The influence of the hormone progesterone on mood is well known. Now researchers from the University of Barcelona have shown how higher levels of progesterone during the menstrual cycle are linked to less distinct patterns of activity in areas of the brain involved in controlling emotions.
The study, in Psychological Medicine published by Cambridge University Press, explored how natural levels of the ovarian hormones estradiol and progesterone influence parts of the brain involved in emotion control, and whether this could help explain differences in mood.
Emotion control is the ability to regulate behavior in response to emotional information, particularly when automatic emotional responses need to be overridden. For example, if someone needed to ask an unfriendly person for help, their instinct might be to avoid them – emotion control would help overcome that impulse and approach them anyway.
Analysis of MRI scan data from study participants revealed that when progesterone levels were higher, there was a less clear distinction between ‘easy’ and ‘difficult’ emotional situations in the brain scans. This suggests that the brain would be less able to distinguish between different emotional situations in real life.
In contrast, participants whose brain scans had a clearer distinction between ‘easy’ and ‘difficult’ emotional situations tended to report better mood in the preceding week.
This brain mechanism accounted for roughly 7% of the variation in mood scores.
Dr Macià Buades-Rotger, lead author of the study from the University of Barcelona, said:
“In our study we found that higher progesterone levels were linked to brain activity patterns that made it harder to tell different emotion control situations apart, which also corresponded with lower mood in participants.
“This suggests that if the brain can tell different emotional situations apart more clearly, it may be better at regulating emotion in daily life.
“While we can’t establish cause and effect from a one-time measurement, it’s exciting because we know something about progesterone that we didn’t know before.”
For the study, 116 naturally cycling women (not using hormonal contraception) completed questionnaires about their mood and period stage, and gave a saliva sample to measure their hormone levels.
They then underwent an MRI scan while conducting a psychological task that stimulated an ‘easy’ or ‘difficult’ emotional response. For the task, they were shown a happy face or an angry face and asked to react naturally (to approach the happy face and avoid the angry face) or counter intuitively (avoid the happy face and approach the angry face). All participants experienced the four different scenarios in the task.
Machine learning analysis of brain activity patterns found that it was possible to tell whether an ‘easy’ or ‘difficult’ emotional response was being elicited from the participant at that moment in time.
But when progesterone levels were higher, the patterns in one area of the brain called the lateral frontal pole were more similar to one another, suggesting that the brain was less able to differentiate between the ‘easy’ and ‘difficult’ task demands.
Professor Ulrike Krämer, an expert in neuroendocrinology from the University of Lübeck, who wasn’t involved in the study, said:
“The findings of this study provide valuable new information about how progesterone influences brain activity in women.
“From a clinical perspective, we know that some women may be more sensitive to progesterone than others, perhaps because their brains have more progesterone receptors. These new findings could help us move towards more personalised approaches to assessing and treating hormone-related mood problems, such as premenstrual dysphoria.
“On a practical level, this could also help women to better understand how hormones affect their own experience and behavior. Some women may feel as if they are responsible for their low mood at certain times of the month, for example, when actually we’re talking about changes to brain chemistry that are outside of their control. I think knowing this may help women to be kinder to themselves when they’re not feeling great.
“In popular culture there’s a misconception that women are the only ones whose emotions are affected by hormones, which is not the case. This is one area of medicine where we actually know less about men’s health than we do about women’s. So it will also be important for future studies to test whether this link between hormones and emotion control exists in men as well.”
Surprisingly, the researchers found no equivalent effect for estradiol, another major ovarian hormone commonly associated with better mood and which is often used to treat symptoms of menopause.
Rosamunde Hendricks, an author of the study currently at the Autonomous University of Barcelona, said:
“Though we didn’t see an equivalent effect for estradiol as we did for progesterone, it is possible that this is because estradiol is more difficult to measure accurately in saliva. So we cannot rule out that estradiol is affecting the brain. Rather, its effects may not have been reliably captured by the measures used in this study.”
A better understanding of these mechanisms could ultimately inform research into conditions in which hormonal fluctuations are associated with changes in mood. More broadly, the findings highlight that hormonal state is an important source of variation in the brain mechanisms underlying mood and how it is regulated.
This study was funded by a 2022 Young Investigator Award granted to Macià Buades-Rotger (30919) by the Brain & Behavior Research Foundation.
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