{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:48:51Z","timestamp":1785527331277,"version":"3.56.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate steroid hormone profiles and therapeutic modulation in Chinese postmenopausal rheumatoid arthritis (RA) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This cross-sectional study enrolled 138 postmenopausal women, including 88 RA patients stratified by treatment status (23 treatment-na\u00efve, 35 on methotrexate [MTX] monotherapy, and 30 receiving MTX plus glucocorticoids [GC]) and 50 age-matched healthy controls. Using liquid chromatography-tandem mass spectrometry (LC-MS\/MS), we quantified 36 steroid hormones\/metabolites to assess treatment-associated endocrine alterations. Group comparisons employed non-parametric Kruskal-Wallis test for multi-group comparisons, with <jats:italic>post-hoc<\/jats:italic> Mann-Whitney U tests and false discovery rate (FDR) correction for multiple comparisons. Statistical significance was defined as p&amp;lt;0.05 after FDR correction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Untreated RA patients demonstrated significant global steroid dysregulation, characterized by marked suppression of multiple adrenal steroids (including aldosterone, cortisol, and testosterone) compared to healthy controls (all FDR&amp;lt;0.05). This was accompanied by profound alterations in estrogen metabolism, notably a hyperactivated 2-hydroxylation pathway and depleted 16-hydroxylation metabolites (FDR&amp;lt;0.001). MTX treatment partially restored steroid homeostasis, significantly improving aldosterone and androgen profiles (FDR&amp;lt;0.05) toward levels observed in healthy controls. However, the addition of GC therapy further disrupted endocrine balance, significantly suppressing cortisol, testosterone, and total estrogens (FDR&amp;lt;0.05), while pathologically amplifying the 4-hydroxylation pathway (FDR&amp;lt;0.001), a process potentially linked to synovial inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrates that impaired steroidogenesis and estrogen pathway dysregulation are characteristic features of postmenopausal RA, with MTX showing unexpected hormone-restorative effects. While GC therapy provides symptomatic relief, it paradoxically exacerbates endocrine disruption, suggesting the need for personalized hormonal monitoring in long-term GC-treated patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1589798","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T05:40:18Z","timestamp":1747028418000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Steroid hormones and influence of therapeutic drugs in Chinese postmenopausal rheumatoid arthritis 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