Can the menstrual cycle "reshape" the brain?

Elma Jashim, a recent college graduate, was looking forward to starting medical school in the fall, but she was also concerned about the mood swings she experienced during her monthly menstrual cycle and the disruption it could cause to her busy academic schedule.

"About two or three days before my period starts, I feel less emotional, less sad, less excited," Jasim said. When Jasim's period starts, this emotional plateau heightens her sensitivity to even the smallest emotional triggers. "If I make a small mistake at work, I almost have a meltdown."

Exactly what happens in her brain to trigger these emotions is not yet clear. But progress is being made in visualizing how sex hormones change certain areas of the brain. Previous studies in rats and other mammals have shown[1][2] that the volume of specific brain regions can change in response to estrogen, a hormone required for female sexual and reproductive development. But whether this powerful hormone changes the structure of the human female brain remains to be seen.

© George Wylesol

New MRI scans of women’s brains recently revealed that the rise and fall of sex hormones during the menstrual cycle—a 29-day period in which sex hormones rise and fall in preparation for a possible pregnancy—dramatically alters brain regions that control mood, memory, behavior, and the efficiency of information transmission. “It’s amazing to see how quickly the adult brain can change,” says Julia Sacher, a psychiatrist and neuroscientist at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany, who led one of the studies.[3]

Catherine Woolley, a neurobiologist at Northwestern University in Evanston, Illinois, notes that changes in the brain over the menstrual cycle are particularly noteworthy, because most women go through nearly 450 menstrual cycles over a period of 30 to 40 years.[4] A strength of these studies, Woolley says, is that brain imaging and hormone measurements were taken during the same phases of the menstrual cycle. “With these studies, we now understand how much these hormones play in shaping the morphological and functional structure of the brain,” says Emily Jacobs, a neuroscientist at the University of California, Santa Barbara.

Hormones drive the menstrual cycle

The menstrual cycle repeats every 25 to 30 days and begins with your "period," or the shedding of the uterine lining. At the beginning of the cycle, estrogen levels in the blood are lowest, but they rise dramatically over the next few weeks. First, estrogen levels rise, signaling endometrial growth. Then estrogen levels fall and the ovaries release an egg, marking the midpoint of the menstrual cycle.

After this, progesterone and estrogen levels increase again for about seven days, preparing the endometrium for possible fertilization of the egg. If pregnancy does not occur, both estrogen and progesterone levels drop, triggering menstrual bleeding. While the menstrual cycle is caused by distinct fluctuations in hormone levels, other hormones, such as testosterone and cortisol, also fluctuate in cycles, rising before dawn and falling in the evening.[5] These daily rhythms exist in both sexes.[6]

Estrogen stimulates cognitive areas of the brain

The brain is made up of densely packed cells called neurons, each of which looks like a miniature tree. Gray matter is the outer layer of brain tissue that contains neurons and short branches called dendrites. The leaf-like projections on dendrites are called spines. The roots of neurons, called axons, are packed into the brain's white matter. Gray matter is responsible for regulating emotions, learning, and memory, while white matter, located deeper in the brain, is responsible for exchanging information and connecting different gray matter areas.

The first areas of the brain that respond to female sex hormones were discovered about 30 years ago. In 1990, Woolley stumbled upon the fact that estrogen regulates the density of dendritic spines in the hippocampus of the rat brain.[7] “This was a very surprising result and caused quite a bit of skepticism in the field,” Woolley recalls, “because at the time, estrogen was thought to be a purely reproductive hormone and not to affect cognitive brain areas like the hippocampus.” The hippocampus—the brain’s cognitive center, which contains both gray and white matter—is a small, curved structure buried deep in the brain behind the ear and is densely packed with sex hormone receptors.

The hippocampus is also the area of ​​the adult brain most sensitive to changes in volume.

Learning a new skill, such as juggling in later life or memorizing maps to pass a London taxi driver’s test, can cause the hippocampus to grow. On the other hand, shrinkage of the hippocampus can be an early sign of dementia, particularly Alzheimer’s disease.[8] Since Woolley’s groundbreaking discovery, scientists have known that menopause reduces the volume of gray matter in certain parts of the brain. However, studies have been limited to snapshots of volunteers’ brains at a single point in time. Scientists wanted to know whether the adult brain changes during the monthly rise and fall of sex hormones.

“Can we be really precise? Can we take one person and measure their brain 30, 50, 100 times?” Jacobs wondered. That prompted one of the scientists on Jacobs’ team to scan her own brain every 24 hours for a full month in 2020. “She’s like the Marie Curie of neuroscience,” Jacobs said. From the woman’s 30 brain scans, Jacobs’ team found that sex hormones remodeled the hippocampus and reorganized the brain’s connections.

However, it is unclear how quickly the fluctuations in hormones during the menstrual cycle can do this.[9] To address this question, scientists in Leipzig and Santa Barbara have now scanned the brains of more than 50 women at multiple points in their menstrual cycles for two unrelated studies.

Thickness of brain region fluctuates during menstrual cycle

In a study published in the journal Nature Mental Health[10], Julia Sacher and her team used ultrasound to determine the exact time of ovulation in 27 female volunteers. This allowed them to collect blood samples at six precise points in the volunteers’ menstrual cycles, which correlated with ovulation and hormone levels in the blood.

They then scanned the brains of the 27 women at six specific time points using ultrahigh-field MRI, a more powerful MRI technique than is commonly used clinically, allowing Sacher's team to obtain high-resolution images of the living brain, something that was previously only possible by directly slicing the brain during autopsy.

Although the hippocampus is a very small structure, Sacher's team was able to observe a series of coordinated changes in different areas of the hippocampus with the menstrual cycle. As estrogen levels rise and progesterone levels fall, the hippocampus's outer layer thickens and its gray matter expands. But when progesterone levels rise, areas associated with memory expand. Another study, which has not yet been peer-reviewed, scanned the brains of 30 volunteers during ovulation, menstruation, and the period in between.

The study found that not only did gray matter thickness fluctuate under the influence of hormones, but the structural properties of white matter also changed. “We measured gray matter and saw that it changed in sync with the hormone fluctuations,” said Elizabeth Rizor, who co-led the study with Viktoriya Babenko, both neuroscientists at the University of California, Santa Barbara. The study suggests that changes in white matter caused by hormone fluctuations may lead to more efficient information transmission between different parts of the brain.[11]

"These changes are quite extensive, not just in the gray matter, but also in brain regions responsible for coordination across regions and across white matter pathways," Babenko said. However, the changes in volume or thickness of brain regions observed in these studies have not yet been linked to specific brain functions. While the studies suggest that some areas of the brain can reshape themselves in response to the fluctuations in hormones during the menstrual cycle, the scientists caution that the studies do not mean that memory or cognition is affected.

“We can’t assume that bigger is better for a particular brain function or process," Woolley said. The studies also don’t reveal whether volume changes are associated with the various mood and cognitive symptoms women experience during their periods. In fact, the studies included only healthy women who didn’t report any of those symptoms. Jacobs said more trials are urgently needed to study women’s unique neuroscience needs.

“There are actual structural changes happening in our brains that may be linked to things like mood swings,” Jassim says. Although women account for 70% of Alzheimer’s cases and 65% of depression cases, only about 0.5% of brain imaging studies involve women.[12]

This imbalance persists even in drug approvals, such as Lecanemab-irmb, which the U.S. Food and Drug Administration recently approved for the treatment of early Alzheimer's disease, which may not slow the disease in women. "It's time to make the brain a major focus of women's health," Saher said.

By Sanjay Mishra

Tempura

Proofreading/Rabbit's Light Footsteps

This article is based on the Creative Commons License (BY-NC) and is published by Tempura on Leviathan

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