Status of Serum Copper, Magnesium, and Total Antioxidant Capacity in Patients with Polycystic Ovary Syndrome

Abstract

This study evaluates serum copper and magnesium and total antioxidant capacity levels in PCOS patients. In this regard, the probable association of copper and magnesium with total antioxidant capacity (TAC) was investigated. In total, 150 women (60 PCOS patients and 90 healthy subjects) participated in this case–control study. PCOS was diagnosed according to the Rotterdam criteria (2003). Serum Cu, Mg, Ca, TAC, insulin levels, and insulin resistance indices were determined. Insulin was measured using ELISA methods. Serum Cu and Mg levels were measured by an atomic absorption spectrophotometer and the Xylidyl Blue method respectively. The correlations between the parameters were analyzed using the Spearman correlation test. Serum Cu level was significantly higher while TAC was significantly lower in the PCOS patients than those in the controls (p = 0.019 and p = 0.002 respectively). No significant difference was detected between the two groups in terms of serum Mg and Ca levels and Ca/Mg ratio. In insulin-resistant PCOS subjects, there was a negative correlation between Mg levels and homeostatic model assessment for insulin resistance (r = − 0.449, p = 0.006) but a positive correlation between Mg levels and quantitative insulin sensitivity check index (r = 0.480, p = 0.003). A negative correlation also existed between Mg levels and TAC in non-insulin-resistant PCOS patients (r = − 0.407, p = 0.04). According to the results, copper and magnesium seem to contribute to oxidative stress and insulin resistance in PCOS patients. Therefore, to prevent long-term metabolic complications in PCOS women, it is recommended that these elements be routinely monitored. Also, significantly lower levels of serum TAC in PCOS patients than in normal women may suggest increased oxidative stress in such patients.

Full text

Status of Serum Copper, Magnesium, and Total Antioxidant Capacity
in Patients with Polycystic Ovary Syndrome
Maryam Kanafchian
1
&Sedigheh Esmaeilzadeh
2
&Soleiman Mahjoub
2
&Maryam Rahsepar
1
&Maryam Ghasemi
2
Received: 1 November 2018 / Accepted: 19 March 2019
#Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract
This study evaluates serum copper and magnesium and total antioxidant capacity levels in PCOS patients. In this regard,
the probable association of copper and magnesium with total antioxidant capacity (TAC) was investigated. In total, 150
women (60 PCOS patients and 90 healthy subjects) participated in this case–control study. PCOS was diagnosed
according to the Rotterdam criteria (2003). Serum Cu, Mg, Ca, TAC, insulin levels, and insulin resistance indices were
determined. Insulin was measured using ELISA methods. Serum Cu and Mg levels were measured by an atomic
absorption spectrophotometer and the Xylidyl Blue method respectively. The correlations between the parameters were
analyzed using the Spearman correlation test. Serum Cu level was significantly higher while TAC was significantly
lower in the PCOS patients than those in the controls (p= 0.019 and p= 0.002 respectively). No significant difference
was detected between the two groups in terms of serum Mg and Ca levels and Ca/Mg ratio. In insulin-resistant PCOS
subjects, there was a negative correlation between Mg levels and homeostatic model assessment for insulin resistance
(r=−0.449, p= 0.006) but a positive correlation between Mg levels and quantitative insulin sensitivity check index (r=
0.480, p= 0.003). A negative correlation also existed between Mg levels and TAC in non-insulin-resistant PCOS patients
(r=−0.407, p= 0.04). According to the results, copper and magnesium seem to contribute to oxidative stress and insulin
resistance in PCOS patients. Therefore, to prevent long-term metabolic complications in PCOS women, it is recom-
mended that these elements be routinely monitored. Also, significantly lower levels of serum TAC in PCOS patients than
in normal women may suggest increased oxidative stress in such patients.
Keywords Polycystic ovary syndrome .Insulin resistance .Copper .Magnesium .Total antioxidant capacity
Abbreviations
PCOS Polycystic ovary syndrome
TAC Total antioxidant capacity
Cu Copper
Mg Magnesium
Ca Calcium
Ca/Mg ratio Calcium/magnesium ratio
G/I ratio Glucose/insulin ratio
BMI Body mass index
FBS Fasting blood sugar
IR Insulin resistance
NIR Non-insulin resistance
HOMA-IR Homeostatic model assessment
for insulin resistance
QUICKI Quantitative insulin sensitivity check index
Introduction
Polycystic ovary syndrome (PCOS) is the most frequent
endocrinopathic disorder among women [1]. The worldwide
prevalence of this syndrome is 5–10%. As reported, 15.2% of
Iranian women at the reproductive age suffer from PCOS [2].
PCOS is prevalently associated with such reproductive abnor-
malities as hyperandrogenism, chronic anovulation, and ab-
normal development of ovarian follicles. The other major fea-
tures of PCOS are insulin resistance and central obesity [1].
*Soleiman Mahjoub
smahjoub20@gmail.com; s.mahjoub@mubabol.ac.ir
1
Student Research Committee, Babol University of Medical Sciences,
Babol, Iran
2
Infertility and Reproductive Health Research Center, Health
Research Institute, Babol University of Medical Sciences, Babol, Iran
Biological Trace Element Research
https://doi.org/10.1007/s12011-019-01705-7

PCOS is associated with certain complications. Maybe, the
most notable of them is the local and systemic progression of
oxidative stress. PCOS features that may cause this to happen
or contribute to it are hyperandrogenism, central obesity, and
insulin resistance [3,4]. Indeed, there seems to be a mutual
relationship between these metabolic disorders and oxidative
stress. In other words, if oxidative stress is allowed to go on,
such disorders may be aggravated [5].
Trace element deficiencies are mostly related to chronic
diseases or to absorption problems. In this regard, one may
refer to chronic hyperglycemia that can cause a significant
change in the state of some micronutrients, some of which
are responsible for the direct modulation of glucose homeo-
stasis [6].
In our previous study on PCOS, we found that the PCOS
women had a significantly higher level of insulin resistance
and oxidative stress than the healthy ones. Also, after evalua-
tion of selenium and zinc in the PCOS patients, both elements
were found significantly lower in the PCOS patients than in
the control group [2,7].
In addition to selenium and zinc mentioned above, copper
plays a role in PCOS too. As an integral part of many enzymes
involved in some vital biological processes, copper plays a
critical role in the function of cytochrome coxidase, ascorbate
oxidase, and superoxide dismutase [8]. Other than its roles in
enzymes, Cu has a role in biological systems for electron
transport [9].
Another element of biological effect is magnesium. As
the second most abundant intracellular cation in the hu-
man body, magnesium is involved in more than 300 ATP
and kinase-dependent enzymatic reactions. Many of these
reactions occur in glucose metabolism, pancreatic insulin
secretion, and insulin actioninperipheraltissues[10].
Deficiency of intracellular magnesium may have an im-
pact on the development of insulin resistance and/or
cause the alteration of the glucose entry into the cell
[11].
In view of these clinical findings, it is important to carefully
monitor PCOS patients by periodic determination of essential
trace element concentrations in those people.
Total antioxidant capacity is the ability of serum to
quench the formation of free radicals and to defend the cell
structure from the damaging effects of those radicals. It is,
indeed, one of the antioxidant defenses present in the body.
Any change in the antioxidant level of plasma or in the
degree of oxidative stress can affect total antioxidant ca-
pacity (TAC) [12].
The present study has been designed to evaluate serum Cu,
Mg, and TAC levels in PCOS patients and control individuals.
Analyses are conducted on the relationship between Cu and
Mg elements and TAC. Also, a part of the study is dedicated to
the correlation of the measured parameters with insulin resis-
tance and body mass index.
Materials and Methods
Ethical Consideration
Approval was obtained from the ethics committee of Babol
University of Medical Sciences (MUBABOL.REC.1394.65).
All the participants were informed of the aims of the study,
and informed consents were obtained from them. The bio-
chemical tests had no cost for the participants, and the results
of these tests were reported to them.
Subjects
The study population consisted of 150 patients aged 20 to 40.
Sixty women diagnosed with PCOS formed the study group,
and 90 age-matched healthy women served as the control
group. These people were introduced to the researchers by
Fatemeh Zahra Infertility and Reproductive Health Research
Center of Babol University of Medical Sciences, Babol, Iran,
in 2015. A sample size with α=0.05, β= 0.2, and power =
80% was selected based on previous studies [7,13].
The patients included in the study were those diagnosed
with PCOS. The diagnosis had been made on the basis of
the criteria set by the Rotterdam consensus in 2003.
According to it, PCOS individuals are those who have two
of the three features including oligo- and/or anovulation, clin-
ical and/or biochemical signs of hyperandrogenism, and poly-
cystic ovaries diagnosed in an ultrasonographic examination
[14]. Those who had used drugs, oral contraceptives, insulin
sensitizers, or mineral supplementation at least 3 months be-
fore participating in the study were excluded. Also, women
with a family history of Cushing’s syndrome, congenital ad-
renal hyperplasia, androgen-secreting tumors,
hyperprolactinemia, thyroid dysfunction, and diabetes
mellitus were not allowed to participate in the study. None
of the subjects had a history of smoking or drug abuse.
The healthy women in the control group had referred to
our research center with regular menstrual cycles and nor-
mal ovarian morphology and had been defined by history,
physical examinations, and ultrasonography. For each sub-
ject, BMI was calculated as weight divided by height
squared (kg/m
2
). Insulin resistance was determined by ho-
meostatic model assessment for insulin resistance (HOMA-
IR) and quantitative insulin sensitivity check index
(QUICKI). It was, indeed, defined as HOMA-IR ≥2.5
and QUICKI ≤%0.333 [15].
These indices were calculated according to the following
formulas [16]:
HOMA−IR ¼fasting insulin μIU=mlðÞ½
fasting glucose mg=dlðÞ½=405
Kanafchian et al.

QUICKI ¼1=log fasting insulin μIU=mlðÞ
þlog fasting glucose mg=dlðÞ
0
B
@
1
C
A
2
6
4
3
7
5
Laboratory Analysis
From each subject, 5 ml of venous blood was taken after an
overnight fast. The serum was separated by centrifugation for
20minat3000rpmandthenstoredat−80 °C until the
analysis.
Cu (mg/dl) levels were measured in the serum samples by
an atomic absorption spectrophotometer (PG-990, China). A
wavelength (λ
max
) of 324.7 nm was used to determine the Cu
levels.
In order to prepare a standard Cu solution, 196 mg of cop-
per sulfate was fed to 0.5 dl of 0.1% nitric acid. Then, using
deionized water, the solution was diluted into concentrations
of 80, 50, 40, 20, and 10 ppb.
In the next step, the samples were diluted. To this end,
10 μl of each serum sample was diluted in 190 μlofdeionized
water. Finally, the standards and samples were injected into
the device, and, according to the standard chart drawn by the
device, the concentration of each sample was calculated in
terms of ppb (it is reported in mg/dl in following tables).
The serum Mg concentration (mg/dl) was measured by the
Xylidyl Blue method using commercial kits (Pars Azmoon,
Tehran, Iran). The fasting blood glucose, FBG (mg/dl), was
analyzed by the glucose oxidase colorimetric method using
commercial kits (Pars Azmoon Tehran, Iran). The serum in-
sulin levels (μIU/ml) were measured by ELISA using com-
mercial kits (Demeditec Diagnostics GmbH, D-24145 Kiel-
Wellsee, Germany). The serum calcium concentration (mg/dl)
was calculated using commercial kits (Darman Faraz Kave,
Iran). Also, the total antioxidant capacity (μmol/l) of the se-
rum samples was measured by spectrophotometry at 593 nm
and the ferric reducing antioxidant power (FRAP) assay [17].
Statistical Analysis
The data were expressed as medians (range) and tested for
normality using the Kolmogorov–Smirnov test. The statistical
analyses included Student’sttest for normally distributed data
and the Mann–Whitney Utest for abnormally distributed data.
When the three groups were analyzed, one-way analysis of
variance (ANOVA) was performed.
The correlations among the evaluated parameters were an-
alyzed using the Spearman correlation test. The statistical
analyses were done using the Statistical Package for the
Social Sciences (SPSS) on the Windows software version
16.0 (SPSS Inc., Chicago, IL, USA). The statistical signifi-
cance was defined as p<0.05.
Results
The overall results obtained in the clinical and biochemical
experiments conducted on the PCOS patients and the control
subjects are presented in Table 1. The two groups were similar
in terms of age and BMI. The median fasting insulin levels
were significantly higher in women with PCOS than those in
the control women, but fasting glucose concentrations were
not different in the two groups. Insulin resistance indices (i.e.,
HOMA, QUICKI, and G/I ratio) were significantly different
in the PCOS and control groups.
The HOMA-IR value was significantly higher in the PCOS
group than that in the controls (p= 0.008). In contrast, the G/I
ratio and the QUICKI value were significantly lower in the
patient group than those in the control group (p= 0.003 and
p= 0.008 respectively).
We found significantly higher Cu levels in the PCOS pa-
tients as compared with the controls (p= 0.019) while no sig-
nificant difference was detected in terms of serum Mg and Ca
levels and Ca/Mg ratio. TAC was significantly lower in the
PCOS group than in the control group (0.002).
Insulin Resistance Classification and Other
Parameters in PCOS
Based on the insulin resistance indices (HOMA-IR ≥2.5 and
QUICKI ≤%0.333), 36 out of 60 patients were insulin-resis-
tant, but the remaining 24 patients had no insulin resistance. A
comparison of the parameters in the insulin-resistant (IR),
non-insulin-resistant (NIR), and control groups showed that
the three groups had statistically significant differences in
terms of fasting blood sugar (FBS), fasting insulin, insulin
resistance indices, and TAC (Table 2).
With regard to the parameters themselves, fasting insulin,
FBS, and IR indices proved to be correlated. In the insulin-
resistant PCOS patients, there emerged a negative correlation
between Mg levels and FBS (r=−0.509, p=0.002)aswellas
Mg levels and HOMA-IR (r=−0.449, p=0.006).Also,there
was a significant and positive correlation between Mg levels
and QUICKI (r=0.480, p= 0.003). Interestingly, Mg levels
and TAC were found negatively correlated (r=−0.407, p=
0.04) in the non-insulin-resistant PCOS patients (Table 3).
BMI Classification and Other Parameters in PCOS
As for BMI, according to the WHO classification of Asian
women in 2004, the PCOS group in our study consisted of
24 obese (BMI ≥30), 20 overweight (BMI ≥25), and 16
normal-weight women (BMI < 25). A comparison of the data
belonging to the overweight, obese, and normal-weight
groups of patients revealed that these three groups were sig-
nificantly different in terms of BMI and TAC (Table 4).
Status of Serum Copper, Magnesium, and Total Antioxidant Capacity in Patients with Polycystic Ovary Syndrome

The median TAC was significantly raised in the obese
group, as compared with the normal-weight one (p=0.04).
In the obese PCOS individuals, a positive correlation was
foundbetweenCuandBMI(r= 0.334, p= 0.01) as well as
TAC and G/I ratio (r= 0.329, p= 0.01). Also, TAC and
HOMA-IR were negatively correlated (r=−0.274, p=0.046).
In the overweight PCOS subjects, a positive correlation
was observed between Cu and G/I ratio (r= 0.277, p=
0.047), Cu and QUICKI (r=0.414, p= 0.02), as well as
TAC a nd QU ICKI (r= 0.325, p=0.019). However, TAC
and fasting insulin were negatively correlated (r=−0.318,
p=0.021).
Table 1 Comparison of clinical
and biochemical parameters in
PCOS and control groups
Parameters PCOS (n= 60) Control (n=90) pvalue
Age (year) 27.50 (25–32.75) 29.0 (25.75–32.50) 0.628
b
BMI (kg/m
2
) 28.40 (23.51–33.33) 27.62 (23.91–31.34) 0.150
a
FBS (mg/dl) 84.71 (73.18–102.67) 84.19 (74.06–97.48) 0.560
a
Fasting insulin (μIU/ml) 13.90 (10.43–21.79) 10.76 (7.65–14.44) 0.003
b
HOMA-IR ≥2.5 2.90 (1.87–4.70) 2.20 (1.60–3.31) 0.008
b
QUICKI ≤0.333 0.325 (0.304–0.347) 0.336 (0.319–0.355) 0.008
a
G/I ratio 6.06 (4.03–8.74) 7.85 (5.72–11.18) 0.003
b
Mg (mg/dl) 1.84 (1.73–1.98) 1.83 (1.64–1.98) 0.322
b
Cu (mg/dl) 0.206 (0.179–0.248) 0.187 (0.154–0.214) 0.019
b
Ca (mg/dl) 9.45 (8.19–11.29) 9.22 (8.51–9.69) 0.154
a
TAC ( μmol/l) 604.00 (531.50–660.42) 646.42 (588.92–746.42) 0.002
a
Ca/Mg ratio 5.20 (4.23–6.05) 5.59 (3.88–6.28) 0.989
a
Data are presented as medians (25–75% quartiles). p<0.05is significant
BMI,bodymassindex;FBS, fasting blood sugar; HOMA-IR, homeostatic model assessment for insulin resistance;
QUICKI, quantitative insulin sensitivity check index; G/I ratio, glucose/insulin ratio; Mg, magnesium; Cu,
copper; Ca, calcium; TAC, total antioxidant capacity; Ca/Mg ratio, calcium/magnesium ratio
a
Student’sttest
b
Mann–Whitney Utest
Table 2 Comparison of clinical
and biochemical parameters in
PCOS patients classified based on
insulin resistance
Parameters IR (n= 36) Non-IR (n= 24) Control (n=90) p
value
Age (year) 27.0 (24.0–31.75) 31.0 (25.25–33.0) 29.0 (25.75–32.50) 0.123
BMI (kg/m
2
) 30.33 (25.84–34.15) 27.04 (23.11–29.69) 27.62 (23.91–31.34) 0.071
FBS (mg/dl) 95.63 (78.99–105.93) 75.21 (65.70–83.92) 84.19 (74.06–97.48) 0.000
Fasting insulin
(μIU/ml)
20.40 (14.60–23.97) 9.08 (6.48–10.78) 10.76 (7.65–14.44) 0.000
HOMA-IR ≥2.5 4.64 (3.07–5.72) 1.66 (1.16–1.99) 2.20 (1.60–3.31) 0.000
QUICKI ≤0.335 0.306 (0.297–0.324) 0.350 (0.343–0.369) 0.336 (0.319–0.355) 0.000
G/I ratio 4.99 (3.77–6.48) 8.73 (6.66–10.81) 7.85 (5.72–11.18) 0.000
Mg (mg/dl) 1.87 (1.78–2.05) 1.83 (1.72–1.85) 1.83 (1.64–1.98) 0.190
Cu (mg/dl) 0.197 (0.171–0.249) 0.206 (0.187–0.248) 0.187 (0.154–0.214) 0.065
Ca (mg/dl) 10.16 (7.83–11.58) 8.96 (8.20–10.54) 9.22 (8.51–9.69) 0.192
TAC ( μmol/l) 582.57 (511.85–622.93) 650.42 (577.57–691.50) 646.42 (588.92–746.42) 0.000
Ca/Mg ratio 5.59 (3.88–6.28) 4.98 (4.55–5.88) 5.59 (3.88–6.28) 1.000
Data are presented as medians (25–75% quartiles). p<0.05is significant
BMI,bodymassindex;FBS, fasting blood sugar; HOMA-IR, homeostatic model assessment for insulin resistance;
QUICKI, quantitative insulin sensitivity check index; G/I ratio, glucose/insulin ratio; Mg,magnesium; Cu,
copper; Ca, calcium; TAC, total antioxidant capacity; Ca/Mg ratio, calcium/magnesium ratio; IR, insulin-
resistance; NIR, non-insulin-resistance
Kanafchian et al.

Discussion
So far, a large bulk of research has been devoted to the phys-
iological levels of elements in PCOS. For instance, there are
reports of correlations between the concentrations of some
elements in most, but not all, women with PCOS [18,19].
However, there still remain a number of unanswered questions
regarding the pathogenesis of this disease.
The aim of the present study is mainly to evaluate serum
Cu, Mg, and TAC levels in PCOS patients. In this respect, an
investigation was conducted on the probable association of
copper and magnesium with TAC and the correlation between
the measured parameters and insulin resistanceand body mass
index.
In this study, serum Cu levels were significantly higher in
the PCOS group than those in the control group. This finding
is in agreement with most previous studies [18,20]. Pratip
et al. [19] reported that PCOS women with insulin resistance
exhibit significantly higher serum levels of copper. In another
study, Celik et al. [21] showed that increased copper levels
may be responsible for the increased risk of early vascular
diseases in women with PCOS.
As revealed by some recent studies, an increase in oxida-
tive stress may play a role in the pathogenesis of PCOS [22,
23]. This increase can possibly become greater by an increase
in serum copper levels. It is found that copper induces oxida-
tive stress by serving as a catalyst in the formation of reactive
oxygen species while decreasing glutathione levels [18]. Cu is
normally bound to proteins, but it may be released to take part
in Fenton-type reactions through which hydroxyl radicals are
produced [9,24]. Insulin resistance can increase oxidative
stress due to hyperglycemia and higher levels of free fatty
acids. This increase, in turn, leads to an increase in the pro-
duction of reactive oxygen species (ROS) [25]. Certain disor-
ders in the structure of arterial walls, stress, infection, and
diabetes mellitus have been found to be linked to Cu concen-
tration in serum [6].
In our study, a positive correlation was found between Cu
and insulin resistance indices (G/I ratio and QUICKI) in over-
weight PCOS patients. Our data also revealed that serum cop-
per was positively correlated with BMI in obese PCOS pa-
tients. However, Kurdoglu et al. [18] reported a contrastive
result; theyfound a negative correlation between the serum Cu
level and BMI.
Table 3 The correlation between
Mg and TAC, FBS, and insulin
resistance indices in PCOS
patients classified based on
insulin resistance
Subgroup Parameters FBS HOMA-IR QUICKI TAC
rprprprp
PCOS-IR Mg −0.509 0.002 −0.449 0.006 0.480 0.003 0.160 0.352
PCOS-NIR Mg 0.206 0.355 0.184 0.391 0.362 0.083 −0.407 0.040
p< 0.05 is significant
Table 4 Comparison of clinical
and biochemical parameters in
PCOS patients classified based on
BMI
Parameters Normal weight (BMI
<25)
Overweight (BMI ≥25) Obese (BMI ≥30) p
value
Numbers 16 (26.66%) 20 (33.33%) 24 (40%) –
Age (year) 29.50 (23.25–32.75) 29.0 (26.0–32.75) 27.5 (25.0–32.5) 0.555
BMI (kg/m
2
) 22.48 (21.75–23.42) 27.55 (26.37–28.57) 33.33 (32.50–35.15) 0.000
FBS (mg/dl) 83.83 (68.96–94.22) 82.42 (75.03–99.94) 85.59 (72.83–99.15) 0.357
Fasting insulin
(μIU/ml)
11.7 8 (10.05–18.53) 11.54 (8.27–15.88) 11.38 (7.77–17.49) 0.210
HOMA-IR > 2.5 2.50 (1.78–3.59) 2.32 (1.68–3.67) 2.38 (1.57–4.02) 0.196
QUICKI < 0.335 0.333 (0.317–0.355) 0.336 (0.309–0.351) 0.328 (0.311–0.352) 0.198
G/I ratio 7.16 (4.68–9.67) 7.35 (4.76–9.97) 6.70 (5.32–9.02) 0.887
Mg (mg/dl) 1.83 (1.64–1.99) 1.83 (1.63–1.95) 1.84 (1.73–1.99) 0.947
Cu (mg/dl) 0.184 (0.153–0.230) 0.201 (0.159–0.243) 0.194 (0.171–0.222) 0.780
Ca (mg/dl) 9.27 (8.43–10.32) 9.48 (8.66–10.16) 9.11 (8.21–10.03) 0.529
TAC ( μmol/l) 646.64 (597.96–751.39) 647.14 (586.78–734.64) 600.21 (522.85–656.17) 0.030
Ca/Mg ratio 5.16 (4.45–5.88) 5.34 (4.55–6.14) 4.92 (4.29–5.53) 0.522
Data are presented as medians (25–75% quartiles). p<0.05is significant
BMI,bodymassindex;FBS, fasting blood sugar; HOMA-IR, homeostatic model assessment for insulin resistance;
QUICKI, quantitative insulin sensitivity check index; G/I ratio, glucose/insulin ratio; Mg; magnesium; Cu,
copper; Ca, calcium; TAC, total antioxidant capacity; Ca/Mg ratio, calcium/magnesium ratio
Status of Serum Copper, Magnesium, and Total Antioxidant Capacity in Patients with Polycystic Ovary Syndrome

As for magnesium, in the present study, the median serum
Mg levels in the PCOS patients were similar to those in the
controls. Although several investigations reported a lower se-
rum Mg level in PCOS patients [26,27], Kauffman et al. and
Kurdoglu et al. [10,18] noted no significant difference be-
tween PCOS patients and the controls in this regard. This is
in accordance with the results of our study. In another study,
Pratip et al. [19] indicated that serum Mg concentrations in
insulin-resistant PCOS women were significantly lower than
those in the control group.
Magnesium is considered so vital for body health. It has
particularly been found that magnesium serves as a second
messenger in insulin function [11]. A deficiency of this ele-
ment has to do with some metabolic disorders like diabetes
mellitus type 2, obesity, insulin resistance, as well as cardio-
vascular diseases, hypertension, and dyslipidemia, which are
also common in PCOS [10].
Sharifietal.[28], however, reported that magnesium defi-
ciency is not associated with IR in PCOS. In this study, we
found a negative correlation between serum Mg levels and the
HOMA-IR indices of insulin resistance but a positive correlation
between serum Mg levels and the QUICKI of insulin resistance.
As indicated in some recent studies, a high calcium level is
needed for both first- and second-phase insulin secretions.
However, cellular calcium level can be adversely affected by
magnesium deficiency [19]. In the present study, serum levels
of calcium and Ca/Mg ratio in the PCOS group were not
significantly different from those in the controls. Our results
contradict the findings of another study that suggests serum
levels of calcium and Ca/Mg ratio in the PCOS population is
significantly higher than those in the control group [19].
TAC is commonly defined as the ability of serum to sup-
press the generation of free radicals and to keep the cell struc-
ture safe from the damaging effects of those materials [29].
Murri et al. conducted a meta-analysis of 470 women includ-
ing 260 women with PCOS and 210 controls. The researchers
found no significant difference in TAC between the PCOS
women and the controls [5]. In the present study, however,
serum TAC levels were significantly lower in the PCOS group
than those in the control group. This result is in agreement
with most previous studies [23,30–32]. As a matter of fact,
a survey of the literature proves that the results of different
studies regarding antioxidant levels are conflicting. What is
generally understood is that there exists an imbalance between
oxidants and antioxidants in PCOS [29].
When the PCOS women were divided into subgroups on
the basis of their BMI values, the median TAC rose signifi-
cantly in the obese group as compared with the normal-weight
group. Also, a negative correlation was found in TAC with
HOMA-IR in obese PCOS patients. This result is consistent
with a previous study [32]. The novel finding of this study
regards the correlation between serum magnesium levels and
TAC in PCOS patients. Interestingly, a negative correlation
was found between Mg levels and TAC in non-insulin-
resistant PCOS patients.
The research may be criticized mainly for its small size
samples, which may have decreased the reliability of the re-
sults. In addition, the levels of superoxide dismutase, catalase,
and cytochrome coxidase should have been evaluated for their
possible relationships with PCOS. Also, considering the meth-
odology used to evaluate insulin resistance (HOMA-IR and
QUICKI), it was better to perform the oral glucose tolerance
test (OGTT) too. Inspite of all these shortcomings, it should be
mentioned that our study was intended just to examine the
relationship of copper and magnesium with TAC. Of course,
the points discussed herein should be investigated with further
trials in order to provide new insights into PCOS.
Conclusion
According to our findings, serum Cu and TAC levels are sig-
nificantly higher and lower in PCOS patients than those in
non-affected individuals respectively. It may be suggestive
of increased oxidative stress in PCOS patients. As the results
indicated, there is a correlation between magnesium and insu-
lin resistance. Also, there is a negative correlation between Mg
levels and TAC. As another finding in this research, copper
and magnesium appear to contribute to oxidative stress and
insulin resistance in patients with PCOS. In other words, with
regard to the relationships detected in this study, it is possible
to deter the growth or development of insulin resistance and
oxidative stress by routine evaluation of serum Mg, Cu, and
TAC levels in such patients.
Acknowledgments We would like to thank the participating patients as
well as the staff of Fatemeh Zahra Infertility and Reproductive Health
Research Center for their valuable cooperation with this project.
Funding information We are grateful for the financial support granted by
Babol University of Medical Sciences, Iran.
Compliance with Ethical Standards Approval was obtained
from the ethics committee of Babol University of Medical Sciences
(MUBABOL.REC.1394.65). All the participants were informed of the
aims of the study, and informed consents were obtained from them. The
biochemical tests had no cost for the participants, and the results of these
tests were reported to them.
Conflict of Interest The authors declare that they have no conflict of
interest.
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Status of Serum Copper, Magnesium, and Total Antioxidant Capacity in Patients with Polycystic Ovary Syndrome