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Menstrual Disorders and Hyperandrogenism in Adolescence

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Pediatric Endocrinology

Abstract

The approach to adolescent menstrual dysfunction must be different than in adult women, as pubertal timing and events must be taken into consideration in diagnosis and management. Acquired or congenital disorders of the genital tract may underlie primary amenorrhea. Acquired or congenital anovulatory disorders of the hormonal cascade regulating ovary function and estrogen production may delay or arrest puberty or cause menstrual disorders (primary amenorrhea, secondary amenorrhea, oligomenorrhea, or excessive uterine bleeding). Hypogonadism may be primary or secondary and cause pubertal delay or menstrual disorders. Hyperandrogenism is a cause of menstrual disorders in adolescents, with polycystic ovary syndrome (PCOS) being the most common cause. Elevated serum testosterone level by high-specificity methodology is the cornerstone for diagnosing hyperandrogenism. Adrenal causes of hyperandrogenism must be excluded before PCOS can be diagnosed. Treatment of adolescent menstrual dysfunction is targeted to the underlying cause. Oral contraceptive medications are the cornerstone of treatment for the menstrual abnormalities and hyperandrogenism of adolescent PCOS, with antiandrogen treatment as an adjunct to treat cutaneous manifestations that are bothersome. Metformin is indicated for the treatment of glucose intolerance or diabetes mellitus in girls with PCOS, but is not primary treatment.

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References

  1. Rosenfield RL, Lipton RB, Drum ML. Thelarche, pubarche, and menarche attainment in children with normal and elevated body mass index. Pediatrics. 2009;123:84–8.

    Article  PubMed  Google Scholar 

  2. Biro FM, Greenspan LC, Galvez MP, Pinney SM, Teitelbaum S, Windham GC, Deardorff J, Herrick RL, Succop PA, Hiatt RA, Kushi LH, Wolff MS. Onset of breast development in a longitudinal cohort. Pediatrics. 2013;132(6):1019(9).

    Article  Google Scholar 

  3. 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;93:1186–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. American Academy of Pediatrics Committee on Adolescence, American College of Obstetricians and Gynecologists Committee on Adolescent Health Care, Diaz A, Laufer MR, Breech LL. Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Pediatrics. 2006;118:2245–50.

    Article  Google Scholar 

  5. Rosenfield RL. The diagnosis of polycystic ovary syndrome in adolescents. Pediatrics. 2015;136:1154–65. https://doi.org/10.1542/peds.2015-1430.

    Article  PubMed  Google Scholar 

  6. Rosenfield RL. Clinical review: adolescent anovulation: maturational mechanisms and implications. J Clin Endocrinol Metab. 2013;98:3572–83. https://doi.org/10.1210/jc.2013-1770.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Apter D, Viinikka L, Vihko R. Hormonal pattern of adolescent menstrual cycles. J Clin Endocrinol Metab. 1978;47:944–54.

    Article  CAS  PubMed  Google Scholar 

  8. Treloar AE, Boynton RE, Behn BG, Brown BW. Variation of the human menstrual cycle through reproductive life. Int J Fertil. 1967;12:77–126.

    CAS  PubMed  Google Scholar 

  9. Rosenfield RL, Cooke DW, Radovick S. Puberty and its disorders in the female. In: Sperling MA, editor. Pediatric endocrinology. 4th ed. Philadelphia: Elsevier; 2014. p. 569–663.

    Google Scholar 

  10. Golan A, Langer R, Bukovsky I, Caspi E. Congenital anomalies of the mullerian system. Fertil Steril. 1989;51:747–55.

    Article  CAS  PubMed  Google Scholar 

  11. Biason-Lauber A, De Filippo G, Konrad D, Scarano G, Nazzaro A, Schoenle EJ. WNT4 deficiency – a clinical phenotype distinct from the classic Mayer-Rokitansky-Kuster-Hauser syndrome: a case report. Hum Reprod. 2007;22:224–9.

    Article  CAS  PubMed  Google Scholar 

  12. March C. Acquired intrauterine adhesions. In: Adashi E, Rock J, Rosenwaks Z, editors. Reproductive endocrinology, surgery, and technology. Philadelphia: Lippincott-Raven; 1996. p. 1475–88.

    Google Scholar 

  13. Gravholt CH, Andersen NH, Conway GS, Dekkers OM, Geffner ME, Klein KO, Lin AE, Mauras N, Quigley CA, Rubin K, Sandberg DE, Sas TCJ, Silberbach M, Söderström-Anttila V, Stochholm K, van Alfen-van derVelden JA, Woelfle J, Backeljauw PF. International Turner Syndrome Consensus Group. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol. 2017;177(3):G1–G70.

    Article  CAS  PubMed  Google Scholar 

  14. Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009;360:606–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Goswami D, Conway GS. Premature ovarian failure. Hum Reprod Update. 2005;11:391–410.

    Article  CAS  PubMed  Google Scholar 

  16. Namnoum AB, Merriam GR, Moses AM, Levine MA. Reproductive dysfunction in women with Albright’s hereditary osteodystrophy. J Clin Endocrinol Metab. 1998;83:824–9.

    CAS  PubMed  Google Scholar 

  17. Layman LC, McDonough PG. Mutations of follicle stimulating hormone-beta and its receptor in human and mouse: genotype/phenotype. Mol Cell Endocrinol. 2000;161:9–17.

    Article  CAS  PubMed  Google Scholar 

  18. de Zegher F, Jaeken J. Endocrinology of the carbohydrate-deficient glycoprotein syndrome type 1 from birth through adolescence. Pediatr Res. 1995;37:395–401.

    Article  PubMed  Google Scholar 

  19. Layman LC. Genetics of human hypogonadotropic hypogonadism. Am J Med Genet. 1999;89:240–8.

    Article  CAS  PubMed  Google Scholar 

  20. Bose HS, Pescovitz OH, Miller WL. Spontaneous feminization in a 46,XX female patient with congenital lipoid adrenal hyperplasia due to a homozygous frameshift mutation in the steroidogenic acute regulatory protein. J Clin Endocrinol Metab. 1997;82:1511–5.

    CAS  PubMed  Google Scholar 

  21. Gordon CM, Kanaoka T, Nelson LM. Update on primary ovarian insufficiency in adolescents. Curr Opin Pediatr. 2015;27:511–9. https://doi.org/10.1097/MOP.0000000000000236.

    Article  CAS  PubMed  Google Scholar 

  22. Pfaeffle RW, Savage JJ, Hunter CS, Palme C, Ahlmann M, Kumar P, Bellone J, Schoenau E, Korsch E, Bramswig JH, Stobbe HM, Blum WF, Rhodes SJ. Four novel mutations of the LHX3 gene cause combined pituitary hormone deficiencies with or without limited neck rotation. J Clin Endocrinol Metab. 2007;92:1909–19.

    Article  CAS  PubMed  Google Scholar 

  23. Boehm U, Bouloux PM, Dattani MT, de Roux N, Dode C, Dunkel L, Dwyer AA, Giacobini P, Hardelin JP, Juul A, Maghnie M, Pitteloud N, Prevot V, Raivio T, Tena-Sempere M, Quinton R, Young J. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism – pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015;11:547–64. https://doi.org/10.1038/nrendo.2015.112.

    Article  PubMed  Google Scholar 

  24. Beranova M, Oliveira LMB, Bedecarrats GY, Schipani E, Vallejo M, Ammini AC, Quintos JB, Hall JE, Martin KA, Hayes FJ, Pitteloud N, Kaiser UB, Crowley WF Jr, Seminara SB. Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2001;86:1580–8.

    CAS  PubMed  Google Scholar 

  25. Komatsu M, Kondo T, Yamauchi K, Yokokawa N, Ichikawa K, Ishihara M, Aizawa T, Yamada T, Imai Y, Tanaka K. Antipituitary antibodies in patients with the primary empty sella syndrome. J Clin Endocrinol Metab. 1988;67:633–8.

    Article  CAS  PubMed  Google Scholar 

  26. Hendricks SA, Lippe BM, Kaplan SA, Bentson JR. Hypothalamic atrophy with progressive hypopituitarism in an adolescent girl. J Clin Endocrinol Metab. 1981;52:562–4.

    Article  CAS  PubMed  Google Scholar 

  27. Rappaport R, Brauner R, Czernichow P, Thibaud E, Renier D, Zucker JM, Lemerle J. Effect of hypothalamic and pituitary irradiation on pubertal development in children with cranial tumors. J Clin Endocrinol Metab. 1982;54:1164–8.

    Article  CAS  PubMed  Google Scholar 

  28. Van den Berghe G, de Zegher F, Bouillon R. Clinical review 95: acute and prolonged critical illness as different neuroendocrine paradigms. J Clin Endocrinol Metab. 1998;83:1827–34.

    PubMed  Google Scholar 

  29. Becker AE, Grinspoon SK, Klibanski A, Herzog DB. Eating disorders. N Engl J Med. 1999;340:1092–8.

    Article  CAS  PubMed  Google Scholar 

  30. Razdan AK, Rosenfield RL, Kim MH. Endocrinologic characteristics of partial ovarian failure. J Clin Endocrinol Metab. 1976;43:449–52.

    Article  CAS  PubMed  Google Scholar 

  31. Gordon CM, Ackerman KE, Berga SL, Kaplan JR, Mastorakos G, Misra M, Murad MH, Santoro NF, Warren MP. Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102(5):1413–39.

    Article  Google Scholar 

  32. Laughlin GA, Dominguez CE, Yen SSC. Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab. 1998;83:25–32.

    CAS  PubMed  Google Scholar 

  33. Sauder SE, Frager M, Case GD, Kelch RP, Marshall JC. Abnormal patterns of pulsatile luteinizing hormone secretion in women with hyperprolactinemia and amenorrhea: responses to bromocriptine. J Clin Endocrinol Metab. 1984;59:941–8.

    Article  CAS  PubMed  Google Scholar 

  34. Colao A, Lombardi G. Growth-hormone and prolactin excess. Lancet. 1998;352:1455–61.

    Article  CAS  PubMed  Google Scholar 

  35. Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, Wass JA, Endocrine Society. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:273–88. https://doi.org/10.1210/jc.2010-1692.

    Article  CAS  PubMed  Google Scholar 

  36. Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev. 2016;37:467–520. https://doi.org/10.1210/er.2015-1104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Srouji SS, Pagan YL, D’Amato F, Dabela A, Jimenez Y, Supko JG, Hall JE. Pharmacokinetic factors contribute to the inverse relationship between luteinizing hormone and body mass index in polycystic ovarian syndrome. J Clin Endocrinol Metab. 2007;92:1347–52.

    Article  CAS  PubMed  Google Scholar 

  38. Al-Safi ZA, Liu H, Carlson NE, Chosich J, Lesh J, Robledo C, Bradford AP, Gee NA, Phang T, Santoro N, Kohrt W, Polotsky AJ. Estradiol priming improves gonadotrope sensitivity and pro-inflammatory cytokines in obese women. J Clin Endocrinol Metab. 2015;100:4372–81. https://doi.org/10.1210/jc.2015-1946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Chrousos GP, Gold PW. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA. 1992;267:1244–52.

    Article  CAS  PubMed  Google Scholar 

  40. Lado-Abeal J, Rodriguez-Arnao J, Newell-Price JD, Perry LA, Grossman AB, Besser GM, Trainer PJ. Menstrual abnormalities in women with Cushing’s disease are correlated with hypercortisolemia rather than raised circulating androgen levels. J Clin Endocrinol Metab. 1998;83:3083–8.

    CAS  PubMed  Google Scholar 

  41. Winters SJ, Berga SL. Gonadal dysfunction in patients with thyroid disorders. Endocrinologist. 1997;7:167–73.

    Article  Google Scholar 

  42. Anonymous. National Institutes of Health evidence-based methodology workshop on polycystic ovary syndrome. 2012; pp. 1–12.

    Google Scholar 

  43. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF, 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. https://doi.org/10.1016/j.fertnstert.2008.06.035.

    Article  PubMed  Google Scholar 

  44. Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E, 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. 2015;21:1291–300. https://doi.org/10.4158/EP15748.DSC.

    Article  PubMed  Google Scholar 

  45. Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, Welt CK, Endocrine Society. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98:4565–92. https://doi.org/10.1210/jc.2013-2350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Witchel SF, Oberfield S, Rosenfield RL, Codner E, Bonny A, Ibanez L, Pena A, Horikawa R, Gomez-Lobo V, Joel D, Tfayli H, Arslanian S, Dabadghao P, Garcia Rudaz C, Lee PA. The diagnosis of polycystic ovary syndrome during adolescence. Horm Res Paediatr. 2015.; doi: 000375530 [pii].

    Google Scholar 

  47. Mortensen M, Rosenfield RL, Littlejohn E. Functional significance of polycystic-size ovaries in healthy adolescents. J Clin Endocrinol Metab. 2006;91:3786–90.

    Article  CAS  PubMed  Google Scholar 

  48. Rosenfield RL. Current concepts of polycystic ovary syndrome. Baillieres Clin Obstet Gynaecol. 1997;11:307–33.

    Article  CAS  PubMed  Google Scholar 

  49. Rosenfield RL, Ehrmann DA, Littlejohn EE. Adolescent polycystic ovary syndrome due to functional ovarian hyperandrogenism persists into adulthood. J Clin Endocrinol Metab. 2015;100:1537–43. https://doi.org/10.1210/jc.2014-4290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. 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.

    Article  CAS  PubMed  Google Scholar 

  51. Eagleson CA, Gingrich MB, Pastor CL, Arora TK, Burt CM, Evans WS, Marshall JC. 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. https://doi.org/10.1210/jcem.85.11.6992.

    Article  CAS  PubMed  Google Scholar 

  52. Rosenfield RL. Ovarian and adrenal function in polycystic ovary syndrome. Endocrinol Metab Clin N Am. 1999;28:265–93.

    Article  CAS  Google Scholar 

  53. Nelson VL, Legro RS, Strauss JF 3rd, JM MA. Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Mol Endocrinol. 1999;13:946–57.

    Article  CAS  PubMed  Google Scholar 

  54. Nelson VL, Qin KN, Rosenfield RL, Wood JR, Penning TM, Legro RS, Strauss JF 3rd, JM MA. The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2001;86:5925–33.

    Article  CAS  PubMed  Google Scholar 

  55. McAllister JM, Legro RS, Modi BP, Strauss JF 3rd. Functional genomics of PCOS: from GWAS to molecular mechanisms. Trends Endocrinol Metab. 2015;26:118–24. https://doi.org/10.1016/j.tem.2014.12.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care. 1999;22:141–6.

    Article  CAS  PubMed  Google Scholar 

  57. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005;352:1223–36.

    Article  CAS  PubMed  Google Scholar 

  58. Wu S, Divall S, Nwaopara A, Radovick S, Wondisford F, Ko C, Wolfe A. Obesity-induced infertility and hyperandrogenism are corrected by deletion of the insulin receptor in the ovarian theca cell. Diabetes. 2014;63(4):1270–82.

    Article  PubMed  Google Scholar 

  59. Du X, Rosenfield RL, Qin K. KLF15 is a transcriptional regulator of the human 17beta-hydroxysteroid dehydrogenase type 5 gene. A potential link between regulation of testosterone production and fat stores in women. J Clin Endocrinol Metab. 2009;94:2594–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hirshfeld-Cytron J, Barnes RB, Ehrmann DA, Caruso A, Mortensen MM, Rosenfield RL. Characterization of functionally typical and atypical types of polycystic ovary syndrome. J Clin Endocrinol Metab. 2009;94:1587–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Dewailly D, Pigny P, Soudan B, Catteau-Jonard S, Decanter C, Poncelet E, Duhamel A. Reconciling the definitions of polycystic ovary syndrome: the ovarian follicle number and serum anti-Mullerian hormone concentrations aggregate with the markers of hyperandrogenism. J Clin Endocrinol Metab. 2010;95:4399–405.

    Article  CAS  PubMed  Google Scholar 

  62. Foecking EM, Szabo M, Schwartz NB, Levine JE. Neuroendocrine consequences of prenatal androgen exposure in the female rat: absence of luteinizing hormone surges, suppression of progesterone receptor gene expression, and acceleration of the gonadotropin-releasing hormone pulse generator. Biol Reprod. 2005;72:1475–83.

    Article  CAS  PubMed  Google Scholar 

  63. Witchel SF, Lee PA, Suda-Hartman M, Hoffman EP. Hyperandrogenism and manifesting heterozygotes for 21-hydroxylase deficiency. Biochem Mol Med. 1997;62:151–8.

    Article  CAS  PubMed  Google Scholar 

  64. Hensleigh PA, Woodruff JD. Differential maternal-fetal response to androgenizing luteoma or hyperreactive luteinalis. Obstet Gynecol Surv. 1978;33:262–71.

    Article  CAS  PubMed  Google Scholar 

  65. Meldrum DR, Frumar AM, Shamonki IM, Benirschke K, Judd HL. Ovarian and adrenal steroidogenesis in a virilized patient with gonadotropin-resistant ovaries and hilus cell hyperplasia. Obstet Gynecol. 1980;56:216–21.

    CAS  PubMed  Google Scholar 

  66. Kaltsas GA, Mukherjee JJ, Jenkins PJ, Satta MA, Islam N, Monson JP, Besser GM, Grossman AB. Menstrual irregularity in women with acromegaly. J Clin Endocrinol Metab. 1999;84:2731–5.

    Article  CAS  PubMed  Google Scholar 

  67. Herzog AG. Menstrual disorders in women with epilepsy. Neurology. 2006;66:S23–8.

    Article  PubMed  Google Scholar 

  68. Martin KA, Chang RJ, Ehrmann DA, Ibanez L, Lobo RA, Rosenfield RL, Shapiro J, Montori VM, Swiglo BA. Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2008;93:1105–20.

    Article  CAS  PubMed  Google Scholar 

  69. Barnes RB, Rosenfield RL, Ehrmann DA, Cara JF, Cuttler L, Levitsky LL, Rosenthal IM. 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.

    CAS  PubMed  Google Scholar 

  70. Qin K, Rosenfield RL. Mutations of the hexose-6-phosphate dehydrogenase gene rarely cause hyperandrogenemic polycystic ovary syndrome. Steroids. 2011;76(1-2):135–9.

    Article  CAS  PubMed  Google Scholar 

  71. Lavery GG, Walker EA, Tiganescu A, Ride JP, Shackleton CH, Tomlinson JW, Connell JM, Ray DW, Biason-Lauber A, Malunowicz EM, Arlt W, Stewart PM. Steroid biomarkers and genetic studies reveal inactivating mutations in hexose-6-phosphate dehydrogenase in patients with cortisone reductase deficiency. J Clin Endocrinol Metab. 2008;93:3827–32. https://doi.org/10.1210/jc.2008-0743.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Lawson AJ, Walker EA, Lavery GG, Bujalska IJ, Hughes B, Arlt W, Stewart PM, Ride JP. Cortisone-reductase deficiency associated with heterozygous mutations in 11beta-hydroxysteroid dehydrogenase type 1. Proc Natl Acad Sci U S A. 2011;108:4111–6. https://doi.org/10.1073/pnas.1014934108.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Noordam C, Dhir V, McNelis JC, Schlereth F, Hanley NA, Krone N, Smeitink JA, Smeets R, Sweep FC, Claahsen-van der Grinten HL, Arlt W. Inactivating PAPSS2 mutations in a patient with premature pubarche. N Engl J Med. 2009;360:2310–8. https://doi.org/10.1056/NEJMoa0810489.

    Article  CAS  PubMed  Google Scholar 

  74. Kaltsas GA, Korbonits M, Isidori AM, Webb JA, Trainer PJ, Monson JP, Besser GM, Grossman AB. How common are polycystic ovaries and the polycystic ovarian syndrome in women with Cushing’s syndrome? Clin Endocrinol. 2000;53:493–500.

    Article  CAS  Google Scholar 

  75. Futterweit W, Krieger DT. Pituitary tumors associated with hyperprolactinemia and polycystic ovarian disease. Fertil Steril. 1979;31:608–13.

    Article  CAS  PubMed  Google Scholar 

  76. Speiser PW, Susin M, Sasano H, Bohrer S, Markowitz J. Ovarian hyperthecosis in the setting of portal hypertension. J Clin Endocrinol Metab. 2000;85:873–7.

    Article  CAS  PubMed  Google Scholar 

  77. Bas S, Guran T, Atay Z, Haliloglu B, Abali S, Turan S, Bereket A. Premature pubarche, hyperinsulinemia and hypothyroxinemia: novel manifestations of congenital portosystemic shunts (abernethy malformation) in children. Horm Res Paediatr. 2015;83:282–7. https://doi.org/10.1159/000369395.

    Article  CAS  PubMed  Google Scholar 

  78. Rosenfield RL. Polycystic ovary syndrome in adolescents. UpToDate. 2015. http://www.uptodate.com/index

  79. Frisch RE, McArthur JW. Menstrual cycles: fatness as a determinant of minimum weight for height necessary for their maintenance or onset. Science. 1974;185:949–51.

    Article  CAS  PubMed  Google Scholar 

  80. Rebar RW, Connolly HV. Clinical features of young women with hypergonadotropic amenorrhea. Fertil Steril. 1990;53:804–10.

    Article  CAS  PubMed  Google Scholar 

  81. Rosner W, Hankinson SE, Sluss PM, Vesper HW, Wierman ME. Challenges to the measurement of estradiol: an endocrine society position statement. J Clin Endocrinol Metab. 2013;98:1376–87. https://doi.org/10.1210/jc.2012-3780.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ibanez L, Potau N, Zampolli M, Virdis R, Gussinye M, Carrascosa A, Saenger P, Vicens-Calvet E. Use of leuprolide acetate response patterns in the early diagnosis of pubertal disorders: comparison with the gonadotropin-releasing hormone test. J Clin Endocrinol Metab. 1994;78:30–5.

    CAS  PubMed  Google Scholar 

  83. Winslow KL, Toner JP, Brzyski RG, Oehninger SC, Acosta AA, Muasher SJ. The gonadotropin-releasing hormone agonist stimulation test – a sensitive predictor of performance in the flare-up in vitro fertilization cycle. Fertil Steril. 1991;56:711–7.

    Article  CAS  PubMed  Google Scholar 

  84. Zimmer CA, Ehrmann DA, Rosenfield RL. Potential diagnostic utility of intermittent administration of short-acting gonadotropin-releasing hormone agonist in gonadotropin deficiency. Fertil Steril. 2010;94:2697–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Rosenfield RL, Bordini B, Yu C. Comparison of detection of normal puberty in girls by a hormonal sleep test and a gonadotropin-releasing hormone agonist test. J Clin Endocrinol Metab. 2013;98:1591–601. https://doi.org/10.1210/jc.2012-4136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Rosenfield RL. What every physician should know about polycystic ovary syndrome. Dermatol Ther. 2008;21:354–61.

    Article  PubMed  Google Scholar 

  87. Legro RS, Schlaff WD, Diamond MP, Coutifaris C, Casson PR, Brzyski RG, Christman GM, Trussell JC, Krawetz SA, Snyder PJ, Ohl D, Carson SA, Steinkampf MP, Carr BR, McGovern PG, Cataldo NA, Gosman GG, Nestler JE, Myers ER, Santoro N, Eisenberg E, Zhang M, Zhang H, for the Reproductive Medicine Network. Total testosterone assays in women with polycystic ovary syndrome: precision and correlation with hirsutism. J Clin Endocrinol Metab. 2010;95:5305–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. 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;101:1135–41.e2. https://doi.org/10.1016/j.fertnstert.2013.12.056.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Rosenfield RL, Mortensen M, Wroblewski K, Littlejohn E, Ehrmann DA. Determination of the source of androgen excess in functionally atypical polycystic ovary syndrome by a short dexamethasone androgen-suppression test and a low-dose ACTH test. Hum Reprod. 2011;26:3138–46. https://doi.org/10.1093/humrep/der291.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93:1526–40. https://doi.org/10.1210/jc.2008-0125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Escobar-Morreale HF, Sanchon R, San Millan JL. A prospective study of the prevalence of nonclassical congenital adrenal hyperplasia among women presenting with hyperandrogenic symptoms and signs. J Clin Endocrinol Metab. 2008;93:527–33.

    Article  CAS  PubMed  Google Scholar 

  92. Bidet M, Bellanne-Chantelot C, Galand-Portier M, Tardy V, Billaud L, Laborde K, Coussieu C, Morel Y, Vaury C, Golmard J, Claustre A, Mornet E, Chakhtoura Z, Mowszowicz I, Bachelot A, Touraine P, Kuttenn F. Clinical and molecular characterization of a cohort of 161 unrelated women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency and 330 family members. J Clin Endocrinol Metab. 2009;94:1570–8.

    Article  CAS  PubMed  Google Scholar 

  93. Lutfallah C, Wang W, Mason JI, Chang YT, Haider A, Rich B, Castro-Magana M, Copeland KC, David R, Pang S. Newly proposed hormonal criteria via genotypic proof for type II 3{beta}-hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab. 2002;87:2611–22.

    CAS  PubMed  Google Scholar 

  94. Joehrer K, Geley S, Strasser-Wozak EM, Azziz R, Wollmann HA, Schmitt K, Kofler R, White PC. CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Hum Mol Genet. 1997;6:1829–34. doi: dda236 [pii].

    Article  CAS  PubMed  Google Scholar 

  95. Valassi E, Klibanski A, Biller BMK. Potential cardiac valve effects of dopamine agonists in hyperprolactinemia. J Clin Endocrinol Metab. 2010;95:1025–33.

    Article  CAS  PubMed  Google Scholar 

  96. Lock J, Le Grange D, Agras WS, Moye A, Bryson SW, Jo B. Randomized clinical trial comparing family-based treatment with adolescent-focused individual therapy for adolescents with anorexia nervosa. Arch Gen Psychiatry. 2010;67:1025–32.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Miller KK, Lee EE, Lawson EA, Misra M, Minihan J, Grinspoon SK, Gleysteen S, Mickley D, Herzog D, Klibanski A. Determinants of skeletal loss and recovery in anorexia nervosa. J Clin Endocrinol Metab. 2006;91:2931–7.

    Article  CAS  PubMed  Google Scholar 

  98. Misra M, Katzman D, Miller KK, Mendes N, Snelgrove D, Russell M, Goldstein MA, Ebrahimi S, Clauss L, Weigel T, Mickley D, Schoenfeld DA, Herzog DB, Klibanski A. Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa. J Bone Miner Res. 2011;26:2430–8. https://doi.org/10.1002/jbmr.447.

    Article  CAS  PubMed  Google Scholar 

  99. Rosenfield RL, Devine N, Hunold JJ, Mauras N, Moshang T Jr, Root AW. Salutary effects of combining early very low-dose systemic estradiol with growth hormone therapy in girls with turner syndrome. J Clin Endocrinol Metab. 2005;90:6424–30.

    Article  CAS  PubMed  Google Scholar 

  100. Chernausek SD, Attie KM, Cara JF, Rosenfeld RG, Frane J. Growth hormone therapy of turner syndrome: the impact of age of estrogen replacement on final height. Genentech, Inc., Collaborative Study Group. J Clin Endocrinol Metab. 2000;85:2439–45.

    CAS  PubMed  Google Scholar 

  101. Woodruff JD, Pickar JH. Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone. The Menopause Study Group. Am J Obstet Gynecol. 1994;170:1213–23.

    Article  CAS  PubMed  Google Scholar 

  102. Stegeman BH, de Bastos M, Rosendaal FR, van Hylckama VA, Helmerhorst FM, Stijnen T, Dekkers OM. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ. 2013;347:f5298. https://doi.org/10.1136/bmj.f5298.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Renoux C, Dell’aniello S, Garbe E, Suissa S. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. BMJ. 2010;340:c2519.

    Article  PubMed  Google Scholar 

  104. Santen RJ, Allred DC, Ardoin SP, Archer DF, Boyd N, Braunstein GD, Burger HG, Colditz GA, Davis SR, Gambacciani M, Gower BA, Henderson VW, Jarjour WN, Karas RH, Kleerekoper M, Lobo RA, Manson JE, Marsden J, Martin KA, Martin L, Pinkerton JV, Rubinow DR, Teede H, Thiboutot DM, Utian WH, Endocrine Society. Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab. 2010;95:s1–s66. https://doi.org/10.1210/jc.2009-2509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, Meyer-Bahlburg HF, Miller WL, Montori VM, Oberfield SE, Ritzen M, White PC, Endocrine Society. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:4133–60. https://doi.org/10.1210/jc.2009-2631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Rosenfield RL, Bickel S, Razdan AK. Amenorrhea related to progestin excess in congenital adrenal hyperplasia. Obstet Gynecol. 1980;56:208–15.

    CAS  PubMed  Google Scholar 

  107. Swiglo BA, Cosma M, Flynn DN, Kurtz DM, Labella ML, Mullan RJ, Erwin PJ, Montori VM. Clinical review: Antiandrogens for the treatment of hirsutism: a systematic review and metaanalyses of randomized controlled trials. J Clin Endocrinol Metab. 2008;93:1153–60.

    Article  PubMed  Google Scholar 

  108. Wild RA, Carmina E, Diamanti-Kandarakis E, Dokras A, Escobar-Morreale HF, Futterweit W, Lobo R, Norman RJ, Talbott E, Dumesic DA. Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol Metab. 2010;95:2038–49.

    Article  CAS  PubMed  Google Scholar 

  109. 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.

    Article  CAS  PubMed  Google Scholar 

  110. Tasali E, Chapotot F, Leproult R, Whitmore H, Ehrmann DA. Treatment of obstructive sleep apnea improves cardiometabolic function in young obese women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2011;96:365–74. https://doi.org/10.1210/jc.2010-1187.

    Article  CAS  PubMed  Google Scholar 

  111. Eid GM, Cottam DR, Velcu LM, Mattar SG, Korytkowski MT, Gosman G, Hindi P, Schauer PR. Effective treatment of polycystic ovarian syndrome with Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2005;1:77–80.

    Article  PubMed  Google Scholar 

  112. Moran LJ, Pasquali R, Teede HJ, Hoeger KM, Norman RJ. 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.

    Article  PubMed  Google Scholar 

  113. Ibanez L, Potau N, Marcos MV, de Zegher F. Treatment of hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism in nonobese, adolescent girls: effect of flutamide. J Clin Endocrinol Metab. 2000;85:3251–5.

    CAS  PubMed  Google Scholar 

  114. Fleming R, Hopkinson ZE, Wallace AM, Greer IA, Sattar N. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. J Clin Endocrinol Metab. 2002;87:569–74.

    Article  CAS  PubMed  Google Scholar 

  115. Moghetti P, Castello R, Negri C, Tosi F, Perrone F, Caputo M, Zanolin E, Muggeo M. 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;85:139–46.

    CAS  PubMed  Google Scholar 

  116. Hoeger K, Davidson K, Kochman L, Cherry T, Kopin L, Guzick DS. The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials. J Clin Endocrinol Metab. 2008;93:4299–306. https://doi.org/10.1210/jc.2008-0461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Eisenhardt S, Schwarzmann N, Henschel V, Germeyer A, von Wolff M, Hamann A, Strowitzki T. Early effects of metformin in women with polycystic ovary syndrome: a prospective randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2006;91:946–52.

    Article  CAS  PubMed  Google Scholar 

  118. Salley KES, Wickham EP, Cheang KI, Essah PA, Karjane NW, Nestler JE. POSITION STATEMENT: glucose intolerance in polycystic ovary syndrome a position statement of the androgen excess society. J Clin Endocrinol Metab. 2007;92:4546–56.

    Article  CAS  PubMed  Google Scholar 

  119. Ehrmann DA, Schneider DJ, Sobel BE, Cavaghan MK, Imperial J, Rosenfield RL, Polonsky KS. Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1997;82:2108–16.

    CAS  PubMed  Google Scholar 

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DiVall, S.A., Rosenfield, R.L. (2018). Menstrual Disorders and Hyperandrogenism in Adolescence. In: Radovick, S., Misra, M. (eds) Pediatric Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-73782-9_28

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