title: Vitamin D in endometriosis: a causative or confounding factor?
abstract: OBJECTIVE
  The aim of this paper is to review the evidence from studies that evaluated the relationship between vitamin D and endometriosis.
  
  
  METHODS
  Comprehensive review.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Lamia
authors.initials: L
authors.lastname: Sayegh
authors.forename: Ghada El-Hajj
authors.initials: Gel-H
authors.lastname: Fuleihan
authors.forename: Anwar H
authors.initials: AH
authors.lastname: Nassar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015551:Autoimmunity; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D059350:Chronic Pain / Q000209:etiology; D019587:Dietary Supplements; D004412:Dysmenorrhea / Q000188:drug therapy / Q000209:etiology; D004715:Endometriosis / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D007247:Infertility, Female / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D053495:Osteopontin / Q000235:genetics; D018167:Receptors, Calcitriol / Q000378:metabolism*; D014807:Vitamin D / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C487049:BXL628; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D007155:Immunologic Factors; D018167:Receptors, Calcitriol; D053495:Osteopontin; C069634:HOXA10 protein, human; D014807:Vitamin D; D002117:Calcitriol
keywords: 1, 25 dihydroxyvitamin D; 1,25(OH)2D; 25-OHD; 25-hydroxyvitamin-D3; DBP; Elocalcitol; Endometrium; Gc; Gc-protein derived macrophage-activating factor; GcMAF; HOXA 10 gene; HOXA10; IBD; MMP; OPN; Osteopontin; VD; VD binding protein; VD responsive element; VDRE; Vitamin D binding protein; group-specific component; homeobox A10; inflammatory bowel disease; matrix metalloproteinase; vitamin D