Background/Aims: The diagnostic criteria for polycystic ovary syndrome (PCOS) in adolescence are controversial, primarily because the diagnostic pathological features used in adult women may be normal pubertal physiological events. Hence, international pediatric and adolescent specialty societies have defined criteria that have sufficient evidence to be used for the diagnosis of PCOS in adolescents. Methods: The literature has been reviewed and evidence graded to address a series of questions regarding the diagnosis of PCOS during adolescence including the following: clinical and biochemical evidence of hyperandrogenism, criteria for oligo-anovulation and polycystic ovary morphology, diagnostic criteria to exclude other causes of hyperandrogenism and amenorrhea, role of insulin resistance, and intervention. Results and Conclusion: Features of PCOS overlap normal pubertal development. Hence, caution should be taken before diagnosing PCOS without longitudinal evaluation. However, treatment may be indicated even in the absence of a definitive diagnosis. While obesity, insulin resistance, and hyperinsulinemia are common findings in adolescents with hyperandrogenism, these features should not be used to diagnose PCOS among adolescent girls.

Keywords:
Hyperandrogenism, Ovarian hyperandrogenism, Ovary, Polycystic ovary syndrome, Puberty
1.
Fauser BC, Tarlatzis RW, Rebar RS, et al: Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril 2012;97:28-38.e25.
2.
Azziz R, Sanchez ES, Knochenhauer C, et al: Androgen excess in women: experience with over 1,000 consecutive patients. J Clin Endocrinol Metab 2004;89:453-462.
3.
Carmina E, Rosato F, Janni A, Rizzo M, Longo RA: Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism. J Clin Endocrinol Metab 2006;91:2-6.
4.
Rosenfield RL: Identifying children at risk of polycystic ovary syndrome. J Clin Endocrinol Metab 2007;92:787-796.
5.
Franks S: Polycystic ovary syndrome in adolescents. Int J Obes (Lond) 2008;32:1035-1041.
6.
Stein IF, Leventhal ML: Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935;29:181-191.
7.
Nelson VL, Legro RS, Strauss JF, McAllister JM: Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Mol Endocrinol 1999;13:946-957.
8.
McAllister JM, Modi B, Miller BA, et al: Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype. Proc Natl Acad Sci USA 2014;111: 1519-E1527.
9.
Ibáñez L, Ong KK, López-Bermejo A, Dunger DB, de Zegher F: Hyperinsulinaemic androgen excess in adolescent girls. Nat Rev Endocrinol 2014;10:499-508.
10.
Zawadzki J, Dunaif A: Diagnostic criteria for polycystic ovary syndrome: towards a rational approach; in Dunaif A, Givens JR, Haseltine FP, Merriam GR (eds): Polycystic Ovary Syndrome. Boston, Blackwell Scientific Publications 1992, vol 4, pp 377-384.
11.
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004;81:19-25.
12.
Azziz R, Carmina E, Dewailly D, et al: The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009;91:456-488.
13.
Johnson T, Kaplan L, Ouyang P, Rizza R: National Institutes of Health Evidence-Based Methodology Workshop on Polycystic Ovary Syndrome (PCOS). NIH EbMW Report. Bethesda, National Institutes of Health, 2012, vol 1, pp 1-14.
14.
Barber TM, Wass JA, McCarthy I, Franks S: Metabolic characteristics of women with polycystic ovaries and oligo-amenorrhoea but normal androgen levels: implications for the management of polycystic ovary syndrome. Clin Endocrinol (Oxf) 2007;66:513-517.
15.
Guastella E, Longo RA, Carmina E: Clinical and endocrine characteristics of the main polycystic ovary syndrome phenotypes. Fertil Steril 2010;94:2197-2201.
16.
Panidis D, Tziomalos K, Misichronis G, et al: insulin resistance and endocrine characteristics of the different phenotypes of polycystic ovary syndrome: a prospective study. Hum Reprod 2012;27:541-549.
17.
Conway G, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Franks S, Gambineri A, Kelestimur F, Macut D, Micic D, Pasquali R, Pfeifer M, Pignatelli D, Pugeat M, Yildiz BO; ESE PCOS Special Interest Group: The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur J Endocrinol 2014;171:P1-P29.
18.
Carmina E, Oberfield SE, Lobo RA: the diagnosis of polycystic ovary syndrome in adolescents. Am J Obstet Gynecol 2010;203:e201-e205.
19.
Legro RS, Arslanian SA, Ehrmann DA, et al: diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2013;98:4565-4592.
20.
Azziz R, Carmina E, Dewailly D, et al: Position statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006;91:4237-4245.
21.
AGREE Collaboration: Development and validation of an International appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project. Qual Saf Health Care 2003;12:18-23.
22.
Escobar-Morreale HF, Carmina E, Dewailly D, et al: Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update 2012;18:146-170.
23.
Deplewski D, Rosenfield RL: Role of hormones in pilosebaceous unit development. Endocr Rev 2000;21:363-392.
24.
Martin KA, Chang RJ, Ehrmann DA, et al: Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008;93:1105-1120.
25.
Merino PM, Codner E, Cassorla F: A rational approach to the diagnosis of polycystic ovarian syndrome during adolescence. Arq Bras Endocrinol Metabol 2011;55:590-598.
26.
Yildiz BO, Bolour S, Woods K, Moore A, Azziz R: Visually scoring hirsutism. Hum Reprod Update 2010;16:51-64.
27.
Li R, Qiao J, Yang D, et al: Epidemiology of hirsutism among women of reproductive age in the community: a simplified scoring system. Eur J Obstet Gynecol Reprod Biol 2012;163:165-169.
28.
Sadat HM, Ramezani TF, Azizi F: The lack of association between idiopathic hirsutism and metabolic disturbances: Iranian PCOS Prevalence Study. Gynecol Endocrinol 2013;29:821-825.
29.
Chen WC, Zouboulis CC: Hormones and the pilosebaceous unit. Dermatoendocrinol 2009;1:81-86.
30.
Hawryluk EB, English JC 3rd: Female adolescent hair disorders. J Pediatr Adolesc Gynecol 2009;22:271-281.
31.
Souter I, Sanchez A, Perez M, Bartolucci A, Azziz R: The prevalence of androgen excess among patients with minimal unwanted hair growth. Am J Obstet Gynecol 2004;191:1914-1920.
32.
Di Fede G, Mansueto P, Pepe G, Rini B, Carmina E: High prevalence of polycystic ovary syndrome in women with mild hirsutism and no other significant clinical symptoms. Fertil Steril 2010;94:194-197.
33.
Ko JH, Huang YH, Kuo TT: Hair counts from normal scalp biopsy in Taiwan. Dermatol Surg 2012;38:1516-1520.
34.
Sperling LC: Hair density in African Americans. Arch Dermatol 1999;135:656-658.
35.
Yaprohm P, Manonukul J, Sontichai V, Pooliam J, Srettabunjong S: Hair follicle counts in Thai population: a study on the vertex scalp area. J Med Assoc Thai 2013;96:1578-1582.
36.
Zhao X, Ni R, Li L, et al: Defining hirsutism in Chinese women: a cross-sectional study. Fertil Steril 2011;96:792-796.
37.
DeUgarte CM, Woods KS, Bartolucci AA, Azziz R: Degree of facial and body terminal hair growth in unselected black and white women: toward a populational definition of hirsutism. J Clin Endocrinol Metab 2006;91:1345-1350.
38.
Archer JS, Chang RJ: Hirsutism and acne in polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 2004;18:737-754.
39.
Franks S: The investigation and management of hirsutism. J Fam Plann Reprod Health Care 2012;38:182-186.
40.
Lucky AW, Biro FM, Daniels SR, Cedars MI, Khoury PR, Morrison A: The prevalence of upper lip hair in black and white girls during puberty: a new standard. J Pediatr 2001;138:134-136.
41.
Ferriman D, Gallwey JD: Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961;21:1440-1447.
42.
Lucky AW, Biro FM, Simbartl LA, Morrison JA, Sorg NW: Predictors of severity of acne vulgaris in young adolescent girls: results of a five-year longitudinal study. J Pediatr 1997;130:30-39.
43.
Eichenfield LF, Krakowski AC, Piggott C, et al: Evidence-based recommendations for the diagnosis and treatment of pediatric acne. Pediatrics 2013;131:S163-S186.
44.
Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H: Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 2007;92:405-413.
45.
Rosner W, Vesper H: Toward excellence in testosterone testing: a consensus statement. J Clin Endocrinol Metab 2010;95:4542-4548.
46.
Legro RS, Schlaff WD, Diamond MP, et al: Total testosterone assays in women with polycystic ovary syndrome: precision and correlation with hirsutism. J Clin Endocrinol Metab 2010;95:5305-5313.
47.
Auchus RJ: Steroid assays and endocrinology: best practices for basic scientists. Endocrinology 2014;155:2049-2051.
48.
Salameh WA, Redor-Goldman MM, Clarke NJ, Mathur R, Azziz R, Reitz RE: Specificity and predictive value of circulating testosterone assessed by tandem mass spectrometry for the diagnosis of polycystic ovary syndrome by the National Institutes of Health 1990 criteria. Fertil Steril 2014;101:1135-1141.
49.
Vermeulen A, Verdonck L, Kaufman JM: A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999;84:3666-3672.
50.
O'Reilly MW, Taylor AE, Crabtree NJ, Hughes BA, Capper F, Crowley RK, Stewart PM, Tomlinson JW, Arlt W: Hyperandrogenemia predicts metabolic phenotype in polycystic ovary syndrome: the utility of serum androstenedione. J Clin Endocrinol Metab 2014;99:1027-1036.
51.
Moll G Jr, Rosenfield RL: Plasma free testosterone in the diagnosis of adolescent polycystic ovary syndrome. J Pediatr 1983;102:461-464.
52.
van Hooff MH, Voorhorst FJ, Kaptein MB, Hirasing RA, Koppenaal C, Schoemaker J: Insulin, androgen, and gonadotropin concentrations, body mass index, and waist to hip ratio in the first years after menarche in girls with regular menstrual cycles, irregular menstrual cycles, or oligomenorrhea. J Clin Endocrinol Metab 2000;85:1394-1400.
53.
Mortensen M, Ehrmann DA, Littlejohn E, Rosenfield RL: Asymptomatic volunteers with a polycystic ovary are a functionally distinct but heterogeneous population. J Clin Endocrinol Metab 2009;94:1579-1586.
54.
Rosenfield RL: Clinical review: adolescent anovulation: maturational mechanisms and implications. J Clin Endocrinol Metab 2013;98:3572-3583.
55.
Apter D, Vihko R: Serum pregnenolone, progesterone, 17-hydroxyprogesterone, testosterone, and 5 alpha-dihydrotestosterone during female puberty. J Clin Endocrinol Metab 1977;45:1039-1048.
56.
Venturoli S, Porcu E, Fabbri R, et al: Menstrual irregularities in adolescents: hormonal pattern and ovarian morphology. Horm Res 1986;24:269-279.
57.
Apter D, Raisanen I, Ylostalo P, Vihko R: Follicular growth in relation to serum hormonal patterns in adolescent compared with adult menstrual cycles. Fertil Steril 1987;47:82-88.
58.
van Hooff MH, Voorhorst FJ, Kaptein MB, Hirasing RA, Koppenaal C, Schoemaker J: Endocrine features of polycystic ovary syndrome in a random population. Hum Reprod 1999;14:2223-2229.
59.
Apter D, Vihko R: Endocrine determinants of fertility: serum androgen concentrations during follow-up of adolescents into the third decade of life. J Clin Endocrinol Metab 1990;71:970-974.
60.
Venturoli S, Porcu E, Fabbri V, et al: Longitudinal change of sonographic ovarian aspects and endocrine parameters in irregular cycles of adolescence. Pediatr Res 1995;38:974-980.
61.
Gambineri A, Fanelli F, Prontera O, Repaci A, Di Dalmazi G, Zanotti L, Pagotto U, Flacco ME, Guidi J, Fava GA, Manzoli L, Pasquali R: Prevalence of hyperandrogenic states in late adolescent and young women: epidemiological survey on Italian high-school students. J Clin Endocrinol Metab 2013;98:1641-1650.
62.
Metcalf MG, Skidmore DS, Lowry GF, Mackenzie JA: Incidence of ovulation in the years after the menarche. J Endocrinol 1983;97:213-219.
63.
Apter D: Endocrine and metabolic abnormalities in adolescents with a PCOS-like condition: consequences for adult reproduction. Trends Endocrinol Metab 1998;9:58-61.
64.
Treloar AE, Boynton RE, Behn BG, Brown BW: Variation of the human menstrual cycle through reproductive life. Int J Fertil 1967;12:77-126.
65.
Vollman RF: The menstrual cycle. Major Probl Obstet Gynecol 1977;7:1-193.
66.
Gardner J: Adolescent menstrual characteristics as predictors of gynaecological health. Ann Hum Biol 1983;10:31-40.
67.
Zhang K, Pollack S, Ghods A, Dicken C, Isaac B, Adel G, Zeitlian G, Santoro N: Onset of ovulation after menarche in girls: a longitudinal study. J Clin Endocrinol Metab 2008;93:1186-1194.
68.
van Hooff MH, Voorhorst FJ, Kaptein MB, 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;19:383-392.
69.
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;85:1021-1025.
70.
Wiksten-Almströmer M, Hirschberg AL, Hagenfeldt K: Prospective follow-up of menstrual disorders in adolescence and prognostic factors. Acta Obstet Gynecol Scand 2008;87:1162-1168.
71.
Southam AL, Richart RM: The prognosis for adolescents with menstrual abnormalities. Am J Obstet Gynecol 1966;94:637-645.
72.
Chumlea WC, Schubert CM, Roche AF, Kulin HE, Lee PA, Himes JH, Sun SS: Age at menarche and racial comparisons in US girls. Pediatrics 2003;111:110-113.
73.
Marshall WA, Tanner JM: Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291-303.
74.
Widholm O, Kantero RL: A statistical analysis of the menstrual patterns of 8,000 Finnish girls and their mothers. Acta Obstet Gynecol Scand Suppl 1971;14:1-36.
75.
Diaz A, Laufer MR, Breech LL: Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Pediatrics 2006;118:2245-2250.
76.
World Health Organization multicenter study on menstrual and ovulatory patterns in adolescent girls. I. A multicenter cross-sectional study of menarche. World Health Organization Task Force on Adolescent Reproductive Health. J Adolesc Health Care 1986;7:229-235.
77.
Flug D, Largo RH, Prader A: 1984 Menstrual patterns in adolescent Swiss girls: a longitudinal study. Ann Hum Biol 1984;11:495-508.
78.
Franks S: Adult polycystic ovary syndrome begins in childhood. Best Pract Res Clin Endocrinol Metab 2002;16:263-272.
79.
Dewailly D, Lujan ME, Carmina E, et al: Definition and significance of polycystic ovarian morphology: a task force report from the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update 2014;20:334-352.
80.
Hickey M, Doherty DA, Atkinson H, Sloboda DM, Franks S, Norman RJ, Hart R: Clinical, ultrasound and biochemical features of polycystic ovary syndrome in adolescents: implications for diagnosis. Hum Reprod 2011;26:1469-1477.
81.
Adams J, Franks Sl, Polson DW, et al: Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotropin releasing hormone. Lancet 1985;2:1375-1379.
82.
Codner E, Villarroel C, Eyzaguirre FC, et al: Polycystic ovarian morphology in postmenarchal adolescents. Fertil Steril 2011;95:702-706, e701-702.
83.
Ersen A, Onal H, Yildirim D, Adal E: Ovarian and uterine ultrasonography and relation to puberty in healthy girls between 6 and 16 years in the Turkish population: a cross-sectional study. J Pediatr Endocrinol Metab 2012;25:447-451.
84.
Hagen CP, Mouritsen A, Mieritz MG, Tinggaard J, Wohlfart-Veje C, Fallentin E, Brocks V, Sundberg K, Jensen LN, Anderson RA, Juul A, Main KM: Circulating AMH reflects ovarian morphology by magnetic resonance imaging and 3D ultrasound in 121 healthy girls. J Clin Endocrinol Metab 2015;100:880-890.
85.
Kelsey TW, Dodwell SK, Wilkinson AG, Greve T, Andersen CY, Anderson RA, Wallace WH: Ovarian volume throughout life: a validated normative model. PLoS One 2013;8:e71465.
86.
Radivojevic UD, Lazovic GN, Kravic-Stevovic TK, et al: Differences in anthropometric and ultrasonographic parameters between adolescent girls with regular and irregular menstrual cycles: a case-study of 835 cases. J Pediatr Adolesc Gynecol 2014;27:227-231.
87.
Barber TM, Alvey C, Greenslade M, et al: Patterns of ovarian morphology in polycystic ovary syndrome: a study utilising magnetic resonance imaging. Eur Radiol 2010;20:1207-2013.
88.
Brown M, Park AS, Shayya RF, Wolfson T, Su HI, Chang RJ: Ovarian imaging by magnetic resonance in adolescent girls with polycystic ovary syndrome and age-matched controls. J Magn Reson Imaging 2013;38:689-993.
89.
Ibáñez L, López-Bermejo A, Díaz M, Marcos MV, de Zegher F: Early metformin therapy (age 8-12 years) in girls with precocious pubarche to reduce hirsutism, androgen excess, and oligomenorrhea in adolescence. J Clin Endocrinol Metab 2011;96:E1262-E1267.
90.
Rosenfield RL, Wroblewski K, Padmanabhan V, Littlejohn E, Mortensen M, Ehrmann DA: Antimüllerian hormone levels are independently related to ovarian hyperandrogenism and polycystic ovaries. Fertil Steril 2012;98:242-249.
91.
Hart R, Doherty DA, Norman RJ, et al: Serum antimullerian hormone (AMH) levels are elevated in adolescent girls with polycystic ovaries and the polycystic ovarian syndrome (PCOS). Fertil Steril 2010;94:1118-1121.
92.
Villarroel C, Merino PM, Lopez P, et al: Polycystic ovarian morphology in adolescents with regular menstrual cycles is associated with elevated anti-Mullerian hormone. Hum Reprod 2011;26:2861-2868.
93.
Dewailly D, Andersen CY, Balen A, Broekmans F, Dilaver N, Fanchin R, Griesinger G, Kelsey TW, La Marca A, Lambalk C, Mason H, Nelson SM, Visser JA, Wallace WH, Anderson RA: The physiology and clinical utility of anti-Mullerian hormone in women. Hum Reprod Update 2014;20:370-385.
94.
Pawelczak M, Kenigsberg L, Milla S, Liu YH, Shah B: Elevated serum anti-Müllerian hormone in adolescents with polycystic ovary syndrome: relationship to ultrasound features. J Pediatr Endocrinol Metab 2012;25:983-989.
95.
Cengiz H, Ekin M, Dagdeviren H, Yildiz S, Kaya C, Kanawati A: Comparison of serum anti-Müllerian hormone levels in normal weight and overweight-obese adolescent patients with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2014;180C:46-50.
96.
Sopher AB, Grigoriev G, Laura D, Cameo T, Lerner JP, Chang RJ, McMahon DJ, Oberfield SE: Anti-Mullerian hormone may be a useful adjunct in the diagnosis of polycystic ovary syndrome in nonobese adolescents. J Pediatr Endocrinol Metab 2014;27:1175-1179.
97.
Trapp CM, Oberfield SE: Recommendations for treatment of nonclassic congenital adrenal hyperplasia (NCCAH): an update. Steroids 2012;77:342-346.
98.
Witchel SF, Azziz R: Nonclassic congenital adrenal hyperplasia. Int J Pediatr Endocrinol 2010;2010:625105.
99.
Speiser PW, Dupont B, Rubinstein P, Piazza A, Kastelan A, New MI: High frequency of nonclassical steroid 21-hydroxylase deficiency. Am J Hum Genet 1985;37:650-667.
100.
Miller WL, Auchus RJ: The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev 2011;32:81-151.
101.
Draper N, Walker EA, Bujalska IJ: Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency. Nat Genet 2003;34:434-439.
102.
Charmandari E, Kino T, Ichijo T, Chrousos GP: Generalized glucocorticoid resistance: clinical aspects, molecular mechanisms, and implications of a rare genetic disorder. J Clin Endocrinol Metab 2008;93:1563-1572.
103.
Unluhizarci K, Kaltsas G, Kelestimur F: Non-polycystic ovary syndrome-related endocrine disorders associated with hirsutism. Eur J Clin Invest 2012;42:86-94.
104.
Filho RB, Domingues L, Naves L, Ferraz E, Alves A, Casulari LA: Polycystic ovary syndrome and hyperprolactinemia are distinct entities. Gynecol Endocrinol 2007;23:267-272.
105.
Ghazi AA, Mofid D, Salehian MT, et al: Functioning adrenocortical tumors in children-secretory behavior. J Clin Res Pediatr Endocrinol 2013;5:27-32.
106.
New MI, Lorenzen F, Lerner AJ, et al: Genotyping steroid 21-hydroxylase deficiency: hormonal reference data. J Clin Endocrinol Metab 1983;57:320-326.
107.
Deneux C, Tardy V, Dib A, et al: Phenotype-genotype correlation in 56 women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 2001;86:207-213.
108.
Azziz R, Hincapie LA, Knochenhauer ES, Dewailly D, Fox L, Boots LR: Screening for 21-hydroxylase-deficient nonclassic adrenal hyperplasia among hyperandrogenic women: a prospective study. Fertil Steril 1999;72:915-925.
109.
Speiser PW, Azziz R, Baskin LS, et al: Congenital adrenal hyperplasia due to steroid 21-hydroxylase due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010;95:4133-4160.
110.
Pall M, Azziz R, Beires J, Pignatell D: The phenotype of hirsute women: a comparison of polycystic ovary syndrome and 21-hydroxylase-deficient nonclassic adrenal hyperplasia. Fertil Steril 2010;94:684-689.
111.
Finkielstain GP, Chen W, Mehta SP, et al: Comprehensive genetic analysis of 182 unrelated families with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 2011;96:E161-E172.
112.
Sultan C, Paris F: Clinical expression of polycystic ovary syndrome in adolescent girls. Fertil Steril 2006;86(suppl 1):S6.
113.
Ibáñez L, Potau N, Zampolli M, Prat N, Virdis R, Vicens-Calvet E, Carrascosa A: Hyperinsulinemia in postpubertal girls with a history of premature pubarche and functional ovarian hyperandrogenism. J Clin Endocrinol Metab 1996;81:1237-1243.
114.
Lewy VD, Danadian K, Witchel SF, Arslanian S: Early metabolic abnormalities in adolescent girls with polycystic ovarian syndrome. J Pediatr 2001;138:38-44.
115.
Apter D, Butzow T, Laughlin GA, et al: Metabolic features of polycystic ovary syndrome are found in adolescent girls with hyperandrogenism. J Clin Endocrinol Metab 1995;80:2966-2973.
116.
Ibáñez L, Díaz R, López-Bermejo A, Marcos MV: Clinical spectrum of premature pubarche: links to metabolic syndrome and ovarian hyperandrogenism. Rev Endocr Metab Disord 2009;10:63-76.
117.
Ibáñez L, Potau N, Marcos MV, de Zegher F: Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age. J Clin Endocrinol Metab 1999;84:4739-4741.
118.
Ibáñez L, Potau N, Zampolli M, Riqué S, Saenger P, Carrascosa A: Hyperinsulinemia and decreased insulin-like growth factor-binding protein-1 are common features in prepubertal and pubertal girls with a history of premature pubarche. J Clin Endocrinol Metab 1997;82:2283-2288.
119.
Gungor N, Saad R, Janosky J, Arslanian S: Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents. J Pediatr 2004;144:47-55.
120.
Glueck CJ, Morrison JA, Friedman LA, Goldenberg N, Stroop DM, Wang P: Obesity, free testosterone, and cardiovascular risk factors in adolescents with polycystic ovary syndrome and regularly cycling adolescents. Metabolism 2006;55:508-514.
121.
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;91:492-497.
122.
Lee S, Gungor N, Bacha F, Arslanian S: Insulin resistance: link to the components of the metabolic syndrome and biomarkers of endothelial dysfunction in youth. Diabetes Care 2007;30:2091-2097.
123.
Leibel NI, Baumann EE, Kocherginsky M, Rosenfield RL: Relationship of adolescent polycystic ovary syndrome to parental metabolic syndrome. J Clin Endocrinol Metab 2006;91:1275-1283.
124.
Rossi B, Sukalich S, Droz J, Griffin A, Cook S, Blumkin A, Guzick DS, Hoeger KM: Prevalence of metabolic syndrome and related characteristics in obese adolescents with and without polycystic ovary syndrome. J Clin Endocrinol Metab 2008;93:4780-4786.
125.
Chin V, Censani M, Lerner S, Conroy R, Oberfield S, McMahon D, Zitsman J, Fennoy I: Gonadal dysfunction in morbidly obese adolescent girls. Fertil Steril 2014;101:1142-1148.
126.
Roe AH, Prochaska E, Smith M, Sammel M, Dokras A: Using the androgen excess-PCOS society criteria to diagnose polycystic ovary syndrome and the risk of metabolic syndrome in adolescents. J Pediatr 2013;162:937-941.
127.
Hart R, Doherty DA, Mori T, Huang RC, Norman RJ, Franks S, Sloboda D, Beilin L, Hickey M: Extent of metabolic risk in adolescent girls with features of polycystic ovary syndrome. Fertil Steril 2011;95:2347-2353.
128.
Palmert MR, Gordon CM, Kartashov AI, et al: Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome. J Clin Endocrinol Metab 2002;87:1017-1023.
129.
Fruzzetti F, Perini D, Lazzarini V, Parrini D, Genazzani AR: Hyperandrogenemia influences the prevalence of the metabolic syndrome abnormalities in adolescents with the polycystic ovary syndrome. Gynecol Endocrinol 2009;25:335-343.
130.
Barbieri RL, Makris A, Randall RW, Daniels G, Kistner RW, Ryan KJ: Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J Clin Endocrinol Metab 1986;62:904-909.
131.
Dunaif A: Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997;18:774-800.
132.
Witchel SF, Arslanian S: Ovarian responses to hCG stimulation: insulin resistance/hyperinsulinaemia vs. insulin deficiency. Clin Endocrinol (Oxf) 1999;51:127-130.
133.
Arslanian SA, Lewy V, Danadian K, Saad R: Metformin therapy in obese adolescents with polycystic ovary syndrome and impaired glucose tolerance: amelioration of exaggerated adrenal response to adrenocorticotropin with reduction of insulinemia/insulin resistance. J Clin Endocrinol Metab 2002;87:1555-1559.
134.
Glueck CJ, Wang P, Fontaine R, Tracy T, Sieve-Smith L: Metformin to restore normal menses in oligo-amenorrheic teenage girls with polycystic ovary syndrome (PCOS). J Adolesc Health 2001;29:160-169.
135.
De Leo V, Musacchio MC, Morgante G, Piomboni P, Petraglia F: Metformin treatment is effective in obese teenage girls with PCOS. Hum Reprod 2006;21:2252-2256.
136.
Tfayli H, Ulnach JW, Lee S, Sutton-Tyrrell K, Arslanian S: Drospirenone/ethinyl estradiol versus rosiglitazone treatment in overweight adolescents with polycystic ovary syndrome: comparison of metabolic, hormonal, and cardiovascular risk factors. J Clin Endocrinol Metab 2011;96:1311-1319.
137.
Reinehr T, de Sousa G, Roth CL, Andler W: Androgens before and after weight loss in obese children. J Clin Endocrinol Metab 2005;90:5588-5595.
138.
Ibáñez L, Valls C, Ferrer A, Marcos MV, Rodriguez-Hierro F, de Zegher F: Sensitization to insulin induces ovulation in nonobese adolescents with anovulatory hyperandrogenism. J Clin Endocrinol Metab 2001;86:3595-3598.
139.
Jaquet D, Leger J, Chevenne D, Czernichow P, Levy-Marchal C: Intrauterine growth retardation predisposes to insulin resistance but not to hyperandrogenism in young women. J Clin Endocrinol Metab 1999;84:3945-3949.
140.
Abbott DH, Bacha F: Ontogeny of polycystic ovary syndrome and insulin resistance in utero and early childhood. Fertil Steril 2013;100:2-11.
141.
Ong KK, Potau N, Petry CJ, Jones R, Ness AR, Honour JW, de Zegher F, Ibáñez L, Dunger DB; Avon Longitudinal Study of Parents and Children Study Team: Opposing influences of prenatal and postnatal weight gain on adrenarche in normal boys and girls. J Clin Endocrinol Metab 2004;89:2647-2651.
142.
Neville KA, Walker JL: Precocious pubarche is associated with SGA, prematurity, weight gain, and obesity. Arch Dis Child 2005;90:258-261.
143.
Littlejohn EE, Weiss RE, Deplewski D, Edidin DV, Rosenfield R: 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.
144.
McCartney CR, Prendergast KA, Blank SK, Helm KD, Chhabra S, Marshall JC: Maturation of luteinizing hormone (gonadotropin-releasing hormone) secretion across puberty: evidence for altered regulation in obese peripubertal girls. J Clin Endocrinol Metab 2009;94:56-66.
145.
McCartney CR, Blank SK, Prendergast KA, Chhabra S, Eagleson CA, Helm KD, Yoo R, Chang RJ, Foster CM, Caprio S, Marshall JC: Obesity and sex steroid changes across puberty: evidence for marked hyperandrogenemia in pre- and early pubertal obese girls. J Clin Endocrinol Metab 2007;92:430-436.
146.
Dokras A, Witchel SF: Are young adult women with polycystic ovary syndrome slipping through the healthcare cracks? J Clin Endocrinol Metab 2014;99:1583-1585.
147.
Teede HJ, Misso ML, Deeks AA, et al: Assessment and management of polycystic ovary syndrome: summary of an evidence-based guideline. Med J Aust 2011;195:S65-S112.
148.
Allen HF, Mazzoni C, Heptulla RA, et al: Randomized controlled trial evaluating response to metformin versus standard therapy in the treatment of adolescents with polycystic ovary syndrome. J Pediatr Endocrinol 2005;18:761-768.
149.
Bridger T, MacDonald S, Baltzer F, Rodd C: Randomized placebo-controlled trial of metformin for adolescents with polycystic ovary syndrome. Arch Pediatr Adolesc Med 2006;160:241-246.
150.
Hoeger K, Davidson K, Kochman L, et al: The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized-placebo controlled trials. J Clin Endocrinol Metab 2008;93:4299-4306.
151.
Chung JP, Yiu AK, Chung TK, Chan SS: A randomized crossover study of medroxyprogesterone acetate and Diane-35 in adolescent girls with polycystic ovarian syndrome. J Pediatr Adolesc Gynecol 2014;27:166-171.
152.
Ibáñez L, Valls C, Ferrer A, et al: Sensitization to insulin induces ovulation in nonobese adolescents with anovulatory hyperandrogenism. J Clin Endocrinol Metab 2001;86:3595-3598.
153.
Rofey D, Szigethy E, Noll RB, et al: Cognitive behavioral therapy for physical and emotional disturbances in adolescent with polycystic ovarian syndrome: a pilot study. J Pediatr Psychol 2009;34:156-163.
154.
Harris-Glocker M, Davidson K, Kotchman L, et al: Improvement in quality of life questionnaire measures in obese adolescent females with polycystic ovarian syndrome treated with lifestyle changes and oral contraceptives with or without metformin. Fertil Steril 2010;93:1006-1019.
155.
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;95:2595-2598.
156.
El-Sharkawy AA, Abdelmoaleb GS, Aly MK, Kabel AM: Effect of metformin on sleep disorders in adolescent girls with polycystic ovarian syndrome. J Pediatr Adolesc Gynecol 2014;27:347-352.
157.
Bredella MA, McManus S, Misra M: Impact of metformin monotherapy versus metformin with oestrogen-progesterone on lipids in adolescent girls with polycystic ovarian syndrome. Clin Endocrinol 2013;79:199-203.
158.
Ibáñez L, de Zegher F: Ethinylestradiol- drospirenone, flutamide-metformin, or both for adolescents and women with hyperinsulinemic hyperandrogenism: opposite effects on adipocytokines and body adiposity. J Clin Endocrinol Metab 2004;89:1592-1597.
159.
Lass N, Kleber M, Winkel K, Wunsch R, Reinehr T: Effect of lifestyle intervention on features of polycystic ovarian syndrome, metabolic syndrome, and intima-media thickness in obese adolescent girls. J Clin Endocrinol Metab 2011;96:3533-3540.
160.
Loverro G, Lorusso F, De Pergola G, et al: Clinical and endocrinological effects of 6 month of metformin treatment in young hyperinsulinemic patients affected by polycystic ovary syndrome. Gynecol Endocrinol 2002;16:217-224.
161.
Díaz MR, Chacón M, López-Bermejo A, et al: Ethinyl estradiol-cyproterone acetate versus low-dose pioglitazone-flutamide-metformin for adolescent girls with androgen excess: divergent effects on CD163, TWEAK Receptor, ANGPTL4 and LEPTIN expression in subcutaneous adipose tissue. J Clin Endocrinol Metab 2012;97:3630-3638.
162.
Ibáñez L, Díaz M, Sebastiani G, Marcos MV, López-Bermejo A, de Zegher F: Oral contraception vs insulin sensitization for 18 months in nonobese adolescents with androgen excess: posttreatment differences in c-reactive protein, intima-media thickness, visceral adiposity, insulin sensitivity, and menstrual regularity. J Clin Endocrinol Metab 2013;98:E902-E907.
163.
Mastorakos G, Koliopoulos C, Creatsas G: Androgen and lipid profiles in adolescents with polycystic ovary syndrome who were treated with two forms of combined oral contraceptives. Fertil Steril 2002;77:919-927.
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2015
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