Serum steroid hormone profiles in reproductive-age women with systemic lupus erythematosus: associations with clinical manifestations and disease activity

Objective: To characterize the serum steroid hormone profile in reproductive-age women with systemic lupus erythematosus (SLE) and evaluate its associations with clinical manifestations and disease activity. Methods: This cross-sectional study enrolled 39 newly diagnosed, treatment-naïve female SLE patients and 37 matched healthy controls. Fasting blood samples were collected in the morning. Serum levels of a comprehensive panel of steroid hormones (including glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens) were simultaneously quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Clinical parameters and disease activity (SLEDAI-2000) were assessed. Results: SLE patients exhibited a globally altered steroid hormone profile compared to controls. Levels of key androgens (androstenedione, testosterone, dihydrotestosterone, dehydroepiandrosterone), glucocorticoids (cortisol, corticosterone, cortisone), and mineralocorticoids (aldosterone) were significantly lower in the SLE group. In contrast, serum melatonin was markedly elevated. Analysis across menstrual phases revealed consistently lower progesterone and 17-hydroxyprogesterone, but higher estradiol levels in SLE patients. Correlation analyses demonstrated that lower glucocorticoid and androgen levels were associated with increased inflammatory markers (e.g., lower complement C3/C4, higher IL-6) and hematological abnormalities. Crucially, reduced aldosterone levels correlated with higher 24-hour proteinuria and SLEDAI scores. Conclusion: Reproductive-age women with SLE display a distinct steroid hormone signature suggestive of hypothalamic-pituitary-adrenal (HPA) axis suppression, characterized by a broad deficiency in adrenal and gonadal steroids alongside hyperestrogenism and elevated melatonin. These hormonal imbalances are significantly correlated with disease activity, inflammation, and renal involvement. The serum steroid hormone profile may serve as a valuable biomarker for assessing SLE activity and provides insights into the endocrine-immune interplay in this disease.