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 ln-transformed and relationships were assessed with Spearman correlations and linear regression.

Results

ln-SHBG (β = −0.40; p < 0.01) and ln-testosterone (β = −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 (β = −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.

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.

Key words: Cardiovascular Diseases, C-Reactive Protein, Gonadal Steroid Hormones, Postmenopause

Selected Abbreviations and Acronyms: BMI, body mass index, CRP, C-reactive protein, CVD, cardiovascular disease, EDTA, ethylenediamine-tetra-acetic acid, FAI, free androgen index, FEI, free estrogen index, HDL, high density lipoprotein, HT, hormone therapy, LN, natural logarithm, SHBG, sex hormone binding globulin, WHS, Women's Health Study

• ∗ Adjusted for age, body mass index, and development of cardiovascular disease.