Cortisol, Testosterone, and Coronary Heart Disease

Nelson Vergel · Feb 26, 2017

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 (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).

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.

http://circ.ahajournals.org/content/112/3/332#ack-1

Fernando Almaguer · Dec 3, 2025

Nelson Vergel said:
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 (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).

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.

http://circ.ahajournals.org/content/112/3/332#ack-1

Doesnt test lower cortisol?

Nelson Vergel · Friday at 7:20 AM

This study looked at the ratio of cortisol to testosterone. High C/T ratio was associated with ischemic heart disease. It means high cortisol/normal T or normal cortisol, low T.

With a little help from my friend Claude, here is what I found:

Testosterone replacement therapy (TRT) has a generally suppressive effect on cortisol levels, though the relationship is nuanced.

Direct effects on cortisol:

Testosterone appears to modulate the hypothalamic-pituitary-adrenal (HPA) axis. Studies have shown that TRT can reduce cortisol levels, particularly in hypogonadal men. The mechanism involves testosterone's influence on corticotropin-releasing hormone (CRH) and ACTH secretion.

Key findings from research:

Exogenous testosterone tends to blunt cortisol responses to stress. In studies measuring salivary cortisol, men on TRT often show lower cortisol reactivity to psychological stressors compared to baseline. Some research suggests testosterone and cortisol have an antagonistic relationship—when testosterone rises, cortisol tends to decrease, and vice versa (the "dual-hormone hypothesis").

Clinical observations:

In practice, many men starting TRT report improvements in stress tolerance and anxiety, which may partly reflect this cortisol-lowering effect. However, the magnitude of cortisol reduction varies considerably between individuals.

Important considerations:

The effect depends on baseline hormonal status, dosing protocol, and individual variation. Supraphysiological doses may have different effects than replacement doses. Time of measurement matters significantly given cortisol's diurnal rhythm.

Both blood and salivary cortisol measurements show similar directional changes with TRT, though salivary cortisol reflects free (bioavailable) cortisol while serum measures total cortisol.