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Current Women`s Health Reviews


ISSN (Print): 1573-4048
ISSN (Online): 1875-6581

Systematic Review Article

Impact of Vitamin D Supplementation on Menstrual Cycle Irregularities among Women with Polycystic Ovary Syndrome who were Treated with Metformin: A Systematic Review with Meta-Analysis

Author(s): Ebtihag O. Alenzi*

Volume 19, Issue 4, 2023

Published on: 26 December, 2022

Article ID: e031122210618 Pages: 8

DOI: 10.2174/1573404819666221103142456

Price: $65


Background: There is inconsistency in the evidence about the effect of adding vitamin D supplements to metformin therapy among women with polycystic ovary syndrome (PCOS).

Objective: In this systematic review, we described the differences in menstrual cycle irregularities between women who received vitamin D supplementation and those who didn’t receive vitamin D among women who diagnosed with PCOS and received metformin.

Methods: We reviewed previous literature to identify all relevant studies. The included studies' quality and risk of bias were assessed using the Consolidated Standards of Reporting Trials (CONSORT) and the Reporting of Observational Studies in Epidemiology (STROBE) instrument. Cochrane's Q-test and I2 statistic were used to assess the heterogeneity across included studies. The fixed-effect model was used to calculate the total effect size.

Results: Six studies were included, involving 633 women diagnosed with PCOS. Supplementation of vitamin D with metformin could have a significant impact on the improvement of menstrual cycles compared to receiving metformin alone (OR = 2.11, 95% CI, 1.40- 3.19). There was no evidence of heterogeneity across included studies. Subgroup analysis showed that the magnitude of the association increased when only infertile women with PCOS were included (OR = 2.37, 95% CI, 1.52-3.72).

Conclusion: This evidence suggests the possible benefit of adding vitamin D to metformin in regulating the menstrual cycle among women with PCOS, especially infertile women.

Keywords: Women, PCOS, menstrual cycle, vitamin D, metformin, infertility.

Graphical Abstract
McGowan, M.P. Polycystic ovary syndrome: A common endocrine disorder and risk factor for vascular disease. Curr. Treat. Options Cardiovasc. Med., 2011, 13(4), 289-301.
[] [PMID: 21562798]
Hart, R.; Hickey, M.; Franks, S. Definitions, prevalence and symptoms of polycystic ovaries and polycystic ovary syndrome. Best Pract. Res. Clin. Obstet. Gynaecol., 2004, 18(5), 671-683.
[] [PMID: 15380140]
Thomson, R.L.; Spedding, S.; Buckley, J.D. Vitamin D in the aetiology and management of polycystic ovary syndrome. Clin. Endocrinol., 2012, 77(3), 343-350.
[] [PMID: 22574874]
Tejpal, C.; Poudel, I.; Jahan, N. Is metformin the answer for distressed females with menstrual irregularities? Cureus, 2019, 11(8), e5460.
[] [PMID: 31475082]
Shojaeian, Z.; Sadeghi, R.; Latifnejad Roudsari, R. Calcium and vitamin D supplementation effects on metabolic factors, menstrual cycles and follicular responses in women with polycystic ocvary syndrome: A systematic review and meta-analysis. Caspian J. Intern. Med., 2019, 10(4), 359-369.
[PMID: 31814932]
Fang, F.; Ni, K.; Cai, Y.; Shang, J.; Zhang, X.; Xiong, C. Effect of vitamin D supplementation on polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials. Complement. Ther. Clin. Pract., 2017, 26, 53-60.
[] [PMID: 28107851]
von Elm, E.; Altman, D.G.; Egger, M.; Pocock, S.J.; Gøtzsche, P.C.; Vandenbroucke, J.P. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet, 2007, 370(9596), 1453-1457.
[] [PMID: 18064739]
The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies: The EQUATOR Network,, 2019. Available from:
Dravecká, I.; Figurová, J.; Javorský, M.; Petríková, J.; Vaľková, M.; Lazúrová, I. The effect of alfacalcidiol and metformin on phenotype manifestations in women with polycystic ovary syndrome - a preliminary study. Physiol. Res., 2016, 65(5), 815-822.
[] [PMID: 27429113]
Firouzabadi, R.; Aflatoonian, A.; Modarresi, S.; Sekhavat, L.; MohammadTaheri, S. Therapeutic effects of calcium & vitamin D supplementation in women with PCOS. Complement. Ther. Clin. Pract., 2012, 18(2), 85-88.
[] [PMID: 22500844]
Kadoura, S.; Alhalabi, M.; Nattouf, A.H. Effect of calcium and vitamin D supplements as an adjuvant therapy to metformin on menstrual cycle abnormalities, hormonal profile, and IGF-1 system in polycystic ovary syndrome patients: A randomized, placebo-controlled clinical trial. Adv. Pharmacol. Sci., 2019, 2019, 1-10.
[] [PMID: 31354810]
Rashidi, B.; Haghollahi, F.; Shariat, M.; Zayerii, F. The effects of calcium-vitamin D and metformin on polycystic ovary syndrome: a pilot study. Taiwan. J. Obstet. Gynecol., 2009, 48(2), 142-147.
[] [PMID: 19574176]
Tehrani, H.G.; Mostajeran, F.; Shahsavari, S. The effect of calcium and vitamin D supplementation on menstrual cycle, body mass index and hyperandrogenism state of women with poly cystic ovarian syndrome. J. Res. Med. Sci., 2014, 19(9), 875-880.
[PMID: 25535503]
Zhuang, L.; Cui, W.; Cong, J.; Zhang, Y. Efficacy of vitamin D combined with metformin and clomiphene in the treatment of patients with polycystic ovary syndrome combined with infertility. Iran. J. Public Health, 2019, 48(10), 1802-1809.
[PMID: 31850257]
Irani, M.; Merhi, Z. Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review. Fertil. Steril., 2014, 102(2), 460-468.e3.
[] [PMID: 24933120]
Luk, J.; Torrealday, S.; Neal Perry, G.; Pal, L. Relevance of vitamin D in reproduction. Hum. Reprod., 2012, 27(10), 3015-3027.
[] [PMID: 22824625]
Hahn, S.; Haselhorst, U.; Tan, S.; Quadbeck, B.; Schmidt, M.; Roesler, S.; Kimmig, R.; Mann, K.; Janssen, O. Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Exp. Clin. Endocrinol. Diabetes, 2006, 114(10), 577-583.
[] [PMID: 17177140]
Yildizhan, R.; Kurdoglu, M.; Adali, E.; Kolusari, A.; Yildizhan, B.; Sahin, H.G.; Kamaci, M. Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome. Arch. Gynecol. Obstet., 2009, 280(4), 559-563.
[] [PMID: 19214546]
Hassan, N.E.; El-Orabi, H.A.; Eid, Y.M.; Mohammed, N.R. Effect of 25-hydroxyvitamin D on metabolic parameters and insulin resistance in patients with polycystic ovarian syndrome. Middle East Fertil. Soc. J., 2012, 17(3), 176-180.
Butts, S.F.; Seifer, D.B.; Koelper, N.; Senapati, S.; Sammel, M.D.; Hoofnagle, A.N.; Kelly, A.; Krawetz, S.A.; Santoro, N.; Zhang, H.; Diamond, M.P.; Legro, R.S.; Vitamin, D. Deficiency Is Associated With Poor Ovarian Stimulation Outcome in PCOS but Not Unexplained Infertility. J. Clin. Endocrinol. Metab., 2019, 104(2), 369-378.
[] [PMID: 30085176]
Laganà, A.S.; Vitale, S.G.; Ban Frangež, H.; Vrtačnik-Bokal, E.; D’Anna, R. Vitamin D in human reproduction: the more, the better? An evidence-based critical appraisal. Eur. Rev. Med. Pharmacol. Sci., 2017, 21(18), 4243-4251.
[PMID: 29028072]

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