Modern Pediatrics. Ukraine. (2022). 4(124): 65-72. doi 10.15574/SP.2022.124.65
Sorokman T. V., Khlunovska L. Yu., Popelyuk N. O.
Bukovynian State Medical University, Chernivtsi, Ukraine

For citation: Sorokman TV, Khlunovska LYu, Popelyuk NO. (2022). Polycystic ovary syndrome in adolescence – a look at the problem. Modern Pediatrics. Ukraine. 4(124): 65-72. doi 10.15574/SP.2022.124.65.
Article received: Jan 28, 2022. Accepted for publication: Apr 20, 2022.

Purpose – to present a review of literature data on the etiology and pathogenesis of polycystic ovary syndrome (PCOS) in adolescents. A review of the scientific literature on PCOS on the keywords «polycystic ovary syndrome – PCOS», «Stein Leventhal syndrome», «functional ovarian hyperandrogenism or functional ovarian hyperandrogenism», «hyperandrogenic chronic anovulation»; «ovarian dysmetabolic syndrome» using as a search engine PubMed.
Currently, PCOS is considered a heterogeneous and complex syndrome, which is accompanied by ovarian dysfunction (absence or irregularity of ovulation, increased secretion of androgens and estrogens), pancreas (insulin hypersecretion), adrenal cortex (hypersecretory adrenal androgens, hypothalamus and pituitary gland and and has negative reproductive and metabolic effects. The prevalence of PCOS in adolescents by various criteria ranges from 8% to 17%. Potential risk of PCOS are low or high birth weight, childhood obesity, prenatal androgenism, metabolic syndrome, genetic mutations in chromosome 18. The most reliable criteria for PCOS in young patients are: a combination of ultrasound (morphological) picture of the ovaries, (the ratio of sex hormones and hyperandrogenism), the dynamics of the menstrual cycle (amenorrhea), against the background of dysmetabolic disorders (obesity, hyperinsulinism, impaired glucose tolerance). An additional diagnostic criterion may be the level of antimullerian hormone.
Conclusions. Clinically, PCOS is a heterogeneous syndrome that manifests itself in all periods of life. The main physiological and pathological mechanism of PCOS is an excess of androgens, which disrupts the development of follicles and promotes the deposition of abdominal adipose tissue, causing insulin resistance and compensatory hyperinsulinism. Exposure to the fetus’ hyperinsulinemic and hyperandrogenic environment of the uterus leads to epigenetic changes, which, in addition to the genetic background, predispose to the development of metabolic disorders in the offspring of women with PCOS. This is a rational basis for finding PCOS at an early age, which will allow to diagnose it in time in adolescence. Not all aspects are covered in detail in this review due to limited scope. Problematic issues of clinically relevant markers of PCOS and its predictors in adolescent patients require in-depth study.
No conflict of interests was declared by the authors.
Key words: polycystic ovary syndrome, adolescent girls.
REFERENCES
1. American College of Obstetricians and Gynecologists, Committee on Practice Bulletins-Gynecology. (2018). ACOG Practice Bulletin No. 194. Polycystic Ovary Syndrome. Obstet Gynecol. 131 (6): e157-e171. https://doi.org/10.1097/AOG.0000000000002656; PMid:29794677

2. Atkins D, Best D, Briss PA et al. (2004). Grading quality of evidence and strength of recommendations. BMJ. 328 (7454): 1490. https://doi.org/10.1136/bmj.328.7454.1490; PMid:15205295 PMCid:PMC428525

3. Aversa A, La Vignera S, Rago R et al. (2020). Fundamental Concepts and Novel Aspects of Polycystic Ovarian Syndrome: Expert Consensus Resolutions. Front. Endocrinol. 11: 516. https://doi.org/10.3389/fendo.2020.00516; PMid:32849300 PMCid:PMC7431619

4. Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS et al. (2016). Polycystic ovary syndrome. Nat Rev Dis Primers. 2: 16057. https://doi.org/10.1038/nrdp.2016.57; PMid:27510637

5. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. (2004). The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 89 (6): 2745-2749. https://doi.org/10.1210/jc.2003-032046; PMid:15181052

6. Behboudi-Gandevani S, Amiri M, Bidhendi Yarandi R et al. (2018). The risk of metabolic syndrome in polycystic ovary syndrome: A systematic review and meta-analysis. Clin Endocrinol (Oxf). 88 (2): 169-184. https://doi.org/10.1111/cen.13477; PMid:28930378

7. Biro FM, Emans SJ. (2008). Whither PCOS? The challenges of establishing hyperandrogenism in adolescent girls. J Adolesc Health. 43: 103-105. https://doi.org/10.1016/j.jadohealth.2008.05.004; PMid:18639782

8. Bruns CM, Baum ST, Colman RJ, Dumesic DA, Eisner JR, Jensen MD et al. (2007). Prenatal androgen excess negatively impacts body fat distribution in a nonhuman primate model of polycystic ovary syndrome. Int J Obes (Lond). 31: 1579-1585. https://doi.org/10.1038/sj.ijo.0803638; PMid:17471299 PMCid:PMC2597033

9. Caanen MR, Peters HE, van de Ven PM et al. (2021). Anti-Müllerian Hormone Levels in Adolescence in Relation to Long-term Follow-up for Presence of Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 106 (3): e1084-e1095. https://doi.org/10.1210/clinem/dgaa949; PMid:33351079 PMCid:PMC7947839

10. Chaudhary H, Patel J, Jain NK, Joshi R. (2021). The role of polymorphism in various potential genes on polycystic ovary syndrome susceptibility and pathogenesis. J Ovarian Res. 14 (1): 125. https://doi.org/10.1186/s13048-021-00879-w; PMid:34563259 PMCid:PMC8466925

11. Cioana M, Deng J, Nadarajah A et al. (2022). Prevalence of Polycystic Ovary Syndrome in Patients With Pediatric Type 2 Diabetes: A Systematic Review and Meta-analysis. JAMA Netw Open. 1; 5 (2): e2147454. https://doi.org/10.1001/jamanetworkopen.2021.47454; PMid:35166782 PMCid:PMC8848210

12. De Zegher F, López-Bermejo A, Ibáñez L. (2018). Central obesity, faster maturation, and 'PCOS' in girls. Trends Endocrinol Metab. 29: 815-818. https://doi.org/10.1016/j.tem.2018.09.005; PMid:30297320

13. Dedov II, Andreeva EN, Karpova EA. (2009). Polycystic ovary syndrome. M.: ITM: 4-5.

14. Desai NA, Tiwari RY, Patel SS. (2018). Prevalence of polycystic ovary syndrome and its associated risk factors among adolescent and young girls in ahmedabad region. Indian Journal of Pharmacy Practice. 11: 119-125. https://doi.org/10.5530/ijopp.11.3.27

15. Dewailly D, Gronier H, Poncelet E et al. (2011). 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. 26: 3123-3129. https://doi.org/10.1093/humrep/der297; PMid:21926054

16. Diamanti-Kandarakis E. (2009). PCOS in adolescents. Best Pract Res Clin Obstet Gynaecol. 24: 173-183. https://doi.org/10.1016/j.bpobgyn.2009.09.005; PMid:19932060

17. Ehrmann DA. (2005). Polycystic ovary syndrome. N Engl J Med. 352: 1223-1236. https://doi.org/10.1056/NEJMra041536; PMid:15788499

18. Farooq R. (2018). Short Review on Polycystic Ovarian Syndrome. Journal of Medicine. 19: 49-53. https://doi.org/10.3329/jom.v19i1.34843

19. Fauser BC, Tarlatzis BC, Rebar RW et al. (2012). Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE / ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 97 (1): 28-38.e25. https://doi.org/10.1016/j.fertnstert.2011.09.024; PMid:22153789

20. Franks S. (2008). Polycystic ovary syndrome in adolescents. Int J Obes. 32: 1035-1041. https://doi.org/10.1038/ijo.2008.61; PMid:18458678

21. Glintborg D, Andersen M. (2017). Management of endocrine disease: morbidity in polycystic ovary syndrome. Eur J Endocrinol. 176 (2): 53-65. https://doi.org/10.1530/EJE-16-0373; PMid:27601016

22. Glintborg D, Rubin KH, Nybo M, Abrahamsen B, Andersen M. (2019). Increased risk of thyroid disease in Danish women with polycystic ovary syndrome: a cohort study Endocr Connect. 8 (10): 1405-1415. https://doi.org/10.1530/EC-19-0377; PMid:31518989 PMCid:PMC6826171

23. Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E. (2015). American Association of Clinical Endocrinologists (AACE); American College of Endocrinology (ACE); Androgen Excess and PCOS Society (AES). 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. 21: 11. https://doi.org/10.4158/EP15748.DSC; PMid:26509855

24. Hakim C, Padmanabhan V, Vyas AK. (2017). Gestational Hyperandrogenism in Developmental Programming. Endocrinology. 158 (2): 199-212. https://doi.org/10.1210/en.2016-1801; PMid:27967205 PMCid:PMC5413081

25. Joo YY, Actkins K, Pacheco JA et al. (2020). A Polygenic and Phenotypic Risk Prediction for Polycystic Ovary Syndrome Evaluated by Phenome-Wide Association Studies. J Clin Endocrinol Metab. 105 (6): 1918-1936. https://doi.org/10.1210/clinem/dgz326; PMid:31917831 PMCid:PMC7453038

26. Joshi B, Mukherjee S, Patil A, Purandare A, Chauhan S, Vaidya R. (2014). A cross-sectional study of polycystic ovarian syndrome among adolescent and young girls in Mumbai, India. Indian J Endocrinol Metab. 18: 317-324. https://doi.org/10.4103/2230-8210.131162; PMid:24944925 PMCid:PMC4056129

27. Khashchenko E, Vysokikh M, Uvarova E et al. (2020). Activation of Systemic Inflammation and Oxidative Stress in Adolescent Girls with Polycystic Ovary Syndrome in Combination with Metabolic Disorders and Excessive Body Weight. J Clin Med. 9: 1399. https://doi.org/10.3390/jcm9051399; PMid:32397375 PMCid:PMC7291245

28. Kim J, Mersereau JE, Khankari N et al. (2016). Polycystic ovarian syndrome (PCOS), related symptoms / sequelae, and breast cancer risk in a population-based case-control study. Cancer Causes Control. 27 (3): 403-414. https://doi.org/10.1007/s10552-016-0716-7; PMid:26797454 PMCid:PMC4981498

29. Koivuaho E, Laru J, Ojaniemi M et al. (2019). Age at adiposity rebound in childhood is associated with PCOS diagnosis and obesity in adulthood-longitudinal analysis of BMI data from birth to age 46 in cases of PCOS. Int J Obes (Lond). 43 (7): 1370-1379. https://doi.org/10.1038/s41366-019-0318-z; PMid:30718819 PMCid:PMC6760596

30. Legro RS, Dodson WC, Gnatuk CL et al. (2012). Effects of gastric bypass surgery on female reproductive function. J Clin Endocrinol Metab. 97 (12): 4540-4548. https://doi.org/10.1210/jc.2012-2205; PMid:23066115 PMCid:PMC3513539

31. Littlejohn EE, Weiss RE, Deplewski D, Edidin DV, Rosenfield R. (2007). Intractable early childhood obesity as the initial sign of insulin resistant hyperinsulinism and precursor of polycystic ovary syndrome. J Pediatr Endocrinol Metab. 20: 41-51. https://doi.org/10.1515/JPEM.2007.20.1.41; PMid:17315528

32. Liu Q, Zhu Z, Kraft P, Deng Q, Stener-Victorin E, Jiang X. (2022). Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis. BMC Med. 20 (1): 66. https://doi.org/10.1186/s12916-022-02238-y; PMid:35144605 PMCid:PMC8832782

33. March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ. (2010). The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 25 (2): 544-551. https://doi.org/10.1093/humrep/dep399; PMid:19910321

34. MedlinePlus. (2020). Bethesda (MD): National Library of Medicine (US). URL: https://medlineplus.gov.

35. Melnik BC. (2018). Acne vulgaris: the metabolic syndrome of the pilosebaceous follicle. Clin Dermatol. 36: 29-40. https://doi.org/10.1016/j.clindermatol.2017.09.006; PMid:29241749

36. Melo AS, Vieira CS, Barbieri MA et al. (2010). High prevalence of polycystic ovary syndrome in women born small for gestational age. Hum Reprod. 25: 2124-2131. https://doi.org/10.1093/humrep/deq162; PMid:20573680

37. Mitrašinović-Brulić M, Buljan M, Suljević D. (2021). Association of LH/FSH ratio with menstrual cycle regularity and clinical features of patients with polycystic ovary syndrome. Middle East Fertil Soc J. 26: 40. https://doi.org/10.1186/s43043-021-00085-0

38. MonDo. (2018). Monarch Disease Ontology release.

39. Moran C, Arriaga M, Arechavaleta-Velasco F, Moran S. (2015). Adrenal Androgen Excess and Body Mass Index in Polycystic Ovary Syndrome. The Journal of Clinical Endocrinology & Metabolism. 100 (3): 942-950. https://doi.org/10.1210/jc.2014-2569; PMid:25514100

40. Mumm H, Kamper-Jorgensen M, Nybo Andersen AM, Glintborg D, Andersen M. (2013). Birth weight and polycystic ovary syndrome in adult life: a register-based study on 523, 757 Danish women born 1973-91. Fertil Steril. 99: 777-782. https://doi.org/10.1016/j.fertnstert.2012.11.004; PMid:23200688

41. National Collaborating Centre for Women's and Children's Health. (2013). Fertility: assessment and treatment for people with fertility problems. London (UK): National Institute for Health and Clinical Excellence. NICE.

42. Naz MSG, Tehrani FR, Majd HA et al. (2019). The prevalence of polycystic ovary syndrome in adolescents: A systematic review and meta-analysis. Int J Reprod Biomed. 17: 533-542. https://doi.org/10.18502/ijrm.v17i8.4818; PMid:31583370 PMCid:PMC6745085

43. NIH Office of Disease Prevention. (2012). Evidence-based Methodology Workshop on Polycystic Ovary Syndrome. Expert Panel Guidelines on PCOS. URL: https://prevention.nih.gov/docs/programs/pcos/FinalReport.pdf.

44. Ollila MM, West S, Keinänen-Kiukaaniemi S et al. (2017). Overweight and obese but not normal weight women with PCOS are at increased risk of Type 2 diabetes mellitus-a prospective population-based cohort study. Hum Reprod. 32 (4): 968. https://doi.org/10.1093/humrep/dex030; PMid:28333219 PMCid:PMC6790519

45. Otaghi M, Azami M, Khorshidi A, Borji M, Tardeh Z. (2019). The association between metabolic syndrome and polycystic ovary syndrome: A systematic review and meta-analysis. Diabetes Metab Syndr. 13 (2): 1481-1489. https://doi.org/10.1016/j.dsx.2019.01.002; PMid:31336510

46. Pasquali R. (2018). Contemporary approaches to the management of polycystic ovary syndrome. Ther Adv Endocrinol Metab. 9: 123-134. https://doi.org/10.1177/2042018818756790; PMid:29619209 PMCid:PMC5871061

47. Rao P, Bhide P. (2020). Controversies in the diagnosis of polycystic ovary syndrome. Ther Adv Reprod Health. 29 (14): 2633494120913032. https://doi.org/10.1177/2633494120913032; PMid:32656532 PMCid:PMC7328349

48. Rubin KH, Glintborg D, Nybo M, Abrahamsen B, Andersen M. (2017). Development and Risk Factors of Type 2 Diabetes in a Nationwide Population of Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 102 (10): 3848-3857. https://doi.org/10.1210/jc.2017-01354; PMid:28938447

49. Saadia Z. (2020). Follicle Stimulating Hormone (LH: FSH) Ratio in Polycystic Ovary Syndrome (PCOS) – Obese vs. Non-Obese Women. Med Arch. 74 (4): 289-293. https://doi.org/10.5455/medarh.2020.74.289-293; PMid:33041447 PMCid:PMC7520057

50. Sadeghi HM, Adeli I, Calina D et al. (2022). Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing. Int J Mol Sci. 23 (2): 583. https://doi.org/10.3390/ijms23020583; PMid:35054768 PMCid:PMC8775814

51. Sharma M, Khapre M, Saxena V, Kaushal P. (2021). Polycystic ovary syndrome among Indian adolescent girls – A systematic review and metanalysis. Nepal J Epidemiol. 11 (3): 1063-1075. https://doi.org/10.3126/nje.v11i3.38460; PMid:34733568 PMCid:PMC8560138

52. Sir-Petermann T, Codner E, Pérez V et al. (2009). Metabolic and reproductive features before and during puberty in daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 94 (6): 1923-1930. https://doi.org/10.1210/jc.2008-2836; PMid:19223518 PMCid:PMC2730345

53. Takeuchi T, Tsutsumi O, Ikezuki Y, Takai Y, Taketani Y. (2004). Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and women with ovarian dysfunction. Endocr J. 51 (2): 165-169. https://doi.org/10.1507/endocrj.51.165; PMid:15118266

54. The Endocrine Society. (2017). Endocrine Facts and Figures: Reproduction and Development. URL: https://endocrinefacts.org/wpcontent/uploads/Endocrine_Facts_Figures_Reproduction_and_Development.pdf.

55. Torchen LC. (2017). Cardiometabolic Risk in PCOS: More than a Reproductive Disorder. Curr Diab Rep. 17 (12): 137. https://doi.org/10.1007/s11892-017-0956-2; PMid:29128916 PMCid:PMC5823507

56. Williams RM, Ong KK, Dunger DB. (2013). Polycystic ovarian syndrome during puberty and adolescence. Mol Cell Endocrinol. 373: 61-67. https://doi.org/10.1016/j.mce.2013.01.005; PMid:23384539

57. Zawadzki J, Dunaif A. (1992). Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. Polycystic Ovary Syndrome. Boston, MA: Blackwell Scientific: 377-384.

58. Zhao X, Jiang Y, Xi H, Chen L, Feng X. (2020). Exploration of the Relationship Between Gut Microbiota and Polycystic Ovary Syndrome (PCOS): A Review. Geburtshilfe Frauenheilkd. 80: 161-171. https://doi.org/10.1055/a-1081-2036; PMid:32109968 PMCid:PMC7035130