OR34-3 Association Between Endogenous Testosterone and Incident Stroke and Ischemic Changes on Brain MRI in Men in the Atherosclerosis Risk in Communities (ARIC) Cohort

Program: Abstracts - Orals, Poster Previews, and Posters
Session: OR34-Testosterone Replacement Therapy: Risks and Benefits
Clinical/Translational
Saturday, March 7, 2015: 11:30 AM-1:00 PM
Presentation Start Time: 12:00 PM
Room 6A (San Diego Convention Center)

Outstanding Abstract Award
Reshmi Srinath, MD1, Rebecca Gottesman, MD PhD2, Kathryn A Carson, ScM3, Sherita Hill Golden, MD, MHS1 and Adrian S Dobs, MD, MHS1
1Johns Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins School of Medicine, Baltimore, MD, 3Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
Introduction: Epidemiologic studies in men suggest both low and high testosterone (T) are associated with atherosclerosis and contribute to clinical cardiac and cerebrovascular events.  We hypothesize that low T is independently associated with incident cerebrovascular events and the presence of ischemic changes on brain MRI.

Methods:  The Atherosclerosis Risk in Communities (ARIC) study is a large prospective multicenter cohort of people aged 45-64 years at baseline followed since 1987 to evaluate risk factors associated with incident cardiovascular disease (CVD). In a sample of male participants at visit 4(1996-1998) who were free of CVD (including stroke) and without prior T therapy, we measured plasma total T by liquid chromatography mass spectrometry using samples obtained prior to 10:30 AM.  Cochran-Armitage test for trend and general linear regression models were used to assess the cross-sectional association of T quartile with demographic characteristics and cardiovascular risk factors. Proportional hazard regression analysis was performed to assess the association of T quartiles with incident stroke through 2011. A subset of participants underwent brain MRI at visit 5 (2011-2013) with semiquantitative evaluation of white matter hyperintensities (WMH) as well as infarcts (cortical or subcortical).  Linear and logistic regression models were used to assess the association of T quartiles with these ischemic changes. Multivariable regression analysis was adjusted for age, race and ARIC center, body mass index (BMI), waist circumference, smoking status, diabetes, hypertension, LDL and HDL.

Results:  In 1558 males (mean (SD) age= 63.1 (5.6) years, BMI=28.2 (4.27) kg/m2) the median (interquartile range) plasma T was 377.6 (288.4-480.1) ng/dL.  Lower T was significantly associated with higher BMI, greater waist circumference, presence of diabetes, hypertension, lower HDL, and never smoking.  Median follow-up for incident stroke was 14.1 years. Following multivariable adjustment, there was no association of T quartile (Q) with incident stroke (hazard ratios (95% CIs) for Q1-Q3, each vs. Q4: 1.08 (0.56-2.08), 0.85 (0.44-1.66), 0.65 (0.33-1.30)]. Similarly there was no association of T quartile with WMH (results not shown), or with cortical and subcortical infarcts on brain imaging (odds ratios (95% CIs) for Q1-Q3, each vs. Q4: 0.65 (0.28-1.49), 0.65 (0.29-1.45), 0.54 (0.26-1.16)).

Conclusions:  After controlling for key CVD risk factors, there was no association between endogenous T and incident stroke or ischemic changes on brain MRI imaging in men within the ARIC cohort.

Disclosure: ASD: Clinical Researcher, Endo Pharmaceuticals, Advisory Group Member, Lipocine, Inc., Advisory Group Member, Endo Pharmaceuticals, Advisory Group Member, AbbVie, Consultant, AbbVie, Clinical Researcher, Clarus. Nothing to Disclose: RS, RG, KAC, SHG

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