Neuroscience has historically turned its back on half of the population. Barely between 2% and 6% of brain studies are exclusively conducted on samples of women. This gender gap has overlooked the most crucial biological processes of women's life cycles. Now, a longitudinal study published in Nature Communications has analyzed the three major hormonal transitions of the female brain: puberty, pregnancy, and menopause.
"For a long time, it seemed like hormones were not taken seriously in science; there was no notion of their enormous impact on the brain," says one of the research authors, Elseline Hoekzema from the Pregnancy Brain Lab at the University of Amsterdam. Co-author Sophie van 't Hof, from the Amsterdam University Medical Center (AUMC), points out that this delay comes from excluding women in research under the excuse of their hormonal fluctuations, "it has always seemed amazing to me; as a researcher, you seek to study complex systems, and the interaction between the brain and hormones is one of the most fascinating."
The results of the research led by Van 't Hof and Hoekzema and based on scans of 1,095 participants show that adolescence (marked by the onset of the first period) and pregnancy cause a drastic brain reorganization with reductions in cortical gray matter.
This is part of a process of neurodevelopmental specialization in the early stage. During pregnancy, the decrease is very precisely located in regions of the association cortex, the default neuronal network, and theory of mind networks, areas that regulate social cognition, self-reference, and empathy. This represents an adaptive remodeling aimed at facilitating maternal care behaviors and the biological bond with the baby.
Puberty and pregnancy: the 'pruning' of gray matter that prepares the brain for motherhood
"We have known for years that the brain changes during pregnancy or adolescence, but they had never been compared to menopause, the great unknown," as reported by Science Media Center (SMC), Sandra Doval Moreno, PhD in Psychology from the Complutense University of Madrid and teaching researcher at the International University of La Rioja. "Puberty and pregnancy involve a loss of gray matter in the association cortex, as if the brain were 'pruning' in a similar way."
The data reveals that menarche leads to a monthly gray matter reduction rate of -0.16%. In pregnant women, the monthly decrease is -0.12%. Although this shrinkage may be alarming, the authors change the narrative. "People associate these reductions with cognitive losses," clarifies Van 't Hof. "But seeing that it also occurs during puberty changes the perspective to a process of fine-tuning or cerebral refinement (neuro fine-tuning): an adaptive and specialized change, not harmful." In fact, the concept of 'matrescence' is consolidated, defined as the birth of a mother, as a biological mirror of adolescence.
In mothers, this remodeling focuses on regions of social cognition and empathy to facilitate bonding. However, this rapid wiring entails emotional vulnerability. From the Spanish Society of Neurology, Susana Arias warns that "this massive and rapid remodeling in periods of high neuroendocrine stress can be a window of high vulnerability for the onset or relapse of neuroaffective disorders."
Menopause: why the brain stops losing volume during the transition
The scientific surprise comes with maturity. While stable premenopausal and postmenopausal women experience a progressive loss of gray matter due to natural aging, those in the midst of menopause maintained their volume intact.
"The study shows a freezing or attenuation of volume loss during the transition to menopause; a clearly different neurobiological dynamic," says Arias. Faced with the drop in estrogen and progesterone, the brain temporarily suspends its usual age-related atrophy.
In response, Van 't Hof urges caution: "We observed a pause in the decline of gray matter, but the effects were distributed throughout the brain and their size is much smaller than the immense remodeling during puberty and pregnancy. In menopause, the effects are much smaller." For Sandra Doval, this finding "opens an interesting path to think about female brain plasticity... as something that could go in both directions, and not just as a decline."
Limitations of the study: Why we can't talk about "brain fog" just yet
The scientific community emphasizes that we are still in a preliminary phase. "Brain volume is a macroscopic measure that does not allow for the identification of changes at the cellular level or functional alterations," points out Rafael Romero García (University of Seville), as reported by SMC. Additionally, he warns that "being an observational study, it does not allow for establishing a causal relationship between hormonal changes and brain changes."
Linking these data to symptoms like "brain fog" is a common mistake. The authors are clear: "It is of utmost importance not to link structural changes with cognitive functioning; we do not have performance data," clarifies Van 't Hof. To this, Hoekzema adds that "there is a subjective complaint of memory loss in mothers, but we still do not know if it is reflected in brain function; we are currently investigating this."
"We are at the fundamental basis," argues Hoekzema, who also comments that "before looking for clinical pathways, it is mandatory to map what happens in the brain as a whole in the healthy population." Uncontrolled factors, such as stress, sleep, prior contraceptive use, or socioeconomic variables, could explain part of the variability observed in the participants.