Circulating estradiol and its biologically active metabolites in endometriosis and in relation to pain symptoms

Jean-Philippe Emond, Jean-Philippe Émond, Patrick Caron, Maja Pušić, Véronique Turcotte, David Simonyan, Andrej Vogler, Joško Osredkar, Tea Lanišnik Rižner, Chantal Guillemette
Frontiers in endocrinology · 2023 · vol. 13 , pp. 1034614 · doi:10.3389/fendo.2022.1034614 · PMID:36743927 · PMC9891204 · W4317215073
article OA: gold CC0 ⤵ 24 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study found that higher levels of the estrogen metabolite 2-hydroxy-3-methoxyestrone were associated with an increased risk of endometriosis, ovarian endometriosis, and related pain symptoms.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 ⓘ

This retrospective case-control study analyzed whether circulating estradiol (E2) and a panel of its biologically active hydroxylated and methylated metabolites are associated with endometriosis risk and pain in 209 endometriosis cases and 115 controls, using preoperative serum mass spectrometry plus patient-reported validated pain questionnaires. Among 16 profiled estrogens, higher levels of 2-hydroxy 3MeO-E1 were linked to increased endometriosis risk, and ovarian endometriosis showed enhanced 2-hydroxylation with higher 2MeO-E1 and 2OH-E1; higher 2OH-3MeO-E1 also correlated with abdominal, pelvic, and back pain. The paper notes key limitations including missingness for several pain outcomes (notably some dysmenorrhea and dyspareunia measures) and its observational, retrospective design. This paper is centrally about endometriosis — it links a specific estradiol metabolite (2-hydroxy 3MeO-E1) and 2-hydroxylation patterns in circulating hormones to endometriosis risk and pain symptoms.

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Abstract

OBJECTIVES: Endometriosis (EM) is an estrogen-dominant inflammatory disease linked to infertility that affects women of reproductive age. EM lesions respond to hormonal signals that regulate uterine tissue growth and trigger inflammation and pain. The objective of this study was to evaluate whether estradiol (E2) and its biologically active metabolites are differentially associated with EM given their estrogenic and non-estrogenic actions including proliferative and inflammatory properties. DESIGN: We performed a retrospective study of 209 EM cases and 115 women without EM. METHODS: Pain-related outcomes were assessed using surveys with validated scales. Preoperative serum levels of estradiol (E2) and estrone (E1), their 2-, 4- and 16- hydroxylated (OH) and methylated (MeO) derivatives (n=16) were measured by mass spectrometry. We evaluated the associations between estrogen levels and EM anatomic sites, surgical stage, risk of EM, and symptoms reported by women. Spearman correlations established the relationships between circulating steroids. RESULTS: Of the sixteen estrogens profiled, eleven were detected above quantification limits in most individuals. Steroids were positively correlated, except 2-hydroxy 3MeO-E1 (2OH-3MeO-E1). Higher 2OH-3MeO-E1 was linked to an increased risk of EM (Odd ratio (OR)=1.91 (95%CI 1.09-3.34); P=0.025). Ovarian EM cases displayed enhanced 2-hydroxylation with higher 2MeO-E1 and 2OH-E1 levels (P< 0.009). Abdominal, pelvic and back pain symptoms were also linked to higher 2OH-3MeO-E1 levels (OR=1.86; 95%CI 1.06-3.27; P=0.032). CONCLUSIONS: The 2-hydroxylation pathway emerges as an unfavorable feature of EM, and is associated with ovarian EM and pain related outcomes.

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Condition tags

endometriosisinfertility

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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