title: Vitamin D Decreases Serum VEGF Correlating with Clinical Improvement in Vitamin D-Deficient Women with PCOS: A Randomized Placebo-Controlled Trial.
abstract: 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.
authors.affiliation: The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY 10021, USA. mohamad.irani@hotmail.com.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Irani
authors.affiliation: Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. dseifer@comcast.net.
authors.forename: David B
authors.initials: DB
authors.lastname: Seifer
authors.affiliation: Genesis Fertility and Reproductive Medicine, Maimonides Medical Center, Brooklyn, NY 11204, USA. rgrazi@genesisfertility.com.
authors.forename: Richard V
authors.initials: RV
authors.lastname: Grazi
authors.affiliation: 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. sarah.irani@hotmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Irani
authors.affiliation: The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY 10021, USA. moi9010@med.cornell.edu.
authors.forename: Zev
authors.initials: Z
authors.lastname: Rosenwaks
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA. resheft@gmail.com.
authors.forename: Reshef
authors.initials: R
authors.lastname: Tal
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy*; D016037:Single-Blind Method; D014280:Triglycerides / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D014807:Vitamin D / Q000008:administration & dosage* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014280:Triglycerides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014807:Vitamin D
keywords: PCOS; VEGF; polycystic ovary syndrome; vascular endothelial growth factor; vitamin D