Vitamin D in endometriosis: a causative or confounding factor?

Metabolism. 2014 Jan;63(1):32-41. doi: 10.1016/j.metabol.2013.09.012. Epub 2013 Oct 14.


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.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Autoimmunity
  • Calcitriol / analogs & derivatives*
  • Calcitriol / blood
  • Calcitriol / pharmacology
  • Chronic Pain / etiology
  • Dietary Supplements
  • Dysmenorrhea / drug therapy
  • Dysmenorrhea / etiology
  • Endometriosis / complications
  • Endometriosis / immunology
  • Endometriosis / metabolism*
  • Endometrium / metabolism*
  • Endometrium / pathology
  • Female
  • Homeobox A10 Proteins
  • Homeodomain Proteins / genetics
  • Humans
  • Immunologic Factors / pharmacology
  • Infertility, Female / etiology
  • Infertility, Female / prevention & control*
  • Mice
  • Osteopontin / genetics
  • Receptors, Calcitriol / metabolism*
  • Vitamin D / administration & dosage
  • Vitamin D / immunology
  • Vitamin D / metabolism*


  • Antineoplastic Agents
  • BXL628
  • Homeobox A10 Proteins
  • Homeodomain Proteins
  • Immunologic Factors
  • Receptors, Calcitriol
  • Osteopontin
  • HOXA10 protein, human
  • Vitamin D
  • Calcitriol