Dr. Claes Ohlsson (University of Gothenburg, Sweden) and colleagues in their paper stated that the association remains even after adjustment for traditional cardiovascular risk factors and excluding those with CVD at baseline.
Senior author Dr. Asa Tivesten (University of Gothenburg) stated that, "This paper is an important start, because previously data have been inconsistent about whether there is an association between serum testosterone and CVD events or not. We now know there is an association, but we don't know what is causing it."
Ohlsson and colleagues analyzed baseline levels of testosterone in 2416 men aged 69 to 81 years who were participating in the prospective, population-based Osteoporotic Fractures in Men Study (MrOS). They also measured sex-hormone-binding globulin (SHBG) and obtained cardiovascular clinical outcomes from central Swedish registries.
This paper is an important start, because previously data have been inconsistent about whether there is an association between serum testosterone and CVD events or not.
Over a median of five years of follow-up, there were 485 fatal and nonfatal cardiovascular events, and both total testosterone and SHBG levels were inversely associated with risk of CV events (trend over quartiles p=0.009 and p=0.012, respectively).
Tivesten said initially they used quartile 1 (i.e., the lowest levels of serum testosterone) as a reference and compared events in this group with those in quartiles 2, 3, and 4. However, they saw no significant difference in the number of CV events between the first three quartiles.
But men in the highest quartile of testosterone (>550 ng/dL) had a lower risk of CV events compared with men in the lower three quartiles (hazard ratio 0.70; p=0.002). This association remained when the first 2.6 years of follow-up were excluded -- in order to rule out any effect of baseline (subacute) disease -- and was only slightly attenuated after adjustment for confounding factors (HR 0.77; p=0.032).
In models that included testosterone and SHBG, testosterone, but not SHBG, predicted risk.
Tivesten says the research does not suggest that testosterone supplements should be used to try to prevent cardiovascular disease and that more work is required to investigate this, because one trial using high doses of exogenous testosterone in older men has actually shown an increase in cardiovascular events.
However, what is established, she says, is that men with testosterone deficiency should receive testosterone supplementation. But there is currently a debate as to what level of testosterone represents a true deficiency, so this is a gray area, she notes.
And in older men, she adds, the issue is confounded by the fact that testosterone levels decline naturally with age: "So should we regard all elderly men as testosterone deficient? Or just look at subgroups?"
Ohlsson C, Barrett-Connor E, Bhasin S, et al. High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MrOS (osteoporotic fractures in men) Study in Sweden. J Am Coll Cardiol, Oct. 2011; 58:1674-1681.