The Male Pill

An oral contraceptive for men is ready for testing in human clinical trials

| 25 Mar 2022 | 02:25

In the 62 years since The Pill appeared, it has been a resounding success at giving women a way to control fertility. By producing a simulated three week “pregnancy” followed by one week’s “breakthrough bleeding that imitates rue menstrual cycle, the oral contraceptive prevents the ovaries from producing and releasing a mature egg. The original pill came with a serious risk of side effects documented in Barbara Seaman’s classic 1969 book, “The Doctor’s Case Against the Pill.” Happily, time, experience and recalibrating the ingredients have reduced although not completely eliminated these problems while providing women virtually 99+% effective protection against unwanted pregnancy, when used precisely as prescribed – no skipped day allowed.

Men have not been so lucky, although not for lack of trying. The first possibilities considered were, naturally, hormone pills to block sperm production or reduce motility, the sperm’s ability to swim to meet the egg. But testosterone not only governs fertility; it also rules performance, so an interfering contraceptive was not an acceptable tradeoff.

That left researchers aiming for non-hormonal alternatives, an interesting path to follow. Back in the 1950s, even before the female pill hit the market, they discovered that a drug originally proposed to control parasite worms actually reduced sperm counts in lab mice with no side effects. Best of all, sperm production went back to normal when the drug stopped. As mice are male but not men, the researchers decided to test it on prisoners, an isolated easy-to-observe population. In just three months, sperm counts dropped, the men were fine, and when the drug stopped, as with the mice, sperm counts returned to normal.

Which seemed perfect until one prisoner somehow got his hands on some smuggled adult beverage, drank it down and slipped into serious stupor because the ingredient in the drug that shut down sperm production also shut down his liver. Which sent male contraception back to where it has stubbornly remained: condoms, vasectomy, and interrupted sex or none at all.

Non-Hormonal Approach

That may be about to change. Last week, at the spring meeting of the American Chemical Society, Abdullah Al Noman and Gunda Georg, from the Department of Medical Chemistry at the University of Minnesota, announced a possible new non-hormonal approach – based on that alcohol-unfriendly pill from the 1950s.

Our bodies hold an enzyme called ALDH which converts the Vitamin A in food into retinoic acid, a compound vital for turning immature sperm cells in the testes into the mature ones that can meet and fertilize an egg. Unlike that earlier pill, which apparently hit the three proteins that make retinoic acid effective, the Minnesota men aimed to disable one specific protein called retinoic acid receptor alpha (RAR-α) which locks onto ALDH and prevents it from making retinoic acid. That means both no new mature ones for male mice reversibly sterile without any obvious side effects.

As you read this, the newest attempt at a non-hormonal male pill is ready for testing in human clinical trials scheduled to start around or after July. With fingers crossed. As Dr. Georg explains, “Because it can be difficult to predict if a compound that looks good in animal studies will also pan out in human trials, we’re currently exploring other compounds, as well.”

Stay tuned. The fate of that date Martini may hang in the balance.

Carol Ann Rinzler is the author of the award-winning “Estrogen & Breast Cancer: A Warning to Women?”