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Horm Metab Res 2016; 48(05): 281-289
DOI: 10.1055/s-0042-105288
Review
© Georg Thieme Verlag KG Stuttgart · New York

The Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Androgen Status in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Clinical Trials

M. Hajishafiee
1   Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2   Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
,
G. Askari
1   Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2   Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
,
B. Iranj
1   Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
,
R. Ghiasvand
1   Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2   Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
,
N. Bellissimo
3   School of Nutrition, Ryerson University, Victoria Street, Toronto, Ontario, Canada
,
J. Totosy de Zepetnek
3   School of Nutrition, Ryerson University, Victoria Street, Toronto, Ontario, Canada
,
A. Salehi-Abargouei
4   Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
5   Department of Nutrition, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
› Author Affiliations
Further Information

Publication History

received 15 January 2016

accepted 10 March 2016

Publication Date:
14 April 2016 (online)

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Abstract

The anti-androgenic role of n-3 polyunsaturated fatty acids (PUFAs) among patients with polycystic ovary syndrome (PCOS) has recently been proposed. The present study aimed to systematically review clinical trials assessing the effects of n-3 PUFAs consumption on androgen status among adult females with PCOS. PubMed, ISI Web of Science, Google Scholar, and Scopus were searched up to December 2015. Clinical investigations assessing the effect of n-3 PUFAs on adult females with PCOS were included. Mean±standard deviation of change in serum total testosterone, sex hormone binding globulin (SHBG), and dehydroepiandrostrone sulfate (DHEAS) were extracted. Eight clinical trials with 298 participants were eligible. Meta-analysis showed that n-3 PUFAs supplementation marginally reduces total testosterone (mean difference [MD]: − 0.19 nmol/l; 95% CI: − 0.39 to 0.00; p=0.054), but not SHBG (MD: 1.75 nmol/l; 95% CI: −0.51 to 4.01; p=0.129) or serum DHEAS levels (Hedes’ g: −0.11 nmol/l; 95% CI: −0.29 to 0.06; p=0.19) among adult females with PCOS. Subgroup analyses showed that only before-after studies (Hedges’ g: 0.15; 95% CI: −0.27 to −0.04; p=0.01) and long-term interventions (>6 weeks) (Hedges’ g: −0.17; 95% CI, −0.29 to −0.05; p=0.004) had reducing effects on serum DHEAS levels. The majority of long-term trials utilized a single group design (no control group). It does not appear that n-3 PUFAs supplementation significantly affects the androgenic profile of females with PCOS; however, some before-after and long-term intervention studies show reduced DHEAS levels. Future studies incorporating double blinded placebo controlled clinical trials with long follow-up periods are warranted.

Key words

n-3 polyunsaturated fatty acids - polycystic ovary syndrome - systematic review - meta-analysis
 

  • References

  • 1 Lorenz LB, Wild RA. Polycystic ovarian syndrome: an evidence-based approach to evaluation and management of diabetes and cardiovascular risks for today’s clinician. Clin Obstetr Gynecol 2007; 50: 226-243
    CrossrefPubMedGoogle Scholar
  • 2 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: 63-71
    CrossrefPubMedGoogle Scholar
  • 3 McGowan MP. Polycystic ovary syndrome: a common endocrine disorder and risk factor for vascular disease. Current treatment options in cardiovascular medicine 2011; 13: 289-301
    CrossrefPubMedGoogle Scholar
  • 4 O’Connor A, Gibney J, Roche HM. Metabolic and hormonal aspects of polycystic ovary syndrome: the impact of diet. Proc Nutr Soc 2010; 69: 628-635
    CrossrefPubMedGoogle Scholar
  • 5 Sartor BM, Dickey RP. Polycystic ovarian syndrome and the metabolic syndrome. The Am J Med Sci 2005; 330: 336-342
    PubMedGoogle Scholar
  • 6 Tomlinson J, Millward A, Stenhouse E, Pinkney J. Type 2 diabetes and cardiovascular disease in polycystic ovary syndrome: what are the risks and can they be reduced?. Diabet Med 2010; 27: 498-515
    CrossrefPubMedGoogle Scholar
  • 7 Wild RA. Dyslipidemia in PCOS. Steroids 2012; 77: 295-299
    CrossrefPubMedGoogle Scholar
  • 8 Hart R, Norman R. Polycystic ovarian syndrome–prognosis and outcomes. Best Pract Res Clin Obstet Gynaecol 2006; 20: 751-778
    CrossrefPubMedGoogle Scholar
  • 9 Moran LJ, Lombard CB, Lim S, Noakes M, Teede HJ. Polycystic ovary syndrome and weight management. Womens Health (Lond Engl) 2010; 6: 271-283
    PubMedGoogle Scholar
  • 10 Jeanes YM, Barr S, Smith K, Hart KH. Dietary management of women with polycystic ovary syndrome in the United Kingdom: the role of dietitians. J Hum Nutr Diet 2009; 22: 551-558
    CrossrefPubMedGoogle Scholar
  • 11 Phelan N, O’Connor A, Kyaw Tun T, Correia N, Boran G, Roche HM, Gibney J. 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: 652-662
    CrossrefPubMedGoogle Scholar
  • 12 Barr S, Hart K, Reeves S, Sharp K, Jeanes YM. Habitual dietary intake, eating pattern and physical activity of women with polycystic ovary syndrome. Eur J Clin Nutr 2011; 65: 1126-1132
    CrossrefPubMedGoogle Scholar
  • 13 Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 2011; 7: 219-231
    CrossrefPubMedGoogle Scholar
  • 14 Asemi Z, Esmaillzadeh A. DASH diet, insulin resistance, and serum hs-CRP in polycystic ovary syndrome: a randomized controlled clinical trial. Horm Metab Res 2015; 47: 232-238
    Google Scholar
  • 15 Marsh K, Brand-Miller J. The optimal diet for women with polycystic ovary syndrome?. Br J Nutr 2005; 94: 154-165
    CrossrefPubMedGoogle Scholar
  • 16 Farshchi H, Rane A, Love A, Kennedy RL. Diet and nutrition in polycystic ovary syndrome (PCOS): pointers for nutritional management. J Obstet Gynaecol 2007; 27: 762-773
    CrossrefPubMedGoogle Scholar
  • 17 Moran LJ, Ko H, Misso M, Marsh K, Noakes M, Talbot M, Frearson M, Thondan M, Stepto N, Teede HJ. Dietary composition in the treatment of polycystic ovary syndrome: a systematic review to inform evidence-based guidelines. J Acad Nutr Diet 2013; 113: 520-545
    CrossrefPubMedGoogle Scholar
  • 18 Sonnenstuhl P. More on PCOS. Adv Nurse Pract 2001; 9: 18
    PubMedGoogle Scholar
  • 19 Kalgaonkar S, Almario RU, Gurusinghe D, Garamendi EM, Buchan W, Kim K, Karakas SE. Differential effects of walnuts vs almonds on improving metabolic and endocrine parameters in PCOS. Eur J Clin Nutr 2011; 65: 386-393
    CrossrefPubMedGoogle Scholar
  • 20 Kasim-Karakas SE, Almario RU, Gregory L, Wong R, Todd H, Lasley BL. Metabolic and endocrine effects of a polyunsaturated fatty acid-rich diet in polycystic ovary syndrome. J Clin Endocrinol Metab 2004; 89: 615-620
    CrossrefPubMedGoogle Scholar
  • 21 Poudyal H, Panchal SK, Diwan V, Brown L. Omega-3 fatty acids and metabolic syndrome: effects and emerging mechanisms of action. Progress in lipid research 2011; 50: 372-387
    CrossrefPubMedGoogle Scholar
  • 22 Risérus U. Fatty acids and insulin sensitivity. Curr Opin Clin Nutr Metab Care 2008; 11: 100
    CrossrefPubMedGoogle Scholar
  • 23 Saldeen P, Saldeen T. Women and omega-3 fatty acids. Obstetr Gynecol Survey 2004; 59: 722-730
    PubMedGoogle Scholar
  • 24 Cussons AJ, Watts GF, Mori TA, Stuckey BGA. 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: 3842-3848
    CrossrefPubMedGoogle Scholar
  • 25 Alvheim AR, Malde MK, Osei-Hyiaman D, Hong Lin Y, Pawlosky RJ, Madsen L, Kristiansen K, Frøyland L, Hibbeln JR. Dietary Linoleic Acid Elevates Endogenous 2-AG and Anandamide and Induces Obesity. Obesity (Silver Spring) 2012; 20: 1984-1994
    CrossrefPubMedGoogle Scholar
  • 26 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: 1711-1718
    CrossrefPubMedGoogle Scholar
  • 27 Shapiro H, Tehilla M, Attal-Singer J, Bruck R, Luzzatti R, Singer P. The therapeutic potential of long-chain omega-3 fatty acids in nonalcoholic fatty liver disease. Clin Nutr 2011; 30: 6-19
    CrossrefPubMedGoogle Scholar
  • 28 Kuzmanov A, Broughton KS. Role of marine omega-3 fatty acids in PCOS cancer risk. 13th World Congress on Controversies in Obsterics, Gynecology, and Infertility (COGI) 2010; 349-354
    PubMedGoogle Scholar
  • 29 Oner G, Muderris II. Efficacy of omega-3 in the treatment of polycystic ovary syndrome. J Obstet Gynaecol 2013; 33: 289-291
    CrossrefPubMedGoogle Scholar
  • 30 Phelan N, Gibney J. What is the potential role of polyunsaturated fatty acids in controlling dyslipidemia in patients with polycystic ovary syndrome?. Clin Lipidol 2012; 7: 5-8
    CrossrefPubMedGoogle Scholar
  • 31 Moher D, Cook DJ, Jadad AR, Tugwell P, Moher M, Jones A, Pham B, Klassen TP. Assessing the quality of reports of randomised trials: implications for the conduct of meta-analyses. Health Technol Assess 1999; 3 (i–iv) 1-98
    PubMedGoogle Scholar
  • 32 Nadjarzadeh A, Dehghani Firouzabadi R, 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: 665-672
    PubMedGoogle Scholar
  • 33 Chalmers I, Hedges LV, Cooper H. A brief history of research synthesis. Eval Health Prof 2002; 25: 12-37
    CrossrefPubMedGoogle Scholar
  • 34 Hedges LV, Pigott TD. The power of statistical tests for moderators in meta-analysis. Psychol Meth 2004; 9: 426-445
    CrossrefPubMedGoogle Scholar
  • 35 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188
    CrossrefPubMedGoogle Scholar
  • 36 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558
    CrossrefPubMedGoogle Scholar
  • 37 Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634
    CrossrefPubMedGoogle Scholar
  • 38 Sterne JA, Egger M, Smith GD. Systematic reviews in health care: Investigating and dealing with publication and other biases in meta-analysis. BMJ 2001; 323: 101-105
    CrossrefPubMedGoogle Scholar
  • 39 Mohammadi E, Rafraf M. Benefits of omega-3 fatty acids supplementation on serum paraoxonase 1 activity and lipids ratios in polycystic ovary syndrome People’s. Health Promot Perspect 2012; 2: 197-204
    PubMedGoogle Scholar
  • 40 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: 511-518
    PubMedGoogle Scholar
  • 41 Platt J, Kuzmanov A, Halliday T, Lindmier M, Peterson N, Broughton KS. Omega-3 fatty acid and vitamin D ingestion and leptin and adiponectin in PCOS. 13th World Congress on Controversies in Obsterics, Gynecology, and Infertility (COGI) 2010; 355-359
    PubMedGoogle Scholar
  • 42 Rafraf M, Mohammadi E, Asghari-Jafarabadi M, Farzadi L. Omega-3 fatty acids improve glucose metabolism without effects on obesity values and serum visfatin levels in women with polycystic ovary syndrome. J Am Coll Nutr 2012; 31: 361-368
    CrossrefPubMedGoogle Scholar
  • 43 Rafraf M, Mohammadi E, Farzadi L, Asghari-Jafarabadi M, Sabour S. Effects of ω-3 Fatty Acid Supplementation on Glycemic Status and High Sensitive C-Reactive Protein in Women with Polycystic Ovary Syndrome. J Ardabil Univ Med Sci 2012; 12: 373-383
    PubMedGoogle Scholar
  • 44 Kohama T, Kobayashi H, Inoue M. The effect of soybeans on the anovulatory cycle. J Med Food 2005; 8: 550-551
    CrossrefPubMedGoogle Scholar
  • 45 Yoon JW, Kim CH, Ahn JW, Kang HJ, Song HJ, Kang BM. Effect of Omega-3-polyunsaturated fatty acids and metfromin on ovarian morphology and Intraovarian blood flow in patients with polycystic ovary sandromne. Fertil Steril 2010; 94: S194-S194
    PubMedGoogle Scholar
  • 46 Dayspring TD. Understanding hypertriglyceridemia in women: clinical impact and management with prescription omega-3-acid ethyl esters. Int J Womens Health 2011; 3: 87-97
    PubMedGoogle Scholar
  • 47 Epstein FH, Moller DE, Flier JS. Insulin resistance—mechanisms, syndromes, and implications. N Eng J Med 1991; 325: 938-948
    CrossrefPubMedGoogle Scholar
  • 48 Franks S, Robinson S, Willis DS. Nutrition, insulin and polycystic ovary syndrome. Rev Reprod 1996; 1: 47-53
    CrossrefPubMedGoogle Scholar
  • 49 Kien CL. Dietary interventions for metabolic syndrome: role of modifying dietary fats. Curr Diabetes Rep 2009; 9: 43-50
    CrossrefPubMedGoogle Scholar
  • 50 Bruni V, Dei M, Pontello V, Vangelisti P. The management of polycystic ovary syndrome. Ann N Y Acad Sci 2003; 997: 307-321
    CrossrefPubMedGoogle Scholar
  • 51 Cussons AJ, Stuckey BG, Walsh JP, Burke V, Norman RJ. Polycystic ovarian syndrome. marked differences between endocrinologists and gynaecologists in diagnosis and management. Clin Endocrinol (Oxf) 2005; 62: 289-295
    CrossrefPubMedGoogle Scholar
  • 52 Franks S, Robinson S, Willis DS. Nutrition, insulin and polycystic ovary syndrome. Rev Reprod 1996; 1: 47-53
    CrossrefPubMedGoogle Scholar
  • 53 Goldenberg N, Glueck C. Medical therapy in women with polycystic ovarian syndrome before and during pregnancy and lactation. Minerva Ginecol 2008; 60: 63-75
    PubMedGoogle Scholar
  • 54 Gonzalez F. Inflammation in Polycystic Ovary Syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids 2012; 77: 300-305
    CrossrefPubMedGoogle Scholar
  • 55 Loria P, Lonardo A, Carulli L, Verrone A, Ricchi M, Lombardini S, Rudilosso A, Ballestri S, Carulli N. Review article: the metabolic syndrome and non-alcoholic fatty liver disease. Aliment Pharmacol Therap 2005; 22: 31-36
    PubMedGoogle Scholar
  • 56 Sathyapalan T, Atkin SL. Recent advances in cardiovascular aspects of polycystic ovary syndrome. Eur J Endocrinol 2012; 166: 575-583
    CrossrefPubMedGoogle Scholar
  • 57 Azadbakht L, Rouhani MH, Surkan PJ. Omega-3 fatty acids, insulin resistance and type 2 diabetes. J Res Med Sci 2011; 16: 1259-1260
    PubMedGoogle Scholar
  • 58 Brostow DP, Odegaard AO, Koh WP, Duval S, Gross MD, Yuan JM, Pereira MA. Omega-3 fatty acids and incident type 2 diabetes: the Singapore Chinese Health Study. Am J Clin Nutr 2011; 94: 520-526
    CrossrefPubMedGoogle Scholar
  • 59 Djousse L, Gaziano JM, Buring JE, Lee IM. Dietary omega-3 fatty acids and fish consumption and risk of type 2 diabetes. Am J Clin Nutr 2011; 93: 143-150
    CrossrefPubMedGoogle Scholar
  • 60 Kaushik M, Mozaffarian D, Spiegelman D, Manson JE, Willett WC, Hu FB. Long-chain omega-3 fatty acids, fish intake, and the risk of type 2 diabetes mellitus. Am J Clin Nutr 2009; 90: 613-620
    CrossrefPubMedGoogle Scholar
  • 61 Horikawa C, Yoshimura Y, Kamada C, Tanaka S, Tanaka S, Hanyu O, Araki A, Ito H, Tanaka A, Ohashi Y, Akanuma Y, Yamada N, Sone H. Dietary intake in Japanese patients with type 2 diabetes: Analysis from Japan Diabetes Complications Study. J Diabetes Investig 2014; 5: 176-187
    CrossrefPubMedGoogle Scholar
  • 62 Kondo K, Morino K, Nishio Y, Kondo M, Nakao K, Nakagawa F, Ishikado A, Sekine O, Yoshizaki T, Kashiwagi A, Ugi S, Maegawa H. A fish-based diet intervention improves endothelial function in postmenopausal women with type 2 diabetes mellitus: A randomized crossover trial. Metabolism 2014; 63: 930-940
    CrossrefPubMedGoogle Scholar
  • 63 Muley A, Muley P, Shah M. ALA, Fatty Fish or Marine n-3 Fatty Acids for Preventing DM?: A Systematic Review and Meta-Analysis. Curr Diabetes Rev 2014; 10: 158-165
    CrossrefPubMedGoogle Scholar
  • 64 Stirban A, Nandrean S, Gotting C, Stratmann B, Tschoepe D. Effects of n-3 polyunsaturated fatty acids (PUFAs) on circulating adiponectin and leptin in subjects with type 2 diabetes mellitus. Horm Metab Res 2014; 46: 490-492
    Article in Thieme ConnectPubMedGoogle Scholar
  • 65 Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997; 18: 774-800
    CrossrefPubMedGoogle Scholar
  • 66 Martinez-Bermejo E, Luque-Ramirez M, Escobar-Morreale HF. Obesity and the polycystic ovary syndrome. Minerva Endocrinol 2007; 32: 129-140
    PubMedGoogle Scholar
  • 67 Moran LJ, Brinkworth G, Noakes M, Norman RJ. Effects of lifestyle modification in polycystic ovarian syndrome. Reprod Biomed Online 2006; 12: 569-578
    CrossrefPubMedGoogle Scholar
  • 68 Botwood N, Hamilton-Fairley D, Kiddy D, Robinson S, Franks S. Sex hormone-binding globulin and female reproductive function. J Steroid Biochem Mol Biol 1995; 53: 529-531
    CrossrefPubMedGoogle Scholar
  • 69 Bays HE, Tighe AP, Sadovsky R, Davidson MH. Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications. Expert Rev Cardiovascul Therap 2008; 6: 391-409
    PubMedGoogle Scholar
  • 70 Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC. Diagnosis and management of the metabolic syndrome an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 2005; 112: 2735-2752
    CrossrefPubMedGoogle Scholar
  • 71 Hauner H, Bender M, Haastert B, Hube F. Plasma concentrations of soluble TNF-alpha receptors in obese subjects. Int J Obes Relat Metab Disord 1998; 22: 1239-1243
    CrossrefPubMedGoogle Scholar
  • 72 Liu LS, Spelleken M, Rohrig K, Hauner H, Eckel J. Tumor necrosis factor-alpha acutely inhibits insulin signaling in human adipocytes: implication of the p80 tumor necrosis factor receptor. Diabetes 1998; 47: 515-522
    CrossrefPubMedGoogle Scholar
  • 73 Davis MB, Duvernoy CS. How to stay heart healthy in 2011: considerations for the primary prevention of cardiovascular disease in women. Womens Health (Lond Engl) 2011; 7: 433-451
    PubMedGoogle Scholar