Effect of omega-3 fatty acids supplementation on testosterone levels in women with polycystic ovary syndrome: Meta-analysis of randomized controlled trials
Background: Scientific literature has shown evidence that omega-3 polyunsaturated fatty acids (PUFA) have anti-androgenic action, and for this reason could be useful as an adjuvant in hyperandrogenism conditions including polycystic ovarian syndrome (PCOS). However, the possible effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on testosterone concentration still remains undetermined. Therefore, we performed a meta-analysis to investigate effects of EPA/DHA supplements on testosterone hormone in PCOS women.
Methods: Randomized controlled trials (RCTs) published until end May 2015 were searched through a comprehensive search of the PubMed and Scopus electronic databases. Included RCTs evaluated omega-3 fatty acids supplements compared with control in patients with PCOS and reported circulatory androgens. The meta-analysis quality assessment was conducted by the Jadad scoring criteria.
Results: Four RCTs were analyzed in this meta-analysis. The dose range for EPA and DHA was 0.9-3.6. Follow-up ranged from 6 to 8 weeks. Meta-analysis on testosterone levels revealed a significant lowering effect (weighted mean difference - 0.264; 95% confidence interval = −0.39, 0.14; p < 0.001) of omega-3 fatty acids for PCOS subjects.
Conclusion: The results of our study revealed benefits on total testosterone with the use of omega-3 PUFA supplements on PCOS patients. Further, high-quality RCTs are required to definitively draw a causal interpretation of our finding.
Salehi M, Bravo-Vera R, Sheikh A, Gouller A,Poretsky L. Pathogenesis of polycystic ovary syndrome: what is the role of obesity? Metabolism. 2004; 53(3): 358-76.
Sirmans SM, Parish RC, Blake S, Wang X.Epidemiology and comorbidities of polycystic ovary syndrome in an indigent population. J Investig Med. 2014; 62(6): 868-74.
Ehrmann DA. Polycystic ovary syndrome. NEngl J Med. 2005; 352(12): 1223-36.
Dunaif A, Graf M, Mandeli J, Laumas V, Dobrjansky A. Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia. J Clin Endocrinol Metab. 1987;65(3): 499-507.
Jakubowicz DJ, Nestler JE. 17a- Hydroxyprogesterone responses to leuprolide and serum androgens in obese women with and without polycystic ovary syndrome after dietary weight loss. Journal of Clinical Endocrinology and Metabolism. 1997; 82(2): 556-60.
Pehlivanov B, Orbetzova M. Characteristics of different phenotypes of polycystic ovary syndrome in a Bulgarian population. Gynecol Endocrinol. 2007; 23(10): 604-9.
Whitaker KN. Polycystic ovary syndrome: an overview. J Pharm Pract. 2011; 24(1): 94-101.
Liepa GU, Sengupta A, Karsies D. Polycystic ovary syndrome (PCOS) and other androgen excess-related conditions: can changes in dietary intake make a difference? Nutr Clin Pract. 2008;23(1): 63-71.
Phelan N, O'Connor A, Kyaw TT, Correia N, Boran G, Roche HM, et al. Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial. Am J Clin Nutr. 2011; 93(3): 652-62.
Deckelbaum RJ, Worgall TS, Seo T. n-3 fatty acids and gene expression. Am J Clin Nutr. 2006;83(6 Suppl): 1520S-5S.
Mohammadi E, Rafraf M, Farzadi L, Asghari- Jafarabadi M, Sabour S. Effects of omega-3 fatty acids supplementation on serum adiponectin levels and some metabolic risk factors in women with polycystic ovary syndrome. Asia Pac J Clin Nutr. 2012; 21(4): 511-8.
Cussons AJ, Watts GF, Mori TA, Stuckey BG.Omega-3 fatty acid supplementation decreases liver fat content in polycystic ovary syndrome: a randomized controlled trial employing proton magnetic resonance spectroscopy. J Clin Endocrinol Metab. 2009; 94(10): 3842-8.
Oner G, Muderris II. Efficacy of omega-3 in the treatment of polycystic ovary syndrome. J Obstet Gynaecol. 2013; 33(3): 289-91.
Kobayashi N, Barnard RJ, Henning SM, Elashoff D, Reddy ST, Cohen P, et al. Effect of altering dietary
?-6/?-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E2. Clin Cancer Res. 2006; 12: 4662.
McEntee MF, Ziegler C, Reel D, Tomer K, Shoieb A, Ray M, et al. Dietary n-3 polyunsaturated fatty acids enhance hormone ablation therapy in androgen-dependent prostate cancer. Am J Pathol. 2008; 173(1): 229-41.
Ouladsahebmadarek E, Khaki A, Khanahmadi S, Ahmadi AH, Paknejad P, Ayubi MR. Hormonal and metabolic effects of polyunsaturated fatty acid (omega-3) on polycystic ovary syndrome induced rats under diet. Iran J Basic Med Sci. 2014; 17(2): 123-7.
Vargas ML, Almario RU, Buchan W, Kim K, Karakas SE. Metabolic and endocrine effects of long-chain versus essential omega-3 polyunsaturated fatty acids in polycystic ovary syndrome. Metabolism. 2011; 60(12): 1711-8.
Picot J, Hartwell D, Harris P, Mendes D, Clegg A, Takeda A. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist; 2012. Available from: URL: http://www.ncbi.nlm.nih.gov/books/NBK98563/
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1): 1-12.
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.
Nadjarzadeh A, Dehghani FR, Vaziri N, Daneshbodi H, Lotfi MH, Mozaffari-Khosravi H. The effect of omega-3 supplementation on androgen profile and menstrual status in women with polycystic ovary syndrome: A randomized clinical trial. Iran J Reprod Med. 2013; 11(8):665-72.
Lennon-Edwards S, Schellhardt TA, Kuczmarski JM. Antioxidant defense is increased in aged hearts following omega-3 supplementation in the absence of changes in inflammation. Physiol Res.2015; 64(3): 433-8.
Maksymchuk OV. [The influence of omega-3 polyunsaturated fatty acids on the expression of enzymes of the prooxidant and antioxidant systems in the rat liver]. Fiziol Zh. 2014; 60(3):32-7.
Miles EA, Calder PC. Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis. Br J Nutr. 2012; 107(Suppl 2): S171-S184.
Mohammadi E, Rafraf M. Benefits of omega-3 fatty acids supplementation on serum paraoxonase 1 activity and lipids ratios in polycystic ovary syndrome. Health Promot Perspect. 2012; 2(2): 197-204.
Sekhon LH, Gupta S, Kim Y, Agarwal A. Female infertility and antioxidants. Current Women's Health Reviews. 2010; 6(2): 84-95.
Ruder EH, Hartman TJ, Blumberg J, Goldman MB. Oxidative stress and antioxidants: exposure and impact on female fertility. Hum Reprod Update. 2008; 14(4): 345-57.