Current aspects of polycystic ovary syndrome I: definition, pathophysiology, clinical manifestations, diagnosis and complications

Open access

Abstract

Polycystic ovary syndrome (PCOS) is the most frequent endocrine disease among women with childbearing potential, the best-known cause of hirsutism, with a hypothesized prevalence of 8-22%. The first part of the paper discusses the conceptional evolution of the syndrome, from its description in 1935 by Stein and Leventhal till today. It describes the changes in the criteria systems, emphasizing that the Rotterdam criteria, proposed in 2003 by the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine, are still valid today. This system basically differs from earlier (1990) NIH-criteria in one aspect: it introduced two newer phenotypes, one without hyperandrogenism and the other with ovulatory cycles, so it distinguishes 4 phenotypes. The etiology and pathogenesis of PCOS is heterogeneous, multifactorial, poorly understood. We present the 3 leading hypotheses (1 - hypothalamo-hypophyseal disturbances, 2 – primary enzyme disorders in ovarian, or ovarian/adrenal steroidogenesis, resulting primarily in hyperactivity of 17alpha-hydroxylase/17,20-lyase, 3 – insulin resistance-hyperinsulinism and other metabolic dysfunctions). We emphasize the role of genetically determined hyperandrogenism, that of insulin resistance-hyperinsulinism and the importance of reinforcing each other. Subsequently, the aggravating aspects of the frequently associated metabolic syndrome are discussed, and then the effects of the mentioned pathological processes on the endocrine and other organ structures participating in the regulation of sexual functions. We stress the hypothetical role of perinatal and pubertal androgen exposition in the pathogenesis of PCOS. The mechanisms of anovulation and those of the endometrial lesions are discussed, too. The clinical manifestations, the paraclinical and laboratory examinations, the positive and differential diagnosis and the complications are also presented. We intend to deal with the therapeutic aspects of PCOS in an upcoming paper.

1. Kun IZ. Klinikai endocrinologia. Erdélyi Múzeum Egyesület, Kolozsvár; 2000. p. 421–30, 296–303.

2. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am. J. Obstet. Gynecol. 1935; 29:181–91.

3. Geisthövel F, Rabe T. The ESHRE/ASRM consensus on polycystic ovary syndrome (PCOS) – an extended critical analysis. Reprod. Biomed. Online. Elsevier; 2007;14:522–35.

4. Stracquadanio M, Ciotta L. Metabolic Aspects of PCOS. Cham: Springer International Publishing; 2015; 5-20

5. Cobin R, Futterweit W, Nestler J, Reaven G, Jellinger P, Handelsman Y, et al. American Association of Clinical Endocrinologists Position Statement on Metabolic and Cardiovascular Consequences of Polycystic Ovary Syndrome. Endocr. Pract. 2005;11:125–34.

6. Homburg R. Pregnancy complications in PCOS. Best Pract. Res. Clin. Endocrinol. Metab. 2006;20:281–92.

7. Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society Disease State Clinical Review: Guide to the Best Practices in the Evaluation and Treatment of Polycystic Ovary Syndrome - Part 1. Endocr. Pract. 2015;21:1291–300.

8. Lakatos P, Gimes G, Speer G. A PCOS klinikai képe felnőttben. In: Lakatos P, Speer G, editors. Policisztás ovarium szindróma. Budapest: Semmelweis Kiadó; 2009. p. 47–66.

9. Speer G. A PCOS patogenezise és epidemiológiája. In: Lakatos P, Speer G, editors. Policisztás ovarium szindróma. Budapest: Semmelweis Kiadó; 2009. p. 29–46.

10. Conway G, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Franks S, Gambineri A, et al. The polycystic ovary syndrome: A position statement from the European Society of Endocrinology. Eur. J. Endocrinol. 2014;171:P1–29.

11. Dimitriadis GK, Kyrou I, Randeva HS. Polycystic Ovary Syndrome as a Proinflammatory State: The Role of Adipokines. Curr. Pharm. Des. 2016;22:5535–46.

12. Delitala AP, Capobianco G, Delitala G, Cherchi PL, Dessole S. Polycystic ovary syndrome, adipose tissue and metabolic syndrome. Arch. Gynecol. Obstet. 2017;296:405–19.

13. Morrison SA, Goss AM, Azziz R, Raju DA, Gower BA. Perimuscular adipose tissue may play a unique role in determining insulin sensitivity/resistance in women with polycystic ovary syndrome. Hum. Reprod. Oxford University Press; 2016;32:185–92.

14. Borsos A, Jakab A. Polycysticus ovarium szindróma. In: Leövey A, Nagy VE, Paragh Gy RK, editors. Az endokrin és anyagcserebetegségek Gyak. kézikönyve. Medicina, Budapest; 2011. p. 388–92.

15. Kun IZ, Szántó Z. Neuroendocrinologia. Kolozsvár: Erdélyi Múzeum Egyesület; 2012.

16. Kun IZ, Szántó Z. Mi változott a metabolikus szindróma értelmezésében, diagnózisában és kórtanában az utóbbi huszonöt évben ? Orvostudományi Értesítő. 2013;88:53–68.

17. Diamanti-Kandarakis E, Piperi C, Kalofoutis A, Creatsas G. Increased levels of serum advanced glycation end-products in women with polycystic ovary syndrome. Clin. Endocrinol. (Oxf). 2005;62:37–43.

18. Diamanti-Kandarakis E, Katsikis I, Piperi C, Kandaraki E, Piouka A, Papavassiliou AG, et al. Increased serum advanced glycation end-products is a distinct finding in lean women with polycystic ovary syndrome (PCOS). Clin. Endocrinol. (Oxf). 2008;69:634–41.

19. Charikleia C, Frangiskos E, Sarantis L, Christina P, Christos A, Evangelos M, et al. Strong and positive association of Endothelin-1 with AGEs in PCOS: A causal relationship or a bystander? Hormones. 2011;10:292–7.

20. Tantalaki E, Piperi C, Livadas S, Kollias A, Adamopoulos C, Koulouri A, et al. Impact of dietary modification of advanced glycation end products (AGEs) on the hormonal and metabolic profile of women with polycystic ovary syndrome (PCOS). Hormones (Athens). 13:65–73.

21. Kavlock RJ, Daston GP, DeRosa C, Fenner-Crisp P, Gray LE, Kaattari S, et al. Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop. Environ. Health Perspect. 1996;104 Suppl 4:715–40.

22. Akın L, Kendirci M, Narin F, Kurtoglu S, Saraymen R, Kondolot M, et al. The endocrine disruptor bisphenol A may play a role in the aetiopathogenesis of polycystic ovary syndrome in adolescent girls. Acta Paediatr. 2015;104:e171–7.

23. Eslami B, Rashidi BH, Amanlou M, Lak TB, Ghazizadeh M, Haghollahi F, et al. The Association Between Bisphenol A and Polycystic Ovarian Syndrome: A Case-Control Study. Acta Med Iran. 2017;55:759–64.

24. Tarantino G, Valentino R, Somma C Di, D’Esposito V, Passaretti F, Pizza G, et al. Bisphenol A in polycystic ovary syndrome and its association with liver-spleen axis. Clin. Endocrinol. (Oxf). 2013;78:447–53.

25. Diamanti-Kandarakis E, Piperi C, Patsouris E, Korkolopoulou P, Panidis D, Pawelczyk L, et al. Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries. Histochem. Cell Biol. 2007;127:581–9.

26. Garg D, Merhi Z. Advanced Glycation End Products: Link between Diet and Ovulatory Dysfunction in PCOS? Nutrients. Multidisciplinary Digital Publishing Institute (MDPI); 2015;7:10129–44.

27. Manikkam M, Guerrero-Bosagna C, Tracey R, Haque MM, Skinner MK. Transgenerational Actions of Environmental Compounds on Reproductive Disease and Identification of Epigenetic Biomarkers of Ancestral Exposures. Shioda T, editor. PLoS One. Public Library of Science; 2012;7:e31901.

28. López de Alda MJ, Barceló D. Determination of steroid sex hormones and related synthetic compounds considered as endocrine disrupters in water by liquid chromatography–diode array detection–mass spectrometry. J. Chromatogr. A. Elsevier; 2000;892:391–406.

29. Gervais G, Bichon E, Antignac J-P, Monteau F, Leroy G, Barritaud L, et al. Differential global profiling as a new analytical strategy for revealing micropollutant treatment by-products: Application to ethinylestradiol and chlorination water treatment. Chemosphere. Pergamon; 2011;83:1553–9.

30. Da Ros CT, Graziottin TM. Environmental Issues Resulting in Hypogonadism in Brazilian Men. Bioenvironmental Issues Affect. Men’s Reprod. Sex. Heal. Elsevier; 2018. p. 33–40.

31. Rasgon N. The relationship between polycystic ovary syndrome and antiepileptic drugs: a review of the evidence. J. Clin. Psychopharmacol. 2004;24:322–34.

32. Kun IZ, Szántó Z, Kun I, Kolcsár M. Konvencionális és atípusos antipszichotikumok okozta metabolikus szindróma. Orvostudományi Értesítő. 2017;90:7–18.

33. Saydam B, Yildiz B. Gut-Brain Axis and Metabolism in Polycystic Ovary Syndrome. Curr. Pharm. Des. 2016;22:5572–87.

34. Abbott DH, Nicol LE, Levine JE, Xu N, Goodarzi MO, Dumesic DA. Nonhuman primate models of polycystic ovary syndrome. Mol. Cell. Endocrinol. Elsevier Ireland Ltd; 2013;373:21–8.

35. Dumesic DA, Goodarzi MO, Chazenbalk GD, Abbott DH. Intrauterine environment and polycystic ovary syndrome. Semin. Reprod. Med. 2014;32:159–65.

36. Barnes RB, Rosenfield RL, Ehrmann DA, Cara JF, Cuttler L, Levitsky LL, et al. Ovarian hyperandrogynism as a result of congenital adrenal virilizing disorders: Evidence for perinatal masculinization of neuroendocrine function in women. J. Clin. Endocrinol. Metab. 1994;79:1328–33.

37. Rosenfield RL. Adolescent anovulation: Maturational mechanisms and implications. J. Clin. Endocrinol. Metab. 2013;98:3572–83.

38. McCartney CR, Blank SK, Prendergast KA, Chhabra S, Eagleson CA, Helm KD, et al. Obesity and sex steroid changes across puberty: Evidence for marked hyperandrogenemia in pre- and early pubertal obese girls. J. Clin. Endocrinol. Metab. 2007;92:430–6.

39. van Hooff MHA, Voorhorst FJ, Kaptein MBH, Hirasing RA, Koppenaal C, Schoemaker J. Predictive value of menstrual cycle pattern, body mass index, hormone levels and polycystic ovaries at age 15 years for oligo-amenorrhoea at age 18 years. Hum. Reprod. 2004;19:383–92.

40. Witchel SF, Tena-Sempere M. The Kiss1 system and polycystic ovary syndrome: lessons from physiology and putative pathophysiologic implications. Fertil. Steril. 2013;100:12–22.

41. Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr. Rev. The Endocrine Society; 2016;37:467–520.

42. Speer G, Lakatos P. A PCOS diagnózisa. In: Lakatos P, Speer G, editors. Policisztás ovarium szindróma. Budapest: Semmelweis Kiadó; 2009. p. 67–72.

43. Azziz R. Diagnosis of Polycystic Ovarian Syndrome: The Rotterdam Criteria Are Premature. J. Clin. Endocrinol. Metab. Oxford University Press; 2006;91:781–5.

44. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. Position Statement: Criteria for Defining Polycystic Ovary Syndrome as a Predominantly Hyperandrogenic Syndrome: An Androgen Excess Society Guideline. JCEM. 2006;91:4237–45.

45. Dewailly D, Gronier H, Poncelet E, Robin G, Leroy M, Pigny P, et al. Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries. Hum. Reprod. 2011;26:3123–9.

46. Tal R, Seifer DB, Khanimov M, Malter HE, Grazi R V, Leader B. Characterization of women with elevated antimüllerian hormone levels (AMH): correlation of AMH with polycystic ovarian syndrome phenotypes and assisted reproductive technology outcomes. Am. J. Obstet. Gynecol. Elsevier Inc; 2014;1–8.

47. Cassar S, Teede HJ, Moran LJ, Joham AE, Harrison CL, Strauss BJ, et al. Polycystic ovary syndrome and anti-Müllerian hormone: role of insulin resistance, androgens, obesity and gonadotrophins. Clin. Endocrinol. (Oxf). 2014;

48. Insler V, Barash A, Shoham Z, Koistinen R, Seppala M, Hen M, et al. Overnight secretion pattern of growth hormone, sex hormone binding globulin, insulin-like growth factor-1 and its binding protein in obese and non-obese women with polycystic ovarian disease. Isr. J. Med. Sci. 1994;30:42–7.

49. Prelević GM, Wurzburger MI, Balint-Perić L, Ginsburg J. Twenty-four-hour serum growth hormone, insulin, C-peptide and blood glucose profiles and serum insulin-like growth factor-I concentrations in women with polycystic ovaries. Horm. Res. Karger Publishers; 1992;37:125–31.

50. Kun IZ, Kun I, Kun IZJ. Metabolikus szindróma, diabetes mellitus és a rosszindulatú daganatok. Orvostudományi Értesítő. 2015;88:7–18.

51. Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. The Endocrine Society; 2010;95:4133–60.

52. Bajnok L, Kemény J, Molnár M, Sipos M, Speer G, Tabák R, et al. A PCOS szövődményei. In: Lakatos P, Speer G, editors. Policisztás ovarium szindróma. Semmelweis Kiadó, Budapest; 2009. p. 130.

Journal Information

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 80 80 33
PDF Downloads 74 74 33