How estrogen and progesterone remodel your brain, and what this means for those on hormones, who have endometriosis, and for Alzheimer's Disease risk
For most of the last century, the adult brain was treated as finished. Built in childhood, fixed by adulthood, slowly declining from there. We now know that was wrong. Your brain is not a static object. It is a living, shifting structure that rebuilds parts of itself on a rhythm, and for women, one of those rhythms is the menstrual cycle.
Recent studies put this to the test with some of the most powerful brain imaging available. Across each menstrual cycle, specific regions of the brain grow and shrink in step with your hormones.
And with this evidence, what do we then see in people with different hormone states, such as those on hormonal contraceptives, or who have endometriosis? Read on to find out..
Study 1 - Same organ, different volume fluctuations, depending on endometriosis, the pill, or ‘typical’ cycles
A 2025 study in Nature Neuroscience scanned women’s brains on weekdays across 5 weeks, covering a full menstrual cycle (1). This study found whole-brain structural changes, but they differed depending on someone’s hormone state.
The 5 participants were:
1. Typical cycle: 37 year old woman, freely cycling
2. Typical cycle: 23 year old woman, freely cycling
3. Endometriosis cycle: 30 year old woman, diagnosed with endometriosis 7 months prior after cyst surgery.
4. OC (oral contraceptives) cycle: 31-year-old woman, on combined pill (ethinyl-estradiol + dienogest) for 3 months prior.
5. Male: 36 year old man
What did they find?
Typically, brain volume follows progesterone as it rises and falls. But in women with endometriosis or on the pill? Their brains were syncing with estrogen instead. Your brain isn’t just affected by your hormones. It’s shaped by them, in real time. And different hormonal environments can influence the pattern entirely. What these findings actually mean beyond that - is yet to be studied.
For the man, no hormone-brain associations were found, as expected.
Study 2 - Zooming in on our memory hub, and why it matters for women’s Alzheimer’s Disease risk
In total, 27 healthy females with regular menstrual cycles were enrolled and underwent 7T Ultra-High-Field MRI, a VERY powerful brain scanning tool (2). Researchers scanned their brains in 6 distinct phases of the menstrual cycle: menstrual, pre-ovulatory, ovulation, post-ovulatory, mid-luteal and premenstrual. The team also controlled for things that can fake a change in brain size, like water content and blood flow, so that what they were measuring was structure, not fluid shifting around. Then they mapped the parts of the brain most involved in memory, emotion and spatial navigation (called the hippocampus, and surrounding regions).
Estrogen and Progesterone Each Sculpt Different Parts of the Hippocampus
Researchers found that when estrogen levels were higher, the volume of a brain region called the hippocampus was bigger. As a whole, the hippocampus is crucial for memory, emotional regulation and cognition. To get more accurate, researchers also looked at the specific sections within the hippocampus, and observed how they change across the menstrual cycle.
CA1 (Memory integration)
Higher estrogen levels → larger CA1 volume but this was weakened by increases in progesterone levels. This region matters for Alzheimer’s risk, which we’ll come back to.
Subiculum (Hippocampal-Cortical Communication)
Higher progesterone levels → larger subiculum volume
Perirhinal Area 35 (Visual memory and processing of objects)
Higher progesterone levels → larger Area 35 volume
Parahippocampal Cortex (Spatial memory and cognitive processing)
Higher estrogen levels → larger parahippocampal volume
The changes aren't new brain cells, it’s your brain rewiring
Interestingly, no changes were seen in the other regions of the hippocampus, notably the dentate gyrus - the site of adult hippocampal neurogenesis (the birth of new neurones) and cell proliferation. Because of this, researchers suggested that these volume changes aren’t driven by new neurones being born to create more brain volume across the cycle. Instead, it’s short term changes to existing neurones, like adding or removing dendritic spines, and remodelling synapses (the gaps between brain cells), and the organisation of these neurones within the brain.
Why estrogen builds and progesterone prunes
In the brain regions specified, there is a high density of estrogen and progesterone receptors, providing a direct pathway for the hormonal shifts of the menstrual cycle to influence brain structure and connectivity. In preclinical research, estrogen is seen to increase synaptogenesis, dendritic spine density and have an overall proliferative effect. In opposition, progesterone seems to suppress these actions, and is seen to decrease dendritic spines in preclinical models. Estrogen and progesterone are working together to shape the brain!
If estrogen and progesterone are actively shaping these vulnerable regions month to month, then the times when those hormones swing most dramatically may also be the times these regions are most exposed. Understanding the ordinary, healthy version of this rhythm is the first step toward understanding what happens when it is disrupted, and toward building care that actually accounts for the female brain rather than treating it as a smaller version of the male one. For example, we know that cognitive vulnerability spikes during perimenopause when these hormones drop and fluctuate dramatically. Could these effects on brain modelling rhythm be one reason why?
Is this one reason why women are diagnosed with Alzheimer’s Disease at twice the rate of men?
Both CA1 and perirhinal area 35 - the same regions we just saw estrogen and progesterone actively building and pruning every cycle - are among the earliest sites of neurodegeneration and atrophy in Alzheimer’s disease; area 35’s cortex is thought to be one of the very first regions affected, years before symptoms appear. Alzheimer’s is typically diagnosed decades after menopause, and some researchers think the permanent hormone decline after menopause may leave these hormone dependent regions more vulnerable over the years to follow. Since women face double the risk of developing Alzheimer's compared to men, understanding these dynamic baseline shifts is crucial for developing targeted, sex-specific clinical strategies.
The takeaway
Together, the two studies suggest the same monthly rhythm is playing out at two scales: the whole brain moving together, and, within it, specific regions responding to their own hormonal cues. Your hormones don't just move your mood across the cycle. They physically reshape parts of your brain, building and pruning as estrogen and progesterone rise and fall - that’s pretty cool if you ask us! The changes are subtle, reversible, and driven by the brain rewiring the neurones it already has rather than growing new ones. Far from being a sign of instability, this is adult neuroplasticity in action, a brain doing exactly what a living, adaptive organ should. The open questions now are about what happens when this rhythm is thrown off, and why the regions that flex the most across the cycle are also the ones most vulnerable later in life.
References
1. Heller, C., Güllmar, D., Colic, L. et al. Hormonal milieu influences whole-brain structural dynamics across the menstrual cycle using dense sampling in multiple individuals. Nat Neurosci 28, 2588–2600 (2025).
2. Zsido, R.G., Williams, A.N., Barth, C. et al. Ultra-high-field 7T MRI reveals changes in human medial temporal lobe volume in female adults during menstrual cycle. Nat. Mental Health 1, 761–771 (2023). https://doi.org/10.1038/s44220-023-00125-w
