Hormone History and Brain Blood Vessels: What an Observational Study Found

The work is an observational study in people, published online in Neurology on November 4, 2026; its journal issue is dated December 8. Researchers followed 352 women from the Gothenburg H70-1944 Birth Cohort, a population-based group. All were about 70 years old and had no cognitive impairment. All 352 had baseline MRI; 205 had usable MRI data five years later.

The team measured reproductive lifespan as age at menopause or ovary removal minus age at first period. They recorded whether each woman had ever used oral contraceptives or menopausal hormone therapy. They then looked at three things: cerebral small vessel disease, thickness of the brain cortex in regions vulnerable to Alzheimer disease, and the integrity of white matter, the brain's wiring.

Small vessel disease was scored from 0 to 4. The score combined four kinds of damage seen on MRI: white matter hyperintensities, lacunes, cerebral microbleeds and perivascular spaces. A longer reproductive span was associated with lower odds of having at least two small-vessel-disease markers rather than none (odds ratio 0.92, 95% confidence interval 0.86–0.99). This association did not remain significant after correction for multiple comparisons. Checking many possible links increases the chance of finding one by chance; this correction accounts for that.

Hormone therapy use was associated with fewer perivascular spaces and fewer cerebral microbleeds before correction for multiple comparisons; these individual-marker findings did not survive that correction. The associations of menopausal hormone therapy with the composite small-vessel-disease burden and white-matter integrity did survive correction. Use of oral contraceptives and of menopausal hormone therapy were each associated with greater white matter integrity. Women who had used both showed the highest integrity compared with women who used neither (β = 0.45, 95% CI 0.12–0.78). There was no multiplicative interaction between the two, though analyses of joint exposure pointed to cumulative effects.

The picture differed by genetics. Among carriers of APOE-ε4, a gene variant linked to higher Alzheimer risk, hormone therapy use was associated with greater cortical thickness in Alzheimer-vulnerable regions (β = 0.38, 95% CI 0.01–0.76). This was seen in carriers only before correction for multiple comparisons, and did not survive that correction. In the longitudinal analysis, estrogen exposure was not significantly associated with five-year changes in cortical thickness or white matter hyperintensity volume.

The authors write that greater lifetime estrogen exposure, both from the body's own hormones and from medicines, was associated with less cerebrovascular pathology. They say the findings support a possible role for blood-vessel mechanisms linking estrogen to brain aging. Women are disproportionately affected by Alzheimer disease, and the authors note this may relate to estrogen changes across life.

Senior author Anna Marseglia said in Karolinska Institutet’s original release that the findings suggest cumulative associations between hormonal exposure and later cerebrovascular health.

Hormone use was self-reported and recorded only as ever or never. First author Giulia Lorenzon said in the same release that the results cannot be used as a basis for recommending hormone therapy for prevention. The paper says possible effects on thinking and memory need further study.

These MRI associations do not establish that hormone therapy prevents dementia. Differences between hormone users and nonusers, self-report and loss to follow-up limit causal interpretation.

WHAT TO WATCH NEXT Studies that record the timing, dose and type of hormone therapy, and that test whether these vessel differences translate into differences in cognition.

Sources: Lorenzon and colleagues, Neurology, full primary report, and Karolinska Institutet original release.