Frequently ignored in research

In the Netherlands, 60% of all women aged between 18 and 25 use a contraceptive pill. And most research participants at universities belong to that age group. Consequently, use of oral contraceptives may influence research findings, because the pill affects not only biological, but also psychological processes. We discovered coincidentally that the pill influences the recognition of emotions.

Impaired emotion recognition in pill users

In 2013, we set up a clinical trial to investigate the potential antidepressant effects of a steroid in healthy female volunteers. Participants received a single dose of this steroid or a placebo pill. Two hours later they completed an emotion recognition task. In this task, facial expressions of anger, disgust, fear, happiness, or sadness were presented at different intensities. As soon as the participant recognized the expression, she had to push the corresponding button as quickly as possible. The facial expression recognition task was of relevance for our study because it is sensitive to antidepressant medications, even at single doses in healthy volunteers. We did not observe the expected antidepressant effect of ‘our’ steroid in our study. But we did find that pill users, compared to naturally cycling women, recognized fewer expressions of emotions.

What happened next?

Intrigued by this observation, we undertook a series of studies in which we controlled for type of oral contraceptive used, menstrual cycle phase of the control group, and active or inactive pill use. Interestingly, women with a genetic predisposition to be more optimistic seemed to be less sensitive to the influence of the pill on emotion cognition. And we observed again that pill users tended to recognize fewer facial expressions of emotion. What does this mean? Do birth-control pills flatten affect variability, or sensitivity to mood? Or are we talking about a baseline difference between naturally cycling women and pill users? These and other questions need to be elucidated in future studies.

Influence of pill use is underinvestigated

More than 100 million women worldwide use the pill. It prevents pregnancy by suppressing natural hormonal fluctuations during the menstrual cycle. The influence of the menstrual cycle on brain activity, behavior, and mood has been widely investigated. Women taking the pill are often excluded from studies, or – more alarmingly – pill use is ignored. Therefore, it is of both scientific and societal relevance to investigate how the contraceptive pill affects mood, behavior, electrophysiology, and brain activity.

Tips and tricks for pill research

Firstly, researchers should check the current literature to assess whether use of oral contraceptives is likely to confound the outcomes of their study. Next, registration of contraceptive use in research participants is a good start. If researchers want to collect more precise data on use of oral contraceptives, they should register not only the duration of use, but also the exact pill composition. They might decide to include only one pill type in their study, because different types of pill may differ in how they influence mood, behavior, and physiology. Finally, researchers should decide whether to test participants in their pill-free week and/or during active pill use.

Loss of research accuracy

Even if researchers are not interested in the birth-control pill as a phenomenon, they should always control for pill use. Why? Researchers should avoid collecting data that are confounded by unknown variables, which may result in a loss of research accuracy.