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Nutrients. 2017 Mar 28;9(4). pii: E334. doi: 10.3390/nu9040334.

Vitamin D Decreases Serum VEGF Correlating with Clinical Improvement in Vitamin D-Deficient Women with PCOS: A Randomized Placebo-Controlled Trial.

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The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
Genesis Fertility and Reproductive Medicine, Maimonides Medical Center, Brooklyn, NY 11204, USA.
Molecular and Cell Biology Program, School of Graduate Studies and Departments of Cell Biology and Pediatrics, State University of New York (SUNY) Downstate Medical Center, Brooklyn, NY 11203, USA.
The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.


Vascular endothelial growth factor (VEGF) has been suggested to play a role in the pathophysiology of polycystic ovary syndrome (PCOS) and may contribute to increased risk of ovarian hyperstimulation syndrome (OHSS) in affected individuals. Vitamin D (VitD) supplementation improves multiple clinical parameters in VitD-deficient women with PCOS and decreases VEGF levels in several other pathologic conditions. Unveiling the basic mechanisms underlying the beneficial effects of vitamin D on PCOS may enhance our understanding of the pathophysiology of this syndrome. It may also suggest a new treatment for PCOS that can improve it through the same mechanism as vitamin D and can be given regardless of vitamin D levels. Therefore, we aimed to explore the effect of VitD supplementation on serum VEGF levels and assess whether changes in VEGF correlate with an improvement in characteristic clinical abnormalities of PCOS. This is a randomized placebo-controlled trial conducted between October 2013 and March 2015. Sixty-eight VitD-deficient women with PCOS were recruited. Women received either 50,000 IU of oral VitD3 or placebo once weekly for 8 weeks. There was a significant decrease in serum VEGF levels (1106.4 ± 36.5 to 965.3 ± 42.7 pg·mL-1; p < 0.001) in the VitD group. Previously reported findings of this trial demonstrated a significant decrease in the intermenstrual intervals, Ferriman-Gallwey hirsutism score, and triglycerides following VitD supplementation. Interestingly, ∆VEGF was positively correlated with ∆triglycerides (R² = 0.22; p = 0.02) following VitD supplementation. In conclusion, VitD replacement significantly decreases serum VEGF levels correlating with a decrease in triglycerides in women with PCOS. This is a novel molecular explanation for the beneficial effects of VitD treatment. It also suggests the need to investigate a potential role of VitD treatment in reducing the incidence or severity of OHSS in VitD-deficient women with PCOS.


PCOS; VEGF; polycystic ovary syndrome; vascular endothelial growth factor; vitamin D

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