Words of wisdom. Re: lower testosterone levels predict incident stroke and transient ischemic attack in older men.

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.