Abstract 11995: Extreme Endogenous Testosterone and Estrogen Concentrations and Risk of Ischemic Stroke in Men and Women: A Prospective Cohort Study and Meta-Analyses
Introduction: Sex hormone concentrations are associated with stroke risk factors and the incidence of ischemic stroke (IS) depends on gender. Whether sex hormones per se associate with IS is unclear.
Hypothesis: Endogenous sex hormone concentrations are associated with risk of IS in men and women.
Methods: In the 1981-1983 examination of the Copenhagen City Heart Study, 4,615 men and 4,724 women from the general population with measures of endogenous estradiol and testosterone were followed for up to 29 years for incident IS. Cox proportional hazard analyses were used to estimate risk of IS for extreme hormone concentrations, followed by mediation analyses. Present and previous findings were summarized in meta-analyses.
Results: In total, 524 men and 563 women developed IS during follow-up, with a median age at diagnosis of 78 years for women and 74 years for men. Testosterone concentrations ≤10th percentile versus 11-90th percentiles were associated with an increased IS risk in men (Hazard ratio (HR): 1.33(95% Confidence interval (CI): 1.04-1.71)), and mediation analysis showed that this risk increase was mediated by body mass index (21%, p=0.002) and hypertension (14%, p=0.023). Furthermore, in stratified analysis, the increased IS risk was found only in men who were both overweight and hypertensive (HR: 1.46 (95% CI: 1.09-1.95)). Also, meta-analysis of four prospective studies showed an increased IS risk in men with testosterone ≤10th percentile (HR: 1.43(95% CI: 1.21-1.70)). Estradiol concentrations were not associated consistently with IS risk in men or women, and neither was testosterone in women. However, estradiol concentrations ≤10th percentile was associated with an increased IS risk in premenopausal women (HR: 2.38 (95% CI: 1.07-5.29)), with limited statistical power.
Conclusions: Extreme low endogenous testosterone levels were associated with up to 43% increased risk of IS in men, a risk mediated partly by overweight and hypertension.
Author Disclosures: H.N. Holmegard: None. B.G. Nordestgaard: None. G.B. Jensen: None. A. Tybjærg-Hansen: None. M. Benn: None.
- © 2014 by American Heart Association, Inc.