Tissue-predominant estrogen metabolic remodeling in adenomyosis revealed by LC-MS/MS profiling

Wang Q, Qing Wang, Liu B, BoYang Liu, Lei Kuang, Kuang L, Lingke Wang, Wang L, 仇颖莹, Chou Y, Yingying Chou, Bei Zhang, Zhang B, Wan G, Guiping Wan, Gui T, Tao Gui
The Journal of steroid biochemistry and molecular biology · 2026 · vol. 265 , pp. 107095 · doi:10.1016/j.jsbmb.2026.107095 · PMID:42532355 · W7171959188
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LC-MS/MS profiling of adenomyosis tissue and serum revealed predominant increases in catechol estrogens within the tissue, linked to dysmenorrhea severity, rather than generalized serum estrogen elevation.

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Abstract

Adenomyosis (AM) is an estrogen-dependent gynecological disorder in which local steroid handling may contribute to clinical heterogeneity. To characterize estrogen metabolic features in AM, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify 13 estrogens and estrogen metabolites in endometrial tissue and serum. Tissue metabolite profiles showed marked increases in catechol estrogens, particularly 2-hydroxyestrone (2-OHE1) and 4-hydroxyestrone (4-OHE1), whereas serum changes were more limited, with 2-methoxyestrone (2-MeOE1) representing the main circulating difference. Pathway- and ratio-based analyses indicated enhanced hydroxylation in tissue without a proportionate increase in downstream methylation-related readouts. Correlation and regression analyses further showed that tissue 2-OHE1 and 4-OHE1 were independently associated with dysmenorrhea severity. In exploratory receiver operating characteristic analyses performed within the discovery cohort, tissue catechol estrogens showed stronger discriminatory ability than serum metabolites. These findings suggested that AM was associated with endometrial tissue-predominant remodeling of estrogen metabolism rather than with generalized elevation of parent estrogens. The present study identified candidate metabolic markers requiring further validation and provided a framework for future investigation of local steroid metabolism in AM.

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SciLite annotations

chemicals 15
estrogen estrogen steroid estrogen estrone estrogen catechol estrone 2-hydroxyestrone 4-hydroxyestrone 2-methoxyestrone xenoestrogen estrogen estrone steroid

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