“It’s like the brain being on a roller coaster every 28 days or so, depending on the length of the cycle,” said Erika Comasco, associate professor of women and children’s health at Uppsala University in Sweden, who was not involved in the research. “The importance of these studies is that they are building knowledge about the impact of these hormonal fluctuations on how the brain is structured.”
“These brain changes may or may not alter the way we actually act, think and feel in our everyday lives. So the important next steps for the science are to put those pieces of the puzzle together,” said Adriene Beltz, associate professor of psychology at the University of Michigan, who was also not involved in the research. “Do the hormonal effects on brain structure influence how the brain works?”
How hormones drive the menstrual cycle
During a woman’s period, which marks the beginning of the menstrual cycle, hormones are at low levels. But they rise dramatically over a few weeks.
Estrogen levels in the blood become eight times higher at ovulation around Day 14, while progesterone levels increase by 80-fold approximately seven days later. The production of follicle-stimulating hormone prompts the growth of an ovarian follicle into a mature egg, while a surge of luteinizing hormone triggers the release of the egg.
A single cycle repeats every 24 to 38 days until the transition to menopause, meaning that the average woman experiences around 450 periods throughout her lifetime.
Changes in the brain during the menstrual cycle
Viktoriya Babenko, who conducted the research as a doctoral candidate at the University of California at Santa Barbara, and her former colleagues at the university, used advanced methods in magnetic resonance imaging (MRI) to map structural changes in the whole brain during three menstrual cycle phases: ovulation, menstruation and mid-luteal.
The mid-luteal phase occurs between ovulation and menstruation, and is marked by a peak in progesterone. The participants — 30 young women with normal cycles — also had their blood drawn to precisely record their hormone levels at the time of the scans. The results, which have not yet been peer reviewed, were posted Oct. 10 to the preprint database bioRxiv.
Higher concentrations of estrogen and luteinizing hormone were both associated with changes that suggest faster information transfer, as the researchers saw when imaging the white matter of the brain. The white matter is deeper brain tissue made up of nerve fibers that relay information to and from parts of the outermost cerebral cortex, known as gray matter — which, in turn, became thicker with a rise in follicle-stimulating hormone.
Follicle-stimulating hormone “was positively associated with cortical thickness, generally across the whole brain,” said Elizabeth Rizor, a doctoral candidate in dynamical neuroscience at the University of California at Santa Barbara, and one of the authors of the study. “Whereas progesterone was kind of the opposite — it was generally associated with less cortical thickness in most regions.”
The other study, published by Nature Mental Health on Oct. 5, scanned 27 healthy participants with high-resolution MRI during six menstrual cycle phases: menstrual, pre-ovulatory, ovulation, post-ovulatory, mid-luteal and premenstrual. The researchers focused on the hippocampus and surrounding areas of the medial temporal lobe, which support a broad range of cognitive and emotional functions. They performed blood draws at each of the six time points to correlate brain changes with concentrations of estrogen and progesterone.
Increases in estrogen were linked to expansion of the parahippocampal cortex, a gray matter cortical region that plays a role in memory encoding and retrieval. Elevated progesterone was tied to greater volume in the perirhinal cortex, an area that receives sensory information and is also important for memory. And high estrogen in combination with low progesterone was associated with an enlarged region of the hippocampus, one essential for autobiographical memory.
The two studies looked at different anatomical features of the brain and so, their results can’t be directly compared. The first scanned the whole brain, including white matter and measured cortical thickness, whereas the second zoomed in on one gray matter region of the brain and analyzed cortical volume. However, both confirm that the morphology of the brain changes across the menstrual cycle, consistently and concurrently with hormone levels.
“For most women, for most of our lives, this ebb and flow of hormones across the menstrual cycle is as steady as the tides,” said preprint study author Emily Jacobs, associate professor of psychological and brain sciences at the University of California at Santa Barbara. “You can think of this pulse like a vital sign because we know hormones drive physiological functions across the whole body. But nobody really knew how it affected the brain in humans.”
Dramatic effects of estrogen on the brain
In the early 1990s, a groundbreaking experiment revealed the dramatic effects of estrogen on the brains of female rats. Scientists counted the number of dendritic spines — small protrusions along the branches of neurons that serve as points of contact from one cell to the next — in the hippocampus across the 4-to-5-day rodent menstrual cycle. A greater density of dendritic spines translates to enhanced connectivity between neurons in the brain.
At the beginning of the cycle, when estrogen is low, dendritic spine density is at its lowest point. Over the next several days, estrogen levels gradually rise and peak. During this time, more spines begin to proliferate, and spine density increases by around 30 percent. Toward the end of the cycle, spines retract, and the process starts all over again.
The current results suggest that a similar cyclical fluctuation in neurons could be happening in humans as well.
“The studies build up a quite robust basis for future studies to investigate if brain structure has an impact on brain function and behavior, which then would become of relevance for mental health,” Comasco said.
Do you have a question about human behavior or neuroscience? Email [email protected] and we may answer it in a future column.
Dr. Debi Johnson is a medical expert and health journalist dedicated to promoting well-being. With a background in medicine, she offers evidence-based insights into health trends and wellness practices. Beyond her reporting, Dr. Debi enjoys hiking, yoga, and empowering others to lead healthier lives.
