Background:
Sex hormones are associated with obesity, diabetes mellitus, and other stroke risk factors; however, studies on sex hormones and stroke risk report inconsistent results. We assessed the associations of testosterone and sex hormone binding globulin (SHBG) with risk of ischemic stroke among men and post-menopausal women in the Atherosclerosis Risk in Communities (ARIC) Study.
Methods:
A total of 4,349 men and 4,720 post-menopausal women who had SHBG and total testosterone measurements at visit 4 (1996-98) were followed through 2018 for the development of ischemic stroke. We examined log transformed SHBG and testosterone exposure as quartiles and as per 1 SD increment. We used Cox regression to estimate the hazard ratios (HR) for ischemic stroke, adjusting for demographic, behavioral and clinical variables. Analyses were stratified by sex and menopausal hormone therapy (HT) use.
Results:
Participants were aged 63±6 years at baseline, 52% were women (25% HT users), and 21% Black. There were 691 strokes over a median follow-up of 19.8 years. Mean log SHBG (nmol/L) and testosterone (nmol/L) were 4.3±0.7 and 3.1±0.5 for HT users, 3.6±0.7 and 3.2±0.5 for non-HT users, and 3.4±0.5 and 6.2±0.5 for men. Quartile 1 vs Q4 for SHBG and testosterone were ≤50.3 vs >121 and ≤16 vs >28 in HT users, ≤23.3 vs >55 and ≤17.9 vs >32.7 in non-HT users, and ≤23.3 vs >41.8 and ≤388 vs >657 in men. SHBG and testosterone were not significantly associated with stroke in any group (Figure). The HRs [95% confidence interval] for highest to lowest SHBG and testosterone quartiles were 1.04 [0.51-2.14] and 1.64 [0.85-3.17] in HT-users, 1.02 [0.70-1.48] and 1.16 [0.83-1.62] in HT non-users, and 0.96 [0.70-1.32] and 0.87 [0.63-1.21] in men, respectively. The HRs for stroke associated with 1 SD increase in SHBG and testosterone were 1.14 [0.88-1.46] and 1.19 [0.96-1.46] in HT users. Associations were also null among non-HT users and men.
Conclusion:
SHBG and testosterone were not associated with ischemic stroke risk in this cohort of older men and post-menopausal women.
STROKE RISK IN POST-MENOPAUSAL WOMEN WITH ATRIAL FIBRILLATION IN THE WOMEN'S HEALTH INITIATIVE: A VALIDATION AND COMPARISON OF THE CHADS2 AND CHA2DS2-VASC RISK SCORES
