Kupelian V et al. (2006) Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. J Clin Endocrinol Metab 91: 843–850

A new study has found that low levels of total testosterone or sex-hormone-binding globulin (SHBG) predict onset of the metabolic syndrome. Kupelian et al. identified 950 men enrolled in the MASSACHUSETTS MALE AGING STUDY with complete follow-up data, who did not have the metabolic syndrome at baseline. The association was strongest for SHBG, particularly in lean men (BMI <25), in whom low SHBG levels conferred a more than twofold increase in risk of incident metabolic syndrome. Among overweight or obese men, on the other hand, the authors observed no increased risk of developing the metabolic syndrome attributable to low hormone levels. Similarly, clinical androgen deficiency only predicted development of the metabolic syndrome in lean men.

These observations strongly support the role of obesity as the predominant risk factor for the development of the metabolic syndrome, say the authors. For men with a BMI ≥25, they suggest that exercise and weight reduction would have a greater effect on their risk of developing the metabolic syndrome than androgen-replacement therapy.

In lean men, who would otherwise be considered at low risk of developing the metabolic syndrome, the presence of low SHBG, total testosterone, or clinical androgen deficiency might be a useful predictive marker not only for the development of the metabolic syndrome, but also for subsequent diabetes or cardiovascular disease. These men could be targeted for early introduction of therapies designed to reduce their cardiovascular risk.