A longer reproductive lifespan and a history of using birth control pills or menopausal hormone therapy were associated with certain signs of blood vessel health in the brain, according to a study published November 4, 2026, in Neurology®, the medical journal of the American Academy of Neurology.
Cerebral small vessel disease affects tiny blood vessels within the brain and is associated with stroke, cognitive impairment and dementia.
The study shows an association and does not prove that longer reproductive lifespan or hormone use directly leads to better brain health; this would require clinical trials.
"Women are affected by Alzheimer's disease more often than men. This may be related, in part, to fluctuations in estrogen levels throughout life," said Anna Marseglia, PhD, of Karolinska Institutet in Stockholm, Sweden. "Estrogen is known to have protective effects on both neuronal cells and blood vessels in the brain. However, its potential role in women's cerebrovascular health in later life has been largely understudied. Our study found that factors associated with longer estrogen exposure were associated with fewer signs of cerebral small vessel disease and better brain health in older age."
The study included 352 women who were 70 years old and without cognitive impairment at the start of the study.
Researchers examined reproductive factors linked to lifetime estrogen exposure. They calculated each woman's reproductive lifespan, defined as the number of years between her first menstrual period and menopause or surgical removal of the ovaries. On average, women had a reproductive lifespan of 37 years.
They also recorded if participants had ever used birth control pills or menopausal hormone therapy. Of participants, 73% had used birth control pills and 61% had used or were currently using menopausal hormone therapy.
Participants had magnetic resonance imaging (MRI) brain scans at age 70 and 75. Researchers examined the scans for four signs of cerebral small vessel disease: areas of damaged tissue called white matter hyperintensities; microbleeds; small fluid-filled cavities called lacunes; and moderate to severe enlargement of spaces surrounding blood vessels. Each participant received a score from zero to four, with one point assigned for each sign present.
After adjusting for factors like education, number of pregnancies and total months breastfeeding, researchers found that women with a longer reproductive lifespan had 8% lower odds of having two or more signs of cerebral small vessel disease.
In a separate analysis that adjusted for factors like education, high blood pressure and heart disease, women who had or were still using menopausal hormone therapy were 59% less risk of having a greater small vessel disease burden, including fewer microbleeds and enlarged spaces around blood vessels. Birth control pills and menopausal hormone therapy use were associated with greater integrity of the brain's white matter microstructure, an early marker of healthier brain tissue.
Researchers also found that women who had used oral contraceptives and later received menopausal hormone therapy showed the most favorable vascular brain health. This group had lowest amount of cerebral small vessel disease and the healthiest white matter integrity compared with women who had never used hormonal therapies.
"What was particularly striking was that the most favorable vascular brain health was observed among women who had used oral contraceptives during their reproductive years and later received menopausal hormone therapy" said Marseglia. "This suggests that hormonal factors acting across different stages of a woman's life may have cumulative associations with cerebrovascular health in older age. While these findings do not establish cause and effect, they underscore the importance of considering women's reproductive and hormonal history when studying brain aging and dementia risk not only in relation to Alzheimer's disease but also to vascular disease."
Limitations of the study include that hormone exposure was reported by participants during the data collection interviews; they may not always have remembered accurately. Researchers could not track individual hormone levels over time, and there was a lack of detailed information on participants' oral contraceptive and hormone therapy use. Because all participants were cisgender women and researchers had limited information on gender identity, the findings may not apply to all women.
The study was supported by: the Swedish Research Council; the Swedish Research Council for Health, Working Life and Welfare; the Center for Innovative Medicine; the Swedish Dementia Foundation; the Swedish Alzheimer's Foundation; and the Gamla Tjännarinor Foundation.
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