Testosterone Level Not Associated with Atherosclerosis Risk, But May Be Marker for Other Cardiovascular Risk Factors

New research suggests that low testosterone levels in older men are less likely to lead to cardiovascular disease than a sign of underlying problems that are the real cause.

Many previous studies have noted a significant negative correlation between initial testosterone and subsequent illness, so researchers from Johns Hopkins University set out to explore the connection.

The researchers used male patient data from the Atherosclerosis Risk in Communities (ARIC) study to assess the cross-sectional relationship between endogenous plasma testosterone, mean carotid intima media thickness (IMT) and subsequent cardiovascular disease, cardiac mortality, and all-cause mortality.

The cohort of the retrospective study included 1,558 men (average initial age, 63.1 years) from visit 4 of the ARIC study, men who used no androgen-boosting medications and had no history of coronary heart disease, stroke or heart failure. The study data documented initial testosterone levels and carotid IMT and followed each patient for an average of 12.8 years.

Testosterone levels were not associated either positively or negatively with carotid IMT. Lower initial testosterone was, however, significantly associated with a number of other conditions that are known to increase the risk of cardiovascular disease: higher body mass index, greater waist circumference, diabetes, hypertension, lower HDL (p=0.01 in all cases).

Lower initial testosterone levels were also associated with a behavior that is known to lower the risk of cardiovascular disease: never smoking (p=0.01).

When researchers used multivariate analysis to adjust for all these factors and then used testosterone levels to break the cohort into quartiles, they found no remaining association between initial testosterone and subsequent cardiovascular disease or death.

“Our results are reassuring that neither high nor low testosterone levels directly predict atherosclerosis, but are a marker for other cardiovascular risk factors,” the study authors wrote in The Journal of Clinical Endocrinology & Metabolism.

Unadjusted data that did not consider the significant negative association between testosterone levels and risk factors like diabetes, hypertension and body mass index would have a shown negative association between initial testosterone and cardiovascular disease, and that finding would have echoed results from many earlier studies.

Just last year, a retrospective study that followed 4,615 men for as many as 29 years found that men with the lowest initial testosterone levels — at or below the tenth percentile when initially measured — were a third more likely to have ischemic strokes than all other men (Hazard ratio [HR], 1.33; 95% Confidence interval [CI], 1.04-1.71).

The same study team then performed a meta-analysis on 4 prospective studies with data from 10,797 men and found that men with the lowest initial testosterone levels faced an even greater elevation in stroke risk (HR, 1.43; 95% CI: 1.21-1.70).

A smaller study performed by researchers from Cedars-Sinai Heart Institute found that lower testosterone levels were associated with a greater risk of sudden cardiac arrest. Men in the study group who had experienced sudden cardiac arrest were found to have a median testosterone level of 4.4 ng/mL. The median testosterone level for men from the control group was 5.4 ng/mL (P= 0.01).

A number of studies have tried to determine whether relative testosterone deficiency is actually a cause of cardiovascular disease but none of them has provided definitive answers. The Hopkins study disagrees with other work that argues low testosterone causes disease by causing some of the risk factors the Hopkins study controlled for.

Studies that have sought the answer by investigating whether testosterone supplementation reduces the risk of cardiovascular disease have reached contradictory conclusions.