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Lower Testosterone Levels Predict Incident Stroke and Transient Ischemic Attack in Older Men

School of Medicine and Pharmacology (B.B.Y., S.A.P.C., L.F., G.J.H.), University of Western Australia, Crawley, WA 6009, Australia; Department of Endocrinology and Diabetes (B.B.Y.), Fremantle Hospital, Fremantle, WA 6959, Australia; WA Centre for Health and Ageing (Z.H., O.P.A., L.F.), University of Western Australia, Crawley, WA 6009, Australia; School of Psychiatry and Clinical Neurosciences (O.P.A.), and School of Surgery (P.E.N.), University of Western Australia, Crawley, WA 6009, Australia; PathWest, Department of Biochemistry (S.A.P.C.), Fremantle Hospital, Fremantle, WA 6959, Australia; School of Population Health and Clinical Practice (K.J.), University of Adelaide, SA 5005, Australia

Address all correspondence and requests for reprints to: A/Prof Bu Beng Yeap, MBBS, Ph.D., School of Medicine and Pharmacology, Level 2, T Block, Fremantle Hospital, Alma Street, P.O. Box 480, Fremantle, WA 6959, Australia. E-mail: byeap{at}cyllene.uwa.edu.au.

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.