We Have Questions: A Male Contraceptive Pill

Since the creation of female hormonal birth control—better known as "the pill"—in 1950, people have often wondered, "Why isn't there a birth control pill for men?"

Researchers at the University of Minnesota pondered the same question. Now they're inching closer to making the seemingly elusive male contraceptive pill a reality.

Currently, birth control options for men are pretty much condoms and vasectomies. Condoms can only be used once and may break, rendering the whole point moot, whereas vasectomies are close to permanent. Yes, the procedure can be reversed, but it's expensive and doesn't always work.

"The pill" for men—especially a nonhormonal one—would be a game changer.

Md Abdullah al Noman is a graduate student at the University of Minnesota working with Gunda Georg, Ph.D., a regents professor in the medicinal chemistry department at UM. In an email interview, Noman, a researcher on the project, explained why now may be the right time for a male contraceptive pill, how it would work, why the nonhormonal aspect is important and how soon the pill could be available.

Editor's note: This interview has been lightly edited for clarity.

Why is a male birth control pill a realistic possibility now? And why is it so important that it's nonhormonal?

Noman: There has been a longstanding effort to develop a male birth control pill since the discovery of the first female birth control pill. Most female contraceptives target sex hormones such as estrogen and progesterone. Efforts have been made to develop male birth control pills by targeting the male sex hormone testosterone. But that leads to side effects, such as weight gain, depression, increased levels of LDL [low-density lipoprotein, or "bad" cholesterol], etcetera.

Since contraceptives are not for curing diseases, the threshold for side effects is rather low. This is a big barrier to developing a male contraceptive. That's why we are trying to develop nonhormonal birth control pills to avoid hormonal side effects.

The strategies for developing hormonal male birth control are few, but recent advances in reproductive biology identified many—more than 1,000—nonhormonal targets for developing male birth control methods. This offers opportunities to find a drug candidate with sufficient safety and efficacy.

In your opinion, why haven't male contraceptive options outside of condoms and vasectomies been available yet?

There have been many clinical trials for male contraceptives; some are still ongoing. The most challenging part of any drug discovery is finding a candidate with good efficacy and safety. We are yet to find a candidate with good efficacy and safety in clinical trials. Typically, for other drug classes, such as anticancer or antidiabetic drugs, there have been concerted efforts from many pharmaceutical companies that lead to clinical trial candidates, and from those, a few successful drugs emerged. Aside from a few past projects, no such effort has been made by Big Pharma to find a male pill.

How would this pill work? What have the results shown during testing?

Men produce about 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 reduces sperm production without interfering with other functions of vitamin A, to preclude side effects. Our current male contraceptive candidate significantly reduced sperm count in mice and nonhuman primates, and was able to prevent 99 percent of pregnancies in mice. This all happened without any observable side effects. We also saw contraceptive effects of this compound in dogs and nonhuman primates. This is a very promising result and the most advanced nonhormonal pill candidate so far.

Our current male contraceptive candidate significantly reduced sperm count in mice and nonhuman primates, and was able to prevent 99 percent of pregnancies in mice.

The molecular target for our candidate is retinoic acid receptor alpha (RAR-α), and our goal is to inhibit the function of RAR-α without interfering with the function of two close proteins, RAR-β and RAR-γ.

If a couple decided to get pregnant, would the male simply stop taking this pill, similar to how a female would stop taking hers?

There would be a waiting time for men to be fertile after stopping the pill. For mice, it's four to six weeks. But for humans, it could be different, and that needs to be figured out in the clinical trial.

Is there a timeline for when this pill might be available to the public?

It's hard to tell because we don't know how long the clinical trial will take. We licensed this candidate to YourChoice Therapeutic and they are planning to take it to clinical trial by the end of this year [2022]. If everything goes well and the drug shows safety and efficacy in the clinical trial, it'd be safe to assume we could see this on the market within the decade, and perhaps as early as five years from now.

In a general, societal sense, what might be the impact of a male birth control pill as another contraceptive option?

Nearly half of the pregnancies in the United States are unplanned, and it leads to poor outcomes in child development and physical and mental health of the mother and the child. A new nonhormonal male birth control pill could reduce the number of unintended pregnancies. Also, it could lessen the burden on women for contraception and it could give men autonomy over their reproductive choice.