Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2010;16(4):347–63.
Zawadzki J, Dunaif A. Current issues in endocrinology and metabolism: Polycystic ovary syndrome. Blackwell Scientific Publications Cambridge, MA:; 1992.
Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19–25.
Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. J Clin Endocrinol Metab. 2006;91(11):4237–45.
Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev. 2012;33(6):981–1030.
Dunaif A, Segal KR, Shelley DR, Green G, Dobrjansky A, Licholai T. Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes. 1992;41(10):1257–66.
LeRoith D, Werner H, Beitner-Johnson D, Roberts CT Jr. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev. 1995;16(2):143–63.
Marshall JC, Dunaif A. Should all women with PCOS be treated for insulin resistance? Fertil Steril. 2012;97(1):18–22.
Stepto NK, Cassar S, Joham AE, Hutchison SK, Harrison CL, Goldstein RF, et al. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp. Hum Reprod. 2013;28(3):777–84.
Alebic MS, Bulum T, Stojanovic N, Duvnjak L. Definition of insulin resistance using the homeostasis model assessment (HOMA-IR) in IVF patients diagnosed with polycystic ovary syndrome (PCOS) according to the Rotterdam criteria. Endocrine. 2014;47(2):625–30.
Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(12):4565–92.
Velazquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism. 1994;43(5):647–54.
Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med. 1996;335(9):617–23.
Morley LC, Tang T, Yasmin E, Norman RJ, Balen AH. 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.
Schweighofer N, Lerchbaum E, Trummer O, Schwetz V, Pieber T, Obermayer-Pietsch B. Metformin resistance alleles in polycystic ovary syndrome: pattern and association with glucose metabolism. Pharmacogenomics. 2014;15(3):305–17.
Ladson G, Dodson WC, Sweet SD, Archibong AE, Kunselman AR, Demers LM, et al. The effects of metformin with lifestyle therapy in polycystic ovary syndrome: a randomized double-blind study. Fertil Steril. 2011;95(3):1059–66 e1–7.
Onalan G, Goktolga U, Ceyhan T, Bagis T, Onalan R, Pabuccu R. Predictive value of glucose-insulin ratio in PCOS and profile of women who will benefit from metformin therapy: obese, lean, hyper or normoinsulinemic? Eur J Obstet Gynecol Reprod Biol. 2005;123(2):204–11.
Moghetti P, Castello R, Negri C, Tosi F, Perrone F, Caputo M, 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 Metab. 2000;85(1):139–46.
McCulloch WS, Pitts W. A logical calculus of the ideas immanent in nervous activity. 1943. Bull Math Biol. 1990;52(1–2):99–115 discussion 73-97.
Eller-Vainicher C, Zhukouskaya VV, Tolkachev YV, Koritko SS, Cairoli E, Grossi E, et al. Low bone mineral density and its predictors in type 1 diabetic patients evaluated by the classic statistics and artificial neural network analysis. Diabetes Care. 2011;34(10):2186–91.
Buscema M, Grossi E, Snowdon D, Antuono P. Auto-contractive maps: an artificial adaptive system for data mining. An application to Alzheimer disease. Curr Alzheimer Res. 2008;5(5):481–98.
Buscema M, Sacco PL. Auto-contractive maps, the H function, and the maximally regular graph (MRG): a new methodology for data mining. In: Capecchi V, Buscema M, Contucci P, D’Amore B, editors. Applications of mathematics in models, artificial neural networks and arts: mathematics and society. Dordrecht: Springer Netherlands; 2010. p. 227–75.
Ly LP, Handelsman DJ. Empirical estimation of free testosterone from testosterone and sex hormone-binding globulin immunoassays. Eur J Endocrinol. 2005;152(3):471–8.
Zhou Z, Ni R, Hong Y, Li Y, Wang Y, Zhao X, et al. Defining hyperandrogenaemia according to the free androgen index in Chinese women: a cross-sectional study. Clin Endocrinol. 2012;77(3):446–52.
Hacivelioglu S, Gungor AN, Gencer M, Uysal A, Hizli D, Koc E, et al. Acne severity and the global acne grading system in polycystic ovary syndrome. Int J Gynaecol Obstet. 2013;123(1):33–6.
Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. 1961;21:1440–7.
Escobar-Morreale HF, Carmina E, Dewailly D, Gambineri A, Kelestimur F, Moghetti P, et al. Epidemiology, diagnosis and management of hirsutism: a consensus statement by the androgen excess and polycystic ovary syndrome society. Hum Reprod Update. 2012;18(2):146–70.
Ludwig E. Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. Br J Dermatol. 1977;97(3):247–54.
Coelho Neto MA, Ludwin A, Borrell A, Benacerraf B, Dewailly D, da Silva CF, et al. Counting ovarian antral follicles by ultrasound: a practical guide. Ultrasound Obstet Gynecol. 2018;51(1):10–20.
Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018;110(3):364–79.
Heart N, Lung, Institute B, Diabetes NIo, Digestive, Diseases K. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report: National Heart, Lung, and Blood Institute; 1998.
Sebo P, Herrmann FR, Haller DM. Accuracy of anthropometric measurements by general practitioners in overweight and obese patients. BMC Obes. 2017;4:23.
Kuczmarski RJ, Carroll MD, Flegal KM, Troiano RP. Varying body mass index cutoff points to describe overweight prevalence among US adults: NHANES III (1988 to 1994). Obes Res. 1997;5(6):542–8.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.
Buscema M. Genetic doping algorithm (GenD): theory and applications. Expert Syst. 2004;21(2):63–79.
Buscema M, Breda M, Lodwick W. Training with input selection and testing (TWIST) algorithm: a significant advance in pattern recognition performance of machine learning. J Intell Learn Syst Appl. 2013;5:29–38.
Buscema M, Grossi E. The semantic connectivity map: an adapting self-organising knowledge discovery method in data bases. Experience in gastro-oesophageal reflux disease. Int J Data Min Bioinform. 2008;2(4):362–404.
Fredman ML, Willard DE. Trans-dichotomous algorithms for minimum spanning trees and shortest paths. J Comput Syst Sci. 1994;48(3):533–51.
Li Y, Tan J, Wang Q, Duan C, Hu Y, Huang W. Comparing the individual effects of metformin and rosiglitazone and their combination in obese women with polycystic ovary syndrome: a randomized controlled trial. Fertil Steril. 2020;113(1):197–204.
Paul C, Laganà AS, Maniglio P, Triolo O, Brady DM. Inositol’s and other nutraceuticals’ synergistic actions counteract insulin resistance in polycystic ovarian syndrome and metabolic syndrome: state-of-the-art and future perspectives. Gynecol Endocrinol. 2016;32(6):431–8.
Pau CT, Keefe C, Duran J, Welt CK. Metformin improves glucose effectiveness, not insulin sensitivity: predicting treatment response in women with polycystic ovary syndrome in an open-label, interventional study. J Clin Endocrinol Metab. 2014;99(5):1870–8.
Kurzthaler D, Hadziomerovic-Pekic D, Wildt L, Seeber BE. Metformin induces a prompt decrease in LH-stimulated testosterone response in women with PCOS independent of its insulin-sensitizing effects. Reprod Biol Endocrinol. 2014;12:98.
Hirsch A, Hahn D, Kempná P, Hofer G, Nuoffer JM, Mullis PE, et al. Metformin inhibits human androgen production by regulating steroidogenic enzymes HSD3B2 and CYP17A1 and complex I activity of the respiratory chain. Endocrinology. 2012;153(9):4354–66.
Mansfield R, Galea R, Brincat M, Hole D, Mason H. Metformin has direct effects on human ovarian steroidogenesis. Fertil Steril. 2003;79(4):956–62.
Nieuwenhuis-Ruifrok AE, Kuchenbecker WK, Hoek A, Middleton P, Norman RJ. Insulin sensitizing drugs for weight loss in women of reproductive age who are overweight or obese: systematic review and meta-analysis. Hum Reprod Update. 2009;15(1):57–68.
Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev. 2012;5:Cd003053.
Moghetti P, Tosi F, Bonin C, Di Sarra D, Fiers T, Kaufman JM, et al. Divergences in insulin resistance between the different phenotypes of the polycystic ovary syndrome. J Clin Endocrinol Metab. 2013;98(4):E628–37.
Díaz M, López-Bermejo A, Sánchez-Infantes D, Bassols J, de Zegher F, Ibáñez L. Responsiveness to metformin in girls with androgen excess: collective influence of genetic polymorphisms. Fertil Steril. 2011;96(1):208–13 e2.
Pau CT, Cheang KI, Modi BP, Kasippillai T, Keefe CC, Shulleeta M, et al. The role of variants regulating metformin transport and action in women with polycystic ovary syndrome. Pharmacogenomics. 2016;17(16):1765–73.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.