Potential Link Discovered Between Low Testosterone and Stroke

A new analysis of several prospective health studies indicates that low testosterone levels at any age are associated with an increased risk ischemic stroke in men.

Researchers from 4 hospitals in Denmark began by pulling records for 4,615 men who were enrolled in the Copenhagen City Heart Study between 1981 and 1983 and followed for up to 29 years. In all, 524 of those men suffered an ischemic stroke, at an average age of 74 years, during the follow-up period.

Men with the lowest 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 study team, which presented its findings at the Scientific Sessions of the American Heart Association’s annual meeting in Chicago, also performed a meta-analysis on 4 prospective studies and found the same association.

In all, they collected records for 10,797 men and found that the increased risk of stroke for men who started with the lowest testosterone levels — again, at or below the tenth percentile at study outset — was even higher than the first analysis suggested (HR, 1.43; 95% CI: 1.21-1.70).

The group’s poster noted that 3 of the studies only enrolled men who were at least 65 years old at the outset but that the largest of the studies enrolled men who were as young as 21 years old.

The researchers reported that they found no connection between extremely low testosterone and ischemic stroke in women and, also, that they found no connection between extremely low estradiol levels and ischemic stroke in either sex.

Still, the researchers concluded, the relationship they discovered between low testosterone and ischemic stroke in men was robust and potentially important.

Previous research has convincingly demonstrated that stroke risk is associated with factors such as obesity that are in turn associated with low testosterone, they said, but previous work had yet to firmly establish that low testosterone was itself associated with ischemic stroke risk in men.

Still, there have been several previous studies that suggest such a link.

Another Danish team published a much-cited paper in Arteriosclerosis, Thrombosis and Vascular Biology that compared testosterone levels of 144 men who had just suffered a stroke with the testosterone levels of 47 healthier controls.

Mean total serum testosterone was 13.8±0.5 nmol/L in stroke patients and 16.5±0.7 nmol/L in control subjects (P=.002). Free serum testosterone, meanwhile averaged 40.8±1.3 pmol/L in stroke patients and 51.0±2.2 pmol/L in control subjects (P=.0001).

“Both total and free testosterone were significantly inversely associated with stroke severity and 6-month mortality, and total testosterone was significantly inversely associated with infarct size,” the study authors wrote.

“The differences in total and free testosterone levels between patients and control subjects could not be explained by 10 putative risk factors for stroke, including age, blood pressure, diabetes, ischemic heart disease, smoking, and atrial fibrillation.”

Of course, different studies have reached different conclusions about whether testosterone replacement therapy increases the risk of stroke, decreases it or has no significant effect.

Large retrospective studies have reached both conclusions and regulators around the world have called for large prospective studies that will settle the matter.