Oxidative stress and outcome of antioxidant supplementation in patients with polycystic ovarian syndrome (PCOS)

Abubakar A. Panti, Constance E. Shehu, Yusuf Saidu, Karima A. Tunau, Emmanuel I. Nwobodo, Abdulgafar Jimoh, Lawal S. Bilbis, Atteque B. Umar, Mairo Hassan


Background: PCOS is a condition with significant decrease in antioxidant with an increased risk of oxidative stress. Antioxidant supplementation has been shown to improve insulin sensitivity in PCOS and may improve outcome of management of PCOS. Objectives of this study were to determine the oxidative stress level of PCOS patients, to assess the effect of antioxidant supplementation on the outcome of management of PCOS and to compare with a control group.

Methods: The study was a single blind randomised control trial involving 200 patients with PCOS. The study was conducted at Usmanu Danfodiyo University Teaching Hospital Sokoto. They were randomly divided into intervention and control groups and base line serum levels of oxidative stress marker, antioxidant enzymes, vitamins and minerals were determined. Antioxidant supplementation and placebo were given to the intervention and control groups respectively. All the patients had ovulation induction with clomiphene citrate and were followed up for 6 months. Outcome measures were clinical pregnancy or menstrual regularisation. Level of significance was <0.05.

Results: There was statistical significance in the serum levels of oxidative stress marker, antioxidant enzymes, vitamins and minerals between the two groups (post intervention). Glutathione peroxidase (p = 0.001), superoxide dismutase (p = 0.0001), catalase (p= 0.0369), melondialdehyde (p= 0.007), Vitamin A, Vitamin C, Vitamin E (p = 0.0001), zinc and copper (p = 0.0001). The clinical pregnancy outcomes were 22 (22%) versus 2 (2%); live births 18 (18%) versus 2 (2%) and menstrual regularisation 48 (48%) versus 46 (46%) in the intervention and control groups respectively.

Conclusions: Antioxidant supplementation in this study significantly affected pregnancy rate in patients with PCOS. Larger studies are suggested to revisit the conclusion of the Cochrane review that antioxidants supplementation had no significant role in female infertility.


Antioxidants, Nigeria, Oxidative stress, PCOS, Supplementation

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Joham AE, Teede HJ, Ronasinha S, Zanges S, Boyle J. Prevalence of infertility and use of fertility treatment in women with polycystic ovary syndrome; data from a large community based study. J Women Health. 2015;24(4):299-307.

Goodarzi MO, Dumestic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome; etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011;7:219-31.

Muni M, Luque-Mirez M, Insenser M, Ojede-Ojede M, Escobar-Morreds HF. Circulating markers of oxidative stress and polycystic ovary syndrome; a systemic review and meta-analysis. Hum Reproduction Update. 2013;19(3):268-88.

Victor VM, Rucha M, Banuls C, Alvarez A, De- Pablo C, Sachez-Ssrrano M, et al. Induction of oxidative stress and human leukocyte/endothelial cell interactions in polycystic ovary syndrome patients with insulin resistance. J Cli Endocrinol Metab. 2011;96(10):3115-22.

Al-Gugory KH, Fowler PA, Garrel C. The role of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcome. Int J Biochem. 2010;42:1634-50.

Burton GJ, Jaumiaux E. Oxidative stress. Best Pract Res Clin Obstet Gynaecol. 2010;25:287-99.

Agarwal A, Saleh RA, Bedaiwy MA. Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil Steril. 2003;79(4):829-43.

Bellver J, Melo MA, Bosch E, Sewa V, Remotin J, Pellier A. Obesity and poor reproductive outcome; the potential role of the endometrium. Fertil Steril. 2007;88(2):446-51.

Miyamoto K, Sato EF, Kasahare E, Jikumaru M, Hiramoto K, Tabate H, et al. Effect of oxidative stress during repeated ovulation on the structure and function of the ovary, oocyte and the mitochondria. Free Radical Biol Med. 2010;49(4):674-81.

Ternopusky MA. The mitochondrial cocktail; rationale for combined nutra centrical therapy in mitochondrial cytoplasm. Advanced Drug Delivery Rev. 2008;60(13):1561-671.

Agarwal A, Said TM, Bedaiwy MA, Banerjeas J, Alvarez JG. Oxidative stress in an assisted reproductive technique setting. Fertil Steril. 2006;86(3):503-12.

Al- Kateen MA, Ibrahim MA, Al- Jammal MHH, Shareef YS, Suleiman MA. Serum antioxidant vitamins changes in women with polycystic ovarian syndrome. J Bahrain Med Sci. 2010;22:68-71.

Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003. Consensus on diagnostic criteria and long-term health risk related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41-7.

Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70(1):158-69.

Marklund SL. Expression of extracellular superoxide dismutase by human cell lines. Biochem J. 1980;266:213-9.

Niehans H, Samuel E. A comparative evaluation of TBARS method for the determination of MDA in biological materials J Rad Biol Med. 1968:15:353-63.

Johansson B, Borg O. The interstitium of human arterial containing catalase. J Physiol. 1998;552(2):335-44.

Hashim SA, Schuttinger GR. Rapid determination of tocopherol in macro- and micro-quantities of plasma. Results obtained in various nutrition and metabolic studies. Ann J Nutr. 1966;19(2):132.

Natelson S. Determination of ascorbic acid using 2, 4-dinitrophenyl hydrazine; technique of clinical chemistry. 3rd edition, Charles Thomas spring field USA; 1991:165-166.

Rutkowski M, Grzegorezyk K, Gendek E, Kedziora J. Laboratory conversional modification of Bassey method of vitamin A determination in blood plasma. J Physiol Pharm. 2006;57(2):221.

Fick KR, Mc Dowell LR, Miles PH, Wilkinson NS, Funk JD, Conrad JH. Method of mineral analysis for plants and animal tissues, 2nd edition. Department of Animal Science, University of Florida, Gainesville; 1979:72-79.

Panti AA, Sununu YT. The profile of infertility in a teaching hospital in North West Nigeria. Sahel Med J. 2014;17(1):7-11.

Agarwal A, Allamenemi SS. Role of radicals in female reproduction. Reprod Biomed Online. 2004;9:339-47.

Deepika MLN, Malini S, Maruthi G, Ramchander V, Ranjith K, Latha KP, et al. Analysis of oxidative stress status through MN test and serum MDA levels in PCOS women. Pak J Biol Sci. 2014;17(4):574-7.

Zhang D, LUO WY, Liao H, Wang CF, Sun F. The effects of oxidative stress to PCOS. Scihuan Da Xua Bao Yi Xua Ban. 2008; 39(3):3333-40.

Panti AA, Ateeque UB, Rabiu UA, Saidu Y, Bilbis LS, Shehu CE, et al. Evaluation of oxidative stress, antioxidants, gonadotropins and prolactin in infertile women. Int J Gynaecol Obstet. 2015;131(5):E314-607.

Majid KH, Hamza JM, Basima S, Al- Ghazah, Thamar MAH. Oxidative stress in primary infertility of women. Global J Med Res Sys. 2013;13(2):1-8.

Michiel C, Raes M, Toussant O, Ramade J. Importance of Se-gluthathione peroxidase, catalase, and cu/zn-sod for cell survival against oxidative stress, free radicals. Biol Med. 1994;17:235-48.

Howard JVC, Davies S, Hunnisset A. Red cell magnesium and glutathione peroxidase in infertile women: effects of oral supplementation with magnesium and selenium. Magnes Res. 1994;7(1):49-57.

Badawy A, EI Nashar BA, Totongy ELM. Clomiphene citrate plus N- acetyl cysteine versus clomiphene citrate for augmentation ovulation in the management of unexplained infertility; a randomized double-blind controlled trial. Fertil Steril. 2006;86(3):647-50.

Ozkaya MO, Mustafa N. Multivitamins and mineral supplementation modulates oxidative stress and antioxidant vitamins levels in serum and follicular fluid of women undergoing in vitro fertilization. Fertile Steril. 2010;94:2465-6.