Polycystic Ovary Syndrome in Adolescents

Abstract

Polycystic ovary syndrome ( PCOS ) is the most important cause of an anovulation, hirsutism and infertility in women. It is a heterogeneous syndrome the etiology of which is not known clearly yet. This multifactorial syndrome starts at puberty and its cardiovascular and metabolic sequelas are observed during menopause. Adolescent patients pose particular diagnostic problems as characteristics of normal puberty often overlap with signs and symptoms of PCOS. However, identification of PCOS during adolescent period is important in order to prevent long term sequelas. It is beneficial to set a behavior pattern in this age group with regard to appropriate diet and exercise. On the other hand, whether to treat PCOS in adolescents in order to prevent long term sequelas is still controversial.

Keywords

• Polycystic ovary syndrome, Adolescent, Diagnosis.

Adolesanda Polikistik Over Sendromu

Öz

Polikistik over sendromu (PKOS), kadınlarda anovülasyon, hirsutizm ve infertilitenin en önemli nedeni olup, etiyolojisi bilinmeyen heterojen bir sendromdur. Bu multifaktöriyel sendrom puberte ile başlayıp, menopoz süresince de kardiyovasküler ve metabolik sekelleri izlenir. Adolesanlarda PKOS' un bulgu ve semptomları ile normal pubertal özelliklerin üst üste gelmesi nedeniyle, özellikle tanısal problemler olabilir. Adolesanda PKOS tanısının konulması uzun dönem sekellerin engellenmesi açısından önem taşımaktadır. Bu yaş grubunda uygun diyet ve egzersiz alışkanlıklarının oluşturulması faydalı olacaktır. Uzun dönem sekellerini engellemek açısından PKOS' un bu kadar erken yaşta tedavi edilip edilmemesi konusu ise hala tartışmalıdır.

Anahtar Kelimeler

• Polikistik over sendromu, Adolesan, Teşhis.

Kaynakça

1. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935; 29: 181-91.
2. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab 1999; 84: 4006-11.
3. Asuncio´ n M, Calvo RM, San Milla´ n JL, et al. A prospective study of the prevalence of the polycystic ovary syndrome in unselected caucasian women from Spain. J Clin Endocrinol Metab 2000; 85: 2434-8.
4. The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19: 41-7.
5. Azziz R, Carmina E, Dewailly D, 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: 4237-45.
6. Azziz R, Carmina E, Dewailly D, et al. Task force on the phenotype of the polycystic ovary syndrome of the androgen excess and PCOS society. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009; 91: 456–88.
7. Sultan C, Paris F. Clinical expression of polycystic ovary syndrome in adolescent girls. Fertil Steril 2006; 86: 6.
8. Carmina E, Oberfield SE, Lobo RA. The diagnosis of polycystic ovary syndrome in adolescents. Am J Obstet Gynecol 2010; 203: 201.e1-201.e5.

9. Diamanti-Kandarakis E, Christakou C, Palioura E, et al. Does polycystic ovary syndrome start in childhood? Pediatr Endocrinol Rev 2008; 5: 904–11.
10. Van Hooff MHA, Voorhoorst FJ, Kaptein MBH, et al. Endocrine features of polycystic ovary syndrome in a random population sample 14–16 year-old adolescents. Hum Reprod 1999; 14: 2223-9.
11. Biro F, Emans S. Whither PCOS? The challenges of establishing hyperandrogenism in adolescent girls. J Adolescent Health 2008; 43: 103–5.
12. Rosner W, Auchus RJ, Azziz R, et al. Utility, limitations, and pitfalls in measuring testosterone: an endocrine society position statement. J Clin Endocrinol Metab 2007; 92: 405–13.
13. Diamanti-Kandarakis E, Piperi C, Spina J, et al. Polycystic ovary syndrome: the influence of environmental and genetic factors. Hormones 2006; 5: 17–34.
14. Diamanti-Kandarakis E, Christakou C, Palioura E, et al. Does polycystic ovary syndrome start in childhood? Pediatr Endocrinol Rev 2008; 5: 904–11.
15. Diamanti-Kandarakis E, Christakou C, Kandarakis H, Alexandraki KI. Early onset adiposity: a pathway to polycystic ovary syndrome in adolescents? Hormones 2007; 6: 210–7.
16. Diamanti-Kandarakis E, Piperi C. Genetics of polycystic ovary syndrome: searching for the way out of the labyrinth. Hum Reprod Update 2005; 11: 631–43.
17. Mohamed-Hussein ZA, Harun S. Construction of a polycystic ovarian syndrome (PCOS) pathway based on the interactions of PCOS-related proteins retrieved from bibliomic data. Theor Biol Med Model 2009; 1: 18.
18. Pastor CL, Griffin-Korf ML, Aloi JA, et al. Polycystic ovary syndrome: evidence for reduced sensitivity of the gonadotropin releasing hormone pulse generator to inhibition by estradiol and progesterone. J Clin Endocrinol Metab 1998; 83: 582–90.
19. Eagleson CA, Gingrich MB, Pastor CL, et al. Polycystic ovarian syndrome: evidence that flutamide restores sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone. J Clin Endocrinol Metab 2000; 85: 4047–52.
20. Blank SK, McCartney CR, Chhabra S, et al. Modulation of GnRH pulse generator sensitivity to progesterone inhibition in hyperandrogenic adolescent girls - Implications for regulation of pubertal maturation. J Clin Endocrinol Metab 2009; 94: 2360–6.
21. Ropelato MG, Garcı´a Rudaz MC, Escobar ME, et al. Acute effects of testosterone infusion on the serum luteinizing hormone profile in eumenorrheic and polycystic ovary syndrome adolescents. J Clin Endocrinol Metab 2009; 94: 3602-10.
22. Chhabra S, McCartney CR, Yoo RY, et al. Progesterone inhibition of the hypothalamic gonadotropin-releasing hormone pulse generator: evidence for varied effects in hyperandrogenemic adolescent girls. J Clin Endocrinol Metab 2005; 90: 2810–5.
23. Ibanez L, Diaz R, Lopez-Bermejo A, Marcos MV. Clinical spectrum of premature pubarche: links to metabolic syndrome and ovarian hyperandrogenism. Rev Endocr Metab Disord 2009; 10: 63–76.
24. Rosenfield RL. Clinical review: identifying children at risk for polycystic ovary syndrome. J Clin Endocrinol Metab 2007; 92: 787–96. de Zegher F, Lopez-Bermejo A, Ibanez L. Adipose tissue expandability and the early origins of PCOS. Trends Endocrinol Metab 2009; 20: 418–23.
25. Abbott DH, Barnett DK, Bruns CM, Dumesic DA. Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome? Hum Reprod Update 2005; 11: 357–74.
26. Nelson VL, Legro RS, Strauss JF, McAllister JM. Augmented androgen production is a stable phenotype of propagated theca cells from polycystic ovaries. Mol Endocrinol 1999; 13: 946–
27. Diamanti-Kandarakis E. Polycystic ovarian syndrome: pathophysiology, molecular aspects and clinical implications. Expert Rev Mol Med 2008; 10: e3.
28. Maciel GA, Baracat EC, Benda JA, et al. Stockpiling of transitional and classic primary follicles in ovaries of women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004; 89: 5321–7.
29. Vendola K, Zhou J, Wang J, Bondy CA. Androgens promote insulin-like growth factor-I and insulin-like growth factor-I receptor gene expression in the primate ovary. Hum Reprod 1999; 14: 2328–32.
30. Greisen S, Ledet T, Ovesen P. Effects of androstenedione, insulin and LH on steroidogenesis in human granulosa luteal cells. Hum Reprod 2001; 16: 2061–5.
31. Jonard S, Dewailly D. The follicular excess in polycystic ovaries, due to intraovarian hyperandrogenism, may be the main culprit for the follicular arrest. Hum Reprod Update 2004; 10: 107–17.
32. Christakou CD, Diamanti-Kandarakis E. Role of androgen excess on metabolic aberrations and cardiovascular risk in women with polycystic ovary syndrome. Womens Health 2008; 4: 583–94.
33. Abbott DH, Tarantal AF, Dumesic DA. Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys. Am J Primatol 2009; 71: 776–84.
34. Kent SC, Gnatuk CL, Kunselman AR, et al. Hyperandrogenism and hyperinsulinism in children of women with polycystic ovary syndrome: a controlled study. J Clin Endocrinol Metab 2008; 93: 1662–9.
35. Smith CP, Archibald HR, Thomas JM, et al. Basal and stimulated insulin levels rise with advancing puberty. Clin Endocrinol 1988; 28: 7–14.
36. Hooff MH, Voorhorst FJ, Kaptein MB, et al. Polycystic ovaries in adolescents and the relationship with menstrual cycle patterns, luteinizing hormone, androgens, and insulin. Fertil Steril 2000; 74: 49–58.
37. Arslanian SA, Lewy VD, Danadian K. Glucose intolerance in obese adolescents with polycystic ovary syndrome: roles of insulin resistance and beta-cell dysfunction and risk of cardiovascular disease. J Clin Endocrinol Metab 2001; 86: 66–71.
38. Fruzzetti F, Perini D, Lazzarini V, et al. Adolescent girls with polycystic ovary syndrome showing different phenotypes have a different metabolic profile associated with increasing androgen levels. Fertil Steril 2009; 92: 626–34.
39. Moran LJ, Pasquali R, Teede HJ, et al. Treatment of obesity in polycystic ovary syndrome: a position statement of the androgen excess and polycystic ovary syndrome society. Fertil Steril 2009; 92: 1966-82.
40. Littlejohn E, Weiss R, Deplewski D, et al. Intractable early childhood obesity as the initial sign of insulin resistant hyperinsulinism and precursor of polycystic ovary syndrome. J Pediatr Endocrinol Metab 2007; 20: 41–51.
41. Nestler JE, Barlascini CO, Matt DW, et al. Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system. J. Clin Endocrinol Metab 1998; 83: 2001–5.
42. Strauss JF, Martinez F, Kiriakidou M. Placental steroid hormone synthesis: unique features and unanswered questions. Biol Reprod 1996; 54: 303–11.
43. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004; 89: 2548–56.
44. Rossi B, Sukalich S, Droz J, et al. Prevalence of metabolic syndrome and related characteristics in obese adolescents with and without polycystic ovary syndrome. J Clin Endocrinol Metab 2008; 93: 4780–6.
45. Coviello AD, Legro RS, Dunaif A. Adolescent girls with polycystic ovary syndrome have an increased risk of the metabolic syndrome associated with increasing androgen levels independent of obesity and insulin resistance. J Clin Endocrinol Metab 2006; 91: 492–7.
46. Vlassara H. Advanced glycation in health and disease: role of the modern environment. Ann N Y Acad Sci 2005; 1043: 452–
47. 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 2005; 62: 37–43.
48. Diamanti-Kandarakis E, Katsikis I, Piperi C, et al. Increased serum advanced glycation end-products is a distinct finding in lean women with polycystic ovary syndrome (PCOS). Clin Endocrinol 2008; 69: 634–41.
49. Avvad CK, Holeuwerger R, Silva VC, et al. Menstrual irregularity in the first postmenarchal years: an early clinical sign of polycystic ovary syndrome in adolescence. Gynecol Endocrinol 2001; 15: 170–7.
50. Gardner J. Adolescent menstrual characteristics as predictors of gynaecological health. Ann Hum Biol 1983; 10: 31–40.
51. Legro RS, Lin HM, Demers LM, Lloyd T. Rapid maturation of the reproductive axis during perimenarche independent of body composition. J Clin Endocrinol Metab 2000; 85: 1021–5.
52. Apter D, Vihko R. Early menarche, a risk factor for breast cancer, indicates early onset of ovulatory cycles. J Clin Endocrinol Metab 1983; 57: 82–6.
53. Cunliffe WJ, Gould DJ. Prevalence of facial acne vulgaris in late adolescence and in adults. Br Med J 1979; 1: 1109–10.
54. Lucky AW, Biro FM, Simbartl LA, et al. Predictors of severity of acne vulgaris in young adolescent girls: results of a fiveyear longitudinal study. J Pediatr 1997; 130: 30–9.
55. Pfeifer SM, Kives S. Polycystic ovary syndrome in the adolescent. Obstet Gynecol Clin North Am 2009; 36: 129–52.
56. Chang WY, Knochenhauer ES, Bartolucci AA, Azziz R. Phenotypic spectrum of polycystic ovary syndrome: clinical and biochemical characterization of the three major clinical subgroups. Fertil Steril 2005; 83: 1717–23.
57. Bridges NA, Cooke A, Healy MJ, et al. Standards for ovarian volume in childhood and puberty. Fertil Steril 1993; 60: 456–
58. Mortensen M, Rosenfield RL, Littlejohn E. Functional significance of polycystic-size ovaries in healthy adolescents. J Clin Endocrinol Metab 2006; 91: 3786–90. Blank SK, Helm KD, McCartney CR, Marshall JC. Polycystic ovary syndrome in adolescence. Ann N Y Acad Sci 2008; 1135: 76–84.
59. Fernandes AR, de Sá Rosa e Silva, Romão GS, et al. Insulin resistance in adolescents with menstrual irregularities. J Pediatr Adolesc Gynecol 2005; 18: 269–74.
60. Venturoli S, Porcu E, Fabbri R, et al. Longitudinal change of sonographic ovarian aspects and endocrine parameters in irregular cycles of adolescence. Pediatr Res 1995; 38: 974–80.
61. Yoo RY, Sirlin CB, Gottschalk M, Chang RJ. Ovarian imaging by magnetic resonance in obese adolescent girls with polycystic ovary syndrome: a pilot study. Fertil Steril 2005; 84: 985–95.
62. Alemzadeh R, Kichler J, Calhoun M. Spectrum of metabolic dysfunction in relationship with hyperandrogenemia in obese adolescent girls with polycystic ovary syndrome. Eur J Endocrinol 2010; 162: 1093–9.
63. Vural B, Caliskan E, Turkoz E, et al. Evaluation of metabolic syndrome frequency and premature carotid atherosclerosis in young women with polycystic ovary syndrome. Hum Reprod 2005; 20: 2409–13.
64. Bruni V, Dei M, Nannini S, et al. Polycystic ovary syndrome in adolescence. Ann N Y Acad Sci 2010; 1205: 175–84. van Hooff, Voorhorst FJ, Kaptein MB et al. 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.
65. Fulghesu A, Magnini R, Portoghese E, et al. Obesity-related lipid profile and altered insulin incretion in adolescents with polycystic ovary syndrome. J Adolesc Health 2010; 46: 474–
66. Sawathiparnich P, Weerakulwattana L, Santiprabhob J, Likitmaskul S. Obese adolescent girls with polycystic ovary syndrome (PCOS) have more severe insulin resistance measured by HOMA-IR score than obese girls without PCOS. J Med Assoc Thai 2005; 88: 33–7.
67. Leibel NI, Baumann EE, Kocherginsky M, Rosenfield RL. Relationship of adolescent polycystic ovary syndrome to parental metabolic syndrome. J Clin Endocrinol Metab 2006; 91: 1275–83.
68. Salley KE, Wickham EP, Cheang KI. et al. Glucose intolerance in polycystic ovary syndrome-a position statement of the Androgen Excess Society. J Clin Endocrinol Metab 2007; 92: 4546–56.
69. Mastorakos G, Lambrinoudaki I, Creatsas G. Polycystic ovary syndrome in adolescents: current and future treatment options. Paediatr Drugs 2006; 8: 311–8.
70. Pasquali R, Gambineri A. Targeting insulin sensitivity in the treatment of polycystic ovary syndrome. Expert Opin Ther Targets 2009; 13: 1205–26.
71. Palomba S, Giallauria F, Falbo A, et al. Structured exercise training programme versus hypocaloric hyperproteic diet in obese polycystic ovary syndrome patients with anovulatory infertility: a 24-week pilot study. Hum Reprod 2008; 23: 642–
72. Ibanez L, Lopez-Bermejo A, Diaz M et al. Metformin treatment for four years to reduce total and visceral fat in low birth weight girls with precocious pubarche. J Clin Endocrinol Metab 2008; 93: 1841–5.
73. Ibanez L, Potau N, Marcos MV, de Zegher F. Treatment of hirsutism, hyper-androgenism, oligomenorrhea, dyslipidemia, and hyperinsulinism in nonobese, adolescent girls: effect of flutamide. J Clin Endocrinol Metab 2000; 85: 3251–5.
74. Ibanez L, de Zegher F. Low-dose flutamide-metformin therapy for hyperinsulinemic hyperandrogenism in non-obese adolescents and women. Hum Reprod Update 2006; 12: 243–52.
75. Nader S, Diamanti-Kandarakis E. Polycystic ovary syndrome, oral contraceptives and metabolic issues: new perspectives and a unifying hypothesis. Hum Reprod 2007; 22: 317–22.
76. Mastorakos G, Koliopoulos C, Deligeoroglou E, et al. Effects of two forms of combined oral contraceptives on carbohydrate metabolism in adolescents with polycystic ovary syndrome. Fertil Steril 2006; 85: 420–7.