Endogenous Testosterone and Incident Stroke

Study Questions:

Are low testosterone levels associated with ischemic stroke and ischemic brain changes?


Data from the ARIC (Atherosclerosis Risk in Communities) study were used for the present analysis. Male participants who completed visit 4 and who had no history of cardiovascular disease (CVD), stroke, or who had used testosterone therapy were included. Plasma total testosterone was measured using liquid chromatography mass spectrometry with morning samples. Testosterone levels were grouped into tertiles (median [25th–75th percentile], 377.6 [288.4–480.1] ng/dl). The primary outcome of interest was stroke with follow-up through 2011. Brain magnetic resonance imaging to look for white matter hyperintensities and prevalent infarcts was completed at visit 5 (2011-2013) in 257 participants.


A total of 1,558 male participants (mean age 63.1 years, body mass index [BMI] 28.2 kg/m2) who completed visit 2 (1996-1998) and who had no clinically diagnosed CVD, stroke, or prior testosterone therapy were included. Low testosterone was associated with higher BMI, greater waist circumference, diabetes mellitus (DM), hypertension, lower high-density lipoprotein cholesterol (HDL-C), and never smoking. Using the middle tertile as a reference group, no association was observed for the lowest testosterone group (tertile 1) with incident stroke (hazard ratio [HR], 1.47; 95% confidence interval [CI], 0.83-2.61). When comparing the highest testosterone group (tertile 3) with tertile 2, no significant association was found with incident stroke (HR, 1.15; 95% CI, 0.62-2.14). Both models were adjusted for age, race, and ARIC center, BMI, waist circumference, smoking status, DM, hypertension, low-density lipoprotein-C, and HDL-C.


The investigators concluded that, after controlling for atherosclerotic risk factors, there was no association between endogenous testosterone and incident clinical stroke or ischemic brain changes in community-dwelling men.


Given the interest in measurement and treatment of low testosterone among men, examining the associations of testosterone levels with CV outcomes is an important first step in understanding the implication of treatment with hormonal replacement in men. However, these observational studies do not replace the need for randomized controlled data.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Prevention, Lipid Metabolism, Nonstatins, Magnetic Resonance Imaging, Hypertension, Smoking

Keywords: Atherosclerosis, Body Mass Index, Brain Ischemia, Cholesterol, HDL, Diabetes Mellitus, Hypertension, Lipoproteins, HDL, Lipoproteins, LDL, Magnetic Resonance Imaging, Mass Spectrometry, Primary Prevention, Risk Factors, Smoking, Stroke, Testosterone, Waist Circumference

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