Recent research has revealed how specific pubertal hormones are related to the physical structure and functional wiring of the female adolescent brain. The findings suggest that hormones such as estradiol and testosterone are associated with different brain regions that support memory, emotion, and spatial cognition. This study was published in the journal human brain mapping.
Adolescence is a period of rapid biological and emotional changes primarily caused by puberty. During this period, the brain undergoes significant development, and scientists believe this may be influenced by increased hormone levels. These changes coincide with an increased risk of mental health problems such as anxiety and depression, especially among young women.
Investigating how hormones shape the developing female brain provides evidence that may explain the emergence of these emotional challenges. To date, studies examining the relationship between hormones and brain development during puberty have yielded mixed results. Many previous research efforts relied on small groups of participants.
Additionally, older studies often focused on only one type of brain image at a time. This particular focus can make it difficult to get a complete picture of how hormones affect the brain as a whole. To address these gaps, the researchers wanted to examine multiple hormones and multiple brain imaging techniques simultaneously in a very large group of young women.
“Puberty is thought to influence how the adolescent brain develops and shapes social and emotional behavior,” said Muskan Khetan, a doctoral candidate at the University of Melbourne and lead author of the study. “While most research has focused on visible physical changes, hormonal changes actually begin earlier than these signs appear, and little is known about their effects on the brain.”
Ketan pointed out that this is an important gap because hormones may act as some of the earliest biological signals indicating the onset of puberty. “Using a larger sample than is typical in this field of research, we set out to map how these hormonal changes organize the brains of adolescent girls, thereby helping us better understand how this developmental period shapes social and emotional development,” Ketan said. “We focused on girls because hormonal patterns during puberty are more complex and relatively less studied.”
To conduct the study, the authors analyzed data from the Adolescent Brain and Cognitive Development Study, a large, ongoing project that tracks the health of children in the United States. They focused on a specific sample of 3,024 female adolescents. Participants’ ages ranged from 8 to 13 years, with an average age of approximately 10 years.
The scientists measured levels of three specific steroid hormones using saliva samples provided by participants. These hormones include the major female hormones estradiol, testosterone, and dehydroepiandrosterone. Testosterone and dehydroepiandrosterone are often classified as male hormones, but they are also present and active in women and play a role in physical growth and brain development.
To understand the brain, researchers used several different types of magnetic resonance imaging. First, they focused on structural images that measure the physical shape, thickness, and volume of the brain’s gray matter. Gray matter is made up of the body of brain cells where information is processed and stored.
They also looked at the brain’s white matter using diffusion-weighted imaging. White matter acts like the brain’s communication highway, consisting of long nerve fibers that connect different areas and allow them to send signals to each other. Analyzing white matter helps researchers understand the strength and organization of these internal pathways.
The research team also used functional magnetic resonance imaging to observe how the brain functions over time. They measured resting-state connectivity, which shows how different brain networks communicate when a person is just lying down. They also recorded brain activity while participants looked at pictures of faces and places and completed a specific task of remembering what they saw.
The researchers used all this data to apply an advanced mathematical model known as elastic net regression. This statistical method allowed them to look at hundreds of brain measurements simultaneously to find the one that best predicted the levels of the three hormones. By training your model on part of your data and testing it on the rest, you can ensure the reliability of your results.
Researchers found that estradiol was most strongly associated with physical structures in the prefrontal and premotor cortex. The prefrontal cortex is located in the front of the brain and helps manage complex behaviors such as planning, emotional regulation, and working memory. Higher levels of estradiol were associated with changes in thickness and folding in these specific regions.
Estradiol also showed a strong relationship with resting-state functional connectivity of the brain. It was related to how the visual network communicates with the thalamus, a deep brain structure that relays sensory information. It was also linked to connections between memory-related brain networks and the caudate nucleus, a region involved in learning and action planning.
Two androgens, testosterone and dehydroepiandrosterone, showed different patterns of association. These hormones were most strongly linked to structures in the parietal and occipital lobes located in the back of the brain. These areas are primarily involved in processing visual information and spatial awareness, helping a person understand where objects are in the environment.
Higher levels of both testosterone and dehydroepiandrosterone were associated with thinner outer layers of the brain in these visual and spatial areas. Thinner brain layers may sound negative, but they are actually part of normal brain maturation during adolescence. Normally, the brain removes unused connections to increase efficiency as the child grows.
Dehydroepiandrosterone was the only hormone in the study that showed a relationship with brain function during active memory and emotional tasks. High levels of this hormone were associated with increased activity in areas of the brain that process faces and emotions. This suggests that this particular hormone may play a role in how young women respond to emotional situations.
Although each hormone has its own association, researchers also found some overlapping effects. All three hormones were associated with structures in the insular cortex, a brain region involved in the experience of internal emotions, and the temporoparietal junction, which helps us understand the thoughts and emotions of others. They were also all associated with white matter fibers that connect the left and right sides of the prefrontal cortex.
“What was striking was the overlapping effects of these hormones on the brain,” Ketan told SciPost. “Existing literature tends to draw fairly sharp lines, such as that estradiol is associated with emotional behavior and testosterone and dehydroepiandrosterone are associated with visuospatial processing. However, our data showed that these hormones are also concentrated in the same brain systems involved in social and emotional processing.”
Ketan explained that this overlap actually reflects established biology. “Testosterone and dehydroepiandrosterone are converted to estradiol in the body and act on the same receptors,” Ketan said. “Seeing common biological mechanisms reflected in brain patterns was one of the more interesting aspects of what we discovered.”
The magnitude of the connections between these hormones and the brain is also an important piece of the puzzle. “The central message is that adolescence is a sensitive period, where hormonal changes can reshape the brain even before physical development is visible,” Ketan explained. “Although our study does not directly measure behavior or clinical outcomes, it shows that these hormones actively organize brain systems central to emotion and visuospatial processing.”
Keetan noted that the statistical effect they found was small, which is common in hormone research because hormone levels can vary widely from person to person. Because of this high variability, large-scale studies are required to identify reliable biological patterns. “In short, puberty is about more than just visible physical changes,” Ketan added. “Key hormonal changes shape the brain, which in turn shapes behavior.”
As with all studies, there are some limitations that should be considered. “This study identifies an association, not establishes cause and effect,” Ketan noted. “It is also noteworthy that we examined the relationship between hormones and the brain at a single point in time, rather than following individuals longitudinally, so we cannot yet speak to how these patterns unfold over development.”
Because age and puberty occur at the same time, it can be difficult to distinguish between changes caused by hormones, especially those that occur naturally as a child grows. “These findings are best read as an early contribution to understanding how hormones shape the adolescent brain, rather than as a complete picture,” Ketan said. “Further research is needed to translate these brain-level findings into specific behavioral or clinical outcomes.”
Another limitation is that the researchers studied only women. The scientists did not measure estradiol in men in the broader study, so they could not compare both sexes. Future studies should include both men and women to see if these hormone-brain relationships apply universally.
Looking to the future, the researchers hope to build on this work by examining how biology and life experience intersect. “Gathering non-invasive hormonal data from adolescents is very difficult, which is part of the reason why research in this area remains underpowered,” Ketan said. “My broader goal is to understand not only how hormone levels change during adolescence, but also how those changes interact with environmental factors such as stress and adversity and physical development to shape the brain and mental health over time.”
Ketan is particularly interested in what causes individual differences, and in particular why some young people are more vulnerable while others are more resilient. “My own research points to two further layers of complexity. One is that the timing and pace at which hormones rise above their absolute levels is important, and the other is that how hormones fluctuate over the month varies from person to person in ways that seem to be related to suitability and risk,” Ketan explained. “Ultimately, we hope this line of research will help identify early biological markers that indicate who is most at risk before problems become apparent.”
The study, “Puberty Hormones and the Female Brain in Early Adolescence: A Diverse Brain MRI Study,” was authored by Muskan Khetan, Nandita Vijahakumar, Ye Ella Tian, Megan M Herting, Michele O’Connell, Marc Seal, and Sarah Whittle.
