Interrelation Between Sex Hormones and Plasma Sex Hormone-Binding Globulin and Hemoglobin A1c in Healthy Postmenopausal Women

Background: Androgenicity, as measured by low sex hormone-binding globulin (SHBG) and elevations in testosterone and free androgen index (FAI), is associated with adverse cardiovascular (CV) outcomes, possibly due to effects on insulin resistance and glycemia. Methods: Glycosylated hemoglobin (HbA1c) concentration, SHBG, and sex hormones were available in 200 nondiabetic postmenopausal women who were not using hormone therapy (HT) in the Women's Health Study. Of these, 98 were cardiovascular disease (CVD) cases; the remainders were matched controls. To achieve normality, continuous values were log transformed and geometric means were calculated. Associations between sex hormones and HbA1c were examined using general linear models (GLM), partial correlations, and multiple linear regression analyses. Results: Lower SHBG levels and higher FAI and HbA1c values were found among the CVD cases, and all analyses were adjusted for this factor. In GLM, higher values of HbA1c were observed in the highest quartiles of FAI and the lowest quartiles of SHBG. However, the correlation between SHBG and HbA1c across quartiles was eliminated after adjusting for body mass index (BMI). In partial correlations, HbA1c values were inversely associated with SHBG (r = -0.19, P = 0.008) and positively associated with FAI (r = 0.19, P = 0.01), even after adjusting for age, CVD case-control status, and BMI. In multivariate models, a significant inverse association between SHBG and HbA1c persisted, as well as a significant positive association between FAI and HbA1c. Conclusions: Androgenicity, as measured by low SHBG and high FAI, is associated with glycemia, and thereby may contribute to CVD risk in postmenopausal women.