“Gender’s Impact on Drug Research: The Importance of Consideration for Reproducible Results”

In the first trial, in which ketamine was effective against depression, the researcher was a man. In the second trial, in which the drug did not work, a woman.

If gender can determine whether a drug works or not, many more factors could play a role in research results. In the worst case, this can mean that doctors prescribe medicines that do not have the expected effect.

Selective with results

In 2011, a rapport of the major pharmaceutical company Bayer shocked the research world.

The company’s researchers scrutinized their own scientific publications on new drugs for cancer, among other things, over the past four years. The published results were compared with all the research results Bayer had obtained in numerous trials, but which had never been published.

It turned out that the published results only matched all available data in one third of the cases. Thus, in 65 percent of the articles, the Bayer researchers selected from their own research results the outcomes that suited them, while less favorable results were ignored.

The tendency to be selective about the results is called cherry picking, and according to a big one investigation from 2016, researchers see this as the main cause of the replication crisis.

In addition to cherry picking, poorly conducted research was also mentioned, for example not taking into account all known and unknown factors that could have an influence.

To make scientific research more reproducible and reliable, it is important to expose as many of these factors as possible so that researchers can take them into account.

That’s why it was a major breakthrough when Todd Gould determined in 2022 that the researchers’ sex can influence the behavior of lab mice.

Men’s sweat makes mice stressed

Gould had the mice sniff cotton pads rubbed over the wrists, or other areas of the skin that produce sweat, of men or women.

He then tested the stress level of the mice through behavioral experiments. For example, the mice were placed in a container with so much water that they could not reach the bottom.

Mice that had smelled women’s sweat soon realized they couldn’t escape and floated around passively.

But mice that had smelled man’s sweat kept swimming for a long time before giving up. That’s a classic sign of stress. After several analyses, Gould concluded that the smell of men causes mice to produce the stress hormone cortisol.

This hormone puts the animals on edge and makes them ready to fight or flee. The stress response to male researchers is likely because the mice instinctively see any male as a threat.

The discovery was not only surprising, Gould was also able to demonstrate that she had direct implications for drug research.

When he tested ketamine in mice, this drug had a clear antidepressant effect if the animals had smelled male researchers. But if they had smelled female researchers, there was no detectable effect.

The antidepressant effect was in fact the result of a complex interplay between the ketamine and the stress hormones released by the male fragrance.

Another trial 2022 study, which researchers at the University of Lethbridge in Canada conducted on rats, came to the same conclusion: the test animals reacted differently depending on whether the researchers were male or female.

Scientists have long been aware that they should test drugs on both sexes, because men and women can react differently. But now their own sex also appears to be a factor.

From now on, every research article will probably state whether the animals were handled by men or women. And if the animals respond to the researchers’ scent, there may be more factors influencing the results.

Consider, for example, the food the animals receive, the way in which they were transported or something as basic as the season.

Todd Gould doesn’t yet know whether stress hormones play the same role in ketamine’s action in humans as they do in mice. But whether or not he’s on the trail of a more effective antidepressant, his research has paved the way for better drugs.

When researchers take into account the importance of gender and other overlooked factors in drug research, new drugs are better tested before they reach the market and benefit patients more.