Positive association between sex hormones and inflammatory cytokines in trauma-exposed premenopausal women

Abstract

Young women are disproportionately affected by trauma, developing post-traumatic stress disorder (PTSD) at roughly twice the rate of men. Elevated levels of C-reactive protein, Interleukin-6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) are frequently found in individuals with trauma history. Given that sex hormones have been shown to have a broad range of both pro- and anti-inflammatory effects, the purpose of our study was to investigate associations of subclinical inflammation and sex hormones in trauma-exposed premenopausal women. We hypothesized that circulatory levels of sex hormones, particularly estradiol, would be negatively associated with concentrations of inflammatory cytokines in our cohort of premenopausal women, underscoring the potent cardioprotective nature of estradiol via inhibition of inflammation. We recruited 113 trauma-exposed (56.5% with PTSD) premenopausal women [Age (28 ± 7 years), BMI (27 ± 6 kg/m2)]. We collected blood samples to quantify serum levels of sex hormones, inflammatory cytokines, using the quantitative sandwich enzyme immunoassay technique (ELISA) and a Luminex assay, respectively. A composite inflammatory score was derived from eleven inflammatory biomarkers (IL-1α, IL-1β, IL-1ra, IL-6, IL-8, IL-17E, MCP-1, IFN-γ, TNF- α, IL-6R, TNF-R2) using principal component analysis. Linear regression models on the entire sample revealed that higher circulatory levels of estradiol and progesterone were associated with higher subclinical inflammation. These findings are contrary to our hypothesis and suggest that trauma and psychopathology in premenopausal women might affect how the immune system responds to circulating levels of sex hormones.