Endocrine Abstracts

JOINT1878

Context/Object: The relationship between hyperandrogenemia and metabolic abnormalities in women with polycystic ovary syndrome (PCOS) is still object of study. The biological effects of testosterone are modulated by SHBG, a protein, regulated by several factors, which binds circulating testosterone and regulates its bioavailability. Both the increase of free testosterone (FT) and the reduction of SHBG have been associated with insulin resistance and metabolic alterations. Whether SHBG may play an independent role in this phenomenon is still unclear, and the use of SHBG in FT calculation makes this analysis very difficult. Aim of this study was to investigate potential differences in the relationships of SHBG and FT with the metabolic, hormonal and phenotypic features of PCOS, using a measurement of serum FT independent of SHBG assay. Study design and Subjects. Cross-sectional study including 280 women with PCOS diagnosed by the Rotterdam criteria.

Methods: FT was measured by equilibrium dialysis with subsequent direct assay of the hormone by LC-MS/MS on the dialysate. Total testosterone and androstenedione were assayed by LC-MS/MS. Insulin sensitivity was measured by the hyperinsulinemic euglycemic clamp.

Results: Both SHBG and FT showed statistically significant and opposite relationships with anthropometric and metabolic parameters. Categorizing women with PCOS on the basis of their SHBG and FT levels (normal SHBG/normal FT, n = 74; low SHBG/normal FT, n = 39; normal SHBG/high FT, n = 39; low SHBG/high FT, n = 128), the two subgroups with low SHBG, and either normal or high FT, had worse anthropometric and metabolic profiles than subjects with normal SHBG/normal FT. This phenomenon was especially enhanced in women with low SHBG/high FT. Conversely, the subgroup with normal SHBG/high FT differed from women with normal SHBG and normal FT only for higher fasting insulin. In multivariable analysis, age, fat mass, insulin sensitivity and FT were all independent predictors of SHBG, whereas only insulin sensitivity and SHBG, but not fat mass, were independent predictors of FT. After adjusting data for age and fat mass, both FT and SHBG were independent predictors of insulin sensitivity. Moreover, in logistic analysis, the presence of metabolic syndrome was independently predicted by SHBG, but not by FT.

Conclusions: In women with PCOS, low SHBG and high FT levels are independently associated with insulin resistance, and the coexistence of these features enhances metabolic abnormalities.