doi:10.1111/jog.12793 J. Obstet. Gynaecol. Res. Vol. 41, No.

11: 17911802, November 2015

Effect of vitamin D on clinical and biochemical parameters in

polycystic ovary syndrome women: A meta-analysis

Xin-Zhuan Jia1, Yong-Mei Wang2, Na Zhang1, Li-Na Guo1, Xiu-Li Zhen1,

Hui Li3 and Lan Wei3
Departments of 1Reproductive Medicine, 2Obstetrics and Gynecology, Fourth Hospital of Hebei Medical University, and
3
Department of Thoracic Surgery, Hebei Chest Hospital, Shijiazhuang, China

Abstract
Aim: Using a meta-analysis framework, we investigated the association between the serum level of vitamin D
and the risk of polycystic ovary syndrome (PCOS) and further examined the therapeutic effect of vitamin D on
the clinical features of PCOS.
Material and Methods: Multiple databases were searched to retrieve studies. We chose clinical studies
that investigated the relation between the serum level of vitamin D and the risk of PCOS or the
therapeutic effect of vitamin D on PCOS. The search results were screened according to strict inclusion
and exclusion criteria to select high-quality studies for inclusion. Statistical analyses were carried out
using STATA 12.0.
Results: Seventeen studies were eligible in this meta-analysis. The levels of 25-hydroxyvitamin D and the quan-
titative insulin-sensitivity check index in the PCOS group were remarkably lower than in the controls, whereas the
homeostasis model assessment of insulin resistance in the PCOS group was markedly higher than in the controls.
No statistically signicant difference was observed in serum parathyroid hormone levels between the two groups.
The 25-hydroxyvitamin D levels were signicantly elevated after PCOS patients received vitamin D3 treatment,
but serum parathyroid hormone concentration, homeostasis model assessment of insulin resistance and quantita-
tive insulin-sensitivity check index did not show any signicant changes, indicating a lack of therapeutic
response.
Conclusion: Our results suggest that the serum level of vitamin D is associated with the risk of PCOS, but the
therapeutic effect of vitamin D on PCOS remains to be further explored.
Key words: endocrine disorder, polycystic ovary syndrome, therapeutic effect, vitamin D, vitamin D3
supplementation.

Introduction dened by the appearance of at least two of the follow-

Polycystic ovary syndrome (PCOS) is the most com-
monly diagnosed female endocrine disorder, with a
prevalence rate of nearly 510% among women of repro-
ductive age.1 PCOS is characterized by elevated ovarian
secretion of adrenal androgens, hyperandrogenic symp-
toms, including hirsutism, menstrual irregularity, acne
and/or alopecia, as well as polycystic ovaries.2 PCOS is
ing criteria: increased androgenic hormones, irregular
or absent ovulation, and enlarged ovaries comprising
over 12 follicles each.3 Moreover, PCOS is correlated
with a variety of cardiovascular risk factors, such as in-
sulin resistance (IR), obesity, impaired glucose tolerance,
hypertension, type 2 diabetes (T2DM), and metabolic
syndrome (MS).4 IR increases the risk of T2DM and con-
sequently might be the common link between PCOS and

Received: January 22 2015.

Accepted: June 1 2015.
Reprint request to: Dr Lan Wei, Department of Thoracic Surgery, Hebei Chest Hospital, Shenglibei Street No. 372, Shijiazhuang 050 041, P.R.
China. Email: weilan_1024@163.com

2015 Japan Society of Obstetrics and Gynecology 1791

X.-Z. Jia et al.
T2DM.4 Women with PCOS usually suffer from meta-
bolic disturbances and IR, which might be associated
with vitamin D metabolism.5 Vitamin D inuences glu-
cose and insulin metabolism, and low vitamin D status
is a risk factor for impaired glucose tolerance, IR and
T2DM.68 Serum 25-hydroxyvitamin D (25OHD) con-
centration is an effective indicator of vitamin D status
in humans,9 and vitamin D metabolism affects glucose
and insulin metabolism and plays a signicant role in
T2DM.10,11 The mechanisms by which serum vitamin D
levels inuence IR or T2DM are not yet clear, but previ-
ous studies found some important clues. First, low
vitamin D concentration leads to an increased serum
parathyroid hormone (PTH) level and elevated concen-
trations of PTH alter glucose metabolism and reduce
insulin sensitivity.12,13 Vitamin D may increase insulin
receptor expression to improve insulin responsiveness
in cells for glucose transport.14 Further, vitamin D and
the vitamin D receptor (VDR) regulate the expression
of more than 300 genes, including the genes associated
with glucose metabolism.15 In view of the above correla-
tions between vitamin D and insulin or glucose metabo-
lism, several previous studies have examined the role of
vitamin D in PCOS.16,17 Although there is still no denite
consensus on the signicance of serum vitamin D levels
in patients with PCOS and those without PCOS, an in-
verse correlation between serum 25OHD concentrations
and metabolic disturbances was reported in PCOS pa-
tients.18 Accordingly, previous studies revealed that
women with PCOS frequently had associated vitamin
D deciency,2,19 whereas others indicated that the lower
vitamin D level found in women with PCOS was not sig-
nicant compared to patients without PCOS.20 More-
over, multiple studies have shown that vitamin D3
supplementation in vitamin D deciency led to improve-
ments in several laboratory and clinical parameters of
PCOS.2123 However, another study failed to observe a
positive inuence of vitamin D3 supplementation on
insulin-sensitivity in PCOS.3 Therefore, our present
study examined the correlation between serum level of
vitamin D and PCOS and the therapeutic effect of vita-
min D on PCOS patients using a meta-analysis
approach.
Methods
Search strategy
To identify all relevant papers that reported the correla-
tion between serum levels of vitamin D and PCOS or
the therapeutic value of vitamin D in PCOS, the elec-
tronic databases PubMed, EBSCO, Ovid Medline,
1792
Springerlink, Wiley Online Library, Web of Science,
Wanfang Data and China National Knowledge
Infrastructure (CNKI) were searched (last updated
search in September 2014) using these selected com-
mon keywords: polycystic ovary syndrome, PCOS,
ovary, vitamin D, vitamins, cholecalciferol, calcitriol,
ergocalciferols and related terms. For example, we
selected (polycystic ovary syndrome or PCOS or
ovary) and (vitamins or vitamin D or cholecal-
ciferol or ergocalciferols or calcitriol).
Inclusion and exclusion criteria
Published papers eligible for our meta-analysis met
the following inclusion criteria: (i) the content of the
research must focus on the relation between the serum
level of vitamin D and PCOS or the therapeutic effect
of vitamin D on PCOS; (ii) included patients must
have been diagnosed with PCOS according to the
2003 Rotterdam criteria24 or the 1990 National
Institute of Child Health and Human Development
criteria;25 (iii) the article must be published with full
text; and (iv) the article must be published in English
or Chinese. Only the complete or latest study was
selected if an extracted study was published by the
same author. Studies were excluded if: (i) the data
integrity could not be ensured; (ii) there were signi-
cant differences in baseline characteristics between
the PCOS group and the control group; (iii) papers
were published repeatedly; or (iv) the diagnostic
criteria for study subjects were not clear.
Data extraction and quality evaluation
To reduce bias and ensure credibility, two reviewers in-
dependently extracted data from the selected studies
and arrived at agreement on all factors of interest. The
following data were extracted (if available): the rst au-
thor, publication year, country, race, language, disease,
criteria for the PCOS diagnosis, method of serum
25OHD measurement, sample size, age, study design,
and follow-up time. If there were disagreements be-
tween the two reviewers during the process of data ex-
traction, the issues were resolved through discussion
among multiple investigators. The quality evaluation of
the included studies was performed via the Methodolog-
ical Index for Non-Randomized Studies (MINORS)
criteria26 by more than two investigators. MINORS is a
validated scoring tool for non-randomized studies, in-
cluding a combination of 12-item assessment. Each item
can be scored from 0 to 2 and the ideal score for non-
comparative studies and comparative studies was,
2015 Japan Society of Obstetrics and Gynecology
 Table 1 Baseline characteristics of 10 eligible casecontrol studies, investigating the correlation between serum level of vitamin D and the risk of PCOS
First author Year Country Diagnostic Detection Number Age (years) Outcomes
criteria method
PCOS Non- PCOS Non-PCOS
PCOS
Mahmoudi 2010 Iran NICHD (1990) IRMA 85 115 28.60 7.18 29.83 4.61 BMI, HOMA-IR, 25OHD,
et al.31 1,25 (OH)2D
Yan et al.32 2010 China Rotterdam ELISA 55 20 27.13 3.08 25.10 3.25 BMI, 25OHD, QUICKI
criteria
Li et al.2 2011 UK Rotterdam Immunoassay 25 27 27.5 (18.6 35.9) 34.6 (27.3 40.4) BMI, HOMA-IR, PTH, 25OHD,

2015 Japan Society of Obstetrics and Gynecology

criteria QUICKI
Savastano 2011 Italy Rotterdam Immunoassay 90 40 24.45 4.3 24.65 4.1 BMI, HOMA-IR, 25OHD
et al.33 criteria
Wehr et al.5 2011 Austria Rotterdam IDS 545 145 27 (2331) 29 (2636) BMI, HOMA-IR, 25OHD, PTH,
criteria QUICKI
Lin et al.35 2012 China Rotterdam Immunoassay 188 143 28.43 0.38 31.83 0.48 BMI, QUICKI, 25OHD
criteria
Mazloomi 2012 Iran Rotterdam ELISA 103 103 24.8 5.6 26.4 6 BMI, 25OHD
et al.36 criteria
Tsakova 2012 Bulgaria Rotterdam Immunoassay 70 33 24.55 4.9 32.0 8.1 BMI, 25OHD
et al.37 criteria
El-Shal et al.38 2013 Egypt Rotterdam Immunoassay 150 150 29.8 5.6 29.3 6.2 BMI, HOMA-IR, 25OHD,
criteria QUICKI
Meng et al.39 2013 China Rotterdam ELISA 72 61 26.85 3.84 27.70 3.17 BMI, 25OHD, HOMA-IR
criteria
25OHD, 25-hydroxyvitamin D; BMI, body mass index; ELISA, enzyme-linked immunoassay; IDS, iduronate sulfatase; HOMA-IR, homeostasis model assessment of insulin resistance; IRMA,
immunoradiometric assay; NICHD, National Institute of Child Health and Human Development; PCOS, polycystic ovary syndrome; PTH, serum parathyroid hormone; QUICKI, quanti-
tative insulin-sensitivity check index.
Vitamin D and PCOS

1793
1794
X.-Z. Jia et al.

Table 2 Baseline characteristics of seven eligible cohort studies, examining the therapeutic effect of vitamin D on PCOS
First author Year Country Diagnostic Detection method Number Age (years) Study Medicine Vitamin D Outcome
criteria design
Kotsa et al.23 2009 Greece Rotterdam Immunoassay 15 28 1.3 Single- Alfacalcidol PTH, 25OHD3
criteria arm (1-a-hydroxyvitamin
D3) :
1 g/day
Selimoglu 2010 Turkey Rotterdam Immunoassay 11 23.6 5.7 Single- Vitamin D3 : 25OHD3, HOMA-IR
et al.40 criteria arm 300 000 IU/day as a
single oral dose
Wehr et al.34 2011 Austria Rotterdam IDS 52 26 6 Single- Vitamin D3 25OHD, PTH, 1,25-Vit
criteria arm (cholecalciferol): D, HOMA-IR, BMI
20 000 IU/week
Firouzabadi 2012 Iran Rotterdam Radioimmunoassay 50 28.46 4.16 RCT Vitamin D3: BMI, 25OHD
et al.4 criteria 100 000 IU/month
+ Metformin: 1500 mg/
day
+ Calcium 1000 mg/
day
Pal et al.41 2012 USA Rotterdam Immunoassay 12 26.42 6.11 Single- Vitamin D3: 2000 IU/ BMI, 25OHD, QUICKI
criteria arm day
+ Vitamin D2 50, 000
IU/month
+ Ca: 530 mg/day
Rahimi- 2013 Iran Rotterdam Immunoassay 24 26.8 4.7 RCT Vitamin D3: 50, 000 IU/ BMI, 25OHD, PTH,
Ardabili criteria 20 days HOMA-IR, QUICKI
et al.42
Raja-Khan 2014 USA NICHD IDS 13 28.2 5.2 RCT Vitamin D3 BMI, 25OHD, QUICKI,
et al.18 1990 (cholecalciferol): PTH, HOMA-IR
12 000 IU/12 weeks
25OHD3, 25-hydroxyvitamin D3; BMI, body mass index; HOMA-IR, homeostasis model assessment of insulin resistance; IDS, iduronate sulfatase; NICHD 1990, 1990 National Institute of
Child Health and Human Development criteria; PTH, serum parathyroid hormone; QUICKI, quantitative insulin-sensitivity check index; RCT, randomized controlled trial; Rotterdam
criteria, 2003 Rotterdam criteria.

2015 Japan Society of Obstetrics and Gynecology


respectively, 16 and 24. The specic criteria are as fol-
lows: clearly stated aim (MINORS 01), inclusion of con-
secutive patients (MINORS 02), prospective collection
of data (MINORS 03), end-points appropriate for aim
(MINORS 04), unbiased assessment of end-point (MI-
NORS 05), appropriate follow-up period (MINORS 06),
loss to follow-up < 5% (MINORS 07), prospective calcu-
lation of study size (MINORS 08), an adequate control
group (MINORS 09), contemporary groups (MINORS
10), baseline equivalence of groups (MINORS 11), and
adequate statistical analyses (MINORS 12).
Statistical analysis
Statistical analyses were carried out using STATA 12.0.
The association between the serum level of vitamin D
and PCOS and the therapeutic effect of vitamin D on
Figure 1 Quality evaluation of in-
cluded studies by applying Metho-
dological Index for Non-Randomized
Studies (MINORS) criteria.
2015 Japan Society of Obstetrics and Gynecology
Vitamin D and PCOS
PCOS was estimated by the standardized mean dif-
ference (SMD) with a 95% condence interval (CI).
The signicance of pooled SMD was determined by
the Z-test. Cochrans Q-statistic (P < 0.05 for signi-
cant) and I2 test (0%, no heterogeneity; 100%, maxi-
mal heterogeneity) were also used to reect the
heterogeneity between studies.27 P < 0.05 or I2 50%
suggested signicant heterogeneity among trials, and
in such case, a random-effect model was employed;
otherwise, a xed-effect model was applied.28,29 Sensi-
tivity analysis was performed by removing studies
one by one to evaluate the inuence of the one single
study on the overall result. A funnel plot was used to
assess publication bias. The symmetrical funnel plot
was further estimated by the Egger test.30 All statisti-
cal tests were two-sided, and P-values < 0.05 were
considered statistically signicant.
1795
X.-Z. Jia et al.

Results and European (n = 8) and African (n = 1) populations.

Baseline characteristics
A total of 241 articles were retrieved from database
searches and by scanning title and key words. Following
the exclusion of duplicates (n = 57), letters, meta-analyses
(n = 21), non-human studies (n = 65), and studies unre-
lated to the research topics (n = 62), the 36 remaining
studies were further reviewed and another 16 trials were
removed because they were not cohort or casecontrol
studies (n = 2), not relevant to vitamin D (n = 4), or not
relevant to PCOS (n = 10). After the remaining 20 trials
were further reviewed, 17 studies were enrolled in the -
nal analysis. In the present meta-analysis, the casecontrol
studies (n = 2220) that investigated the correlation between
the serum level of vitamin D and the risk of PCOS
contained patients with PCOS (n = 1383) and healthy
controls (n = 837).2,3139 The clinical cohort studies that
examined the therapeutic effect of vitamin D on PCOS
included PCOS patients (n = 177).4,18,23,34,4042 The se-
lected trials were published between 2009 and 2014.
The study subjects were from Asian (n = 8), American
The baseline characteristics and MINORS scores of the
included studies are shown in Table 1, Table 2 and
Figure 1.
Vitamin D and PCOS
Ten studies reported the correlation between the serum
level of vitamin D and PCOS. Heterogeneity was ob-
served across studies (25OHD: I2 = 97.2%, P < 0.001; ho-
meostasis model assessment of insulin resistance
[HOMA-IR]: I2 = 79.1%, P < 0.001; PTH: I2 = 83.0%,
P = 0.015; quantitative insulin-sensitivity check index
[QUICKI]: I2 = 97.1%, P < 0.001), and therefore a random
effect model was employed. The results of the meta-
analysis indicated that the levels of 25OHD and QUICKI
were notably lower in the PCOS group than in the con-
trol group (25OHD: SMD = 0.86, 95%CI = 1.46 ~ 0.26,
P = 0.005; QUICKI: SMD = 0.76, 95%CI = 1.520.00,
P = 0.050) and that the HOMA-IR was markedly ele-
vated in the PCOS group compared with the control
group (SMD = 0.50, 95%CI = 0.240.77, P < 0.001).

Figure 2 Forest map of association between serum level of vitamin D and polycystic ovary syndrome (PCOS). Comparisons on
the levels of 25-hydroxyvitamin D (25OHD), the quantitative insulin-sensitivity check index (QUICKI), the homeostasis model
assessment of insulin resistance (HOMA-IR) and serum parathyroid hormone (PTH) levels between PCOS group and control
group. CI, condence interval; SMD, standardized mean difference.

1796 2015 Japan Society of Obstetrics and Gynecology

 Vitamin D and PCOS

However, there was no difference in the PTH levels be-
tween the two groups (SMD = 0.33, 95%CI = 0.080.74,
P = 0.113) (Fig. 2).
Therapeutic effect of vitamin D3 on PCOS
Differences in the therapeutic efcacy of vitamin D3 sup-
plementation in patients with PCOS were reported in
seven studies. The heterogeneity test revealed that het-
erogeneity existed among the studies with regard to
25OHD level and PTH (25OHD: I2 = 83.2%, P < 0.001;
PTH: I2 = 90.7%, P < 0.001); therefore, a random effects
model was used. No heterogeneity existed among the
studies related to HOMA-IR and QUICKI (HOMA-IR:
I2 = 0.0%, P = 0.457; QUICKI: I2 = 0.0%, P = 0.905), so we
used a xed effect model. The 25OHD levels increased
after PCOS patients received vitamin D3 treatment
(SMD = 2.32, 95%CI = 3.04 ~ 1.61, P < 0.001), but the
PTH level, HOMA-IR and the QUICKI index showed
no marked changes (PTH: SMD = 1.29, 95%CI = 0.08
2.65, P = 0.064; HOMA-IR index: SMD = 0.01,
95%CI = 0.280.27, P = 0.964; QUICKI: SMD = 0.09,
95%CI = 0.310.48, P = 0.662) (Fig. 3).
Sensitivity analysis and publication bias
Sensitivity analysis was carried out to identify whether
this meta-analysis was stable. The sensitivity analysis
demonstrated that all included studies had no obvious
inuence on the pooled SMD of the differences in the
correlations between the serum level of vitamin D and
PCOS or the clinical therapeutic effect of vitamin D3 on
PCOS patients (Fig. 4). Both the symmetry of the funnel
plot and the Egger test suggested there was no evident
publication bias (P 0.05). Therefore, the conclusion of this
study achieved high reliability (Fig. 5).
Discussion
PCOS is the most frequent endocrine disorder among
women of reproductive age.1 Vitamin D deciency is a
general problem in PCOS patients,3 and debate con-
tinues regarding whether vitamin D concentrations are
correlated with PCOS risk and whether vitamin D
supplementation is an effective therapy for PCOS.
Consequently, we examined the association between
the serum level of vitamin D and PCOS as well as the

Figure 3 Forest plots of therapeutic effect of vitamin D supplementation on polycystic ovary syndrome, comparing the
25-hydroxyvitamin D (25OHD) levels, the quantitative insulin-sensitivity check index (QUICKI), the homeostasis
model assessment of insulin resistance (HOMA-IR) and serum parathyroid hormone (PTH) levels before and after
vitamin D3 treatment.

2015 Japan Society of Obstetrics and Gynecology 1797

X.-Z. Jia et al.

Figure 4 Sensitivity analyses of association between vitamin D and polycystic ovary syndrome and the therapeutic effect of vi-
tamin D supplementation on polycystic ovary syndrome. 25OHD, 25-hydroxyvitamin D; CI, condence interval; PCOS, poly-
cystic ovary syndrome.

1798 2015 Japan Society of Obstetrics and Gynecology

 Vitamin D and PCOS

Figure 5 Funnel plots of association between vitamin D and polycystic ovary syndrome and the therapeutic effect of vitamin D
supplementation on polycystic ovary syndrome. HOMA-IR, homeostasis model assessment of insulin resistance; PCOS, poly-
cystic ovary syndrome; PTH, serum parathyroid hormone; QUICKI, quantitative insulin-sensitivity check index.

2015 Japan Society of Obstetrics and Gynecology 1799

X.-Z. Jia et al.
therapeutic effect of vitamin D supplementation in
PCOS patients, based on the published data from
previous studies.
Ten studies included in the present meta-analysis
focused on the correlations between the serum concen-
tration of vitamin D and PCOS. The results of the meta-
analysis showed that 25OHD concentrations and the
QUICKI of PCOS patients were lower than those of sub-
jects without PCOS and that HOMA-IR was signicantly
higher in PCOS patients than in women without PCOS,
suggesting that serum vitamin D concentration was neg-
atively associated with IR in PCOS. This nding was
consistent with previous studies revealing a negative
association of 25OHD and HOMA-IR in PCOS
women.23,43 The 25OHD concentration is an indicator
of vitamin D status in the human body,9 and vitamin D
deciency is a major problem in PCOS because it relates
to metabolic syndrome, which includes obesity, IR, and
glucose intolerance.23 Our results indicated that women
with PCOS had markedly lower 25OHD concentrations,
consistent with the ndings of previous studies that
reported lower vitamin D levels in PCOS patients than
in non-PCOS patients,2,19 which may be explained by
an association of vitamin D with androgens or sex
hormone binding globulin (SHBG).20 Some authors
found a direct relation between hyperandrogenism and
vitamin D deciency, revealing a possible interaction
between androgens and vitamin D balance, mediated by
a not yet completely known mechanism.43 Moreover, a
previous study also mentioned that androgens and
hyperinsulinemia may also play a signicant role in
vitamin D levels.19 QUICKI is used to assess insulin sensi-
tivity,5 and low insulin sensitivity can result in IR, which
is one of the features of PCOS.44 The results of the meta-
analysis revealed that PCOS patients had lower QUICKI,
indicating that PCOS patients had lower insulin sensiti-
vity and an elevated risk for IR. This may contribute to
the low vitamin D concentration because vitamin D might
directly increase insulin sensitivity via stimulating the ex-
pression of insulin receptors in peripheral tissues.45 How-
ever, vitamin D deciency can also disrupt extracellular
and intracellular calcium balance and thereby interfere
with insulin secretion.3 Changes in the intracellular
calcium level in peripheral tissues may also lead to
peripheral IR,46 and vitamin D can also affect IR
through the reninangiotensinaldosterone pathway.
IR was evaluated using the HOMA-IR, and high
HOMA-IR suggested increased IR.5 PCOS patients
have a high prevalence of IR; therefore, it is consistent
that we observed higher HOMA-IR in PCOS patients
than in subjects without PCOS in our meta-analysis.
1800
Seven of the included studies reported the therapeutic
effect of vitamin D3 on PCOS. The meta-analysis results
revealed that after receiving vitamin D3 supplementa-
tion, although the 25OHD concentrations in PCOS pa-
tients were remarkably elevated, the HOMA-IR, PTH
levels, and QUICKI showed no signicant changes, sug-
gesting that vitamin D3 supplementation did not exhibit
an effective therapeutic effect in PCOS, which is consis-
tent with the ndings reported by Ardabili et al.3 How-
ever, the results of vitamin D supplementation on
insulin homeostasis are controversial. In a recent study,
administration of cholecalciferol for half a year to
Asian women who were vitamin D decient and insu-
lin resistant found a signicant improvement in insu-
lin sensitivity and IR, but no changes on insulin
secretion were observed.47 In a recent controlled
study, the administration of cholecalciferol in patients
with type 2 diabetes showed no signicant improve-
ments in IR or glycosylated hemoglobin.48 Several fac-
tors may be able to explain the conicting results,
including the different characteristics of the research
subjects, the length of study and the various vitamin
D forms used for supplementation.3
Our meta-analysis has some limitations. First, the
small number of included studies and the relatively
small number of study subjects might inuence the sta-
tistical analysis of the therapeutic effect of vitamin D3
on PCOS, which might contribute to the non-signicant
outcomes. Second, the measurement of 25OHD did not
involve a uniform method across the selected studies,
so the different methods used might impact the results.
Third, the follow-up duration was different among the
included studies exploring the therapeutic effect of vita-
min D on PCOS, which might also inuence our result to
some extent.
In conclusion, our results strongly suggest that the
serum concentration of vitamin D is associated with
the risk of PCOS. However, we failed to detect any ther-
apeutic effect of vitamin D3 supplementation in PCOS,
which will be a topic of further study.
Acknowledgments
We acknowledge the valuable feedback on this article
provided by our reviewers.
Disclosure
None declared.
2015 Japan Society of Obstetrics and Gynecology

References
1. Patra SK, Nasrat H, Goswami B, Jain A. Vitamin D as a predic-
tor of insulin resistance in polycystic ovarian syndrome. Diabe-
tes Metab Syndr 2012; 6: 146149.
2. Li HW, Brereton RE, Anderson RA, Wallace AM, Ho CK. Vita-
min D deciency is common and associated with metabolic risk
factors in patients with polycystic ovary syndrome. Metabolism
2011; 60: 14751481.
3. Ardabili HR, Gargari BP, Farzadi L. Vitamin D supplementa-
tion has no effect on insulin resistance assessment in women
with polycystic ovary syndrome and vitamin D deciency. Nutr
Res 2012; 32: 195201.
4. Firouzabadi R, Aatoonian A, Modarresi S, Sekhavat L,
MohammadTaheri S. Therapeutic effects of calcium & vitamin
D supplementation in women with PCOS. Complement Ther
Clin Pract 2012; 18: 8588.
5. Wehr E, Trummer O, Giuliani A, Gruber HJ, Pieber TR,
Obermayer-Pietsch B. Vitamin D-associated polymorphisms
are related to insulin resistance and vitamin D deciency in
polycystic ovary syndrome. Eur J Endocrinol 2011; 164: 741749.
6. Gulseth HL, Gjelstad IM, Tierney AC et al. Serum vitamin D
concentration does not predict insulin action or secretion in Eu-
ropean subjects with the metabolic syndrome. Diabetes Care
2010; 33: 923925.
7. George PS, Pearson ER, Witham MD. Effect of vitamin D supple-
mentation on glycaemic control and insulin resistance: A system-
atic review and meta-analysis. Diabet Med 2012; 29: e142e150.
8. Dalgard C, Petersen MS, Weihe P, Grandjean P. Vitamin D sta-
tus in relation to glucose metabolism and type 2 diabetes in
septuagenarians. Diabetes Care 2011; 34: 12841288.
9. Pramyothin P, Biancuzzo RM, Lu Z, Hess DT, Apovian CM,
Holick MF. Vitamin D in adipose tissue and serum 25-
hydroxyvitamin D after roux-en-Y gastric bypass. Obesity
(Silver Spring) 2011; 19: 22282234.
10. Pinelli NR, Jaber LA, Brown MB, Herman WH. Serum 25-
hydroxy vitamin d and insulin resistance, metabolic syndrome,
and glucose intolerance among Arab Americans. Diabetes Care
2010; 33: 13731375.
11. Scragg R, Sowers M, Bell C. Third National Health and
Nutrition Examination Survey. Serum 25-hydroxyvitamin D,
diabetes, and ethnicity in the Third National Health and
Nutrition Examination Survey. Diabetes Care 2004; 27:
28132818.
12. Hutchinson MS, Grimnes G, Joakimsen RM, Figenschau Y,
Jorde R. Low serum 25-hydroxyvitamin D levels are associated
with increased all-cause mortality risk in a general population:
The Troms study. Eur J Endocrinol 2010; 162: 935942.
13. Tao MF, Zhang Z, Ke YH et al. Association of serum 25-
hydroxyvitamin D with insulin resistance and beta-cell func-
tion in a healthy Chinese female population. Acta Pharmacol
Sin 2013; 34: 10701074.
14. Bellia A, Garcovich C, DAdamo M et al. Serum 25-
hydroxyvitamin D levels are inversely associated with systemic
inammation in severe obese subjects. Intern Emerg Med 2013;
8: 3340.
15. Kim JJ, Choi YM, Chae SJ et al. Vitamin D deciency in women with
polycystic ovary syndrome. Clin Exp Reprod Med 2014; 41: 8085.
16. Thomson RL, Spedding S, Buckley JD. Vitamin D in the
aetiology and management of polycystic ovary syndrome. Clin
Endocrinol (Oxf) 2012; 77: 343350.
2015 Japan Society of Obstetrics and Gynecology
Vitamin D and PCOS
17. Naqvi SH, Moore A, Bevilacqua K et al. Predictors of depression
in women with polycystic ovary syndrome. Arch Womens Ment
Health 2014; 18: 95101.
18. Raja-Khan N, Shah J, Stetter CM et al. High-dose vitamin D sup-
plementation and measures of insulin sensitivity in polycystic
ovary syndrome: A randomized, controlled pilot trial. Fertil
Steril 2014; 101: 17401746.
19. Gallea M, Granzotto M, Azzolini S et al. Insulin and body
weight but not hyperandrogenism seem involved in seasonal
serum 25-OH-vitamin D3 levels in subjects affected by PCOS.
Gynecol Endocrinol 2014; 30: 739745.
20. Yildizhan R, Kurdoglu M, Adali E et al. Serum 25-
hydroxyvitamin D concentrations in obese and non-obese
women with polycystic ovary syndrome. Arch Gynecol Obstet
2009; 280: 559563.
21. Irani M, Minkoff H, Seifer DB, Merhi Z. Vitamin D increases se-
rum levels of the soluble receptor for advanced glycation end
products in women with PCOS. J Clin Endocrinol Metab 2014;
99: E886E890.
22. Irani M, Seifer D, Minkoff H, Merhi Z. Vitamin d normalizes ab-
normally elevated serum antimullerian hormone levels usually
noted in women with polycystic ovary syndrome. Obstet
Gynecol 2014; 123: 189S.
23. Kotsa K, Yavropoulou MP, Anastasiou O, Yovos JG. Role of vi-
tamin D treatment in glucose metabolism in polycystic ovary
syndrome. Fertil Steril 2009; 92: 10531058.
24. Rotterdam EA-SPcwg. Revised 2003 consensus on diagnostic
criteria and long-term health risks related to polycystic ovary
syndrome (PCOS). Hum Reprod 2004; 19: 4147.
25. Zawadzki JK, Dunaif A. Diagnostic criteria for polycystic ovary
syndrome: towards a rational approach[J]. Polycystic ovary
syndrome. Boston: Blackwell Scientic, 1992; 377384.
26. Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J.
Methodological index for non-randomized studies (minors):
Development and validation of a new instrument. ANZ J Surg
2003; 73: 712716.
27. Zintzaras E, Ioannidis JP. HEGESMA: Genome search meta-
analysis and heterogeneity testing. Bioinformatics 2005; 21:
36723673.
28. Zintzaras E, Ioannidis JP. Heterogeneity testing in meta-
analysis of genome searches. Genet Epidemiol 2005; 28: 123137.
29. Higgins JP, Thompson SG. Quantifying heterogeneity in a
meta-analysis. Stat Med 2002; 21: 15391558.
30. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-
analysis detected by a simple, graphical test. BMJ 1997; 315:
629634.
31. Mahmoudi T, Gourabi H, Ashra M, Yazdi RS, Ezabadi Z.
Calciotropic hormones, insulin resistance, and the polycystic
ovary syndrome. Fertil Steril 2010; 93: 12081214.
32. Yan WJ, Yang J, Zhang B, Yin TL, Jie Z. Preliminary study on
the relationship between vitamin D and polycystic ovary syn-
drome. Prog Obstet Gynaecol 2010; 19: 844846.
33. Savastano S, Valentino R, Di Somma C et al. Serum 25-
Hydroxyvitamin D levels, phosphoprotein enriched in diabetes
gene product (PED/PEA-15) and leptin-to-adiponectin ratio in
women with PCOS. Nutr Metab (Lond) 2011; 8: 84. http://www.
nutritionandmetabolism.com/content/8/1/84
34. Wehr E, Pieber TR, Obermayer-Pietsch B. Effect of vitamin D3
treatment on glucose metabolism and menstrual frequency in
polycystic ovary syndrome women: A pilot study. J Endocrinol
Invest 2011; 34: 757763.
1801
X.-Z. Jia et al.
35. Lin MW, Tsai SJ, Chou PY, Huang MF, Sun HS, Wu MH. Vita-
min D receptor 1a promotor 1521 G/C and 1012 A/G poly-
morphisms in polycystic ovary syndrome. Taiwan J Obstet
Gynecol 2012; 51: 565571.
36. Mazloomi S, Shari F, Hajihosseini R, Kalantari S,
Mazloomzadeh S. Association between hypoadiponectinemia
and low serum concentrations of calcium and vitamin D in
women with polycystic ovary syndrome. ISRN Endocrinol
2012; 2012: 949427.
37. Tsakova AD, Gateva AT, Kamenov ZA. 25(OH) vitamin D
levels in premenopausal women with polycystic ovary
syndrome and/or obesity. Int J Vitam Nutr Res 2012; 82:
399404.
38. El-Shal AS, Shalaby SM, Aly NM, Rashad NM, Abdelaziz AM.
Genetic variation in the vitamin D receptor gene and vitamin D
serum levels in Egyptian women with polycystic ovary syn-
drome. Mol Biol Rep 2013; 40: 60636073.
39. Jie M, Di W, Ji-hui A, Lie-gang L, Han-wang Z. The corre-
lation analysis of serum 25 hydroxyvitamin D levels and
polycystic ovarian syndrome. J Huazhong Univ Sci Tech
2013; 28: 13331335.
40. Selimoglu H, Duran C, Kiyici S et al. The effect of vitamin D
replacement therapy on insulin resistance and androgen levels
in women with polycystic ovary syndrome. J Endocrinol Invest
2010; 33: 234238.
41. Pal L, Berry A, Coraluzzi L et al. Therapeutic implications of
vitamin D and calcium in overweight women with polycystic
ovary syndrome. Gynecol Endocrinol 2012; 28: 965968.
1802
42. Rahimi-Ardabili H, Pourghassem Gargari B, Farzadi L. Effects
of vitamin D on cardiovascular disease risk factors in polycystic
ovary syndrome women with vitamin D deciency. J Endocrinol
Invest 2013; 36: 2832.
43. Hahn S, Haselhorst U, Tan S et al. 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: 577583.
44. Manneras-Holm L, Leonhardt H, Kullberg J et al. Adipose tissue
has aberrant morphology and function in PCOS: Enlarged
adipocytes and low serum adiponectin, but not circulating sex
steroids, are strongly associated with insulin resistance. J Clin
Endocrinol Metab 2011; 96: E304E311.
45. Sung CC, Liao MT, Lu KC, Wu CC. Role of vitamin D in insulin
resistance. J Biomed Biotechnol 2012; 2012: 634195.
46. Jorde R, Figenschau Y. Supplementation with cholecalciferol
does not improve glycaemic control in diabetic subjects with
normal serum 25-hydroxyvitamin D levels. Eur J Nutr 2009;
48: 349354.
47. von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementa-
tion reduces insulin resistance in South Asian women living in
New Zealand who are insulin resistant and vitamin D decient
- a randomised, placebo-controlled trial. Br J Nutr 2010; 103:
549555.
48. Witham MD, Dove FJ, Dryburgh M, Sugden JA, Morris AD,
Struthers AD. The effect of different doses of vitamin D(3) on
markers of vascular health in patients with type 2 diabetes: A
randomised controlled trial. Diabetologia 2010; 53: 21122119.
2015 Japan Society of Obstetrics and Gynecology