Vitamin D Supplementation Decreases TGF-β1 Bioavailability in PCOS: A Randomized Placebo-Controlled Trial

Context: There is an abnormal increase in TGF-beta 1 bioavailability in women with polycystic ovary syndrome (PCOS), which might play a role in the pathophysiology of this syndrome. VitaminD(VD) supplementation improves various clinical manifestations of PCOS and decreases TGF-beta 1 levels in several diseases including myelofibrosis. Objective: The objective of the studywasto determine the effect of VD supplementationonTGF-beta 1 bioavailability in VD-deficient women with PCOS and assess whether changes in TGF-beta 1/soluble endoglin (sENG) levels correlate with an improvement in PCOS clinical manifestations. Design: This was a prospective, randomized, placebo-controlled trial. Setting: The study was conducted at an academic-affiliated medical center. Participants: Sixty-eight VD-deficient women with PCOS who were not pregnant or taking any exogenous hormones were recruited between October 2013 and January 2015. Interventions: Forty-five women received 50 000 IU of oral vitamin D3 and 23 women received oral placebo once weekly for 8 weeks. Main Outcomes Measures: Serum TGF-beta 1, sENG, lipid profile, testosterone, dehydroepiandrosterone sulfate, and insulin resistance were measured. The clinical parameters were evaluated before and 2 months after treatment. Results: The VD level significantly increased and normalized after VD supplementation (16.3 +/- 0.9 [SEM] to 43.2 +/- 2.4 ng/mL; P < .01), whereas it did not significantly change after placebo. After the VD supplementation, there was a significant decrease in the following: the interval between menstrual periods (80 +/- 9 to 60 +/- 6d; P = .04), Ferriman-Gallwey score (9.8 +/- 1.5 to 8.1 +/- 1.5; P < .01), triglycerides (138 +/- 22 to 117 +/- 20 mg/dL; P = .03), and TGF-beta 1 to sENG ratio (6.7 +/- 0.4 to 5.9 +/- 0.4; P = .04). In addition, the Delta TGF-beta 1 to sENG ratio was positively correlated with Delta triglycerides (r = 0.59; P = .03). Conclusions: VD supplementation in VD-deficient women with PCOS significantly decreases the bioavailability of TGF-beta 1, which correlates with an improvement in some abnormal clinical parameters associated with PCOS. This is a novel mechanism that could explain the beneficial effects of VD supplementation in women with PCOS. These findings may support new treatment modalities for PCOS, such as the development of anti-TGF-beta drugs.