de Lange · Human brain mapping 2020 · cross-sectional cohort study · n=16,854

Women's brain aging: Effects of sex-hormone exposure, pregnancies, and genetic risk for Alzheimer's disease.

Cited 98 times in the scientific literature.

Level 3 - non-randomized controlled study

Observational cohort study using neuroimaging biomarkers and exposure data.

PubMed 32856754 · doi:10.1002/hbm.25180 · record verified 2026-08-30

What was done

Analyzed neuroimaging-derived biomarkers of brain aging in relation to endogenous and exogenous sex-hormone exposure, parity, and Alzheimer's disease (AD) genetic risk profiles in a cohort of 16,854 middle- to older-aged women from the UK Biobank.

What was found

In contrast to parity, higher cumulative lifetime sex-hormone exposure was associated with more evident brain aging. Among women using hormone replacement therapy (HRT), initiating treatment earlier was associated with less evident brain aging, an effect observed exclusively in women carrying genetic risk for AD. The abstract reported no numerical effect sizes, test statistics, or confidence intervals.

Why it matters

The findings indicate that apparent brain-aging benefits linked to childbirth cannot be explained simply by cumulative hormone exposure. They also suggest that genetic risk for AD may influence whether early initiation of HRT confers neuroprotective benefits.

Limits

The abstract provides no numerical values, effect sizes, or definitions of the cumulative exposure metric. Exposure histories rely on retrospective self-reports subject to recall bias, and the observational cross-sectional design cannot establish causality.

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