Sex hormone-binding globulin and serum testosterone are inversely associated with C-reactive protein levels in postmenopausal women at high risk for cardiovascular disease

PURPOSE: 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. METHODS: 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 In-transformed and relationships were assessed with Spearman correlations and linear regression. RESULTS: In-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 In-SHBG and In-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 In-SHBG and In-CRP was strongest among the leanest women. None of the sex-hormones predicted In-CRP among HT-users. CONCLUSIONS: 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.