Vitamin D and Endometriosis

The authors reviewed the Vitamin D and its possible roles in the normal and pathological endometria.

Key Points

Highlights

• The role of vitamin D (VD) and Vitamin D Receptor (VDR)-mediated signaling pathways seem to be dysregulated in endometriosis, and in endometrial cancer; however, the results are contradictory and more studies are needed to confirm a beneficial role of VD treatment on endometrial cancer and/or endometriosis.

Importance

• VD is a known anti-proliferative, anti-inflammatory, and even an immunomodulatory agent.
• High circulating levels of VD are associated with a reduced risk of developing certain cancer types (breast, colorectal, gastric, hematological, head and neck, kidney, lung, ovarian, pancreatic liver, prostate, and skin cancer). Investigation of the potential molecular mechanisms at the basis of the local action of VD in endometrial cancer seems worthy.

What’s done here

• This is a review article where PubMed Database was searched for articles published in the English language. Articles referring to the physiological endometrium, endometriosis, and endometrial cancer with available molecular data were included.

Key results

• The knowledge about the effects of VD in the physiological endometrium is poor and that the molecular mechanisms involved are still to be completely defined. 
• VDR-mediated signaling pathways seem to be dysregulated in pathological conditions of the endometrium; but, the results are contradictory. 

Limitations 

• The majority of the studies has been done using immortalized endometrial cancer cells; primate models and clinical trials are necessary to evaluate the possible therapeutic benefit of VD and/or VDR agonists in women with endometriosis.
• The findings on in vivo or ex vivo studies to examine the molecular mechanisms of VD in endometrial cancer are scant and require further appraisal.

Lay Summary

Scientists from Milan, Italy reviewed the effects of vitamin D on the reproductive health, and in particular "endometriosis" in their article which appeared in International Journal of Molecular Sciences.

Vitamin D (VD), is a steroid hormone that is activated in the skin, under UVB light, undergoes two more hydroxylation steps mainly in the liver and in the proximal tubules of the kidneys; that mainly acts by VD receptor (VDR) that belongs to the nuclear receptor superfamily to interact with the DNA to to regulate the transcription of target genes involved in calcium and phosphate homeostasis, cell proliferation, differentiation, and immune response. 

Various animal models have demonstrated that activated VD deficient female rats show reduced fertility rates, and VDR knockout female mice have defective uterine development. The role of VD in uterine physiology seems to be essential for the normal differentiation of decidual cells. 

Using animal models, a regression of the endometriotic implants after VD or VDR agonist treatment has been described, however, the mechanism underlying endometriosis development is not clear yet. 

Although there is suggestive evidence of an inhibitory effect of VD on endometrial cancer, the majority of the studies concerning VD and endometrial cancer has been done using immortalized endometrial cancer cells. Also, the findings on in vivo or ex vivo studies to investigate molecular mechanisms of VD in endometrial cancer are few that necessitates further investigation. 

The authors concluded that the VDR-mediated signaling pathways seem to be dysregulated in pathological conditions of the endometrium, and further studies are needed to confirm the beneficial role of VD treatment on endometrial cancer and endometriosis.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/30096760