Sex steroid concentrations and incident ischemic stroke in older men without cardiovascular disease in the Cardiovascular Health Study

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 554-583-Male Reproductive Endocrinology & Case Reports
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-582
Molly M Shores*1, Alice M Arnold2, Mary L Biggs3, William T Longstreth Jr.4, Nicholas L Smith5, Calvin H Hirsch6, Anne R Cappola7 and Alvin M Matsumoto8
1VA-Puget Sound, Seattle, WA, 2University of Washington and CHS Coordinating Center, Seattle, WA, 3University of Washington and CHS Coordinating Center, 4University of Washington, 5University of Washington and VA Puget Sound Health Care System, Seattle, WA, 6University of California-Davis, 7University of Penn, Philadelphia, PA, 8VA Puget Sound Hlth Care Sys, Seattle, WA
Context. Low serum testosterone (T) levels have been associated with cardiovascular events, but few studies have examined this association in elderly men with no history of cardiovascular disease (CVD).  

Objective. To examine the associations between T, free T, dihydrotestosterone (DHT), free DHT, and sex hormone-binding globulin (SHBG), and incident ischemic stroke.

Design. Prospective cohort study of men in the Cardiovascular Health Study (CHS).  

Outcome. Adjudicated incident ischemic stroke.

Methods. We assayed T and DHT by mass spectrometry and SHBG by immunoassay in sera from 1128 men without CVD at the 1994 CHS exam.  Levels of free T and free DHT were calculated.(1)  We used restricted cubic splines to explore the relationships between analytes and incident stroke and selected the simplest form that adequately characterized each association.  Cox regression models were used to estimate the hazard ratio (HR) for incident ischemic stroke associated with total T, free T, DHT, free DHT, and SHBG.  Analyses were adjusted for age, systolic blood pressure, prevalent atrial fibrillation and diabetes.  

Results. Over a median follow-up of 10 years, 112 men experienced incident ischemic stroke.  An inverse linear association with risk for ischemic stroke was apparent for free T and free DHT, and a quadratic association for total T, DHT, and SHBG.  For total T, the lowest risk for stroke occurred between 400-600 ng/dL; for DHT, between 0.50-0.75 ng/mL; and for SHBG, between 60-90 nmol/L.  In adjusted analyses, associations with incident ischemic stroke were significant for DHT (p=0.007), but marginal for total T (p=0.08) and SHBG (p=0.07).  Similarly, associations were significant for free DHT, HR 0.77 (95% confidence interval (CI): 0.62, 0.97) per SD [0.23 ng/mL] of DHT, but not for free T, HR 0.92 (95% CI: 0.75, 1.15) per SD [2.29 ng/dL].  Significant interactions were not found for age, hypertension, atrial fibrillation, or diabetes.

Conclusions. In this well-characterized cohort of elderly men, we did not find significant associations with incident ischemic stroke for total T or free T.  We did find a significant quadratic association with DHT and a significant inverse linear association with free DHT.  These findings suggest that serum DHT levels may be an independent risk factor for incident ischemic stroke in older men without CVD.  Further studies are needed to confirm these results and to elucidate the mechanism of such associations.

 (1) Mazer NA. Steroids.  2009; 74:512.  

Disclosure: AMM: Investigator, Abbott Laboratories, Investigator, GlaxoSmithKline, Consultant, Lilly USA, LLC, Consultant, GTx, Editor, Up To Date, Grant Review Panel, Partnership for Clean Competition. Nothing to Disclose: MMS, AMA, MLB, WTL Jr., NLS, CHH, ARC

*Please take note of The Endocrine Society's News Embargo Policy at

Sources of Research Support: This research was supported by VA Research Service, the VA Epidemiology Research and Information Center (ERIC), and the VA Geriatric Research and Information Center (GRECC).  NHLBI contracts HHSN268201200036C, N01-HC-85239, N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and NHLBI grant HL080295, with additional contribution from NINDS. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the NIA. See also