Clin Endocrinol (Oxf). 2009 Sep 10

Association between sex steroids and cognition in elderly men.

Leblanc ES, Wang PY, Janowsky JS, Neiss MB, Fink HA, Yaffe K, Marshall LM, Lapidus JA, Stefanick ML, Orwoll ES; for the Osteoporotic Fractures in Men (MrOS) Research Group.

Division of Endocrinology, Oregon Health & Science University, Portland OR (ESL) Bone and Mineral Unit, Oregon Health & Science University, Portland OR (PYW, LMM, JAL, ESO), Behavioral Neuroscience Department, Oregon Health & Science University, Portland OR (JSJ, MBN), Geriatric Research Education and Clinical Center, VA Medical Center, Minneapolis, MN (HAF), Departments of Psychiatry, Neurology and Epidemiology University of California, San Francisco, San Francisco, CA (KF) Stanford Prevention Research Center, Stanford University School of Medicine, Stanford CA (MLS).

Objective. Examine the association of cognitive function with sex steroid and sex hormone binding globulin (SHBG) levels among elderly men. Design. Prospective cohort study, The Osteoporotic Fractures in Men Study (MrOS), consisting of 5995 US community dwelling men 65 years or older. Patients. 1602 men chosen randomly from MrOS cohort for sex steroid level measurements by Mass Spectrometry (MS) at baseline. 2623 MrOS participants with sex steroids measured using RIA were also examined. Measurements. Baseline and follow-up (4.5 years later) performance on two cognitive tests: Trails B (executive function and motor speed) and 3MS (global cognitive function). Baseline total testosterone and estradiol were measured by MS. Free testosterone (free-T) and free estradiol (free-E) were calculated. SHBG was measured by radioimmunoassay. Data were analyzed using linear regression. Results. Baseline free-T and free-E levels were not associated with cognitive performance or change in cognition, following adjustment for age, education, race, health status and alcohol use. Baseline SHBG levels were inversely associated with follow-up trails B (p=0.03) and 3MS performance (p=0.02). Higher SHBG was associated with an increased risk of cognitive decline. Total sex steroid levels were not associated with cognitive performance. Conclusions. Despite large numbers of participants and rigorous sex steroid measurements, we did not observe an association between cognition and either testosterone or estradiol levels. We conclude that endogenous sex steroids in the normal range are not related to executive function or global cognitive function in elderly men. High SHBG deserves further examination as a risk factor for cognitive decline.