Vitamin D supplementation decreases TGF-β1 bioavailability in PCOS: A randomized placebo-controlled trial

Mohamad Irani, David B. Seifer, Richard V. Grazi, Nitasha Julka, Devika Bhatt, Bharati Kalgi, Sara Irani, Oded Tal, Geralyn Lambert-Messerlian, Reshef Tal

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


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. VitaminD(VD) supplementation improves various clinical manifestations of PCOS and decreases TGF-β1 levels in several diseases including myelofibrosis. Objective: The objective of the studywasto determine the effect ofVDsupplementationonTGF-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±9to60±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-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.

Original languageEnglish (US)
Pages (from-to)4307-4314
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number11
StatePublished - Nov 2015

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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