Disturbed sex hormone milieu in males and females with major depressive disorder and low-grade inflammation

Sex hormones have biological effects on inflammation, and these might contribute to the sex -specific features of depression. C -reactive protein (CRP) is the most widely used inflammatory biomarker and consistent evidence shows a significant proportion (20 -30 %) of patients with major depressive disorder (MDD) have CRP levels above 3 mg/L, a threshold indicating at least low-grade inflammation. Here, we investigate the interplay between sex hormones and CRP in the cross-sectional, observational Biomarkers in Depression Study. We measured serum high -sensitivity (hs-)CRP, in 64 healthy controls and 178 MDD patients, subdivided into those with hs-CRP below 3 mg/L (low -CRP; 53 males, 72 females) and with hs-CRP above 3 mg/L (high -CRP; 19 males, 34 females). We also measured interleukin-6, testosterone, 17-8-estradiol (E2), progesterone, sex -hormone binding globulin (SHBG), follicle -stimulating and luteinising hormones, and calculated testosterone -to -E2 ratio (T/E2), free androgen and estradiol indexes (FAI, FEI), and testosterone secretion index. In males, high -CRP patients had lower testosterone than controls ( p = 0.001), and lower testosterone ( p = 0.013), T/E2 ( p < 0.001), and higher FEI ( p = 0.015) than low -CRP patients. In females, high -CRP patients showed lower SHGB levels than controls ( p = 0.033) and low -CRP patients ( p = 0.034). The differences in testosterone, T/E2 ratio, and FEI levels in males survived the Benjamini-Hochberg FDR correction. In linear regression analyses, testosterone (8 = -1.069 p = 0.033) predicted CRP concentrations (R 2 = 0.252 p = 0.002) in male patients, and SHBG predicted CRP levels (8 = -0.628 p = 0.009, R 2 = 0.172 p = 0.003) in female patients. These findings may guide future research investigating interactions between gonadal and immune systems in depression, and the potential of hormonal therapies in MDD with inflammation.