Circulating estradiol and its biologically active metabolites in endometriosis and in relation to pain symptoms
ID Emond, Jean-Philippe (Author), ID Caron, Patrick (Author), ID Pušić Novak, Maja (Author), ID Turcotte, Véronique (Author), ID Simonyan, David (Author), ID Vogler, Andrej (Author), ID Osredkar, Joško (Author), ID Lanišnik-Rižner, Tea (Author), ID Guillemette, Chantal (Author)

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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.

Keywords:endometriosis, catechol estrogens, steroids
Work type:Article
Typology:1.01 - Original Scientific Article
Organization:FFA - Faculty of Pharmacy
MF - Faculty of Medicine
Publication status:Published
Publication version:Version of Record
Number of pages:Str. 1-13
Numbering:Vol. 13
PID:20.500.12556/RUL-143965-7a918e87-ce41-5e9d-5716-8fa65ecab628 This link opens in a new window
ISSN on article:1664-2392
DOI:10.3389/fendo.2022.1034614 This link opens in a new window
COBISS.SI-ID:136322563 This link opens in a new window
Publication date in RUL:24.01.2023
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Title:Frontiers in endocrinology
Publisher:Frontiers Research Foundation.
COBISS.SI-ID:3340154 This link opens in a new window


License:CC BY 4.0, Creative Commons Attribution 4.0 International
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

Keywords:endometrioza, katehol estrogeni, steroidi


Funder:Drugi - Drug financer ali več financerjev
Funding programme:Canadian Institutes of Health Research
Project number:FRN-167269

Funder:Drugi - Drug financer ali več financerjev
Funding programme:Canada Research Chair

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Project number:J3-1755
Name:Biokemijski označevalci endometrioze: študije transkriptoma in proteoma

Funder:EC - European Commission
Funding programme:H2020
Project number:101008193
Name:Translational Research on Endometriosis

Funder:Drugi - Drug financer ali več financerjev
Funding programme:Fonds de recherche du Québec – Santé, Studentship award

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