Summary: A large brain-imaging study led by researchers at the University of Kansas examined how lifetime exposure to reproductive hormones relates to brain structure in older women. The results reveal that greater cumulative exposure to estrogen — from early-life hormonal birth control, midlife menopausal hormone therapy (MHT), or a naturally later menopause — is linked with larger brain volumes and thicker cortex in regions important for memory, cognition, and information processing.
The study assessed 459 women between the ages of 65 and 80 and used whole-brain imaging techniques to evaluate gray matter volume and cortical thickness. Women with higher lifetime estrogen exposure showed structural brain characteristics typically associated with healthier aging and lower risk for neurodegenerative decline.
Key Facts
- Lifetime perspective: Unlike many prior studies that focus mainly on menopause, this research shows that estrogen exposure in young adulthood — specifically use of estrogen-based oral contraceptives — leaves a measurable structural imprint on the brain decades later.
- Neuroprotective roles of estrogen: Estrogen supports white matter integrity, protects neurons from age-related damage, strengthens synaptic connections, and contributes to healthy cerebral vascular function.
- Cortical thickness link: Women who experienced later natural menopause, and therefore longer endogenous exposure to ovarian hormones, had thicker cortex in posterior brain regions often vulnerable to Alzheimer’s-related changes.
- Surgical menopause outcomes: The study found that women who underwent early surgical removal of the ovaries (oophorectomy) showed pronounced structural benefits when they received appropriate post‑surgical estrogen replacement.
- Reevaluating past guidance: These findings add to a growing body of evidence that refines earlier interpretations of the 2002 Women’s Health Initiative results and supports a more individualized approach to hormone therapies.
Source: University of Kansas
Study overview: Researchers from the University of Kansas linked reproductive hormone exposures across the lifespan to structural brain measures in 459 women ages 65 to 80. The team reported that older women who had used hormonal birth control in young adulthood, or who used menopausal hormone therapy in midlife, were more likely to show larger volumes and thicker cortex in brain areas that support memory, processing speed, and higher cognitive functions.
The study was published in the peer-reviewed journal NeuroImage.
“These results indicate a protective association — estrogen-based therapies were associated with structural features of a healthier brain in older women,” said Amber Watts, co-lead author and professor of psychology at KU. “What makes this work distinctive is that it considers hormone exposures both in early adulthood and in midlife and finds links between both periods and brain health decades later.”
The researchers evaluated three types of hormone exposure: use of hormonal birth control (BC) in early adulthood, use of menopausal hormone therapy (MHT) during midlife or menopause, and natural hormone exposure as estimated by age at natural menopause.
- Use of hormonal birth control
- Use of menopausal hormone therapy (MHT)
- Age at natural menopause (as a proxy for endogenous hormone exposure)
“Most prior aging studies single out menopause as the primary hormonal event worth studying, but hormones also influence brain development in adolescence and early adulthood,” Watts added. “Early-life exposures may have long-term implications for how the brain ages.”
The Centers for Disease Control report that most U.S. women of childbearing age use birth control; however, many users may not consider the possible lifelong implications of hormonal contraceptive use when deciding among options.
Watts emphasized that the findings should encourage clinicians and patients to weigh long-term brain health when discussing hormonal treatments. Women account for nearly two-thirds of Alzheimer’s patients, and understanding whether reproductive hormones protect the aging brain could inform strategies to reduce dementia risk and promote cognitive longevity.
“Estrogen is neuroprotective,” Watts said. “Beyond reproductive functions, it benefits white matter integrity, helps protect neurons, supports synaptic strength, and contributes to vascular health. Estrogen also plays important roles in heart health, bone density, and immune function.”
Specific study findings included associations between birth control use and greater gray matter volume in temporal, occipital, and frontal regions; longer birth control duration linked to larger fusiform gyrus volume; combined BC and MHT use associated with greater parietal and temporal volume and thicker cortex in posterior cingulate and temporal gyri; and later menopause linked to greater posterior cortical thickness. The investigators did not find consistent associations for the timing of MHT initiation or the age at which birth control was first started.
The study also supports prior work showing that women who undergo early surgical menopause benefit structurally from appropriate hormone replacement after oophorectomy.
Looking ahead, Watts and colleagues are recruiting participants for additional menopause-related studies and encourage interested women to consider participation in future research efforts.
Co-lead author Robyn Honea collaborated with Watts, and other core contributors included members of the KU Alzheimer’s Disease Research Center and multiple academic partners across institutions who contributed to data collection and analysis.
Key Questions Answered:
A: Most studies focus narrowly on menopause, but hormones influence the brain across the lifespan. By assessing both early-life oral contraceptive use and midlife hormone therapy, the study demonstrates that cumulative estrogen exposure — beginning in young adulthood — can relate to preserved brain structure many decades later.
A: Estrogen supports multiple processes that protect brain health: it helps maintain white matter tracts, shields neurons from oxidative and metabolic stress, promotes synaptic remodeling and connectivity, and supports cerebral blood flow and vascular function, all of which help prevent tissue loss over time.
A: The 2002 Women’s Health Initiative originally led to widespread avoidance of hormone therapy due to broadly applied conclusions. Subsequent reanalyses and newer studies have clarified limitations of that original work. This study adds evidence that, when tailored appropriately, hormone therapy can support structural brain health and should be considered within a personalized clinical framework.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full for accuracy.
- Additional explanatory context was added by staff to clarify study methods and findings.
About this brain aging and estrogen research news
Author: Brendan Lynch
Source: University of Kansas
Contact: Brendan Lynch – University of Kansas
Image: Credit to Watts et al
Original Research: Open access. “Lifespan exposure to hormone therapies and structural brain morphometry in older women” by Robyn A. Honea, Amber Watts, Shannon D. Donofry, Cristina Molina-Hidalgo, Hayley S. Ripperger, Sarah L. Aghjayan, Chaeryon Kang, Swathi Gujral, Lauren E. Oberlin, George Grove, Haiqing Huang, Bradley P. Sutton, Jeffrey M. Burns, Eric D. Vidoni, Arthur F. Kramer, Edward McAuley, Charles H. Hillman, Anna L. Marsland, M. Ilyas Kamboh, and Kirk I. Erickson. NeuroImage. DOI: 10.1016/j.neuroimage.2026.121974
Abstract
Lifespan exposure to hormone therapies and structural brain morphometry in older women
Background
Although many studies suggest estrogens and other ovarian hormones have neuroprotective effects, imaging results have been inconsistent. Few prior investigations have examined both early- and midlife hormone exposures together or used whole-brain, voxel-wise methods. This study evaluated how hormonal birth control (BC), menopausal hormone therapy (MHT), and timing of menopause relate to brain structure in older women.
Methods
The analysis used baseline data from 459 women (ages 65–80) enrolled in the multi-site IGNITE trial, a 12-month randomized aerobic exercise study. Researchers correlated retrospective self-reported BC and MHT use with structural MRI measures, employing voxel-based morphometry (VBM) to assess gray matter volume and surface-based morphometry (SBM) to measure cortical thickness.
Findings
Compared with no birth control use, BC use was associated with greater gray matter volume in temporal, occipital, and frontal regions. Longer BC duration correlated with larger fusiform gyrus volume. Combined BC and MHT use, compared with no use, was associated with greater parietal and temporal volume and thicker cortex in the posterior cingulate and temporal gyri. Later menopause onset was linked to greater posterior cortical thickness. The study did not find consistent associations for the timing of MHT initiation or age at BC initiation.
Interpretations
Both endogenous and exogenous lifetime exposure to ovarian hormones were associated with structural brain measures that are generally consistent with preserved brain aging. These results emphasize the importance of exposure timing across a woman’s life and suggest hormone exposure history may be relevant to Alzheimer’s disease risk reduction and prevention strategies.