Sex Hormone-Binding Globulin and Serum Testosterone are Inversely Associated with C-Reactive Protein Levels in Postmenopausal Women at High Risk for Cardiovascular Disease

Abstract

C-reactive protein (CRP), androgens, and menopausal loss of endogenous estrogens are associated with cardiovascular disease (CVD). We hypothesized that high androgens, low estradiol, and low sex hormone-binding globulin (SHBG) would be associated with high CRP in postmenopausal women. CRP, SHBG, estradiol, and total testosterone were measured using baseline bloods of 221 hormone therapy (HT)-nonusers and 162 HT-users from a cross-sectional analysis in a nested case-control sample of the Women's Health Study. Hormones and CRP were ln-transformed and relationships were assessed with Spearman correlations and linear regression. ln-SHBG (beta=-0.40; p<0.01) and ln-testosterone (beta=-0.24; p=0.04) were the only independent hormonal predictors of ln-CRP among HT-nonusers after adjusting for age, hypertension, smoking, body mass index, diabetes, exercise, HDL cholesterol, alcohol intake, and CVD occurrence during follow-up. Upon stratification, the association between ln-SHBG and ln-CRP persisted among HT nonusers who subsequently developed CVD (beta=-0.55; p=0.01), but not among women who remained CVD-free (p=0.28). The inverse relationship between ln-SHBG and ln-CRP was strongest among the leanest women. None of the sex-hormones predicted ln-CRP among HT-users. SHBG and total testosterone were inversely associated with CRP among HT nonusers in this study. The relationship between SHBG and CRP was more strongly inverse among leaner women.