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

• Published in: The journal of clinical endocrinology and metabolism 2015-11, Vol.100 (11), p.4307-4314
• Main Authors: Irani, Mohamad, Seifer, David B, Grazi, Richard V, Julka, Nitasha, Bhatt, Devika, Kalgi, Bharati, Irani, Sara, Tal, Oded, Lambert-Messerlian, Geralyn, Tal, Reshef
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antigens, CD - blood; Biological Availability; Cholecalciferol - pharmacology; Dehydroepiandrosterone Sulfate - blood; Endoglin; Female; Humans; Insulin Resistance; Lipids - blood; Polycystic Ovary Syndrome - drug therapy; Polycystic Ovary Syndrome - metabolism; Prospective Studies; Receptors, Cell Surface - blood; Socioeconomic Factors; Testosterone - blood; Transforming Growth Factor beta1 - drug effects; Transforming Growth Factor beta1 - metabolism; Vitamin D - therapeutic use; Vitamin D Deficiency - drug therapy; Vitamin D Deficiency - metabolism; Vitamins - therapeutic use; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2015-2580

Context: There is an abnormal increase in TGF-β1 bioavailability in women with polycystic ovary syndrome (PCOS), which might play a role in the pathophysiology of this syndrome. Vitamin D (VD) supplementation improves various clinical manifestations of PCOS and decreases TGF-β1 levels in several diseases including myelofibrosis. Objective: The objective of the study was to determine the effect of VD supplementation on TGF-β1 bioavailability in VD-deficient women with PCOS and assess whether changes in TGF-β1/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-β1, 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 ± 6 d; 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-β1 to sENG ratio (6.7 ± 0.4 to 5.9 ± 0.4; P = .04). In addition, the ΔTGF-β1 to sENG ratio was positively correlated with Δtriglycerides (r = 0.59; P = .03). Conclusions: VD supplementation in VD-deficient women with PCOS significantly decreases the bioavailability of TGF-β1, 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-β drugs.