Men with elevated serum sex hormone-binding globulin (SHBG) or lower total testosterone (T) levels might be at greater risk for cardiovascular disease (CVD) and CVD-related mortality, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

To evaluate the associations between serum SHBG, total T, incident CVD, and CVD-related mortality in men, researchers conducted a prospective study of 1492 community-dwelling middle-aged or elderly men (aged 35-80 years) from a previous cohort. Men were eligible for inclusion if they were without prevalent CVD and had complete data for serum SHBG and total T levels provided at baseline and follow-up (median, 4.94 years). They also could not be receiving anti-androgen therapy.

Of the total population, 6.7% (n=101) developed incident CVD over follow-up. At baseline, men who developed CVD tended to be older, have hypertension, and have type 2 diabetes, as well as higher waist circumference, low-density lipoprotein cholesterol levels, hemoglobin A1c, SHBG levels, and plasma high-sensitivity C-reactive protein levels, and lower total T and physical activity levels.

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Using multivariable models, the researchers discovered incident CVD was significantly and independently associated with higher baseline SHBG (odds ratio [OR], 1.54 per SD increase; P =.003) and lower baseline total T (OR, 0.71 per SD decrease; P =.03). Furthermore, a decrease in total T between baseline and follow-up was associated with incident CVD (OR, 0.72; P =.01). However, CVD mortality at any age was not associated with SHBG (hazard ratio [HR], 0.69; P =.40) or total T (HR, 0.60; P =.18).

Several limitations were noted for this study, including a small number of incident CVD cases and CVD-related mortality.

Despite discovering significant associations, the investigators said, “[m]ore research is needed to replicate these findings with larger populations. The reason for the associations with SHBG and whether treatment with testosterone will abrogate the risk of CVD, needs to be determined.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Reference

Gyawali P, Martin SA, Heilbronn LK, et al. Higher serum sex hormone-binding globulin (SHBG) levels are associated with incident cardiovascular disease (CVD) in men [published online August 7, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2019-01317