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Vitamin D in endometriosis: A causative or confounding factor?

  • Lamia Sayegh
    Affiliations
    Department of Obstetrics and Gynecology, American University of Beirut Medical Center, Beirut, Lebanon
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  • Ghada El-Hajj Fuleihan
    Affiliations
    Department of Internal Medicine, Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, Division of Endocrinology, American University of Beirut Medical Center, Beirut, Lebanon
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  • Anwar H. Nassar
    Correspondence
    Corresponding author. Professor of Obstetrics and Gynecology and Interim Chairperson PO BOX: 11-0236, Riad El Solh 1107 2020, Beirut, Lebanon. Tel.: +961 1 350 000x5600; fax: +961 1 744464.
    Affiliations
    Department of Obstetrics and Gynecology, American University of Beirut Medical Center, Beirut, Lebanon
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Published:October 16, 2013DOI:https://doi.org/10.1016/j.metabol.2013.09.012

      Abstract

      Objective

      The aim of this paper is to review the evidence from studies that evaluated the relationship between vitamin D and endometriosis.

      Design

      Comprehensive review.

      Materials and Methods

      Systematic literature search in Medline for relevant publications from 1946 until June 2013.

      Results

      Endometriosis risk may be influenced by dietary vitamin D intake and plasma hydroxyvitamin D concentration. Vitamin D receptor and vitamin D metabolizing enzymes, 24-hydroxylase and 1-α hydroxylase, are found in the normal cycling endometrium and also in the eutopic and ectopic endometrium of women with endometriosis. The endometrium is a target of 1, 25 dihydroxyvitamin D actions through regulation of specific genes and via immunomodulation. The endometrium in endometriosis expresses dysregulation of some vitamin D enzymes and receptors. If vitamin D and its metabolites are implicated in endometriosis-associated infertility, it is likely through interference with HOXA10 gene expression. The Gc2 phenotype of vitamin D binding protein is prevalent in women with endometriosis and may be implicated in its pathogenesis. In a mouse model, Elocalcitol, a VDR-agonist was shown to reduce the development of endometriotic lesions and recurrence.

      Conclusion

      A biological plausibility for a role of vitamin D, as an immunomodulator and anti-inflammatory agent, in the pathogenesis and treatment of endometriosis is suggested in this article, but is difficult to illustrate due to sparse evidence from human studies limited primarily to case–control studies. A significant knowledge gap precludes the establishment of a clear cause–effect relationship. The intriguing leads presented herein need to be investigated further with placebo-controlled supplementation trials.

      Abbreviations:

      VD (vitamin D), DBP (VD binding protein), Gc (group-specific component), GcMAF (Gc-protein derived macrophage-activating factor), HOXA10 (homeobox A10), IBD (inflammatory bowel disease), 25-OHD (25-hydroxyvitamin-D3), MMP (matrix metalloproteinase), 1,25(OH)2D (1, 25 dihydroxyvitamin D), VDRE (VD responsive element), OPN (Osteopontin)

      Keywords

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