Efficacy of vitamin D supplementation on polycystic ovary syndrome: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LIU Yuyu ^1,2 , YUAN Tao ^3,4,5 ,  LI Haihong ^1,2 ,  QIU Jie ² , QIU Wenwen ^1,2 , HU Yaguang ² , YANG Kehu ^4,5

1. School of Nursing, Gansu University of Chinese Medicine, Lanzhou 730000, P.R.China;
2. Gansu Provincial Maternity and Childcare Hospital, Lanzhou 730050, P.R.China;
3. Department of Pain Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, P.R.China;
4. Evidence-based Medicine Center of Lanzhou University, Lanzhou 730000, P.R.China;
5. Key Laboratory of Evidence-based Medicine and Clinical Transformation in Gansu Province, Lanzhou 730000, P.R.China;

Corresponding author：

LI Haihong, Email: 1439447925@qq.com; QIU Jie, Email: qiujieqssfy@163.com

Keywords：

Vitamin D; Polycystic ovary syndrome; Efficacy; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.201910015

Video：

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Objective To systematically review the efficacy of vitamin D supplementation on patients with polycystic ovary syndrome (PCOS).Methods PubMed, EMbase, The Cochrane Library, Web of Science, EBSCO, CBM, WanFang Data, CNKI and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on the efficacy of vitamin D supplementation for PCOS from inception to July 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.Results A total of 11 RCTs involving 692 patients were included. The results of meta-analysis showed that compared with placebo, vitamin D could reduce the level of hypersensitive C-reactive protein (hs-CRP) (MD=−0.54, 95%CI −1.00 to −0.08, P=0.02) and total testosterone (MD=−0.17, 95%CI −0.29 to −0.05, P=0.004), and increase endometrial thickness (MD=1.78, 95%CI 0.49 to 3.06, P=0.007). However, there were no significant differences between two groups in the incidence of sex hormone binding globulin (SHBG) level and hypertrichosis’s score (mF-G) (P>0.05).Conclusions Current evidence indicates that vitamin D supplementation can significantly reduce the level of total testosterone and hs-CRP, and increase endometrial thickness of PCOS. Due to the limited quality and quantity of the included studies, more high quality studies are required to verify the above conclusions.

Citation： LIU Yuyu, YUAN Tao, LI Haihong, QIU Jie, QIU Wenwen, HU Yaguang, YANG Kehu. Efficacy of vitamin D supplementation on polycystic ovary syndrome: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2020, 20(6): 695-701. doi: 10.7507/1672-2531.201910015 Copy

1.	Goodman NF, Cobin RH, Futterweit W, et al. American association of clinical endocrinologists, American college if endocrinology, and androgen excess and PCOS society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome-part 2. Endocr Pract, 2015, 21(11): 1291-1300.
2.	Artimani T, Karimi J, Mehdizadeh M, et al. Evaluation of pro-oxidant-antioxidant balance (PAB) and its association with inflammatory cytokines in polycystic ovary syndrome (PCOS). Gynecol Endocrinol, 2018, 34(2): 148-152.
3.	Walters KA, Gilchrist RB, Ledger WL, et al. New perspectives on the pathogenesis of PCOS: neuroendocrine origins. Trends Endocrinol Metab, 2018, 29(12): 841-852.
4.	Fauser BC, Tarlatzis BC, Rebar RW, et al. Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril, 2012, 97(1): 28-38.
5.	Barbieri R, Ehrmann D. Diagnosis of polycysticovary syndrome in adults, 2018. Available at: www.uptodate.com.
6.	Lv Y, Sun C, Tian Y, et al. Association study of HNF1A in women with polycystic ovary syndrome. J Assist Reprod Genet, 2017, 34(5): 677-682.
7.	Ostadmohammadi V, Jamilian M, Bahmani F, et al. Vitamin D and probiotic co-supplementation affects mental health, hormonal, inflammatory and oxidative stress parameters in women with polycystic ovary syndrome. J Ovarian Res, 2019, 12(1): 5.
8.	Ganie MA, Marwaha RK, Nisar S, et al. Impact of hypovitaminosis D on clinical, hormonal and insulin sensitivity parameters in normal body mass index polycystic ovary syndrome women. J Obstet Gynaecol, 2016, 36(4): 508-512.
9.	Higgins JPT, Green S (editors). Cochrane handbook for systematic reviews of interventions version 5.1.0(updated March 2011). Available at: www.cochrane-handbook.org.
10.	El-Aal Alomda, FA, El-Latef H, Mahmmod A, et al. The effect of vitamin D supplementation on the androgenic profile in patient with polycystic ovary syndrome. Egypt J Hosp Med, 2019, 75(3): 2461-2466.
11.	Maktabi M, Jamilian M, Asemi Z. Magnesium-Zinc-Calcium-Vitamin D co-supplementation improves hormonal profiles, biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Biol Trace Elem Res, 2018, 182(1): 21-28.
12.	Jamilian M, Samimi M, Mirhosseini N, et al. The influences of vitamin D and omega-3 co-supplementation on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome. J Affect Disord, 2018, 238(1): 32-38.
13.	Jafari-Sfidvajani S, Ahangari R, Hozoori M, et al. 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. J Endocrinol Invest, 2018, 41(5): 597-607.
14.	Maktabi M, Chamani M, Asemi Z. The effects of vitamin D supplementation on metabolic status of patients with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Horm Metab Res, 2017, 49(7): 493-498.
15.	Jamilian M, Foroozanfard F, Rahmani E, et al. Effect of two different doses of vitamin d supplementation on metabolic profiles of insulin-resistant patients with polycystic ovary syndrome. Nutrients, 2017, 9(12): 1280.
16.	Razavi M, Jamilian M, Karamali M, et al. The effects of vitamin D-K-Calcium co-supplementation on endocrine, inflammation, and oxidative stress biomarkers in vitamin d-deficient women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Horm Metab Res, 2016, 48(7): 446-451.
17.	Raja-Khan N, Shah J, Stetter CM, et al. High-dose vitamin D supplementation and measures of insulin sensitivity in polycystic ovary syndrome: a randomized, controlled pilot trial. Fertil Steril, 2014, 101(6): 1740-1746.
18.	Asadi M, Matin N, Frootan M, et al. Vitamin D improves endometrial thickness in PCOS women who need intrauterine insemination: a randomized double-blind placebo-controlled trial. Arch Gynecol Obstet, 2014, 289(4): 865-870.
19.	Rahimi-Ardabili H, Pourghassem G B, Farzadi L. Effects of vitamin D on cardiovascular disease risk factors in polycystic ovary syndrome women with vitamin D deficiency. J Endocrinol Invest, 2013, 36(1): 28-32.
20.	Palomba S, Santagni S, Falbo A, et al. Complications and challenges associated with polycystic ovary syndrome: current perspectives. Int J Womens Health, 2015, 31(7): 745-763.
21.	Thomson RL, Spedding S, Buckley JD. Vitamin D in the aetiology and management of polycystic ovary syndrome. Clin Endocrinol (Oxf), 2012, 77(3): 343-350.
22.	Krul-Poel YHM, Koenders PP, Steegers-Theunissen RP, et al. Vitamin D and metabolic disturbances in polycystic ovary syndrome (PCOS): A cross-sectional study. PloS One, 2018, 13(12): e0204748.
23.	Maidana P, Fritzler A, Mocarbel Y, et al. Association between vitamin D and adrenal parameters with metabolic and inflammatory markers in polycystic ovary syndrome. Sci Rep, 2019, 9(1): 3968.
24.	Jackson JL, Judd SE, Panwar B, et al. Associations of 25-hydroxyvitamin D with markers of inflammation, insulin resistance and obesity in black and white community-dwelling adults. J Clin Transl Endocrinol, 2016, 5(C): 21-25.
25.	Al-Rasheed NM, Bassiouni YA, Hasan IH, et al. Vitamin D attenuates pro-inflammatory TNF-alpha cytokine expression by inhibiting NF-small ka, CyrillicB/ p65 signaling in hypertrophied rat hearts. J Physiol Biochem, 2015, 71(2): 289-299.
26.	Khoo AL, Chai LY, Koenen HJ, et al. Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals. Clin Exp Immunol, 2011, 164(1): 72-79.
27.	Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of vitamin D supplementation on biomarkers of inflammation and oxidative stress among women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Horm Metab Res, 2018, 50(4): 271-279.
28.	Yao K, Bian C, Zhao X. Association of polycystic ovary syndrome with metabolic syndrome and gestational diabetes: aggravated complication of pregnancy (Review). Exp Ther Med, 2017, 14(2): 1271-1276.
29.	Muscogiuri G, Altieri B, de Angelis C, et al. Shedding new light on female fertility: The role of vitamin D. Rev Endocr Metab Disord, 2017, 18(3): 273-283.
30.	Deswal R, Nanda S, Dang AS. Association of Luteinizing hormone and LH receptor gene polymorphism with susceptibility of polycystic ovary syndrome. Syst Biol Reprod Med, 2019, 65(5): 400-408.
31.	Lerchbaum E, Obermayer-Pietsch B. Vitamin D and fertility: a systematic review. Eur J Endocrinol, 2012, 166(5): 765-778.
32.	Fritz J. Vitamin D regulates steroidogenesis and insulin-like growth factor binding protein-1(IGFBP-1) production in human ovarian cells. Horm Metab Res, 2010, 42(10): 754-757.
33.	Ozkan S, Jindal S, Greenseid K, et al. Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertil Steril, 2010, 94(4): 1314-1319.

1. Goodman NF, Cobin RH, Futterweit W, et al. American association of clinical endocrinologists, American college if endocrinology, and androgen excess and PCOS society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome-part 2. Endocr Pract, 2015, 21(11): 1291-1300.
2. Artimani T, Karimi J, Mehdizadeh M, et al. Evaluation of pro-oxidant-antioxidant balance (PAB) and its association with inflammatory cytokines in polycystic ovary syndrome (PCOS). Gynecol Endocrinol, 2018, 34(2): 148-152.
3. Walters KA, Gilchrist RB, Ledger WL, et al. New perspectives on the pathogenesis of PCOS: neuroendocrine origins. Trends Endocrinol Metab, 2018, 29(12): 841-852.
4. Fauser BC, Tarlatzis BC, Rebar RW, et al. Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril, 2012, 97(1): 28-38.
5. Barbieri R, Ehrmann D. Diagnosis of polycysticovary syndrome in adults, 2018. Available at: www.uptodate.com.
6. Lv Y, Sun C, Tian Y, et al. Association study of HNF1A in women with polycystic ovary syndrome. J Assist Reprod Genet, 2017, 34(5): 677-682.
7. Ostadmohammadi V, Jamilian M, Bahmani F, et al. Vitamin D and probiotic co-supplementation affects mental health, hormonal, inflammatory and oxidative stress parameters in women with polycystic ovary syndrome. J Ovarian Res, 2019, 12(1): 5.
8. Ganie MA, Marwaha RK, Nisar S, et al. Impact of hypovitaminosis D on clinical, hormonal and insulin sensitivity parameters in normal body mass index polycystic ovary syndrome women. J Obstet Gynaecol, 2016, 36(4): 508-512.
9. Higgins JPT, Green S (editors). Cochrane handbook for systematic reviews of interventions version 5.1.0(updated March 2011). Available at: www.cochrane-handbook.org.
10. El-Aal Alomda, FA, El-Latef H, Mahmmod A, et al. The effect of vitamin D supplementation on the androgenic profile in patient with polycystic ovary syndrome. Egypt J Hosp Med, 2019, 75(3): 2461-2466.
11. Maktabi M, Jamilian M, Asemi Z. Magnesium-Zinc-Calcium-Vitamin D co-supplementation improves hormonal profiles, biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Biol Trace Elem Res, 2018, 182(1): 21-28.
12. Jamilian M, Samimi M, Mirhosseini N, et al. The influences of vitamin D and omega-3 co-supplementation on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome. J Affect Disord, 2018, 238(1): 32-38.
13. Jafari-Sfidvajani S, Ahangari R, Hozoori M, et al. 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. J Endocrinol Invest, 2018, 41(5): 597-607.
14. Maktabi M, Chamani M, Asemi Z. The effects of vitamin D supplementation on metabolic status of patients with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Horm Metab Res, 2017, 49(7): 493-498.
15. Jamilian M, Foroozanfard F, Rahmani E, et al. Effect of two different doses of vitamin d supplementation on metabolic profiles of insulin-resistant patients with polycystic ovary syndrome. Nutrients, 2017, 9(12): 1280.
16. Razavi M, Jamilian M, Karamali M, et al. The effects of vitamin D-K-Calcium co-supplementation on endocrine, inflammation, and oxidative stress biomarkers in vitamin d-deficient women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Horm Metab Res, 2016, 48(7): 446-451.
17. Raja-Khan N, Shah J, Stetter CM, et al. High-dose vitamin D supplementation and measures of insulin sensitivity in polycystic ovary syndrome: a randomized, controlled pilot trial. Fertil Steril, 2014, 101(6): 1740-1746.
18. Asadi M, Matin N, Frootan M, et al. Vitamin D improves endometrial thickness in PCOS women who need intrauterine insemination: a randomized double-blind placebo-controlled trial. Arch Gynecol Obstet, 2014, 289(4): 865-870.
19. Rahimi-Ardabili H, Pourghassem G B, Farzadi L. Effects of vitamin D on cardiovascular disease risk factors in polycystic ovary syndrome women with vitamin D deficiency. J Endocrinol Invest, 2013, 36(1): 28-32.
20. Palomba S, Santagni S, Falbo A, et al. Complications and challenges associated with polycystic ovary syndrome: current perspectives. Int J Womens Health, 2015, 31(7): 745-763.
21. Thomson RL, Spedding S, Buckley JD. Vitamin D in the aetiology and management of polycystic ovary syndrome. Clin Endocrinol (Oxf), 2012, 77(3): 343-350.
22. Krul-Poel YHM, Koenders PP, Steegers-Theunissen RP, et al. Vitamin D and metabolic disturbances in polycystic ovary syndrome (PCOS): A cross-sectional study. PloS One, 2018, 13(12): e0204748.
23. Maidana P, Fritzler A, Mocarbel Y, et al. Association between vitamin D and adrenal parameters with metabolic and inflammatory markers in polycystic ovary syndrome. Sci Rep, 2019, 9(1): 3968.
24. Jackson JL, Judd SE, Panwar B, et al. Associations of 25-hydroxyvitamin D with markers of inflammation, insulin resistance and obesity in black and white community-dwelling adults. J Clin Transl Endocrinol, 2016, 5(C): 21-25.
25. Al-Rasheed NM, Bassiouni YA, Hasan IH, et al. Vitamin D attenuates pro-inflammatory TNF-alpha cytokine expression by inhibiting NF-small ka, CyrillicB/ p65 signaling in hypertrophied rat hearts. J Physiol Biochem, 2015, 71(2): 289-299.
26. Khoo AL, Chai LY, Koenen HJ, et al. Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals. Clin Exp Immunol, 2011, 164(1): 72-79.
27. Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of vitamin D supplementation on biomarkers of inflammation and oxidative stress among women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Horm Metab Res, 2018, 50(4): 271-279.
28. Yao K, Bian C, Zhao X. Association of polycystic ovary syndrome with metabolic syndrome and gestational diabetes: aggravated complication of pregnancy (Review). Exp Ther Med, 2017, 14(2): 1271-1276.
29. Muscogiuri G, Altieri B, de Angelis C, et al. Shedding new light on female fertility: The role of vitamin D. Rev Endocr Metab Disord, 2017, 18(3): 273-283.
30. Deswal R, Nanda S, Dang AS. Association of Luteinizing hormone and LH receptor gene polymorphism with susceptibility of polycystic ovary syndrome. Syst Biol Reprod Med, 2019, 65(5): 400-408.
31. Lerchbaum E, Obermayer-Pietsch B. Vitamin D and fertility: a systematic review. Eur J Endocrinol, 2012, 166(5): 765-778.
32. Fritz J. Vitamin D regulates steroidogenesis and insulin-like growth factor binding protein-1(IGFBP-1) production in human ovarian cells. Horm Metab Res, 2010, 42(10): 754-757.
33. Ozkan S, Jindal S, Greenseid K, et al. Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertil Steril, 2010, 94(4): 1314-1319.

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