Cross-sectional association between markers of inflammation and serum sex steroid levels in the postmenopausal estrogen/progestin interventions trial

Background: Standard risk factors do not adequately capture cardiovascular risk in postmenopausal women. We sought to determine the associations between levels of sex steroids and levels of inflammatory markers in postmenopausal women. Methods: We analyzed baseline data from a subset of postmenopausal women aged 45-64 years who had stored samples during a randomized controlled trial. We measured levels of C-reactive protein (CRP), interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), soluble intercellular adhesion molecule (sICAM), and circulating sex steroids. Multiple linear regression models were created with each of the following hormone levels as the primary exposure variable: estrone, total estradiol, bioavailable estradiol, total testosterone, bioavailable testosterone, progesterone, and sex hormone-binding globulin (SHBG). Sociodemographic and lifestyle covariates were derived from standardized self-report questionnaires and direct measurement (weight, height). Results: Mean age of the 623 women was 56 years. After adjustment for age, body mass index (BMI), physical activity, alcohol consumption, and smoking, the bioavailable testosterone level (p = 0.03) was positively and the SHBG level (p = 0.001) was negatively associated with the logCRP level. The increment in CRP level between the highest and lowest quartile of bioavailable testosterone was 1.28 mu g/mL. The increment in CRP level between the lowest and highest quartile of SHBG was 2.62 mu g/mL. Compared with SHBG or bioavailable testosterone as predictors of logCRP in separate regression models, when both SHBG and bioavailable testosterone were included in the same multivariate linear regression model, only SHBG remained a statistically significant predictor of logCRP. Progesterone level was positively associated with the logMMP-9 level (p < 0.001); no other sex steroid level was associated with the logMMP-9 level. In multiply adjusted models, no association was found between levels of any sex steroid and IL-6 or sICAM level.