Vitamin D and Endometriosis: Is There a Mechanistic Link?

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.