Sex hormones and inflammation in trauma-exposed premenopausal women

Women, particularly young women, are disproportionately affected by trauma, experiencing post-traumatic stress disorder (PTSD) at roughly twice the rate of men. Increased inflammation is a hallmark of PTSD and is also a known risk factor for cardiovascular disease (CVD). Given that estradiol (E2), progesterone (P4), and testosterone (T) have been shown to have a broad range of both pro- and anti-inflammatory effects, the purpose of our study was to investigate whether plasma levels of sex hormones are associated with subclinical inflammation in premenopausal women with PTSD. We hypothesized that E2, P4, and T would be negatively associated with inflammatory cytokines such as tumor necrosis factor (TNF), Interleukins (IL) and interferons (IFN), individually and/or combined as an inflammatory score. We recruited 115 trauma-exposed premenopausal women [Age (27.87 ± 6.9 years), BMI (27.07 ± 6.26 kg/m 2 )]. We collected blood samples to quantify plasma levels of E2, P4, T, and inflammatory biomarkers, using the quantitative sandwich enzyme immunoassay technique (ELISA) and a Luminex assay, respectively. A composite inflammatory score was derived from six biomarkers (TNF-R2, IL-1α, IL-17E, IL-8, IL-6R, IFN-γ) via principal component (PC) analysis. Each hormone was divided into tertiles based on their distribution (T1 = low, T2 = medium, T3 = high). These tertile groupings were created to evaluate potential relationships between hormone levels and inflammation. In subsequent analyses, the tertiles were used in one-way ANOVA models to compare mean values of the composite inflammatory score (PC1) across hormone levels, providing a hormone–inflammation association before fitting linear regression models to the continuous hormone data. The composite inflammation score (PC1) differed across T1, T2, and T3 for E2 (P = 0.013) and T (P < 0.001) and remained consistent even after adjusting for age and BMI. Tukey’s pairwise comparison for E2 indicated that T3 had a significantly lower inflammation score than T1 (difference = −1.03, 95 % CI −1.86 to −0.20, P = 0.011). Likewise, for T, women in both T2 (P = 0.023) and T3 (P < 0.001) had lower inflammation scores than T1. Linear regression models underscored that overall, higher E2 and T levels were associated with lower inflammation, whereas there was no association found with P4. In conclusion, these findings suggest that the subclinical inflammation observed in PTSD might be dependent on circulating levels of sex hormones for premenopausal women. Support or Funding Information: This study was supported by grants K01HL161027, R03HL174817, UMN CTSI UL1TR002494 and U54AT012307. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.