Cortisol, Testosterone, and Coronary Heart Disease

Abstract

Background-There is a popular belief that chronic stress causes heart disease through psychoneuroendocrine mechanisms. We have examined whether an elevated circulating cortisol-to-testosterone ratio increases the risk of ischemic heart disease. Methods and Results-We undertook 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 (PϽ0.001). 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, Pϭ0.003). 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, Pϭ0.18). 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, Pϭ0.81). Conclusions-This is the first population-based prospective study that has found a specific association between cortisol:testosterone ratio and incident ischemic heart disease, apparently mediated through the insulin resistance syndrome. Whether this reflects the effects of chronic stress, behavioral factors, or genetic influences remains to be determined. (Circulation. 2005;112:332-340.)

Androgen deficiency: effects on body composition

“…Four large Pituitary (2009) epidemiologic studies examined the relationship between testosterone levels and mortality to determine whether hypogonadism is a risk factor for mortality, particularly cardiovascular mortality. Two demonstrated an increase in all-cause mortality rates, including cardiovascular mortality [46,47], whereas the other two found no association [48,49]. It has been noted that the difference in the study results may reflect differences in mean age and baseline testosterone levels.…”

Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study

“…Studies performed in community-dwelling males have provided conflicting results (see for review reference (1)). Some authors did not report any association between testosterone levels and CV morbidity, after adjusting for confounders (33,70,71,(105)(106)(107)(108). Conversely, data from the Health In Men Study (74) suggested a strong relationship between low to normal levels of TT and incidence of cerebrovascular events, whereas overt low testosterone levels (TT!8 nmol/l) were not significantly related to incidence of transitory ischemic attack (TIA) and stroke in elderly men.…”

Use of the Testosterone/Cortisol Ratio Variable in Sports

“…Extreme levels of circulating androgens, whether high or low can have negative effects on women's health. In a population-based prospective study of chronic stress-related heart disease in men, high cortisol to testosterone ratio showed strong positive associations with the components of insulin resistance syndrome [6]. In women, the chronic hypercortisolism was found to be associated with isolated exercise-induced amenorrhea.…”

“…Trained runners presented mild hypercortisolism while in basal conditions and, during exercise, they had milder responses of the HPA axis [2,49]. Smith [6] associated the general concept of stress to the relationship between cortisol and testosterone and found that the high cortisol to testosterone ratio showed strong positive associations with the components of insulin resistance syndrome. Nevertheless, the association of the stress caused by physical exercise with general health outcomes, especially in men, is an issue that still needs to be deepened.…”