SHBG an independent predictor for the metabolic syndrome
MedWire News: Sex hormone-binding globulin (SHBG) levels but not testosterone levels are an independent predictor for incident and prevalent metabolic syndrome, show US researchers.
Although their analyses initially revealed a significant association of total and free testosterone levels with risk for the metabolic syndrome, only SHBG was associated both cross-sectionally and longitudinally with the risk, they say.
The authors say the evidence for a relationship between free testosterone and the metabolic syndrome has been inconsistent or weak, "suggesting that SHBG may be the primary determinant of the apparent relationship between total testosterone and the metabolic syndrome."
To investigate, Shalender Bhasin (Boston University, Massachusetts, USA) and colleagues analyzed associations between hormone levels and the metabolic syndrome in 1407 men from the offspring (generation 2) of original participants of the Framingham Heart Study. The men have completed eight examinations since enrollment, at 4-to-8-year intervals.
As reported in the journal Diabetes Care, cross-sectional analyses revealed that both total and free testosterone were significantly associated with risk for the metabolic syndrome. The men in the lowest quartile of total testosterone were 4.5 times more likely to have the metabolic syndrome than those in the highest quartile. For free testosterone, the risk was increased 1.9 times in the lowest quartile compared with the highest.
However, these associations were substantially attenuated after adjusting for age, smoking, SHBG, body mass index (BMI), and homeostatic model assessment of insulin resistance (HOMA-IR).
The authors also found that SHBG levels were significantly negatively associated with risk for the metabolic syndrome in cross-sectional analysis. Men in the lowest quartile of SHBG had nearly a five-fold greater probability of having the metabolic syndrome than those in the highest quartile.
However, unlike total and free testosterone, this association remained after adjusting for covariates.
These findings were confirmed in a validation sample comprising 1912 men from generation 3.
Furthermore, longitudinal analysis revealed that SHBG at the seventh examination, but not total or free testosterone, was significantly associated with incident metabolic syndrome at the eighth examination.
Again, the relationship persisted after adjusting for age, smoking, BMI, and HOMA-IR.
"These data have clinical implications and suggest that previously reported relationships between testosterone and the metabolic syndrome should be interpreted cautiously," write Bhasin and team.
They say their findings indicate that prevention strategies should focus on factors such as adiposity, insulin resistance, and inflammation - which may affect SHBG levels as well as risk for the metabolic syndrome - rather than on testosterone therapy.
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By Sally Robertson