The Association of Sex Hormones with Incident Stroke in the UK Biobank

Background/Objectives: There are well-established sex differences in the epidemiology of stroke, but current data does not provide a clear mechanism to explain this phenomenon. This study asked if relationships between circulating sex hormone levels and stroke incidence could explain the sex differences in stroke rates. Methods: A total of 393,158 participants from the UK Biobank aged 40–69 were followed for a mean duration of 13.2 years. The incidence of ischemic stroke (IS) and intracerebral haemorrhage (ICH) was analysed in relation to baseline and changing levels of testosterone, sex hormone binding globulin (SHBG) and oestradiol. Results: A total of 3844 participants experienced an IS and/or ICH, with incidence higher in men than women in this population. In both sexes, a U-shaped association between total testosterone and ICH was found, independent of common cerebrovascular disease risk factors (p = 0.006). Higher SHBG levels were associated with higher risk of IS (Q4 hazard ratio = 1.18; p < 0.001) in both men and women, independent of common cerebrovascular risk factors. No significant associations were observed between oestradiol levels and stroke events after making demographic adjustments. Conclusions: These data highlight the nuanced roles that sex hormones play in the epidemiology of stroke between sexes. Whilst sex hormones are implicated in modulating stroke risk, this study demonstrated the complexity of this relationship.