Young women with higher natural levels of the hormone progesterone tend to show less distinct brain activity patterns when they must override their automatic emotional impulses, according to a new neuroimaging study published in Psychological Medicine. The findings suggest that progesterone may blur the neural signals that help the brain regulate emotional actions. Reduced precision in a frontal brain region also accounted for an indirect statistical pathway linking higher progesterone to worse recent mood.
In everyday life, people naturally gravitate toward positive or rewarding things and pull away from threats or unpleasant situations. Psychologists refer to this automatic habit as approach-avoidance behavior. Overriding these instincts, such as stepping toward an angry person or walking away from something appealing, requires active emotional control.
This regulatory process relies heavily on the lateral frontal pole, a brain structure located at the very front of the cerebral cortex just behind the forehead. A 2020 neuroimaging study indicated that the lateral frontal pole plays a key role in overriding automatic impulses when people have to make these kinds of emotional choices. When this region fails to properly guide behavior, people tend to struggle with emotional regulation, as seen in a 2023 study covered by PsyPost showing that highly anxious individuals have difficulty recruiting the lateral frontal pole and must rely on other brain regions instead.
Scientists have also found that sex hormones can influence these exact brain circuits. For example, a study covered by PsyPost in 2023 indicated that high levels of the hormone testosterone are associated with reduced activity in the anterior prefrontal cortex during emotional control in adulthood. Far less is known about how the female ovarian hormones estradiol and progesterone shape these regulatory networks.
“Historically, neuroscience research has disproportionately focused on men, partly because hormonal fluctuations across the menstrual cycle were considered a source of unwanted variability,” study author Macià Buades-Rotger, an associate professor of clinical psychology and psychobiology at the University of Barcelona, told PsyPost. “As a result, we still know surprisingly little about how naturally occurring changes in ovarian hormones influence the brain and behavior.”
“At the same time, the relationship between female hormones and emotions is surrounded by sexist stereotypes and assumptions that often have little scientific basis,” Buades-Rotger added. “I was interested in moving beyond these simplistic narratives to investigate what hormones actually do in the brain, particularly how they might influence the mechanisms that allow us to control our automatic emotional responses.”
Both estradiol and progesterone fluctuate naturally throughout the menstrual cycle, and shifts in these hormones are frequently tied to changes in emotional well-being. The authors of a 2020 review argued that progesterone can act like a double-edged sword: one of its chemical byproducts has proven useful for treating depression after childbirth, yet the hormone may trigger negative symptoms in women with premenstrual syndrome or premenstrual dysphoric disorder, a severe form of premenstrual mood disturbance. Meanwhile, a 2019 neuroimaging study of naturally cycling women found that during the cycle phase when progesterone is high, frontal and striatal regions tended to be more active during mental tasks.
Most earlier brain imaging studies looked only at whether entire brain regions became more or less active overall in response to hormones. Buades-Rotger and his colleagues wanted to look deeper by examining whether estradiol and progesterone relate to fine-grained patterns of brain activity during emotional control, and whether those patterns connect to recent mood.
To investigate this in a preregistered study, the researchers recruited 116 healthy, naturally cycling women between the ages of 18 and 35. None of the participants were using hormonal contraceptives or had a history of neurological, hormonal, or recent psychiatric disorders. Before entering the brain scanner, each participant provided a saliva sample (stimulated by chewing gum) so the researchers could measure their current levels of estradiol and progesterone.
Participants also completed questionnaires measuring their typical emotion regulation habits and their mood over the preceding seven days. The mood survey assessed feelings of friendliness, vigor, fatigue, anger, tension, and depression, which the researchers combined into a single overall mood score. All testing sessions took place between 4 p.m. and 7 p.m. to minimize natural daily fluctuations in hormone levels.
Inside a functional magnetic resonance imaging scanner, which tracks brain activity by measuring changes in blood flow, the women completed a 240-trial approach-avoidance task. During the task, they viewed photographs of actors displaying happy or angry facial expressions. Depending on the instructions for each block of trials, participants pressed buttons to either “approach” a face, which made the image grow larger as if looming closer, or “avoid” a face, which made the image shrink as if receding.
In half of the trials, the instructions matched natural human instincts: approaching happy faces and avoiding angry ones. In the other half, the instructions went against those instincts, requiring participants to approach angry faces and avoid happy ones. After excluding six participants with unusually high error rates, the researchers analyzed the behavioral responses of 110 women.
As expected, overriding automatic emotional tendencies took more effort. When participants had to approach angry faces, their average reaction time was 0.782 seconds with an error rate of 1.52 percent, compared to 0.663 seconds and a 0.55 percent error rate when approaching happy faces. Similarly, avoiding happy faces took an average of 0.762 seconds with a 1.36 percent error rate, compared to 0.684 seconds and a 0.64 percent error rate when avoiding angry faces.
Next, the researchers examined the brain scans of 106 participants, after excluding four additional women who moved too much in the scanner. Instead of just measuring overall blood flow in a given brain area, the team used a machine learning technique called multivoxel pattern analysis. A voxel is a tiny three-dimensional unit of brain tissue, similar to a three-dimensional pixel.
The computer algorithm looked at the detailed grid of activity across thousands of voxels during odd-numbered trials and tried to predict which task condition the participant was performing during even-numbered trials. If the computer could accurately tell whether a participant was overriding their instincts or following them based on a region’s activity pattern, it meant that brain area was distinctly encoding the rules of emotional control.
The algorithm had to sort each trial into one of the four task conditions, so guessing would be right 25 percent of the time. Activity patterns in several regions allowed it to beat that chance level, including the lateral frontal pole, the striatum (a cluster of neurons deep beneath the cortex that helps manage movement and reward), the central insula (a region involved in processing internal bodily states and emotions), the primary visual cortex, the cerebellum, and the periaqueductal gray (a brainstem area involved in threat responses). The amygdala, a threat-processing region the researchers had planned in advance to examine, did not distinguish between the conditions. The algorithm mainly succeeded at telling instinct-opposing trials apart from instinct-matching ones, while often confusing the two conditions within each type.
When the researchers combined the brain data, hormone levels, and mood scores for the 101 participants who had complete data across all measures, they found a consistent link with progesterone. Women with higher concentrations of salivary progesterone showed lower classification accuracy in both the lateral frontal pole (r = −0.25) and the striatum (r = −0.26). In other words, in women with higher progesterone, the brain activity patterns representing emotional control in these two regions were less distinct and harder for the algorithm to tell apart.
“In everyday life, we constantly encounter situations in which our automatic emotional reactions conflict with what we actually need to do,” Buades-Rotger explained. “Imagine needing to ask a grumpy colleague for help: your instinct might be to avoid them, but achieving your goal requires approaching them instead. Our findings suggest that higher progesterone levels may make the brain’s representation of these competing emotional demands less clear, potentially making it harder to distinguish when to follow an instinctive reaction and when to override it. This could be one way in which natural hormonal fluctuations subtly influence how we navigate emotionally challenging situations.”
Sharper activity patterns in the lateral frontal pole were also associated with better mood over the past week (r = 0.26). Even without a direct correlation between progesterone and mood reported in the study, a preregistered mediation analysis found a small indirect pathway: higher progesterone was linked to less distinct frontal patterns, which were in turn linked to worse recent mood. The model explained 7.1 percent of the variation in mood scores, and a reversed version that swapped the roles of progesterone and the brain patterns produced a weaker effect that was not statistically significant.
Contrary to the researchers’ initial expectations, estradiol levels were not linked to brain decoding accuracy or to mood. In addition, neither estradiol nor progesterone correlated with how quickly or accurately participants pressed the buttons during the behavioral task. When the researchers divided participants into early and late stages of the menstrual cycle based on self-reported cycle length, they found higher progesterone in the late phase as expected, but cycle phase by itself was not linked to differences in mood, task performance, or brain decoding accuracy.
“What surprised me most was the absence of comparable effects for estradiol,” Buades-Rotger noted. “Both estradiol and progesterone are known to influence brain function, and we had good reasons to expect that either hormone might be associated with how emotional control is represented in the brain. Instead, the associations we identified were specific to progesterone. This does not mean that estradiol has no role in emotional regulation, but it suggests that the two hormones may influence these processes through different mechanisms.”
The authors suggest that progesterone may make brain activity patterns more diffuse across frontal and striatal circuits. While this blurring of emotional signals might make it harder to actively regulate mood and impulses, the researchers note that a slight blunting of emotional representations could be helpful in other ways, such as reducing sensitivity to physical pain during the second half of the menstrual cycle.
As with all research, there are some caveats to consider when interpreting these findings. Because the researchers collected only a single saliva sample and brain scan from each woman at one point in time, the study cannot prove that higher progesterone directly causes changes in brain patterns or mood. In addition, the 101 participants included in the correlation analyses fell short of the preregistered target of 120, leaving the study with 71 percent statistical power to detect effects of the observed size. Tracking the same individuals across multiple days of their menstrual cycles in future studies will be necessary to separate temporary hormonal states from stable personal traits.
“One important misconception would be that higher progesterone necessarily makes women more emotional or less capable of controlling their behavior,” Buades-Rotger emphasized. “That is not what our study shows. We examined statistical associations between naturally occurring hormone levels, patterns of brain activity, and mood in healthy young women; we did not experimentally manipulate progesterone or demonstrate that these neural differences cause changes in emotional behavior. It is also important to remember that hormonal effects vary considerably between individuals, and many women experience little or no noticeable mood changes across the menstrual cycle.”
Methodological factors may have also introduced measurement noise that masked potential effects of estradiol. The researchers used chewing gum to help participants produce saliva, which is known to alter measured concentrations of steroid hormones, and salivary estradiol is a poor marker of menstrual cycle phase. In this sample, estradiol did not differ between the early and late phases of the cycle, while progesterone did. Finally, the pathway linking progesterone, frontal brain patterns, and mood accounted for just over 7 percent of the variation in mood among participants, meaning most of the differences in how participants felt were explained by other factors.
“The associations we observed were relatively modest, which is unsurprising given that mood and emotional regulation depend on many interacting biological, psychological, and environmental factors,” Buades-Rotger said. “Progesterone is certainly not a master switch that determines how someone feels or behaves. The significance of our findings lies primarily in identifying a potential brain mechanism linking hormonal variation to mood, rather than demonstrating a large or immediately noticeable effect on everyday behavior.”
Looking ahead, the researchers hope to test these hormonal pathways more directly over time. “An important next step would be to follow the same women across different phases of the menstrual cycle to determine whether changes in progesterone are accompanied by corresponding changes in neural representations of emotion control,” Buades-Rotger said. “Pharmacological studies that experimentally manipulate progesterone levels or the activity of its neuroactive metabolites would provide a more direct test of causality. Ultimately, understanding these mechanisms could help explain why some women are particularly sensitive to hormonal fluctuations, including those who experience premenstrual dysphoria, and potentially inform future approaches to treatment.”
“I think our findings also illustrate the value of looking beyond conventional measures of brain activation,” Buades-Rotger concluded. “This allowed us to investigate how information about emotional control is represented in the brain. More broadly, the study highlights why hormonal state should be taken seriously as a meaningful source of variation in neuroscience, rather than simply treated as a nuisance variable.”
The study, “Endogenous progesterone blurs frontostriatal representations of emotion control in healthy young women,” was authored by Macià Buades-Rotger, Rosamunde Hendricks, Beatrice Roncarati, Marta Calderón-García, Kaja Bergmann, and Francisco José Pérez-Cano.