The Association Between Sex Hormone Binding Globulin And C-Reactive Protein Levels in Premenopausal Women

Abstract

Uncertainty remains regarding the effect of female sex hormones on the immune system and inflammation process. Sex Hormone Binding Globulin (SHBG) modulates the relative effects of estrogen and testosterone, specifically promoting estrogen effects systemically. Furthermore, estrogen enhances the synthesis of SHBG and was reported to have a role in immune modulation. Thus, it is believed that SHBG can influence inflammation and associated inflammatory markers such as C-Reactive Protein (CRP). There are few studies on the association between SHBG and CRP levels in premenopausal women. If this association is proven to be true, it could explain the mechanism by which some inflammatory and autoimmune diseases flare up or remit in women during their reproductive years. This study investigated the association between SHBG and CRP in premenopausal women (age 20-44 yrs) using NHANES national data for the cycle 2015- 2016. Women who were pregnant, breast feeding, had hysterectomy or both ovaries removed, had menarche at age > or = 20, had not started menarche yet, or currently had specific comorbidities were excluded. The outcome variable was CRP concentration and the main independent variable was SHBG concentration. Univariate and bivariate analysis were used to describe the sample and test the correlation of independent variables with CRP. Multivariable linear regression analysis was used to test the association between SHBG and CRP while controlling for estrogen and markers of metabolic syndrome (e.g. BMI) following diagnostics analysis. Although SHBG was significantly and inversely associated with CRP in the unadjusted bivariate analysis (r= -0.14), it was found to have non-statistically significant weak positive association with CRP (r= 0.05) after controlling for multiple covariates and including significant interaction terms. BMI contributed the most to CRP variance in this study full model (semi-partial R2= 0.12). The positive association between SHBG and CRP persists after replicating an existing model in the literature. Further research is needed to test this research question in reproductive age-women using nationally representative samples after excluding women using exogenous hormones, controlling serum progesterone and defining the current phase of menstrual cycle.