By Sahar Bedrood B.S. and Asher Kimchi M.D.

Bristol, UK- The contributions of stress to many disease processes have been studied for many years. While the stressors and physical symptoms of stress can be subjective, biological markers have been used to study stress-associated disease. A prospective cohort study conducted by George Davey Smith, DSc et al from the University of Bristol in the United Kingdom, compared cortisol to testosterone ratios to incidence and mortality of ischemic heart disease (IHD). The study found a specific association between cortisol:testosterone ratio and incident ischemic heart disease, apparently mediated through the insulin resistance syndrome. This study was published in the July 19, 2005 issue of Circulation. 

Neuroendocrine changes have been considered a central component of stress for many years. Speculation about the biological effects of stress on disease processes has particularly focused on glucocorticoids, which can show long-term elevation in response to chronic stressors. Glucocorticoids also suppress testosterone levels in men. A high cortisol to testosterone ratio is a biological indicator of chronic high stress.  

This study was a prospective, cohort study of 2512 men aged 45 to 59 years between 1979 and 1983 from Caerphilly, South Wales, with a mean follow-up of 16.5 years. Subjects underwent a clinical examination, and morning fasting blood samples were taken for analysis of cortisol levels, testosterone levels, and other cardiovascular risk factors. The ratio of cortisol to testosterone showed weak associations with potential confounding factors but strong positive associations with components of the insulin resistance syndrome (P<0.001). A positive linear trend was seen across quintiles of cortisol:testosterone ratio for incident ischemic heart disease (age-adjusted OR per z score change in ratio 1.22, 95% CI 1.07 to 1.38, P=0.003). This was markedly attenuated after adjustment for components of the insulin resistance syndrome (age-adjusted OR per z score change in ratio 1.10, 95% CI 0.96 to 1.25, P=0.18). There was no association between the cortisol:testosterone ratio and other causes of death (age-adjusted hazard ratio 0.99, 95% CI 0.88 to 1.11, P=0.81). 

In this prospective study, C/T ratio was positively associated with IHD mortality and incidence. Adjustment for potential socioeconomic and behavioral confounding variables had little influence on these associations, but they appeared to be mediated by components of the insulin resistance syndrome (elevated blood pressure, triglyceride levels, body mass index, total cholesterol, HDL cholesterol, and impaired glucose tolerance). This suggests that methods of reducing the C/T ratio may improve insulin resistance and reduce the risk of CHD. 
 
Co-authors: George Davey Smith, DSc; Yoav Ben-Shlomo, BSc, MBBS, MRCP, FFPHM, PhD; Andrew Beswick, BSc; John Yarnell, MBChB, DPH, MSCM, MD, MFPHM (Ire), FFPHM; Stafford Lightman, MBChB, PhD, FMedSci; Peter Elwood, DSc, MD, FRCP, FFPHM