Vitamin D and Endometriosis: Is There a Mechanistic Link?

Abstract

Endometriosis is a prevalent chronic gynaecological disorder, but its cause is still unclear, and both genetic and environmental factors may contribute disease aetiology. Prominent amongst the latter is vitamin D which can be obtained either by the action of sunlight on skin or from dietary sources. Serum levels of the main circulating form of vitamin D, 25-hydroxvitamin D (25(OH)D), have been reported to be inversely correlated with endometriosis, suggesting that vitamin D-deficiency may be a risk factor for the disease. Crucially, the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)₂D) is known to exert many functions beyond its established role in the endocrinology of mineral homoeostasis and prevention of rickets. Several of these extra-skeletal effects of 1,25(OH)₂D may impact the risk and progression of endometriosis. The following review details the studies that have assessed associations between vitamin D status/supplementation and endometriosis severity and disease progression, but also describes the mechanistic targets for 1,25(OH)₂D in endometriosis with specific reference to immunomodulatory responses and effects on angiogenesis. Endometriosis is an under-reported health issue with poor non-invasive options for diagnosis. Given that vitamin D-deficiency may trigger or exacerbate key pathophysiological responses linked to endometriosis, analysis of vitamin D status in women may provide an alternative risk marker for endometriosis. Treatment options for endometriosis are also limited and the review will also consider whether vitamin D supplementation has a role in the management of endometriosis, either in prevention or treatment.

Keywords: endometriosis; immune; inflammation; steroidogenic; vitamin D.

Figure 1

Effects of vitamin D supplementation on endometriosis. Summary of mouse, rat and human studies in vivo and ex vivo. Interleukin‐17 (IL‐17), IL‐6, IL‐8, matrix metalloproteinase‐2 (MMP‐2), MMP‐9, cluster designation 44 (CD44), endometrial stromal cell (ESC), vascular endothelial growth factor‐A (VDGF‐A), nuclear factor kappa‐B (NF‐κB), prostaglandin E2 (PGE2), cyclooxygenase‐2 (COX‐2). Peritoneal fluid (PF).

Figure 2

Local effects of PGE2 in endometriosis.