Hormonal factors moderate the associations between vascular risk factors and white matter hyperintensities

To examine the moderation effects of hormonal factors on the associations between vascular risk factors and white matter hyperintensities in men and women, separately. White matter hyperintensities were automatically segmented and quantified in the UK Biobank dataset (N = 18,294). Generalised linear models were applied to examine (1) the main effects of vascular and hormonal factors on white matter hyperintensities, and (2) the moderation effects of hormonal factors on the relationship between vascular risk factors and white matter hyperintensities volumes. In men with testosterone levels one standard deviation higher than the mean value, smoking was associated with 27.8% higher white matter hyperintensities volumes in the whole brain. In women with a shorter post-menopause duration (one standard deviation below the mean), diabetes and higher pulse wave velocity were associated with 28.8% and 2.0% more deep white matter hyperintensities, respectively. These findings highlighted the importance of considering hormonal risk factors in the prevention and management of white matter hyperintensities.