The effect of vitamin D supplementation in combination with low-calorie diet on anthropometric indices and androgen hormones in women with polycystic ovary syndrome: a double-blind, randomized, placebo-controlled trial

  • S. Jafari-Sfidvajani
  • R. Ahangari
  • M. Hozoori
  • H. Mozaffari-Khosravi
  • H. Fallahzadeh
  • A. Nadjarzadeh
Original Article

Abstract

Purpose

Polycystic ovary syndrome (PCOS) is known as the most common endocrine disorder in reproductive age women. The aim of this studywas to evaluate the effects of vitamin D supplementation in combination with low-calorie diet on anthropometric indices, reproductive hormones and menstrual regularity in overweight and obese PCOS women.

Methods

In this randomized controlled clinical trial, 60 PCOS women with vitamin D insufficiency were randomly assigned to 12 weeks of either (1) weight-loss intervention + 50,000 IU/week oral vitamin D3 or (2) weight-loss intervention + placebo. At the beginning and end of the study, the anthropometric indices, body composition, 25-hydroxyvitamin D, total testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and free androgen index (FAI) were measured and regularity of menses was compared among the two groups.

Result

After 12-week intervention, median of serum 25-hydroxyvitamin D3 significantly increased from 18.5 (10.75–20) ng/ml to 42.69 (34–53.25) ng/ml in vitamin D group compared to placebo group (p < 001). Moreover, there was a significant improvement in frequency regular menstrual cycle (p = 0.01). Mean of weight, body mass index, fat mass, waist and hip circumference and waist-to-hip ratio significantly decreased in both groups, but was not different between two groups. Mean of total testosterone insignificantly decreased from 0.7 to 0.5 ng/ml in vitamin D group (p = 0.18). In addition, we did not observe significant differences regarding DHEAS, FAI and SHBG between two groups.

Conclusions

In women with PCOS, androgen profile did not change with vitamin D supplementation when combined with low-calorie diet, but menstrual frequency significantly improved.

Clinical Trial Registration Number

IRCT2016062710826N19.

Keywords

Polycystic ovary syndrome Vitamin D Androgens Low-calorie diet Menstrual cycle Randomized controlled trial 

Notes

Acknowledgements

The authors thank all the women that participated in the present study. This study was done as a MS thesis in Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Compliance with ethical standards

Funding

Financial support for this study was provided by Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Conflict of interest

The authors declare that they have no conflict of interests.

Ethical approval

This research conducted according to Helsinki statement and the protocol was approved by Ethics Committee in Shahid Sadoughi University of Medical Sciences.

Informed consent

All participants completed written informed consent.

References

  1. 1.
    Lobo RA, Carmina E (2000) The importance of diagnosing the polycystic ovary syndrome. Ann Intern Med 132(12):989–993PubMedCrossRefGoogle Scholar
  2. 2.
    Farquhar CM, Birdsall M, Manning P, Mitchell JM, France JT (1994) The prevalence of polycystic ovaries on ultrasound scanning in a population of randomly selected women. Aust N Z J Obstet Gynaecol 34(1):67–72PubMedCrossRefGoogle Scholar
  3. 3.
    Mehrabian F, Khani B, Kelishadi R, Ghanbari E (2011) The prevalence of polycystic ovary syndrome in Iranian women based on different diagnostic criteria. Endokrynol Pol 62(3):238–242PubMedGoogle Scholar
  4. 4.
    Rotterdam E (2004) Group A-SPCW. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod (Oxford, England) 19(1):41CrossRefGoogle Scholar
  5. 5.
    Wehr E, Möller R, Horejsi R, Giuliani A, Kopera D, Schweighofer N et al (2009) Subcutaneous adipose tissue topography and metabolic disturbances in polycystic ovary syndrome. Wien Klin Wochenschr 121(7):262–269PubMedCrossRefGoogle Scholar
  6. 6.
    Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W et al (2009) The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 91(2):456–488PubMedCrossRefGoogle Scholar
  7. 7.
    Moran LJ, Brinkworth GD, Norman RJ (eds) Dietary therapy in polycystic ovary syndrome. Seminars in reproductive medicine; 2008: © Thieme Medical PublishersGoogle Scholar
  8. 8.
    Donà S, Bacchi E, Moghetti P (2017) Is cardiorespiratory fitness impaired in PCOS women? A review of the literature. J Endocrinol Investig 40(5):463–469CrossRefGoogle Scholar
  9. 9.
    Karakose M, Demircan K, Tutal E, Demirci T, Arslan M, Sahin M et al (2016) Clinical significance of ADAMTS1, ADAMTS5, ADAMTS9 aggrecanases and IL-17A, IL-23, IL-33 cytokines in polycystic ovary syndrome. J Endocrinol Investig 39(11):1269–1275CrossRefGoogle Scholar
  10. 10.
    Spritzer PM, Lecke SB, Satler F, Morsch DM (2015) Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome. Reproduction 149(5):R219–R227PubMedCrossRefGoogle Scholar
  11. 11.
    Pasquali R, Casimirri F, Vicennati V (1997) Weight control and its beneficial effect on fertility in women with obesity and polycystic ovary syndrome. Hum Reprod 12(suppl 1):82–87PubMedCrossRefGoogle Scholar
  12. 12.
    Panidis D, Farmakiotis D, Rousso D, Kourtis A, Katsikis I, Krassas G (2008) Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels. Fertil Steril 89(4):899–906PubMedCrossRefGoogle Scholar
  13. 13.
    Costello MF, Misso ML, Wong J, Hart R, Rombauts L, Melder A et al (2012) The treatment of infertility in polycystic ovary syndrome: a brief update. Aust N Z J Obstet Gynaecol 52(4):400–403PubMedCrossRefGoogle Scholar
  14. 14.
    Dunaif A (1997) Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis 1. Endocr Rev 18(6):774–800PubMedGoogle Scholar
  15. 15.
    Yildizhan R, Kurdoglu M, Adali E, Kolusari A, Yildizhan B, Sahin HG et al (2009) Serum 25-hydroxy vitamin D concentrations in obese and non-obese women with polycystic ovary syndrome. Arch Gynecol Obstet 280(4):559PubMedCrossRefGoogle Scholar
  16. 16.
    Martínez-García MÁ, Gambineri A, Alpañés M, Sanchón R, Pasquali R, Escobar-Morreale HF (2012) Common variants in the sex hormone-binding globulin gene (SHBG) and polycystic ovary syndrome (PCOS) in Mediterranean women. Hum Reprod 27(12):3569–3576PubMedCrossRefGoogle Scholar
  17. 17.
    Pasquali R, Casimirri F, Plate L, Capelli M (1990) Characterization of obese women with reduced sex hormone-binding globulin concentrations. Horm Metab Res 22(05):303–306PubMedCrossRefGoogle Scholar
  18. 18.
    Nestler JE, Powers LP, Matt DW, Steingold KA, Plymate SR, Rittmaster RS et al (1991) A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab 72(1):83–89PubMedCrossRefGoogle Scholar
  19. 19.
    Cobin R, Futterweit W, Nestler J, Reaven G, Jellinger P, Handelsman Y et al (2005) American Association of Clinical Endocrinologists position statement on metabolic and cardiovascular consequences of polycystic ovary syndrome. Endocr Pract 11(2):125–134CrossRefGoogle Scholar
  20. 20.
    Thomson RL, Spedding S, Buckley JD (2012) Vitamin D in the aetiology and management of polycystic ovary syndrome. Clin Endocrinol 77(3):343–350CrossRefGoogle Scholar
  21. 21.
    Lagunova Z, Porojnicu AC, Lindberg F, Hexeberg S, Moan J (2009) The dependency of vitamin D status on body mass index, gender, age and season. Anticancer Res 29(9):3713–3720PubMedGoogle Scholar
  22. 22.
    Mahmoudi T, Gourabi H, Ashrafi M, Yazdi RS, Ezabadi Z (2010) Calciotropic hormones, insulin resistance, and the polycystic ovary syndrome. Fertil Steril 93(4):1208–1214PubMedCrossRefGoogle Scholar
  23. 23.
    Rodríguez-Rodríguez E, Navia-Lomban B, López-Sobaler A, Ortega R (2010) Associations between abdominal fat and body mass index on vitamin D status in a group of Spanish schoolchildren. Eur J Clin Nutr 64(5):461–467PubMedCrossRefGoogle Scholar
  24. 24.
    Wehr E, Pilz S, Schweighofer N, Giuliani A, Kopera D, Pieber T et al (2009) Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome. Eur J Endocrinol 161(4):575–582PubMedCrossRefGoogle Scholar
  25. 25.
    Ding C, Gao D, Wilding J, Trayhurn P, Bing C (2012) Vitamin D signalling in adipose tissue. Br J Nutr 108(11):1915–1923PubMedCrossRefGoogle Scholar
  26. 26.
    Jones G, Strugnell SA, DeLUCA HF (1998) Current understanding of the molecular actions of vitamin D. Physiol Rev 78(4):1193–1231PubMedGoogle Scholar
  27. 27.
    Mahmoudi T (2009) Genetic variation in the vitamin D receptor and polycystic ovary syndrome risk. Fertil Steril 92(4):1381–1383PubMedCrossRefGoogle Scholar
  28. 28.
    Ranjzad F, Mahban A, Shemirani AI, Mahmoudi T, Vahedi M, Nikzamir A et al (2011) Influence of gene variants related to calcium homeostasis on biochemical parameters of women with polycystic ovary syndrome. J Assist Reprod Genet 28(3):225–232PubMedCrossRefGoogle Scholar
  29. 29.
    Wehr E, Trummer O, Giuliani A, Gruber H-J, Pieber TR, Obermayer-Pietsch B (2011) Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol 164(5):741–749PubMedCrossRefGoogle Scholar
  30. 30.
    Sørensen LB, Søe M, Halkier KH, Stigsby B, Astrup A (2012) Effects of increased dietary protein-to-carbohydrate ratios in women with polycystic ovary syndrome. Am J Clin Nutr 95(1):39–48PubMedCrossRefGoogle Scholar
  31. 31.
    Trumbo P, Schlicker S, Yates AA, Poos M (2002) Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. J Am Diet Assoc 102(11):1621–1630PubMedCrossRefGoogle Scholar
  32. 32.
    Pasco J, Sanders K, Henry M, Nicholson G, Seeman E, Kotowicz M (2000) Calcium intakes among Australian women: geelong osteoporosis study. Intern Med J 30(1):21–27Google Scholar
  33. 33.
    Sharpe RM, Franks S (2002) Environment, lifestyle and infertility—an inter-generational issue. Nat Cell Biol 4(S1):S33–S40PubMedCrossRefGoogle Scholar
  34. 34.
    Norman RJ, Davies MJ, Lord J, Moran LJ (2002) The role of lifestyle modification in polycystic ovary syndrome. Trends Endocrinol Metab 13(6):251–257PubMedCrossRefGoogle Scholar
  35. 35.
    Norman RJ, Noakes M, Wu R, Davies MJ, Moran L, Wang JX (2004) Improving reproductive performance in overweight/obese women with effective weight management. Hum Reprod Update 10(3):267–280PubMedCrossRefGoogle Scholar
  36. 36.
    Norman RJ, Masters SC, Hague W, Beng C, Pannall P, Wang JX (1995) Metabolic approaches to the subclassification of polycystic ovary syndrome. Fertil Steril 63(2):329–335PubMedCrossRefGoogle Scholar
  37. 37.
    Pasquali R, Casimirri F, Venturoli S, Antonio M, Morselli L, Reho S et al (1994) Body fat distribution has weight-independent effects on clinical, hormonal, and metabolic features of women with polycystic ovary syndrome. Metabolism 43(6):706–713PubMedCrossRefGoogle Scholar
  38. 38.
    Dunaif A, Xia J, Book C-B, Schenker E, Tang Z (1995) Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome. J Clin Investig 96(2):801PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Ehrmann DA, Sturis J, Byrne MM, Karrison T, Rosenfield RL, Polonsky KS (1995) Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus. J Clin Investig 96(1):520PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Holte J, Bergh T, Berne C, Berglund L, Lithell H (1994) Enhanced early insulin response to glucose in relation to insulin resistance in women with polycystic ovary syndrome and normal glucose tolerance. J Clin Endocrinol Metab 78(5):1052–1058PubMedGoogle Scholar
  41. 41.
    Ciampelli M, Fulghesu A, Cucinelli F, Pavone V, Caruso A, Mancuso S et al (1997) Heterogeneity in beta cell activity, hepatic insulin clearance and peripheral insulin sensitivity in women with polycystic ovary syndrome. Hum Reprod 12(9):1897–1901PubMedCrossRefGoogle Scholar
  42. 42.
    Jakubowicz DJ, Nestler JE (1997) 17α-Hydroxyprogesterone responses to leuprolide and serum androgens in obese women with and without polycystic ovary syndrome after dietary weight loss 1. J Clin Endocrinol Metabol 82(2):556–560Google Scholar
  43. 43.
    Pasquali R, Gambineri A, Biscotti D, Vicennati V, Gagliardi L, Colitta D et al (2000) Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab 85(8):2767–2774PubMedCrossRefGoogle Scholar
  44. 44.
    Moran L, Noakes M, Clifton P, Tomlinson L, Norman R (2003) Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab 88(2):812–819PubMedCrossRefGoogle Scholar
  45. 45.
    Hamilton-Fairley D, Kiddy D, Anyaoku V, Koistinen R, Seppälä M, Franks S (1993) Response of sex hormone binding globulin and insulin-like growth factor binding protein-1 to an oral glucose tolerance test in obese women with polycystic ovary syndrome before and after calorie restriction. Clin Endocrinol 39(3):363–367CrossRefGoogle Scholar
  46. 46.
    Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE et al (2001) Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86(5):1930–1935PubMedCrossRefGoogle Scholar
  47. 47.
    Orio F Jr, Palomba S, Cascella T, Milan G, Mioni R, Pagano C et al (2003) Adiponectin levels in women with polycystic ovary syndrome. J Clin Endocrinol Metab 88(6):2619–2623PubMedCrossRefGoogle Scholar
  48. 48.
    Andersen P, Seljeflot I, Abdelnoor M, Arnesen H, Dale PO, Løvik A et al (1995) Increased insulin sensitivity and fibrinolytic capacity after dietary intervention in obese women with polycystic ovary syndrome. Metabolism 44(5):611–616PubMedCrossRefGoogle Scholar
  49. 49.
    Pasquali R, Fabbri R, Venturoli S, Paradisi R, Antenucci D, Melchionda N (1986) Effect of weight loss and antiandrogenic therapy on sex hormone blood levels and insulin resistance in obese patients with polycystic ovaries. Am J Obstet Gynecol 154(1):139–144PubMedCrossRefGoogle Scholar
  50. 50.
    Nestler JE, Barlascini CO, Matt DW, Steingold KA, Plymate SR, Clore JN et al (1989) Suppression of serum insulin by diazoxide reduces serum testosterone levels in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 68(6):1027–1032PubMedCrossRefGoogle Scholar
  51. 51.
    Pasquali R, Antenucci D, Casimirri F, Venturoli S, Paradisi R, Fabbri R et al (1989) Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss. J Clin Endocrinol Metab 68(1):173–179PubMedCrossRefGoogle Scholar
  52. 52.
    Van Dam EW, Roelfsema F, Veldhuis JD, Helmerhorst FM, Frölich M, Meinders AE et al (2002) Increase in daily LH secretion in response to short-term calorie restriction in obese women with PCOS. Am J Physiol-Endocrinol Metab 282(4):E865–E872PubMedCrossRefGoogle Scholar
  53. 53.
    Hahn S, Haselhorst U, Tan S, Quadbeck B, Schmidt M, Roesler S et al (2006) Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 114(10):577–583PubMedCrossRefGoogle Scholar
  54. 54.
    Freundlich M, Quiroz Y, Zhang Z, Zhang Y, Bravo Y, Weisinger JR et al (2008) Suppression of renin-angiotensin gene expression in the kidney by paricalcitol. Kidney Int 74(11):1394–1402PubMedCrossRefGoogle Scholar
  55. 55.
    Pittas AG, Lau J, Hu FB, Dawson-Hughes B (2007) The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab 92(6):2017–2029PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Chiu KC, Chu A, Go VLW, Saad MF (2004) Hypovitaminosis D is associated with insulin resistance and β cell dysfunction. Am J Clin Nutr 79(5):820–825PubMedGoogle Scholar
  57. 57.
    Isaia G, Giorgino R, Adami S (2001) High prevalence of hypovitaminosis D in female type 2 diabetic population. Diabetes Care 24(8):1496PubMedCrossRefGoogle Scholar
  58. 58.
    Mason C, Tapsoba JDD, Duggan C, Imayama I, Wang C-Y, Korde LA et al (2016) Effects of vitamin D supplementation during weight loss on sex hormones in postmenopausal women. Menopause 23(6):645–652PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Lorvand AH, Agah S, Mousavi S, Hosseini A, Shidfar F (2016) Regression of Non-alcoholic fatty liver by vitamin D supplement: a double-blind randomized controlled clinical trial. Arch Iran Med 19(9):631–638Google Scholar
  60. 60.
    Marsh KA, Steinbeck KS, Atkinson FS, Petocz P, Brand-Miller JC (2010) Effect of a low glycemic index compared with a conventional healthy diet on polycystic ovary syndrome. Am J Clin Nutr 92(1):83–92PubMedCrossRefGoogle Scholar
  61. 61.
    Azadi-Yazdi M, Karimi-Zarchi M, Salehi-Abargouei A, Fallahzadeh H, Nadjarzadeh A (2016) Effects of Dietary Approach to Stop Hypertension diet on androgens, antioxidant status and body composition in overweight and obese women with polycystic ovary syndrome: a randomised controlled trial. J Hum Nutr Dietetics 30(3):275–283CrossRefGoogle Scholar
  62. 62.
    Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 72(3):690–693PubMedGoogle Scholar
  63. 63.
    Del Valle HB, Yaktine AL, Taylor CL, Ross AC (2011) Dietary reference intakes for calcium and vitamin D. National Academies Press, USAGoogle Scholar
  64. 64.
    Rayalam S, Della-Fera MA, Ambati S, Yang JY, Park HJ, Baile CA (2008) Enhanced effects of 1, 25 (OH) 2D3 plus genistein on adipogenesis and apoptosis in 3T3-L1 adipocytes. Obesity. 16(3):539–546PubMedCrossRefGoogle Scholar
  65. 65.
    Mason C, Xiao L, Imayama I, Duggan CR, Bain C, Foster-Schubert KE et al (2011) Effects of weight loss on serum vitamin D in postmenopausal women. Am J Clin Nutr 94(1):95–103PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Rock CL, Emond JA, Flatt SW, Heath DD, Karanja N, Pakiz B et al (2012) Weight loss is associated with increased serum 25-Hydroxyvitamin D in overweight or obese women. Obesity 20(11):2296–2301PubMedCrossRefGoogle Scholar
  67. 67.
    Crosignani PG, Colombo M, Vegetti W, Somigliana E, Gessati A, Ragni G (2003) Overweight and obese anovulatory patients with polycystic ovaries: parallel improvements in anthropometric indices, ovarian physiology and fertility rate induced by diet. Hum Reprod 18(9):1928–1932PubMedCrossRefGoogle Scholar
  68. 68.
    Thys-Jacobs S, Donovan D, Papadopoulos A, Sarrel P, Bilezikian JP (1999) Vitamin D and calcium dysregulation in the polycystic ovarian syndrome. Steroids 64(6):430–435PubMedCrossRefGoogle Scholar
  69. 69.
    Du H, Daftary GS, Lalwani SI, Taylor HS (2005) Direct regulation of HOXA10 by 1, 25-(OH) 2D3 in human myelomonocytic cells and human endometrial stromal cells. Mol Endocrinol 19(9):2222–2233PubMedCrossRefGoogle Scholar
  70. 70.
    Halloran BP, Deluca HF (1980) Effect of vitamin D deficiency on fertility and reproductive capacity in the female rat. J Nutr 110(8):1573–1580PubMedGoogle Scholar
  71. 71.
    Kovacs CS, Woodland ML, Fudge NJ, Friel JK (2005) The vitamin D receptor is not required for fetal mineral homeostasis or for the regulation of placental calcium transfer in mice. Am J Physiol-Endocrinol Metab 289(1):E133–E144PubMedCrossRefGoogle Scholar
  72. 72.
    Yoshizawa T, Handa Y, Uematsu Y, Takeda S, Sekine K, Yoshihara Y et al (1997) Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Genet 16(4):391–396PubMedCrossRefGoogle Scholar
  73. 73.
    De Felici M, Dolci S, Siracusa G (1991) An increase of intracellular free Ca2 + is essential for spontaneous meiotic resumption by mouse oocytes. J Exp Zool Part A: Ecol Genet Physiol 260(3):401–405CrossRefGoogle Scholar
  74. 74.
    Anagnostis P, Karras S, Goulis DG (2013) Vitamin D in human reproduction: a narrative review. Int J Clin Pract 67(3):225–235PubMedCrossRefGoogle Scholar
  75. 75.
    Das M, Djahanbakhch O, Hacihanefioglu B, Saridogan E, Ikram M, Ghali L et al (2008) Granulosa cell survival and proliferation are altered in polycystic ovary syndrome. J Clin Endocrinol Metab 93(3):881–887PubMedCrossRefGoogle Scholar
  76. 76.
    Parikh G, Varadinova M, Suwandhi P, Araki T, Rosenwaks Z, Poretsky L et al (2010) Vitamin D regulates steroidogenesis and insulin-like growth factor binding protein-1 (IGFBP-1) production in human ovarian cells. Horm Metab Res 42(10):754–757PubMedCrossRefGoogle Scholar
  77. 77.
    Wehr E, Pieber T, Obermayer-Pietsch B (2011) Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: a pilot study. J Endocrinol Invest 34(10):757–763PubMedGoogle Scholar
  78. 78.
    Bonakdaran S, Khorasani ZM, Davachi B, Khorasani JM (2012) The effects of calcitriol on improvement of insulin resistance, ovulation and comparison with metformin therapy in PCOS patients: a randomized placebo-controlled clinical trial. Iran J Reprod Med 10(5):465PubMedPubMedCentralGoogle Scholar
  79. 79.
    Selimoglu H, Duran C, Kiyici S, Ersoy C, Guclu M, Ozkaya G et al (2010) The effect of vitamin D replacement therapy on insulin resistance and androgen levels in women with polycystic ovary syndrome. J Endocrinol Invest 33(4):234–238PubMedCrossRefGoogle Scholar
  80. 80.
    Raja-Khan N, Shah J, Stetter CM, Lott ME, Kunselman AR, Dodson WC et al (2014) High-dose vitamin D supplementation and measures of insulin sensitivity in polycystic ovary syndrome: a randomized, controlled pilot trial. Fertil Steril 101(6):1740–1746PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2017

Authors and Affiliations

  1. 1.Nutrition and Food Security Research CenterShahid Sadoughi University of Medical SciencesYazdIran
  2. 2.Department of Nutrition, School of Public HealthShahid Sadoughi University of Medical SciencesYazdIran
  3. 3.Obstetric and Gynecology Department, Faculty of MedicineQom University of Medical SciencesQomIran
  4. 4.Nutritional Community Medicine Qom University of Medical SciencesQomIran
  5. 5.Diabetic Research CenterShahid Sadoughi University of Medical SciencesYazdIran
  6. 6.Research Center for Prevention and Epidemiology of Non-communicable Disease, Shahid Sadoughi University of Medical SciencesYazdIran

Personalised recommendations