intrigued by drugs like morphine and penicillin.

“The female birth control pill was approved by the FDA in 1960, and also drugs for high blood pressure and high blood cholesterol, and deaths from cardiovascular disease plummeted,” she says. “I wanted to be part of this revolution. I was intrigued by the female pill—that was really important. 

“I got a PhD so I could make drugs. Designing molecules, making and testing them—it’s exciting to do that.” 

She began the work leading to YCT-529 by noting that sperm production depends on the activity of one gene. This gene is activated in cells within the testes by contact with a particular protein molecule. But this interaction will only occur if the protein first binds to a molecule of retinoic acid, a vitamin A derivative.

In other words, the protein must be “loaded” with retinoic acid before it can seek out the gene and activate it. Georg decided to throw a molecular monkey wrench into the process. 

Her strategy was to build a new “decoy” molecule, similar to retinoic acid, that could bind to the protein so well that it could replace retinoic acid. But when loaded with the decoy, the protein would be unable to activate the gene. 

If this sounds like a tall order, it was.

“We made lots of drug designs that failed—around 400 molecules,” Georg recalls. “We tested several at a time and used computers to model their behavior. We tended to test the designs that looked good on the computer. 

“We made YCT-529 in 2015 and saw its potential in 2018.” 

A short history of YCT-529 trials

The Georg team’s research leading to YCT-529 was supported by the National Institutes of Health. In 2021, the University of Minnesota filed a patent application and licensed the technology to YourChoice Therapeutics, a San Francisco Bay Area biotech company.

YourChoice has supported trials of the drug, whose costs far outweigh what a university can afford. Studies with mice and nonhuman primates indicated the drug was safe, effective, and reversible.

The company has also sponsored two human trials. In the first, done in Great Britain, vasectomized men took YCT-529 in a test of its safety. No ill effects were found. The second trial, in New Zealand, began in September 2024 and will conclude on January 28, 2026. 

“These men are scheduled for vasectomy or don’t want children, so they are motivated,” Georg notes. The men receive doses from 15 to 180 milligrams of the drug, which the researchers hope will lower sperm counts. "We expect that men on the higher doses will have more significant sperm reduction," she says.

“In order to be effective, the sperm count has to be lower than one million per milliliter,” Georg adds. “The normal number is 60 million to 600 million sperm, in an average man’s volume of about four milliliters.”

So many sperm are necessary because only one in 10 million sperm reaches the woman’s fallopian tube, where fertilization occurs.

“If [the New Zealand trial] works, there will be other clinical trials with larger numbers,” Georg says. “Eventually, you’ll have to have a real-life trial with only the pill. [If that happens soon enough,] the pill could be on the market in five years—it’s now mostly a matter of money to pay for additional clinical trials.”

But to market and distribute a drug like YCT-529, “a larger company has to take over. That will be a challenge because none is working in this area.” 

Today, Georg hopes that if YCT-529 can clear hurdles like securing FDA approval and finding a manufacturer, it will be affordable. 

With all this work and uncertainty, what would she say to a young person considering a career in drug development?

“It’s a wonderful profession,” she instantly replies. “A wonderful job.”

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Interested in a career in drug development? Explore the University of Minnesota College of Pharmacy programs.

Read a previous story about tests of YCT-529 with nonhuman animals.