Vitamin D deficiency and pain severity in endometriosis: a phenotype-based retrospective observational study

İsmail Bağlar, Fatih Şanlıkan, Esra Keleş, Aslı Sasmaz, Kubra Karakas Soylu, Murat Apı
BMC women's health · 2026 · vol. 26(1) · doi:10.1186/s12905-026-04542-8 · PMID:42210340 · PMC13471360 · W7162651146
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Lower serum vitamin D levels are associated with increased pain severity in women with endometriosis, particularly those with deep infiltrating endometriosis.

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This retrospective observational study evaluated 427 women with surgically and histopathologically confirmed endometriosis to determine whether serum 25-hydroxyvitamin D levels are associated with pain severity, and whether this association differs between ovarian endometrioma (OE) and deep infiltrating endometriosis (DIE) phenotypes. Vitamin D was categorized as deficient, insufficient, or sufficient, and pain outcomes (dysmenorrhea, chronic pelvic pain, and dyspareunia) were measured with Visual Analog Scale scores; multivariable linear regression adjusted for age, BMI, and seasonal variation. Lower 25(OH)D levels were inversely associated with all pain measures, with vitamin D deficiency showing higher median VAS scores than sufficient levels, and a significant interaction indicated a stronger association in the DIE phenotype than in OE. Because the design was retrospective and cross-sectional, causality could not be inferred. This paper is centrally about endometriosis — it analyzes how vitamin D deficiency relates to pain severity across endometriosis phenotypes (DIE vs OE).

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Abstract

OBJECTIVE: To evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and pain severity in women with surgically and histopathologically confirmed endometriosis, and to assess whether this association differs between ovarian endometrioma (OE) and deep infiltrating endometriosis (DIE) phenotypes. METHODS: This retrospective observational analytical study included 427 women with surgically confirmed endometriosis. Patients were classified according to dominant phenotype as OE (n=231) or DIE (n=196). Serum 25(OH)D levels were categorized as deficient (<20 ng/mL), insufficient (20-30 ng/mL), and sufficient (≥30 ng/mL). Pain severity-including dysmenorrhea, chronic pelvic pain, and dyspareunia-was assessed using the Visual Analog Scale (VAS). Multivariable linear regression analyses were performed to examine the association between vitamin D levels and pain scores, adjusting for age, body mass index, and seasonal variation. RESULTS: Serum 25(OH)D levels were inversely associated with all pain parameters (p<0.001). Patients with vitamin D deficiency had higher median VAS scores compared to those with sufficient levels [7.0 (6.0-8.0) vs 4.0 (3.0-5.0), p<0.001]. In multivariable analyses, lower 25(OH)D levels remained significantly associated with higher pain severity (β = -0.28, p<0.001). A significant interaction between vitamin D levels and disease phenotype was observed (interaction p=0.004), suggesting that the association between lower vitamin D levels and higher pain scores was more pronounced in patients with the DIE phenotype compared to those with OE. A threshold value of 18.5 ng/mL demonstrated 74% sensitivity for identifying patients with severe pain (VAS ≥7). CONCLUSION: Lower serum vitamin D levels are significantly associated with greater pain severity in women with endometriosis, with a stronger association observed in the DIE phenotype. However, given the retrospective and cross-sectional nature of the analysis, causality cannot be inferred. Prospective studies are needed to further clarify these associations and their potential clinical implications.
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Abstract

Objective To evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and pain severity in women with surgically and histopathologically confirmed endometriosis, and to assess whether this association differs between ovarian endometrioma (OE) and deep infiltrating endometriosis (DIE) phenotypes.

Methods

This retrospective observational analytical study included 427 women with surgically confirmed endometriosis. Patients were classified according to dominant phenotype as OE (n=231) or DIE (n=196). Serum 25(OH)D levels were categorized as deficient (<20 ng/mL), insufficient (20–30 ng/mL), and sufficient (≥30 ng/mL). Pain severity—including dysmenorrhea, chronic pelvic pain, and dyspareunia—was assessed using the Visual Analog Scale (VAS). Multivariable linear regression analyses were performed to examine the association between vitamin D levels and pain scores, adjusting for age, body mass index, and seasonal variation.

Results

Serum 25(OH)D levels were inversely associated with all pain parameters (p<0.001). Patients with vitamin D deficiency had higher median VAS scores compared to those with sufficient levels [7.0 (6.0–8.0) vs 4.0 (3.0–5.0), p<0.001]. In multivariable analyses, lower 25(OH)D levels remained significantly associated with higher pain severity (β = -0.28, p<0.001). A significant interaction between vitamin D levels and disease phenotype was observed (interaction p=0.004), suggesting that the association between lower vitamin D levels and higher pain scores was more pronounced in patients with the DIE phenotype compared to those with OE. A threshold value of 18.5 ng/mL demonstrated 74% sensitivity for identifying patients with severe pain (VAS ≥7).

Conclusion

Lower serum vitamin D levels are significantly associated with greater pain severity in women with endometriosis, with a stronger association observed in the DIE phenotype. However, given the retrospective and cross-sectional nature of the analysis, causality cannot be inferred. Prospective studies are needed to further clarify these associations and their potential clinical implications. Similar content being viewed by others Abbreviations - 25(OH)D: - 25-hydroxyvitamin D - AUC: - Area under the curve - BMI: - Body mass index - CA125: - Cancer antigen 125 - CI: - Confidence interval - CPP: - Chronic pelvic pain - DIE: - Deep infiltrating endometriosis - GnRH: - Gonadotropin-releasing hormone - IQR: - Interquartile range - NRS: - Numeric Rating Scale - OE: - Ovarian endometrioma - PPV: - Positive predictive value - NPV: - Negative predictive value - rASRM: - Revised American Society for Reproductive Medicine - ROC: - Receiver operating characteristic - SPSS: - Statistical Package for the Social Sciences - VAS: - Visual Analog Scale - VDBP: - Vitamin D binding protein - VDR: - Vitamin D receptor

Acknowledgements

Not applicable. Funding The authors received no financial support for the research, authorship, and/or publication of this article. Author information Authors and Affiliations Corresponding author Ethics declarations Ethics approval and consent to participate This retrospective observational study was approved by the Ethics Committee of University of Health Sciences Turkey, Kartal Dr. Lütfi Kırdar City Hospital (Approval No: 2026/010.99/25/7, Date: 24.02.2026. Due to the retrospective design of the study and the use of anonymized patient data, the requirement for informed consent was waived by the ethics committee. The study was conducted in accordance with the Declaration of Helsinki. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. About this article Cite this article Baglar, I., Sanlikan, F., Keles, E. et al. Vitamin D deficiency and pain severity in endometriosis: a phenotype-based retrospective observational study. BMC Women's Health (2026). https://doi.org/10.1186/s12905-026-04542-8 Received: Accepted: Published: DOI: https://doi.org/10.1186/s12905-026-04542-8

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Outcome instruments

VAS-pain

Condition tags

endometriosisdie_deep_infiltratingendometriomachronic_pelvic_paindysmenorrheadyspareunia

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.

References (35)

SciLite annotations

chemicals 3
vitamin d vitamin d vitamin d

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