Hormonal Factors Moderate the Associations Between Vascular Risk Factors and White Matter Hyperintensities

Abstract: Objective: To examine the moderation effects of hormonal factors on the associations between vascular risk factors and white matter hyperintensities (WMH) in men and women, separately. Methods: WMH 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 (body mass index, hip to waist ratio, pulse wave velocity, hypercholesterolemia, diabetes, hypertension, smoking status) and hormonal (testosterone levels, contraceptive pill, hormone replacement therapy, menopause) factors on WMH, and 2) the moderation effects of hormonal factors on the relationship between vascular risk factors and WMH volumes. Results: In men with testosterone levels one standard deviation (SD) higher than the mean value, increased body mass index and pulse wave velocity, and smoking were associated with higher WMH volumes. The association between body mass index and WMH was more significant in the periventricular white matter regions, whilst the relationship between pulse wave velocity and WMH was restricted to deep white matter regions. Men with low testosterone levels (one SD below the mean level) showed a significant association between hypercholesterolemia and higher deep WMH volumes. Hypertensive women showed higher WMH volumes than women without hypertension regardless of whether hormone replacement therapy was used. However, higher WMH volumes, especially in the deep white matter regions, were found in women who did not use hormone replacement therapy or use it for a shorter duration. Conclusion: These findings highlighted the importance of considering hormonal risk factors in the prevention and management of WMH.