Lower Testosterone Levels Predict Incident Stroke and Transient Ischemic Attack in Older Men

Abstract

CONTEXT: Lower circulating testosterone concentrations are associated with metabolic syndrome, type 2 diabetes, carotid intima-media thickness, and aortic and lower limb arterial disease in men. However, it is unclear whether lower testosterone levels predict major cardiovascular events. OBJECTIVE: We examined whether lower serum testosterone was an independently significant risk factor for symptomatic cerebrovascular events in older men. DESIGN: This was a prospective observational study with median follow-up of 3.5 yr. SETTING: Community-dwelling, stroke-free older men were studied. PARTICIPANTS: A total of 3443 men at least 70 yr of age participated in the study. MAIN OUTCOME MEASURES: Baseline serum total testosterone, SHBG, and LH were assayed. Free testosterone was calculated using mass action equations. Incident stroke or transient ischemic attack (TIA) was recorded. RESULTS: A first stroke or TIA occurred in 119 men (3.5%). Total and free testosterone concentrations in the lowest quartiles (<11.7 nmol/liter and <222 pmol/liter) were associated with reduced event-free survival (P = 0.014 and P = 0.01, respectively). After adjustment including age, waist-hip ratio, waist circumference, smoking, hypertension, dyslipidemia, and medical comorbidity, lower total testosterone predicted increased incidence of stroke or TIA (hazard ratio = 1.99; 95% confidence interval, 1.33-2.99). Lower free testosterone was also associated (hazard ratio = 1.69; 95% confidence interval, 1.15-2.48), whereas SHBG and LH were not independently associated with incident stroke or TIA. CONCLUSIONS: In older men, lower total testosterone levels predict increased incidence of stroke or TIA after adjusting for conventional risk factors for cardiovascular disease. Men with low-normal testosterone levels had increased risk. Further studies are warranted to determine whether interventions that raise circulating testosterone levels might prevent cerebrovascular disease in men.