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


METHODS
This was a prospective, randomized, placebo-controlled trial.


METHODS
The study was conducted at an academic-affiliated medical center.


METHODS
Sixty-eight VD-deficient women with PCOS who were not pregnant or taking any exogenous hormones were recruited between October 2013 and January 2015.


METHODS
Forty-five women received 50 000 IU of oral vitamin D3 and 23 women received oral placebo once weekly for 8 weeks.


METHODS
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.
Departments of Obstetrics and Gynecology (M.I., N.J., D.B., B.K., S.I.) and Genesis Fertility and Reproductive Medicine (R.V.G.), Maimonides Medical Center, Brooklyn, New York 11219; Department of Reproductive Endocrinology and Infertility (D.B.S.), Oregon Health & Science University, Portland, Oregon 97239; School of Business and Hospitality (O.T.), Conestoga College, Kitchener, Ontario, Canada N2G 4M4; Division of Medical Screening and Special Testing (G.L.-M.), Women and Infants Hospital, Providence, Rhode Island 02905; and Division of Reproductive Endocrinology and Infertility (R.T.), Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520.
Mohamad
M
Irani
Departments of Obstetrics and Gynecology (M.I., N.J., D.B., B.K., S.I.) and Genesis Fertility and Reproductive Medicine (R.V.G.), Maimonides Medical Center, Brooklyn, New York 11219; Department of Reproductive Endocrinology and Infertility (D.B.S.), Oregon Health & Science University, Portland, Oregon 97239; School of Business and Hospitality (O.T.), Conestoga College, Kitchener, Ontario, Canada N2G 4M4; Division of Medical Screening and Special Testing (G.L.-M.), Women and Infants Hospital, Providence, Rhode Island 02905; and Division of Reproductive Endocrinology and Infertility (R.T.), Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520.
David B
DB
Seifer
Departments of Obstetrics and Gynecology (M.I., N.J., D.B., B.K., S.I.) and Genesis Fertility and Reproductive Medicine (R.V.G.), Maimonides Medical Center, Brooklyn, New York 11219; Department of Reproductive Endocrinology and Infertility (D.B.S.), Oregon Health & Science University, Portland, Oregon 97239; School of Business and Hospitality (O.T.), Conestoga College, Kitchener, Ontario, Canada N2G 4M4; Division of Medical Screening and Special Testing (G.L.-M.), Women and Infants Hospital, Providence, Rhode Island 02905; and Division of Reproductive Endocrinology and Infertility (R.T.), Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520.
Richard V
RV
Grazi
Departments of Obstetrics and Gynecology (M.I., N.J., D.B., B.K., S.I.) and Genesis Fertility and Reproductive Medicine (R.V.G.), Maimonides Medical Center, Brooklyn, New York 11219; Department of Reproductive Endocrinology and Infertility (D.B.S.), Oregon Health & Science University, Portland, Oregon 97239; School of Business and Hospitality (O.T.), Conestoga College, Kitchener, Ontario, Canada N2G 4M4; Division of Medical Screening and Special Testing (G.L.-M.), Women and Infants Hospital, Providence, Rhode Island 02905; and Division of Reproductive Endocrinology and Infertility (R.T.), Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520.
Nitasha
N
Julka
Departments of Obstetrics and Gynecology (M.I., N.J., D.B., B.K., S.I.) and Genesis Fertility and Reproductive Medicine (R.V.G.), Maimonides Medical Center, Brooklyn, New York 11219; Department of Reproductive Endocrinology and Infertility (D.B.S.), Oregon Health & Science University, Portland, Oregon 97239; School of Business and Hospitality (O.T.), Conestoga College, Kitchener, Ontario, Canada N2G 4M4; Division of Medical Screening and Special Testing (G.L.-M.), Women and Infants Hospital, Providence, Rhode Island 02905; and Division of Reproductive Endocrinology and Infertility (R.T.), Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520.
Devika
D
Bhatt
Departments of Obstetrics and Gynecology (M.I., N.J., D.B., B.K., S.I.) and Genesis Fertility and Reproductive Medicine (R.V.G.), Maimonides Medical Center, Brooklyn, New York 11219; Department of Reproductive Endocrinology and Infertility (D.B.S.), Oregon Health & Science University, Portland, Oregon 97239; School of Business and Hospitality (O.T.), Conestoga College, Kitchener, Ontario, Canada N2G 4M4; Division of Medical Screening and Special Testing (G.L.-M.), Women and Infants Hospital, Providence, Rhode Island 02905; and Division of Reproductive Endocrinology and Infertility (R.T.), Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520.
Bharati
B
Kalgi
Departments of Obstetrics and Gynecology (M.I., N.J., D.B., B.K., S.I.) and Genesis Fertility and Reproductive Medicine (R.V.G.), Maimonides Medical Center, Brooklyn, New York 11219; Department of Reproductive Endocrinology and Infertility (D.B.S.), Oregon Health & Science University, Portland, Oregon 97239; School of Business and Hospitality (O.T.), Conestoga College, Kitchener, Ontario, Canada N2G 4M4; Division of Medical Screening and Special Testing (G.L.-M.), Women and Infants Hospital, Providence, Rhode Island 02905; and Division of Reproductive Endocrinology and Infertility (R.T.), Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520.
Sara
S
Irani
Departments of Obstetrics and Gynecology (M.I., N.J., D.B., B.K., S.I.) and Genesis Fertility and Reproductive Medicine (R.V.G.), Maimonides Medical Center, Brooklyn, New York 11219; Department of Reproductive Endocrinology and Infertility (D.B.S.), Oregon Health & Science University, Portland, Oregon 97239; School of Business and Hospitality (O.T.), Conestoga College, Kitchener, Ontario, Canada N2G 4M4; Division of Medical Screening and Special Testing (G.L.-M.), Women and Infants Hospital, Providence, Rhode Island 02905; and Division of Reproductive Endocrinology and Infertility (R.T.), Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520.
Oded
O
Tal
Departments of Obstetrics and Gynecology (M.I., N.J., D.B., B.K., S.I.) and Genesis Fertility and Reproductive Medicine (R.V.G.), Maimonides Medical Center, Brooklyn, New York 11219; Department of Reproductive Endocrinology and Infertility (D.B.S.), Oregon Health & Science University, Portland, Oregon 97239; School of Business and Hospitality (O.T.), Conestoga College, Kitchener, Ontario, Canada N2G 4M4; Division of Medical Screening and Special Testing (G.L.-M.), Women and Infants Hospital, Providence, Rhode Island 02905; and Division of Reproductive Endocrinology and Infertility (R.T.), Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520.
Geralyn
G
Lambert-Messerlian
Departments of Obstetrics and Gynecology (M.I., N.J., D.B., B.K., S.I.) and Genesis Fertility and Reproductive Medicine (R.V.G.), Maimonides Medical Center, Brooklyn, New York 11219; Department of Reproductive Endocrinology and Infertility (D.B.S.), Oregon Health & Science University, Portland, Oregon 97239; School of Business and Hospitality (O.T.), Conestoga College, Kitchener, Ontario, Canada N2G 4M4; Division of Medical Screening and Special Testing (G.L.-M.), Women and Infants Hospital, Providence, Rhode Island 02905; and Division of Reproductive Endocrinology and Infertility (R.T.), Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520.
Reshef
R
Tal
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000097:blood; D001682:Biological Availability; D002762:Cholecalciferol / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D000071063:Endoglin; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000378:metabolism*; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000097:blood; D012959:Socioeconomic Factors; D013739:Testosterone / Q000097:blood; D053773:Transforming Growth Factor beta1 / Q000187:drug effects* / Q000378:metabolism*; D014807:Vitamin D / Q000627:therapeutic use*; D014808:Vitamin D Deficiency / Q000188:drug therapy / Q000378:metabolism; D014815:Vitamins / Q000627:therapeutic use*; D055815:Young Adult
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D008055:Lipids; D011956:Receptors, Cell Surface; D053773:Transforming Growth Factor beta1; D014815:Vitamins; D014807:Vitamin D; D002762:Cholecalciferol; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate