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The estrogen drop: How the menstrual cycle shapes fear, memory, and trauma risk
Many people with cycles experience something medicine has historically overlooked: certain points in the menstrual cycle can feel different. Emotional reactions may feel sharper, sleep more easily disrupted, or difficult experiences harder to shake.
These experiences suggest that hormonal changes across the menstrual cycle can affect how the brain manages stress, emotion, and memory—systems that play an important part in mental health.
These systems are especially important in post-traumatic stress disorder (PTSD). Women are more than twice as likely to develop PTSD compared to men (1).
For a long time, researchers have believed that changes in hormones—especially a drop in estrogen—can change how the brain reacts to danger (2). These shifts might also affect how the brain remembers and holds onto stressful experiences.
This had never been directly tested in humans. Estradiol, the primary form of estrogen produced by the ovaries, fluctuates across the menstrual cycle. It reaches its highest peak just before ovulation and then falls sharply in the days after (3). These rapid hormonal changes can make it challenging to capture the brain at precisely the right moment.
In this research, we designed two experiments to do exactly that—examining how this hormonal window influences the brain.
Trauma can disrupt how hormones regulate the brain’s alarm system
To capture this moment, participants tracked their cycles using the Clue app. They then confirmed ovulation with home hormone tests. This allowed us to carry out brain scans during the brief window just after ovulation, when estradiol levels naturally fall.
In one experiment, we temporarily restored estradiol using a skin patch before scanning. This allowed us to directly test how estrogen levels influence brain activity.
During the scan, we showed participants images of fearful faces. At the same time, we watched activity in a part of their brain called the amygdala. This is a key brain structure involved in detecting and responding to threat (4).
In women with little or no past trauma, restoring estradiol reduced activity in the right side of the amygdala when they saw threatening faces.
This is important because the amygdala acts like the brain’s alarm system, helping us rapidly detect potential danger (5,6). In people with PTSD, this alarm system is often overactive, responding strongly even when threats are not immediate (5,6). Estradiol appeared to turn down the volume on this alarm response.
However, this effect disappeared in women who had experienced trauma. For those women, estradiol did not reduce amygdala reactivity, and their threat responses remained high.
These findings suggest that traumatic stress may disrupt how hormones normally regulate fear in the brain. In some women, the hormonal “brake” on the alarm system may no longer function as expected.
The estrogen drop after ovulation may also strengthen negative memories
In a second study, we looked at how estradiol levels influence how memories are formed.
We focused on a part of the brain called the entorhinal cortex. This acts as the gateway into the hippocampus, where detailed personal memories are stored (7,8).
When estradiol dropped after ovulation, activity in this region predicted stronger recall of negative experiences later on. When estradiol was experimentally restored, that effect disappeared.
So, lower estradiol appeared to make the brain more likely to store negative experiences more strongly in memory. This pattern was seen in all participants, regardless of whether they had a history of trauma or PTSD.
This suggests that if two identical stressful experiences happen at different points in the menstrual cycle, the brain might remember them differently.
Understanding mental health requires studying sex differences
How the brain detects danger and stores emotional memories plays an important role in many mental health conditions, including PTSD (9).
But much of what we know about the brain and trauma comes from studies of male military veterans and first responders (10). Women are more likely to experience PTSD, but historically their biology—including hormonal cycles—has often been treated as a complication rather than something important to study.
Our findings reinforce something neuroscience has long overlooked: the brain does not operate in a constant hormonal environment. Across the menstrual cycle, shifting levels of estrogen interact with brain systems that regulate threat detection, emotional responses, and memory.
They also push back against the idea that hormonal influences on anxiety and cognition are “just anecdotal.” These effects can be measured directly in the brain.
Studying differences in physiology between men and women is not just about comparing them. It’s essential for understanding how mental health conditions develop and why risk may differ from person to person.
What this means for individuals and clinicians
For individuals, paying attention to patterns across the menstrual cycle can be helpful. Tracking mood, stress, or other related symptoms over time can sometimes reveal patterns that might otherwise go unnoticed.
Bringing these patterns to a healthcare provider can help make sense of how hormones may be influencing mental health and guide decisions about care.
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For clinicians, these findings add to growing evidence that times of rapid hormonal change—during the menstrual cycle, puberty, pregnancy, postpartum, and perimenopause—may represent windows of increased vulnerability for mental health challenges.
Recognizing these patterns can help clinicians plan ahead for times when extra support may be needed and offer more tailored care.
Research like this moves us closer to more responsive and personalized mental health care. Instead of treating hormones as background noise, we are starting to see them as part of the biology that shapes how the brain responds to stress and stores emotional experiences.
Understanding these rhythms may help us better explain why certain experiences affect us so deeply—and how care can better reflect the full complexity of human biology.
We are deeply grateful to the participants who made this research possible.
Read the original research papers:
Funding sources: National Institute of Mental Health, National Science Foundation, National Center for Advancing Translational Sciences, NIH Office of the Director. Grant/award numbers R01MH117009, T32NS096050, F31MH126623, NSF 1937971, UL1TR002378, P51 OD011132
You can find out more about research at Clue by checking out our scientific research page.
