A recent study has identified how specific puberty hormones relate to the physical structure and functional wiring of the adolescent female brain. The findings suggest that hormones like estradiol and testosterone are linked to distinct brain regions that support memory, emotion, and spatial awareness. This research was published in the journal Human Brain Mapping.
Adolescence is a period of rapid biological and emotional change driven largely by puberty. During this time, the brain undergoes significant development, which scientists suspect is influenced by rising hormone levels. These changes coincide with a higher risk for mental health issues like anxiety and depression, particularly in young females.
Exploring how hormones shape the developing female brain provides evidence that might explain the emergence of these emotional challenges. In the past, studies looking at the relationship between hormones and brain development in adolescents have produced mixed results. Many previous research efforts relied on small groups of participants.
In addition, older studies often focused on only one type of brain imaging at a time. This specific focus can make it difficult to see the full picture of how hormones affect the entire brain. To address these gaps, researchers wanted to look at multiple hormones and multiple brain imaging techniques simultaneously in a very large group of young females.
“Puberty is thought to influence how the adolescent brain develops, shaping social and emotional behavior,” said Muskan Khetan, a doctoral candidate at the University of Melbourne and the lead author of the study. “Most research has focused on visible physical changes, but hormone changes actually begin earlier, before these signs appear, and we know far less about their effects on the brain.”
Khetan noted that this is an important gap, because hormones may serve as some of the earliest biological signals that puberty has begun. “Using a larger sample than is typical in this area of research, we set out to map how these hormonal changes organize the brain in adolescent girls, thereby helping us to better understand how this developmental period shapes social and emotional development,” Khetan said. “We focused on girls because their hormone patterns during puberty are more complex and have been relatively understudied.”
To conduct the study, the authors analyzed data from the Adolescent Brain Cognitive Development Study, which is a massive ongoing project tracking child health in the United States. They focused on a specific sample of 3,024 adolescent females. The participants ranged in age from eight to thirteen years old, with an average age of about ten.
The scientists measured the levels of three specific steroid hormones using saliva samples provided by the participants. These hormones included estradiol, which is a primary female sex hormone, as well as testosterone and dehydroepiandrosterone. While testosterone and dehydroepiandrosterone are often categorized as male hormones, they are present and active in females as well, playing a role in physical growth and brain development.
To understand the brain, the researchers used several different types of magnetic resonance imaging. First, they looked at structural imaging, which measures the physical shape, thickness, and volume of the brain’s gray matter. Gray matter consists of the main bodies of brain cells where information is processed and stored.
They also used diffusion-weighted imaging to look at the brain’s white matter. White matter acts like the brain’s communication highway, consisting of long nerve fibers that connect different regions and allow them to send signals to one another. Analyzing white matter helps researchers understand the strength and organization of these internal pathways.
The team also used functional magnetic resonance imaging to see how the brain operates over time. They measured resting-state connectivity, which shows how different brain networks communicate when a person is just lying still. They also recorded brain activity while the participants completed a specific task that required them to look at pictures of faces and places and remember what they had seen.
With all this data, the researchers applied an advanced mathematical model known as elastic-net regression. This statistical technique allowed them to look at hundreds of brain measurements simultaneously to find which ones best predicted the levels of the three hormones. They trained their model on a portion of the data and tested it on the rest, which helps ensure the results are reliable.
The researchers found that estradiol was most strongly associated with the physical structure of the prefrontal cortex and premotor regions. The prefrontal cortex is located at the front of the brain and helps manage complex behaviors like planning, regulating emotions, and working memory. Higher levels of estradiol were linked to variations in the thickness and folding of these specific areas.
Estradiol also showed a strong relationship with the brain’s resting-state functional connectivity. It was associated with how the visual networks communicated 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, an area involved in learning and action planning.
The two androgens, testosterone and dehydroepiandrosterone, showed a different pattern of associations. These hormones were most strongly connected to the structure of the parietal and occipital lobes, which are located toward the back of the brain. These regions are primarily involved in processing visual information and spatial awareness, helping a person understand where objects are in their environment.
Higher levels of both testosterone and dehydroepiandrosterone were associated with a thinner outer layer of the brain in these visual and spatial areas. While a thinner brain layer might sound negative, it is actually a normal part of brain maturation during adolescence. The brain typically prunes away unused connections to become more efficient as a child grows.
Dehydroepiandrosterone was the only hormone in the study that showed a relationship with how the brain functioned during the active memory and emotion task. Higher levels of this hormone were linked to increased activity in areas of the brain that process faces and emotions. This suggests that this specific hormone might play a role in how young females react to emotional situations.
Even though the hormones had their own unique associations, the researchers also found some overlapping effects. All three hormones were linked to the structure of the insula, a brain region involved in experiencing internal emotions, and the temporoparietal junction, which helps people understand the thoughts and feelings of others. They were also all associated with the white matter fibers connecting the left and right sides of the prefrontal cortex.
“What stood out was the overlapping effects of these hormones on the brain,” Khetan told PsyPost. “The existing literature tends to draw fairly clean lines, estradiol linked to emotional behavior, testosterone and dehydroepiandrosterone to visuospatial processing, but our data showed these hormones also converge on the same brain systems involved in social and emotional processing.”
Khetan explained that this overlap actually reflects well-established biology. “Testosterone and dehydroepiandrosterone can be converted into estradiol in the body, where it then acts on the same receptors,” Khetan said. “Seeing that shared biological mechanism reflected in brain patterns was one of the more interesting aspects of what we found.”
The magnitude of these hormone-brain connections is also an important piece of the puzzle. “The core message is that puberty is a sensitive period, and hormonal changes may be reshaping the brain even before physical development is visible,” Khetan explained. “Our study doesn’t directly measure behavior or clinical outcomes, but it shows that these hormones are actively organizing brain systems central to both emotion and visuospatial processing.”
Khetan pointed out that the statistical effects they found were small, which is a common occurrence in hormone research because hormone levels can vary a lot from person to person. Because of this high variability, large studies are needed to identify reliable biological patterns. “In short, puberty is not just about visible physical changes,” Khetan added. “Important hormonal shifts shape the brain, and thereby behavior.”
As with all research, there are some limitations to consider. “This study identifies associations, it does not establish cause and effect,” Khetan noted. “It’s also worth noting that we examined hormone-brain relationships at a single point in time rather than tracking individuals longitudinally, so we can’t yet speak to how these patterns unfold over the course of development.”
Because age and puberty happen at the same time, it can be difficult to separate changes caused specifically by hormones from changes that just happen naturally as a child gets older. “These findings are best read as an early contribution to understanding how hormones shape the adolescent brain, not as a complete picture,” Khetan said. “Translating these brain-level findings into specific behavioral or clinical outcomes will require further research.”
Another limitation is that the researchers only studied females. Because the scientists did not have estradiol measurements for the males in the broader study, they could not compare the two sexes. Future research will need to include both males and females to see if these hormone-brain relationships apply universally.
Looking ahead, the researchers hope to build on this work by examining how biology and life experiences intersect. “Collecting non-invasive hormonal data from adolescents is genuinely challenging, which is part of why this area remains understudied,” Khetan said. “My broader goal is to understand not just how hormone levels change during puberty, but how those changes interact with environmental factors, such as stress or adversity, and with physical development, to shape the brain and mental health over time.”
Khetan is especially interested in what drives individual differences, specifically why some adolescents show greater vulnerability while others remain resilient. “My own research points to two additional layers of complexity: the timing and pace at which hormones rise matter beyond their absolute levels, and the way hormones fluctuate across a month varies between individuals in ways that appear relevant to adaptability and risk,” Khetan explained. “Ultimately, I hope this line of research can help identify early biological markers that flag who may be most at risk, before problems have a chance to emerge.”
The study, “Pubertal Hormones and the Early Adolescent Female Brain: A Multimodality Brain MRI Study,” was authored by Muskan Khetan, Nandita Vijayakumar, Ye Ella Tian, Megan M Herting, Michele O’Connell, Marc Seal, and Sarah Whittle.
