See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/263888944

Antioxidant Status in Women with Polycystic Ovary Syndrome

Article · April 2014

CITATION READS

1 605

4 authors, including:

Priyanka Maleedhu Dr. Praveen Kumar Kodumuri

Kannur Medical College Tomo Riba Institute of Health and Medical Sciences
2 PUBLICATIONS   16 CITATIONS    10 PUBLICATIONS   21 CITATIONS   

SEE PROFILE SEE PROFILE

Vijayabhaskar Madrol
Nizam's Institute of Medical Sciences
19 PUBLICATIONS   79 CITATIONS   

SEE PROFILE

All content following this page was uploaded by Dr. Praveen Kumar Kodumuri on 14 July 2014.

The user has requested enhancement of the downloaded file.

 e-ISSN: 2319-9865
p-ISSN: 2322-0104
RESEARCH AND REVIEWS: JOURNAL OF MEDICAL AND
HEALTH SCIENCES
Antioxidant Status in Women with Polycystic Ovary Syndrome.
Priyanka Maleedhu*1, Vijayabhaskar M2, Prabhakara Rao P3, and Praveen K Kodumuri4.
1 & 2Departmentof Biochemistry, Mamata Medical College, Khammam, India.
3Department of Biochemistry, SV Medical College, Tirupati, India.
4Department of Physiology, Mamata Medical College, Khammam, India.

Research Article

Received: 22/03/2014 ABSTRACT

Revised: 11/04/2014
Accepted: 14/04/2014
*For Correspondence
Department of Physiology,
Mamata Medical College,
Khammam, India.
Telephone:+91 9393246688
Keywords: Polycystic ovary
syndrome(PCOS), oxidative
stress, total antioxidant
capacity(TAC),
malondialdehyde(MDA),
cardiovascular disease(CVD).
Polycystic ovary syndrome is a heterogenous condition
characterized by hyperandrogenism, ovulatory dysfunction and
polycystic ovaries (PCO). Oxidative stress, which is well-known to
participate in the pathogenesis of cardiovascular disease (CVD), was
documented in PCOS. Obesity is a well-defined independent risk
factor for the development of type 2 diabetes and cardiovascular
disease. Central obesity is also related to increased oxidant status
and is an important and independent cardiovascular risk factor. To
evaluate antioxidant status in women with polycystic ovary
syndrome and to correlate MDA and TAC with BMI and waist. Study
group comprised of 142 women with PCOS and 65 healthy non
PCOS controls. BMI, Waist circumference serum MDA and TAC were
measured in PCOS subjects and age matched controls. All values
are expressed as mean ± SD. The results obtained are analysed
statistically using the unpaired student‘t’ test and pearsons
correlation. The mean BMI, Waist and serum MDA values are
significantly increased and serum TAC is significantly decreased in
PCOS subjects when compared with non PCOS controls. The present
study has demonstrated increase in mean serum MDA and
decreased TAC levels in women with PCOS.

INTRODUCTION

Polycystic ovary syndrome is a heterogenous condition characterized by hyperandrogenism,

ovulatory dysfunction and polycystic ovaries (PCO) [1]. Women with PCOS also display a number of
metabolic abnormalities including hyperinsulinemia, insulin resistance, dyslipidemia, and obesity[2]. All
these features are components of the metabolic syndrome, and women with PCOS are therefore at risk of
developing type 2 diabetes (T2DM) which, in turn, puts them at increased risk of developing cardiovascular
disease (CVD)[3].

Antioxidant status is a critical tool for assessing redox status which is defined as balance between
oxidants (free radicals and other reactive species).Oxidative stress is commonly referred as the imbalance
between oxidants and antioxidants. When the imbalance favors oxidants, generation of excessive amounts
of reactive oxygen species harm our body in various ways.[4]. Reproductive cells and tissues will remain
stable only when antioxidant and oxidant status is in balance. Oxidative stress, which is well-known to
participate in the pathogenesis of cardiovascular disease (CVD), was documented in PCOS [5]. Insulin
resistance and hyperglycemia are profound factors to increase oxidative stress, but non-obese PCOS
patients without IR were also reported to have elevated oxidant status [6]. Alteration in the oxidant -
antioxidant profile is known to occur in polycystic ovary syndrome [7]. In PCOS, oxidative stress in response
to hyperglycemia may be capable of directly stimulating hyperandrogenism.

RRJMHS | Volume 3 | Issue (Supplement 2) | April - June, 2014 91

 e-ISSN: 2319-9865
p-ISSN: 2322-0104
MDA is a marker of lipid peroxidation and increases in oxidative stress. Increased reactive oxygen
species (ROS) may cause intracellular damage causing an increase in MDA levels [8]. Total antioxidant
capacity is the ability of serum to quench free radical production, protecting the cell structure from
molecular damage. This assay measures the combined antioxidant capacity of all its components including
vitamins, proteins, lipids, glutathione, uric acid, etc. [9]. The degree of antioxidant defense present is often
expressed as total antioxidant capacity (TAC) [4]. TAC is sensitive to the changes in plasma antioxidant
levels and degree of oxidative stress [10]. Recent studies have documented increased oxidative stress in
patients with PCOS [11,12] which may increase the risk of cardiovascular disease in such patients.

Obesity is a well defined independent risk factor for the development of type 2 diabetes and
cardiovascular disease .Obesity is more common in women with PCOS, and can lead to severe
hyperandrogenism. Obesity aggravates preexisting clinical, hormonal and metabolic features in most
women with PCOS [13]. Obesity, in particular, central obesity, plays a central role in the development of
PCOS.

Central obesity is also related to increased oxidant status [5]. Obesity has been shown to play an
important role in elevated oxidative stress, which contributes to IR [14]. Several studies have documented
that atleast 30-40% of PCOS patients were obese or overweight and obesity has an aggravating role in
PCOS [15,16].

Central obesity is an important and independent cardiovascular risk factor [17]. Obesity and PCOS
interact to promote premature atherosclerosis and increase cardiovascular mortality [18]. The prevention of
obesity, can be a crucial factor against the increased incidence of PCOS and its associated physiological
and pathological abnormalities, especially during childhood and preadolescent years [19]. The aim of this
study is to evaluate antioxidant status in women with polycystic ovary syndrome.

MATERIALS AND METHODS

The present study was carried out in department of biochemistry, Mamata Medical College and
General Hospital. The study was approved by human ethical committee. Informed consent was obtained
from the patients selected. 142 PCOS cases were selected from the OP and IP departments of obstrectics
and Gynaecology unit of Mamata General Hospital, and hospitals in the khammam town, Andhra Pradesh.
65 healthy non PCOS controls were included in the study. Controls included were volunteers from relatives
of the patients, staff and students. The diagnosis was based on Rotterdam criteria [20]. Body weight, height
and waist circumference were measured and BMI was calculated as weight (kg) divided by height in square
meter (m2). Waist circumference is a measure of abdominal or centralized obesity, and is taken
approximately midpoint between the lower margin of last palpable rib and top of iliac crest.

PCOS cases were categeorised into normal (BMI<23), overweight (BMI 23-25) and obese
(BMI≥25). Patients were divided into two groups based on the BMI, sub group 1 consisting of patients with
normal BMI (<23) and subgroup 2 consisting of patients with increased BMI(≥23)(overweight+obese).
Based on waist circumference, PCOS were categorized into two groups, normal cases (waist<80) and
obese cases (waist≥80). Controls were also sub categorized based on BMI and waist.

5 ml of blood was collected from the subjects as well as controls after overnight fasting (12hr) by
venipuncture. After collection of blood sample, the blood was allowed to clot (for 10 min) and serum was
separated by centrifugation at 2500 rpm for 20 min. Malondialdehyde is determined as Thiobarbituric acid
reactive substances(TBARS)[21] and TAC was estimated by using ferric reducing ability of plasma(FRAP)
assay [22].

The present clinical study was cross -sectional comparative study. All the patients in the age group
of 20-35 were diagnosed for PCOS using Rotterdam criteria. Subjects with normal kidney function were
included. The subjects having Diabetes mellitus, Hypertension, Coronary heart disease and endocrine
disorders were excluded. Alcoholics, smokers, pregnant women, subjects on vitamin supplementation and
subjects with altered kidney function(random urinary protein >16mg/dl, serum creatinine >1.1mg/dl) are
also excluded from the study.

RRJMHS | Volume 3 | Issue (Supplement 2) | April - June, 2014 92

 e-ISSN: 2319-9865
p-ISSN: 2322-0104
Statistical analysis

All values were expressed as mean ± SD. The results obtained were analysed statistically using
the unpaired student‘t’ test to evaluate the significance of differences between the mean values.
Pearson’s correlation coefficient was used for correlation among variables.

RESULTS

Prevalence of obesity is more in PCOS cases. When compared with BMI central obesity is more
pronounced in PCOS cases.(Table 1)

Our results have shown an increase in the mean BMI , waist circumference and serum MDA levels
and decrease in mean TAC levels in PCOS cases when compared with non PCOS controls. (Table 2)

There was an incremental increase of serum MDA levels and incremental decrease in serumTAC
from normal, overweight and obese cases when compared with their respective controls (Table 3).

When the PCOS cases were divided into two subgroups based on BMI: Subgroup 1 with normal
BMI(<23) and subgroup 2 with increased BMI(≥23), serum MDA is increased with increase in BMI.(Table
4)

Based on waist cases were divided into two subgroups: normal cases and obese cases, there was
significant increase in the mean values.(Table 5)

When comparision was made between subgroups based on waist: significant increase of mean
serum MDA was observed in normal and obese cases compared with respective controls. Significant
incremental increase of serum MDA was observed from normal controls, obese controls, normal cases and
obese cases. TAC also showed significant difference in cases when compared with their respective
controls. (Table6).

Based on Pearson’s correlation MDA showed positive correlation with BMI and waist.(Table 7)

Table 1: Prevalence of obesity in cases

Based on BMI: Based on waist:

Normal cases (n=61): 43% (<23) Normal cases (n=58): 41% (<80)
Overweight cases (n=26): 18% (23-25) Obese cases (n=84): 59% (≥ 80)
Obese cases (n=55): 39% ( ≥ 25)

Table 2: Mean ±SD and P values of various biochemical parameters in PCOS cases (n=142) and nonPCOS
controls (n=65)

Mean±SD Mean±SD (Total

Parameter P-value
(Total Cases) Controls)
BMI (kg/m2) 24.31 ± 4.42 24.14 ±5.20 0.8153
Waist (cm) 82.07±9.47 79.95 ±9.90 0.1430
MDA (µmol/L) 4.44 ±2.05 1.63 ±0.67 <0.0001*
TAC (mmol/L) 0.54 ±0.17 0.96 ±0.27 <0.0001*
*statastically significant

Table 3: Based on BMI Mean ±SD of normal controls (n=32) and normal cases (n=61), overweight controls
(n=13) and overweight cases (n=26), obese controls(n=20) and obese cases (n=55).

Parameter Normal controls vs Overweightcontrols vs Obese controls vs

normal cases overweight cases obese cases
MDA 1.38 ±0.37 vs 3.53 ±1.35* 2.01 ±0.71 vs 4.97 ±2.12* 1.73 ±0.86 vs 5.20±2.29*
TAC 1.03 ±0.27 vs 0.56 ±0.20* 0.87±0.30 vs 0.55 ±0.14* 0.89 ±0.24 vs 0.50±1.37*
*statastically significant

RRJMHS | Volume 3 | Issue (Supplement 2) | April - June, 2014 93

 e-ISSN: 2319-9865
p-ISSN: 2322-0104
Table 4: Sub group 1: Normal BMI (BMI<23) (n=61): vs Sub group 2 : Increased BMI (overweight + obese)
(BMI ≥ 23) (n= 81) (Mean ±SD )

Mean ±SD (sub group 1 Mean ±SD (sub group

Parameter P-value
BMI<23) 2 BMI ≥ 23)
BMI 20.44 ±1.87 27.23 ±3.44 <0.0001*
MDA 3.54 ±1.36 5.13 ±2.23 <0.0001*
TAC 0.57 ±0.20 0.52 ±0.14 0.0988NS
*statastically significant, NS: not significant

Based on waist:
Table 5: Normal cases(<80) (N=58) and obese cases (≥ 80) (N=84): (Mean ±SD)

(normal cases (Obese cases

Parameter P-value
Waist < 80) Waist ≥ 80)
Waist 73.2414 ±6.0533 88.1667 ±5.9492 <0.0001*
MDA 3.5714 ±1.7588 5.0520 ±2.0408 <0.0001*
TAC 0.5316 ±0.1590 0.5487 ±0.1796 0.5593NS
*statastically significant, NS: not significant

Table 6: Comparision based on waist between normal controls and normal cases (< 80), obese controls
and obese cases (≥ 80) (Mean ±SD )

Parameter Normal Controls Normal cases Obese Controls Obese cases

Waist 72.85±4.678 73.241±6.05 87.74±8.075 88.16±5.94
MDA 1.41±0.423 3.57±1.76* 1.87±0.8217 5.05 ±2.04*
TAC 1.05±0.25 0.53±0.16* 0.86±0.28 0.54±0.17*
*statastically significant

Table 7: Pearson’s correlation of MDA and TAC with BMI and waist

Variable MDA TAC

BMI(kg/m2) 0.36*** -0.09NS
Waist(cm) 0.44*** 0.01NS
MDA 1.00 -.16NS
TAC -0.16NS 1.00
***Highly significant, NS: not significant

DISCUSSION

In the present study antioxidant status was decreased in PCOS cases. The mean serum MDA
levels have been increased significantly in the patients with polycystic ovary syndrome compared to
controls. The increase was more pronounced with increase in BMI and waist. Higher levels were observed
in obese cases when compared with normal cases and controls. The increasing global prevalence of
obesity may play a key role in promoting the development of PCOS in susceptible individuals. In addition,
there is no doubt that obesity aggravates preexisting clinical, hormonal and metabolic features in most
women with PCOS[23].

Our findings were similar to those of Sabuncu et al. [5], Yilmaz et al. [24] and Kuscu et al. [25]. On the
other hand Erdogan et al. showed no statistically significant difference in mean MDA levels between PCOS
patients and control group [26]. It has been shown that increased production of ROS in PCOS may causes
tissue damage [27]. Lipid peroxidation is supposed to be one of the tissue damage mechanisms of
oxidative stress and it has been shown as the damage of unsaturated fatty acids that is dependent on free
radicals and oxygen [5]. Rise in MDA could be due to increased generation of reactive oxygen species (ROS)
due to the excessive oxidative damage generated in these patients. These oxygen species in turn can
oxidize many other important biomolecules including membrane lipids. Although exact mechanism has not
been clearly understood, hyperandrogenemia in PCOS may be the reason for these higher MDA levels.

We observed a significant decrease in the levels of TAC in patients with PCOS when compared to
controls. Our findings are consistent with a previous study by Fenkci et al. (2003) [11]. However, Verit et al.
(2008) reported that TAC levels were significantly higher in PCOS patients compared with age and BMI-

RRJMHS | Volume 3 | Issue (Supplement 2) | April - June, 2014 94

 e-ISSN: 2319-9865
p-ISSN: 2322-0104
matched controls [6]. In our study antioxidant status was compared among PCOS cases and controls as well
as in subgroups based on BMI and waist circumference.

CONCLUSION

Our study revealed that there is an imbalance of antioxidant status in women with PCOS.
Increased oxidative stress and decreased antioxidant capacity may contribute to the increased risk of CVD
in women with PCOS. The role of oxidative stress in the pathogenesis of PCOS is not fully understood.
Further research on oxidative stress in PCOS is needed. Antioxidant supplementation can reduce
cardiovascular risk. The results of our study emphasize the need for initiating life style measures early and
in the overweight category itself. This will supplement PCOS treatment and can help in minimizing future
cardiovascular risk.

REFERENCES

1. Abbott DH, Dumesic DA, Franks S. Developmental origin of polycystic ovary syndrome - a
hypothesis. J Endocrinol 2002; 174: 1-5.
2. Talbott EO, Guzick DS, Clerici A, Berga S, Detre K, Weimer K, Kuller L. Coronary heart disease risk
factors in women with polycystic ovary syndrome. Arterioscler Thromb Vasc Biol 1995; 15:821–
826
3. Teede H, Hutchison S, Zoungas S, Meyer C. Insulin resistance, the metabolic syndrome, diabetes,
and cardiovascular disease risk in women with PCOS. Endocrine 2006; 30: 45‐53.
4. Agarwal A, Gupta S, Sharma R. Role of oxidative stress in female reproduction. Reprod Biol
Endocrinol 2005; 3: 28.
5. Sabuncu T, Vural H, Harma M, Harma M. Oxidative stress in polycystic ovary syndrome and its
contribution to the risk of cardiovascular disease. Clin Biochem. 2001;34:407-13.
6. Verit FF, Erel O. Oxidative stress in non-obese women with polycystic ovary syndrome: correlations
with endocrine and screening parameters. Gynecol Obstet Invest. 2008; 65:233-9.
7. Fatma Ferda Verit, Ozcan Erel. Oxidative Stress in Nonobese Women with Polycystic Ovary
Syndrome: Correlations with Endocrine and Screening Parameters, Gynecology Obstetrics
Investigations,2008; 65, 233-239.
8. Knight JA, Smith SE, Kinder VE and Anstall (HB). Reference intervals for plasma lipoperoxides age,
sex and specimen-related variations. Clin Chem; 1987; 33: 2289-2291.
9. Mahfouz R, Sharma R, Sharma D, Sabanegh E, Agarwal A. Diagnostic value of the total antioxidant
capacity (TAC) in human seminal plasma. Fertil Steril 2009; 91(3): 805-11.
10. Garibaldi S, Valantini S, Aragno I, Pronzato MA, Traverso N and Odethi P. Plasma protein oxidation
and antioxidant defense during aging. Int. J Vitam Nutr Res; 2001; 7: 332-338.
11. Fenkci V, Fenkci S, Yilmazer M and Serteser M. Decreased total antioxidant status and increased
oxidative stress in women with polycystic ovary syndrome may contribute to the risk of
cardiovascular disease. Fertil Steril; 2003; 80: 123-127.
12. Zhang D, Luo WY, Liao H, Wang CF, Sun Y. The effects of oxidative stress to PCOS. Sichuan Da Xue
Xue Bao Yi Xue Ban 2008; 39(3): 421-3.
13. Pasquali, R., A. Gambineri, and U. Pagotto. The Impact of Obesity on Reproduction in Women with
Polycystic Ovary Syndrome. BJOG: An International Journal of Obstetrics and Gynaecology 2006;
113(10): 1148-1159.
14. Urakawa H, Katsuki A, Sumida Y, et al. Oxidative stress is associated with adiposity and insulin
resistance in men. J Clin Endocrinol Metab 2003; 88(10): 4673-6.
15. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, Zapanti ED,
Bartzis MI: A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and
metabolic profile. J Clin Endocrinol Metab 1999; 84(11): 4006–4011.
16. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES and Ylldiz BO. The prevalence and features
of polycystic ovary syndrome in an unselected population. J din Endocrinol Metab; 2004; 89:
2745-2749.
17. Norman RJ, Masters L, Milner CR, Wang JX, Davies MJ. Relative risk of conversion from
normoglycaemia to impaired glucose tolerance or non-insulin dependent diabetes mellitus in
polycystic ovarian syndrome. Hum Reprod 2001; 16(9): 1995-1998.
18. Amato MC, Verghi M, Galluzzo A & Giordano C. The oligomenorrhoic phenotypes of polycystic ovary
syndrome are characterized by a high visceral adiposity index: a likely condition of cardiometabolic
risk. Hum Reprod 2011;Vol. 26, No. issue 6, 1486-94.
19. Farell K & Antoni M. Insulin resistance, obesity, inflammation, and depression in polycystic ovary
syndrome: biobehavioral mechanisms and interventions. FertilSteril 2010; 94(5): 1565-1574.

RRJMHS | Volume 3 | Issue (Supplement 2) | April - June, 2014 95

 e-ISSN: 2319-9865
p-ISSN: 2322-0104
20. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003
consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.
Fertil Steril 2004; 81(1): 19–25.
21. Iris F.F. Benzie and J.J. Strain. The Ferric Reducing Ability of Plasma (FRAP) as a Measure of
“Antioxidant Power”: The FRAP Assay. Analytical biochemistry 1996; 239:70-76.
22. Sangeetha P, U. N. Das, Koratkar. R, Surya prabha. P. Increase in Free radical lipid peroxidation
following chemotherapy in cancer; Free radical Biol Med 1990; 8: 15-19.
23. Pasquali R, Gambineri A, Pagotto U. The impact of obesity on reproduction in women with
polycystic ovary syndrome. BJOG 2006; 113:1148‐1159
24. Yılmaz M, Bukan N, Ayvaz G, Karakoç A, Törüner F, Cakir N, Arslan M. The effects of
rosiglitazone and metformin on oxidative stress and homocysteine levels in lean patients with
polycystic ovary syndrome. Hum Reprod. 2005; 20(12):3333-40.
25. Kuscu NK, Var A. Oxidative stress but not endothelial dysfunction exists in non-obese, young group
of patients with polycystic ovary syndrome. Acta Obstet Gynecol Scand. 2009; 88(5):612-7.
26. Erdogan M, Karadeniz M, Berdeli A, Alper G, Caglayan O, Yilmaz C. The relationship of the
interleukin-6 -174 G>C gene polymorphism with oxidative stress markers in Turkish polycystic
ovary syndrome patients. J Endocrinol Invest. 2008; 31(7):624-9.
27. Gonzalez F, Rote NS, Minium J, Kirwan JP. Reactive oxygen species-induced oxidative stress in the
development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. J Clin
Endocrinol Metab. 2006; 91:336-40.

RRJMHS | Volume 3 | Issue (Supplement 2) | April - June, 2014 96

View publication stats