292
Views
3
CrossRef citations to date
0
Altmetric
POLYCYSTIC OVARY SYNDROME

Metformin does not improve insulin sensitivity over hypocaloric diets in women with polycystic ovary syndrome: a systematic review of 12 studies

, , , ORCID Icon & ORCID Icon
Pages 968-976 | Received 01 Dec 2020, Accepted 01 Apr 2021, Published online: 26 Apr 2021

References

  • Franik S, Eltrop SM, Kremer JA, et al. Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2018;5(5):CD010287.
  • Meier RK. Polycystic Ovary Syndrome. Nurs Clin North Am. 2018;53(3):407–420.
  • Cree-Green M, Rahat H, Newcomer BR, et al. Insulin resistance, hyperinsulinemia, and mitochondria dysfunction in nonobese girls with polycystic ovarian syndrome. J Endocrine Soc. 2017;1(7):931–944.
  • Lizneva D, Suturina L, Walker W, et al. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril. 2016;106(1):6–15.
  • Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev. 2016;37(5):467–520.
  • Ovalle F, Azziz R. Insulin resistance, polycystic ovary syndrome, and type 2 diabetes mellitus. Fertil Steril. 2002;77(6):1095–1105.
  • Barber TM, Golding SJ, Alvey C, et al. Global adiposity rather than abnormal regional fat distribution characterizes women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2008;93(3):999–1004.
  • Huang ZH, Manickam B, Ryvkin V, et al. PCOS is associated with increased CD11c expression and crown-like structures in adipose tissue and increased central abdominal fat depots independent of obesity. J Clin Endocrinol Metab. 2013;98(1):E17–24.
  • Porchia LM, Hernandez-Garcia SC, Gonzalez-Mejia ME, et al. Diets with lower carbohydrate concentrations improve insulin sensitivity in women with polycystic ovary syndrome: a meta-analysis. Euro J Obstetr Gynecol Reproduct Biol. 2020;248:110–117.
  • Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2016;164(11):740–751.
  • Amiri M, Golsorkhtabaramiri M, Esmaeilzadeh S, et al. Effect of metformin and flutamide on anthropometric indices and laboratory tests in obese/overweight pcos women under hypocaloric diet. J Reproduc Infertility. 2014;15(4):205–213.
  • Esfahanian F, Zamani MM, Heshmat R, et al. Effect of metformin compared with hypocaloric diet on serum C-reactive protein level and insulin resistance in obese and overweight women with polycystic ovary syndrome. J Obstet Gynaecol Res. 2013;39(4):806–813.
  • Ladson G, Dodson WC, Sweet SD, et al. The effects of metformin with lifestyle therapy in polycystic ovary syndrome: a randomized double-blind study. Fertil Steril. 2011;95(3):1059–1066 e1-7.
  • Panidis D, Tziomalos K, Papadakis E, et al. The guidelines issued by the European Society for Human Reproduction and Embryology and the American Society for Reproductive Medicine regarding the induction of ovulation with metformin in patients with the polycystic ovary syndrome potentially require reconsideration. Hormones. 2013;12(2):192–200.
  • Helena T, Marie M, Michael C, et al. International evidence-based guideline for the assessment and management of polycystic ovary syndrome. 2018.
  • Moghetti P, Castello R, Negri C, et al. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metabol. 2000;85(1):139–146.
  • Morley LC, Tang T, Yasmin E, et al. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev. 2017;11(11):CD003053.
  • Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–605.
  • Miller JJ. The Inverse of the freeman – tukey double arcsine transformation. Am Statistician. 1978;32(4):138–138.
  • DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled Clinical Trials. 1986;7(3):177–188.
  • Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–1101.
  • Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–634.
  • Wetterslev J, Jakobsen JC, Gluud C. Trial Sequential Analysis in systematic reviews with meta-analysis. BMC Med Res Methodol. 2017;17(1):39.
  • Curi DD, Fonseca AM, Marcondes JA, et al. Metformin versus lifestyle changes in treating women with polycystic ovary syndrome. Gynecol Endocrinol. 2012;28(3):182–185.
  • Fux Otta C, Wior M, Iraci GS, et al. Clinical, metabolic, and endocrine parameters in response to metformin and lifestyle intervention in women with polycystic ovary syndrome: a randomized, double-blind, and placebo control trial. Gynecol Endocrinol. 2010;26(3):173–178.
  • Gambineri A, Patton L, Vaccina A, et al. Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-month, placebo-controlled study. J Clinical Endocrinol Metabol. 2006;91(10):3970–3980.
  • Ladson G, Dodson WC, Sweet SD, et al. Effects of metformin in adolescents with polycystic ovary syndrome undertaking lifestyle therapy: a pilot randomized double-blind study. Fertil Steril. 2011;95(8):2595–2598 e1-6.
  • Pagotto U, Gambineri A, Vicennati V, et al. Plasma ghrelin, obesity, and the polycystic ovary syndrome: correlation with insulin resistance and androgen levels. J Clin Endocrinol Metabol. 2002;87(12):5625–5629.
  • Pasquali R, Gambineri A, Biscotti D, et al. Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab. 2000;85(8):2767–2774.
  • Qublan HS, Yannakoula EK, Al-Qudah MA, et al. Dietary intervention versus metformin to improve the reproductive outcome in women with polycystic ovary syndrome. Saudi Med J. 2007;28(11):1694–1699.
  • Tang T, Glanville J, Hayden CJ, et al. Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome. A randomized, placebo-controlled, double-blind multicentre study. Human Reproduc. 2006;21(1):80–89.
  • Carmina E, Campagna AM, Lobo RA. A 20-year follow-up of young women with polycystic ovary syndrome. Obstetr Gynecol. 2012;119(2 Pt 1):263–269.
  • Diamanti-Kandarakis E, Spritzer PM, Sir-Petermann T, et al. Insulin resistance and polycystic ovary syndrome through life. Curr Pharm Des. 2012;18(34):5569–5576.
  • Dunaif A, Graf M, Mandeli J, et al. Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia. J Clin Endocrinol Metab. 1987;65(3):499–507.
  • Robinson S, Kiddy D, Gelding SV, et al. The relationship of insulin insensitivity to menstrual pattern in women with hyperandrogenism and polycystic ovaries. Clin Endocrinol. 1993;39(3):351–355.
  • Dunaif A, Graf M. Insulin administration alters gonadal steroid metabolism independent of changes in gonadotropin secretion in insulin-resistant women with the polycystic ovary syndrome. J Clin Invest. 1989;83(1):23–29.
  • Franks S, Gilling-Smith C, Watson H, et al. Insulin action in the normal and polycystic ovary. Endocrinol Metab Clin North Am. 1999;28(2):361–378.
  • Kravariti M, Naka KK, Kalantaridou SN, et al. Predictors of endothelial dysfunction in young women with polycystic ovary syndrome. J Clin Endocrinol Metabol. 2005;90(9):5088–5095.
  • Paradisi G, Steinberg HO, Hempfling A, et al. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation. 2001;103(10):1410–1415.
  • Ciaraldi TP, el-Roeiy A, Madar Z, et al. Cellular mechanisms of insulin resistance in polycystic ovarian syndrome. J Clin Endocrinol Metab. 1992;75(2):577–583.
  • Dunaif A, Xia J, Book CB, et al. Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome. J Clin Invest. 1995;96(2):801–810.
  • Venkatesan AM, Dunaif A, Corbould A. Insulin resistance in polycystic ovary syndrome: progress and paradoxes. Recent Prog Horm Res. 2001;56:295–308.
  • Li W, Ma L, Li Q. Insulin resistance but not impaired β-cell function: a key feature in Chinese normal-weight PCOS women with normal glucose regulation. Gynecol Endocrinol. 2012;28(8):598–601.
  • Hurliman A, Keller Brown J, Maille N, et al. Hyperandrogenism and Insulin Resistance, Not Changes in Body Weight, Mediate the Development of Endothelial Dysfunction in a Female Rat Model of Polycystic Ovary Syndrome (PCOS). Endocrinology. 2015;156(11):4071–4080.
  • Bridges HR, Jones AJ, Pollak MN, et al. Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria. Biochem J. 2014;462(3):475–487.
  • Lord JM, White SI, Bailey CJ, et al. Effect of metformin on insulin receptor binding and glycaemic control in type II diabetes. Br Med J. 1983;286(6368):830–831.
  • Fullerton MD, Galic S, Marcinko K, et al. Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nat Med. 2013;19(12):1649–1654.
  • Kim CH, Chon SJ, Lee SH. Effects of lifestyle modification in polycystic ovary syndrome compared to metformin only or metformin addition: a systematic review and meta-analysis. Sci Rep. 2020;10(1):7802.
  • Otto-Buczkowska E, Grzyb K, Jainta N. Polycystic ovary syndrome (PCOS) and the accompanying disorders of glucose homeostasis among girls at the time of puberty. Pediatr Endocrinol Diabetes Metab. 2018;24(1):40–44.
  • Johnston CS, Sears B, Perry M, et al. Use of novel high-protein functional food products as part of a calorie-restricted diet to reduce insulin resistance and increase lean body mass in adults: a randomized controlled trial. Nutrients. 2017;9(11):1182.
  • Yarar-Fisher C, Li J, McLain A, et al. Utilizing a low-carbohydrate/high-protein diet to improve metabolic health in individuals with spinal cord injury (DISH): study protocol for a randomized controlled trial. Trials. 2019;20(1):466.
  • Wang B, Smyl C, Chen CY, et al. Suppression of postprandial blood glucose fluctuations by a low-carbohydrate, high-protein, and high-omega-3 diet via inhibition of gluconeogenesis. IJMS. 2018;19(7):1823.
  • Jakubowicz D, Wainstein J, Landau Z, et al. High-energy breakfast based on whey protein reduces body weight, postprandial glycemia and HbA(1C) in Type 2 diabetes. J Nutr Biochem. 2017;49:1–7.
  • Samkani A, Skytte MJ, Kandel D, et al. A carbohydrate-reduced high-protein diet acutely decreases postprandial and diurnal glucose excursions in type 2 diabetes patients. Br J Nutr. 2018;119(8):910–917.
  • Moran LJ, Ko H, Misso M, et al. Dietary composition in the treatment of polycystic ovary syndrome: a systematic review to inform evidence-based guidelines. J Acad Nutr Diet. 2013;113(4):520–545.
  • Marsh KA, Steinbeck KS, Atkinson FS, et al. Effect of a low glycemic index compared with a conventional healthy diet on polycystic ovary syndrome. Am J Clin Nutr. 2010;92(1):83–92.
  • González F, Considine RV, Abdelhadi OA, et al. Oxidative stress in response to saturated fat ingestion is linked to insulin resistance and hyperandrogenism in polycystic ovary syndrome. J Clin Endocrinol Metab. 2019;104(11):5360–5371.
  • Yogalakshmi B, Bhuvaneswari S, Sreeja S, et al. Grape seed proanthocyanidins and metformin act by different mechanisms to promote insulin signaling in rats fed high calorie diet. J Cell Commun Signal. 2014;8(1):13–22.
  • Xu Y, Wu Y, Huang Q. Comparison of the effect between pioglitazone and metformin in treating patients with PCOS:a meta-analysis. Arch Gynecol Obstet. 2017;296(4):661–677.
  • Brettenthaler N, De Geyter C, Huber PR, et al. Effect of the insulin sensitizer pioglitazone on insulin resistance, hyperandrogenism, and ovulatory dysfunction in women with polycystic ovary syndrome. J Clin Endocrinol Metabol. 2004;89(8):3835–3840.
  • Aigner E, Bachofner N, Klein K, et al. Retinol-binding protein 4 in polycystic ovary syndrome-association with steroid hormones and response to pioglitazone treatment. J Clin Endocrinol Metab. 2009;94(4):1229–1235.
  • Nestler JE, Unfer V. Reflections on inositol(s) for PCOS therapy: steps toward success. Gynecol Endocrinol. 2015;31(7):501–505.
  • Unfer V, Nestler JE, Kamenov ZA, et al. Effects of inositol(s) in women with PCOS: a systematic review of randomized controlled trials. Int J Endocrinol. 2016;2016:1849162.
  • Romualdi D, Versace V, Lanzone A. What is new in the landscape of insulin-sensitizing agents for polycystic ovary syndrome treatment. Ther Adv Reprod Health. 2020;14:2633494120908709.
  • Genazzani AD, Shefer K, Della Casa D, et al. Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients. J Endocrinol Invest. 2018;41(5):583–590.
  • De Cicco S, Immediata V, Romualdi D, et al. Myoinositol combined with alpha-lipoic acid may improve the clinical and endocrine features of polycystic ovary syndrome through an insulin-independent action. Gynecol Endocrinol. 2017;33(9):698–701.
  • Cappelli V, Di SA, Musacchio MC, et al. Evaluation of a new association between insulin-sensitizers and α-lipoic acid in obese women affected by PCOS. Minerva Ginecol. 2013;65(4):425–433.
  • Kite C, Lahart IM, Afzal I, et al. Exercise, or exercise and diet for the management of polycystic ovary syndrome: a systematic review and meta-analysis. Syst Rev. 2019;8(1):51.
  • Dos Santos IK, Ashe MC, Cobucci RN, et al. The effect of exercise as an intervention for women with polycystic ovary syndrome: A systematic review and meta-analysis. Medicine. 2020;99(16):e19644.
  • Tiwari N, Pasrija S, Jain S. Randomised controlled trial to study the efficacy of exercise with and without metformin on women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2019;234:149–154.
  • Wang A, Mo T, Li Q, et al. The effectiveness of metformin, oral contraceptives, and lifestyle modification in improving the metabolism of overweight women with polycystic ovary syndrome: a network meta-analysis. Endocrine. 2019;64(2):220–232.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.