Sex-hormone-binding Globulin a Potential Biomarker for Heart Risks in Men

NEW YORK (Reuters Health) – Levels of sex-hormone-binding globulin (SHBG) may serve as a biomarker for cardiovascular disease (CVD) risks in middle-aged and older men, independent of total testosterone levels, according to a large observational study.

In men aged 40 to 69 years, endogenous total testosterone levels were not associated with risk of CVD events, but men with lower SHBG levels had higher risk for myocardial infarction (MI), the study team reports in Annals of Internal Medicine.

SHBG is the major binding protein for circulating testosterone, but few studies have looked at whether the SHBG level, independent of testosterone, is associated with CVD events.

To investigate, Dr. Bu Yeap of the University of Western Australia in Crawley and colleagues used UK Biobank data to analyze the association of serum testosterone and SHBG levels with CVD events in more than 210,000 men aged 40 to 69 years.

Over nine years, 8,790 men (4.2%) had a CVD event. After fully adjusting for sociodemographic, lifestyle and medical factors, and for SHBG, total testosterone levels were not associated with risk of any CVD events.

In contrast, after adjusting for all these factors, and for total testosterone, men with lower SHBG levels were at significantly increased risk of MI (hazard ratio, 1.23) but at lower risk of ischemic stroke (HR, 0.79) and heart failure (HR, 0.69), compared with men with higher SHBG levels.

The findings suggest that total testosterone levels do not predict CVD events middle-aged and older men, but that SHBG levels could serve as a biomarker for CVD risk, the researchers say.

Strengths of the study include the large sample size, duration of follow-up and large numbers of outcome events. Limitations include its observational nature, which can’t address causality and the fact that serum total testosterone and SHBG and other covariates were measured only once at baseline, the researchers note.

In a linked editorial, Dr. Di Zhao and Dr. Eliseo Guallar of Johns Hopkins University in Baltimore, Maryland, say the finding that endogenous testosterone levels in middle-aged and older men were not independently associated with CV events indicates that it is “unlikely that the decline in serum testosterone levels is a major explanation for the age-related increase in CVD.”

“These findings also provide some warning against the use of testosterone therapy for the prevention of CVD in men. The cardiovascular safety profile of testosterone therapy is still uncertain, and careful evaluation of the individual cardiovascular risk profile is needed before initiation of testosterone therapy for any patient,” they write.

Funding for the study was provided by the Western Australian Health Translation Network, Medical Research Future Fund, and Lawley Pharmaceuticals.

SOURCE: and Annals of Internal Medicine, online December 27, 2021.

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