The pediatric origins of polycystic ovary syndrome

Polycystic Ovary Syndrome, Second Edition

Volumn 9780521848497, Issue , 2007, Pages 233-261

  Roldán, Belén ^a   Escobar Morreale, Héctor F ^a  

^a HOSPITAL RAMÓN Y CAJAL   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84896885805     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1017/CBO9780511545191.015     Document Type: Chapter

References (139)

1. Adams J., Polson D.W., Abdulwahid N., et al. (1985) Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotrophin releasing hormone. Lancet ii:1375-1378.
2. Adashi E. Y., Hsueh A. J., and Yen S. S. (1981) Insulin enhancement of luteinizing hormone and follicle-stimulating release by cultured pituitary cells. Endocrinology 108:1441-1449.
3. Adashi E. Y., Resnick C. E., D'Ercole A. J., Svoboda M. E., and van Wyk J. J. (1985) Insulin-like growth factors as intraovarian regulators of granulosa cell growth and function. Endocr. Rev. 6:400-420.
4. American Diabetes Association (2000) Type 2 diabetes in children and adolescents. Pediatrics 105:671-680.
5. Amiel S. A., Sherwin R. S., Simonson D. C., Lauritano A. A., and Tamborlane W.V. (1986) Impaired insulin action in puberty: a contributing factor to poor glycemic control in adolescents with diabetes. N. Engl. J. Med. 315:215-219.
6. Amiel S. A., Caprio S., Sherwin R. S., et al. (1991) Insulin resistance of puberty: a defect restricted to peripheral glucose metabolism. J. Clin. Endocrinol. Metab. 72:277-282.
7. Apter D. (1998) Endocrine and metabolic abnormalities in adolescents with a PCOS-like condition: consequences for adult reproduction. Trends Endocrinol. Metab. 9:58-61.
8. Apter D., Butzow T. L., Laughlin G. A., and Yen S. S. (1993) Gonadotropin-releasing hormone pulse generator activity during pubertal transition in girls: pulsatile and diurnal patterns of circulating gonadotropins. J. Clin. Endocrinol. Metab. 76:940-949.
9. Apter D., Butzow T., Laughlin G. A., and Yen S. S. (1994) Accelerated 24-hour luteinizing hormone pulsatile activity in adolescent girls with ovarian hyperandrogenism: relevance of the developmental phase of polycystic ovarian syndrome. J. Clin. Endocrinol. Metab. 79:119-125.
10. Apter D., Butzow T., Laughlin G. A., and Yen S. S. (1995) Metabolic features of polycystic ovary syndrome are found in adolescent girls with hyperandrogenism. J. Clin. Endocrinol. Metab. 80:2966-2973.
11. Argente J., Barrios V., Pozo J., et al. (1993) Normative data for insulin like growth factors (IGFs), IGF-binding proteins, and growth hormone-binding protein in a healthy Spanish pediatric population: age-and sex-related changes. J. Clin. Endocrinol. Metab. 77:1522-1528.
12. Arslanian S. A., Lewy V.D., and Danadian K. (2001) Glucose intolerance in obese adolescents with polycystic ovary syndrome: roles of insulin resistance and b-cell dysfunction and risk of cardiovascular disease. J. Clin. Endocrinol. Metab. 86:66-71.
13. Arslanian S. A., Lewy V., Danadian K., and Saad R. (2002) 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. 87:1555-1559.
14. Asunción M., Calvo R. M., San Millán J. L., et al. (2000) A prospective study of the prevalence of the polycystic ovary syndrome in unselected caucasian women from Spain. J. Clin. Endocrinol. Metab. 85:2434-2438.
15. Auchus R. J., Geller D. H., Lee T. C., and Miller W. L. (1998) The regulation of human P450c17 activity: relationship to premature adrenarche, insulin resistance and the polycystic ovary syndrome. Trends Endocrinol. Metab. 9:47-50.
16. Avvad C. K., Holeuwerger R., Silva V. C., Bordallo M. A., and Breitenbach M. M. (2001) Menstrual irregularity in the first postmenarchal years: an early clinical sign of polycystic ovary syndrome in adolescence. Gynecol. Endocrinol. 15:170-177.
17. Banerjee S., Raghavan S., Wasserman E. J., et al. (1998) Hormonal findings in African-American and Caribbean Hispanic girls with premature adrenarche: implications for polycystic ovarian syndrome. Pediatrics 102:E-36.
18. Barker D. J. and Clark P. M. (1997) Fetal undernutrition and disease in later life. Rev. Reprod. 2:105-112.
19. Barker D. J. P., Hales C. H.D., Osmond C., and Clark P. M. S. (1993) Type 2 (non-insulindependent) diabetes mellitus, hypertension and hyperlipidemia (syndrome X): relation to reduced fetal growth. Diabetologia 36:62-67.
20. Barnes R. B., Rosenfield R. L., Burstein S., and Ehrmann D. A. (1989) Pituitary-ovarian responses to nafarelin testing in the polycystic ovary syndrome. N. Engl. J. Med. 320:559-565.
21. Battaglia C., Regnani G., Mancini F., et al. (2002) Isolated premature pubarche: ultrasonographic and color Doppler analysis-a longitudinal study. J. Clin. Endocrinol. Metab. 87:3148-3154.
22. Bloch C. A., Clemons P., and Sperling M. A. (1987) Puberty decreases insulin sensitivity. J. Pediatr. 110:481-487.
23. Bridges N. A., Cooke A., Healy M. J. R., Hindmarsh P. C., and Brook C. G.D. (1995) Ovaries in sexual precocity. Clin. Endocrinol. (Oxf.) 42:135-140.
24. Caprio S., Plewe G., Diamond M. P., et al. (1989) Increased insulin secretion in puberty: a compensatory response to reductions in insulin sensitivity. J. Pediatr. 114:963-967.
25. Caprio S., Hyman L.D., Limb C., et al. (1995) Central adiposity and its metabolic correlates in obese adolescent girls. Am. J. Physiol. Endocrinol. Metab. 269:E118-E126.
26. Carmina E. and Lobo R. A. (1999) Polycystic ovary syndrome (PCOS): arguably the most common endocrinopathy is associated with significant morbidity in women. J. Clin. Endocrinol. Metab. 84:1897-1899.
27. Chang R. J., Nakamura R. M., Judd H. L., and Kaplan S. A. (1983) Insulin resistance in nonobese patients with polycystic ovarian disease. J. Clin. Endocrinol. Metab. 57:356-359.
28. Cizza G., Dorn L.D., Lotsikas A., et al. (2001) Circulating plasma leptin and IGF-1 levels in girls with premature adrenarche: potential implications of a preliminary study. Horm. Metab. Res. 33:138-143.
29. Conwell L. S., Trost S. G., Brown W. J., and Batch J. A. (2004) Indexes of insulin resistance and secretion in obese children and adolescents: a validation study. Diabetes Care 27:314-319.
30. Cresswell J. L., Barker D. J. P., Osmond C., et al. (1997) Fetal growth, length of gestation, and polycystic ovaries in adult life. Lancet 350:1131-1135.
31. Crowther N. J., Cameron N., Trusler J., and Gray I. P. (1998) Association between poor glucose tolerance and rapid postnatal weight gain in seven-year-old children. Diabetologia 41:1163-1167.
32. Davis P. H., Dawson J.D., RileyW. A., and Lauer R. M. (2001) Carotid intimal-medial thickness is related to cardiovascular risk factors measured from childhood through middle age: the Muscatine Study. Circulation 104:2815-2819.
33. Diamanti-Kandarakis E., Kouli C. R., Bergiele A. T., et al. (1999) A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J. Clin. Endocrinol. Metab. 84:4006-4011.
34. Diamond J. F. B. and Eichler D. C. (2002) Leptin and the adipocyte endocrine system. Crit. Rev. Clin. Lab. Sci. 39:499-525.
35. DiMartino-Nardi J. (1999) Premature adrenarche: findings in prepubertal African-American and Caribbean-Hispanic girls. Acta Paediatr. 88(Suppl. 433):67-72.
36. Dunaif A. (1995) Hyperandrogenic anovulation (PCOS): a unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus. Am. J. Med. 98(Suppl. 1A):335-395.
37. Dunaif A. (1997) Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr. Rev. 18:774-800.
38. Dunaif A., Graf M., Mandeli J., Laumas V., and Dobrjansky A. (1987) Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance and/or hyperinsulinemia. J. Clin. Endocrinol. Metab. 65:499-507.
39. Dunaif A., Segal K. R., Futterweit W., and Dobrjansky A. (1989) Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 38:1165-1174.
40. Dunaif A., Xia J., Book C., Schenker E., and Tang Z. (1995) Excessive insulin receptor serine phosphorylation in cultured fibroblasts and skeletal muscle. J. Clin. Invest. 96:801-810.
41. Ehrmann D. A., Rosenfield R. L., Barnes R. B., Brigell D. F., and Sheikh Z. (1992) Detection of functional ovarian hyperandrogenism in women with androgen excess. N. Engl. J. Med. 327:157-162.
42. Ehrmann D. A., Barnes R. B., and Rosenfield R. L. (1995) Polycystic ovary syndrome as a form of functional hyperandrogenism due to dysregulation of androgen secretion. Endocr. Rev. 16:322-353.
43. Ehrmann D. A., Barnes R. B., Rosenfield R. L., Cavaghan M. K., and Imperial J. (1999) Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 22:141-146.
44. El Mkadem S. A., Lautier C., Macari F., et al. (2001) Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome. Diabetes 50:2164-2168.
45. Escobar-Morreale H. F., San Millan J. L., Smith R. R., Sancho J., and Witchel S. F. (1999) The presence of the 21-hydroxylase deficiency carrier status in hirsute women: phenotype-genotye correlations. Fertil. Steril. 72:629-638.
46. Escobar-Morreale H. F., Villuendas G., Botella-Carretero J. I., Sancho J., and San Millan J. L. (2003) Obesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women. Diabetologia 46:625-633.
47. Escobar-Morreale H. F., Luque-Ramirez M., and San Millan J. L. (2005) The molecular-genetic basis of functional hyperandrogenism and the polycystic ovary syndrome. Endocr. Rev. 26:251-282.
48. Fernandez-Real J. M. and Ricart W. (2003) Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr. Rev. 24:278-301.
49. Franks S. (1995) Polycystic ovary syndrome. N. Engl. J. Med. 333:853-861.
50. Garcıá-Rudaz M. C., Ropelato M. G., Escobar M. E., Veldhuis J.D., and Barontini M. (2002) Amplified and orderly growth hormone secretion characterizes lean adolescents with polycystic ovary syndrome. Eur. J. Endocrinol. 147:207-216.
51. Glueck C. J., Wang P., Fontaine R., Tracy T., and Sieve-Smith L. (2001) Metformin to restore normal menses in oligo-amenorrheic teenage girls with polycystic ovary syndrome (PCOS). J. Adolesc. Health 29:160-169.
52. Goldzieher J.W. (1973) Polycystic ovarian disease. Clin. Obstet. Gynecol. 16:82-105.
53. Goran M. I., Ball G.D. C., and Cruz M. L. (2003) Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents. J. Clin. Endocrinol. Metab. 88:1417-1427.
54. Gungor N., Saad R., Janosky J., and Arslanian S. (2004) Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents. J. Pediatr. 144:47-55.
55. Hales C. N. and Barker D. J. (1992) Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 35:595-601.
56. Hindmarsh P., Di S. L., Pringle P. J., Kurtz A. B., and Brook C. G. (1988) Changes in serum insulin concentration during puberty and their relationship to growth hormone. Clin. Endocrinol. (Oxf.) 28:381-388.
57. Holly J. M., Biddlecombe R. A., Dunger D. B., et al. (1988) Circadian variation of GH-independent IGF-binding protein in diabetes mellitus and its relationship to insulin: a new role for insulin? Clin. Endocrinol. (Oxf.) 29:667-675.
58. Holly J. M., Smith C. P., Dunger D. B., et al. (1989) Relationship between the pubertal fall in sex hormone binding globulin and insulin-like growth factor binding protein-I: a synchronized approach to pubertal development? Clin. Endocrinol. (Oxf.) 31:277-284.
59. Homburg R. (2002) What is polycystic ovarian syndrome? A proposal for a consensus on the definition and diagnosis of polycystic ovary syndrome. Hum. Reprod. 17:2495-2499.
60. Hornsby P. J. (1997) DHEA: a biologist's perspective. J. Am. Geriatr. Soc. 45:1395-1401.
61. Ibañez L. and de Zegher F. (2004) Ethinylestradiol-drospirenone, flutamide-metformin, or both for adolescents and women with hyperinsulinemic hyperandrogenism: opposite eVects on adipocytokines and body adiposity. J. Clin. Endocrinol. Metab. 89:1592-1597.
62. Ibañez L., Virdis R., Potau N., et al. (1992) Natural history of premature pubarche: an auxological study. J. Clin. Endocrinol. Metab. 74:254-257.
63. Ibañez L., Potau N., Virdis R., et al. (1993) Postpubertal outcome in girls diagnosed of premature pubarche during childhood: increased frequency of functional ovarian hyperandrogenism. J. Clin. Endocrinol. Metab. 76:1599-1603.
64. Ibañez L., Potau N., Zampolli M., et al. (1994) Source localization of androgen excess in adolescent girls. J. Clin. Endocrinol. Metab. 79:1778-1784.
65. Ibañez L., Potau N., Georgopoulos N., et al. (1995) Growth hormone, insulin-like growth factor-1 axis, and insulin secretion in hyperandrogenic adolescents. Fertil. Steril. 64:1113-1119.
66. Ibañez L., Potau N., Zamboni M., et al. (1996) Hyperinsulinemia in postpubertal girls with a history of premature pubarche and functional ovarian hyperandrogenism. J. Clin. Endocrinol. Metab. 81:1237-1243.
67. Ibañez L., Potau N., Zampolli M., et al. (1997a) 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. 82:2283-2288.
68. Ibañez L., Potau N., Zampolli M., Street M. E., and Carrascosa A. (1997b) Girls diagnosed with premature pubarche show an exaggerated ovarian androgen synthesis from the early stages of puberty: evidence from gonadotropin-releasing hormone agonist testing. Fertil. Steril. 67:849-855.
69. Ibañez L., Potau N., and Carrascosa A. (1998a) Possible genesis of polycystic ovary syndrome in the periadolescent girl. Curr. Opin. Endocrinol. Diabetes 5:19-26.
70. Ibañez L., Potau N., Chacon P., Pascual C., and Carrascosa A. (1998b) Hyperinsulinemia, dyslipidemia and cardiovascular risk in girls with a history of premature pubarche. Diabetologia 41:1057-1063.
71. Ibañez L., Potau N., Francois I., and de Zegher F. (1998c) Precocious pubarche, hyperinsulinism and ovarian hyperandrogenism in girls: relation to reduced fetal growth. J. Clin. Endocrinol. Metab. 83:3558-3562.
72. Ibañez L., Castell C., Tresserras R., and Potau N. (1999a) Increased prevalence of type 2 diabetes mellitus and impaired glucose tolerance in first-degree relatives of girls with a history of precocious pubarche. Clin. Endocrinol. (Oxf.) 51:395-401.
73. Ibañez L., de Zegher F., and Potau N. (1999b) Anovulation after precocious pubarche: early markers and time course in adolescence. J. Clin. Endocrinol. Metab. 84:2691-2695.
74. Ibañez L., Potau N., Marcos M. V., and de Zegher F. (1999c) Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age. J. Clin. Endocrinol. Metab. 84:4739-4741.
75. Ibañez L., DiMartino-Nardi J., Potau N., and Saenger P. (2000a) Premature adrenarche: normal variant or forerunner of adult disease? Endocr. Rev. 21:671-696.
76. Ibañez L., Valls C., Potau N., Marcos M.V., and de Zegher F. (2000b) Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious pubarche. J. Clin. Endocrinol. Metab. 85:3520-3525.
77. Ibañez L., Valls C., Ferrer A., et al. (2001) Sensitization to insulin induces ovulation in nonobese adolescents with anovulatory hyperandrogenism. J. Clin. Endocrinol. Metab. 86:3595-3598.
78. Ibañez L., Aulesa C., Potau N., et al. (2002a) Plasminogen activator inhibitor-1 in girls with precocious pubarche: a premenarcheal marker for polycystic ovary syndrome? Pediatr. Res. 51:244-248.
79. Ibañez L., Marcos M. V., Potau N., et al. (2002b) Increased frequency of the G972R variant of the insulin receptor substrate-1 (IRS-1) gene among girls with a history of precocious pubarche. Fertil. Steril. 78:1288-1293.
80. Ibañez L., Valls C., Ferrer A., et al. (2002c) Additive eVects of insulin-sensitizing and antiandrogen treatment in young, nonobese women with hyperinsulinism, hyperandrogenism, dyslipidemia, and anovulaton. J. Clin. Endocrinol. Metab. 87:2870-2874.
81. Ibañez L., Ferrer A., Ong K., et al. (2004a) Insulin sensitization early after menarche prevents progression from precocious pubarche to polycystic ovary syndrome. J. Pediatr. 144:23-29.
82. Ibañez L., Valls C., Marcos M. V., et al. (2004b) Insulin sensitization for girls with precocious pubarche and with risk for polycystic ovary syndrome: eVects of prepubertal initiation and postpubertal discontinuation of metformin treatment. J. Clin. Endocrinol. Metab. 89:4331-4337.
83. Jaquet D., Leger J., Chevenne D., Czernichow P., and Levy-Marchal C. (1999) Intrauterine growth retardation predisposes to insulin resistance but not to hyperandrogenism in young women. J. Clin. Endocrinol. Metab. 84:3945-3949.
84. Kent S. C. and Legro R. S. (2002) Polycystic ovary syndrome in adolescents. Adolesc. Med. 13:73-88.
85. Knochenhauer E. S., Key T. J., Kahsar-Miller M., et al. (1998) Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J. Clin. Endocrinol. Metab. 83:3078-3082.
86. Laitinen, J., Taponen, S., Martikainen, H., et al. (2003) Body size from birth to adulthood as a predictor of self-reported polycystic ovary syndrome symptoms. Int. J. Obes. Relat. Metab. Disord. 27:710-715.
87. L'Allemand D., Penhoat A., Lebrethon M. C., et al. (1996) Insulin-like growth factors enhance steroidogenic enzyme and corticotropin receptor messenger ribonucleic acid levels and corticotropin steroidogenic responsiveness in cultured human adrenocortical cells. J. Clin. Endocrinol. Metab. 81:3892-3897.
88. Lapillonne A., Braillon P., Chatelain P. G., Delmar P.D., and Salle, B.D. (1997) Body composition in appropriate and small for gestational age infants. Acta Paediatr. 86:196-200.
89. Legro R. S. (2003) Polycystic ovary syndrome and cardiovascular disease: a premature association? Endocr. Rev. 24:302-312.
90. Legro R. S., Driscoll D., Strauss J. F. I., Fox J., and Dunaif A. (1998) Evidence for a genetic basis for hyperadrogenemia in polycystic ovary syndrome. Proc. Natl. Acad. Sci. U.S.A. 95:14956-14960.
91. Legro R. S., Kunselman A. R., Dodson W. C., and Dunaif A. (1999) Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 aVected women. J. Clin. Endocrinol. Metab. 84:165-169.
92. Legro R. S., Bentley-Lewis R., Driscoll D., Wang S. C., and Dunaif A. (2002a) Insulin resistance in the sisters of women with polycystic ovary syndrome: association with hyperandrogenemia rather than menstrual irregularity. J. Clin. Endocrinol. Metab. 87:2128-2133.
93. Legro R. S., Kunselman A. R., Demers L., et al. (2002b) Elevated dehydroepiandrosterone sulfate levels as the reproductive phenotype in the brothers of women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 87:2134-2138.
94. Lewy V.D., Danadian K., Witchel S. F., and Arslanian S. (2001) Early metabolic abnormalities in adolescent girls with polycystic ovarian syndrome. J. Pediatr. 138:38-44.
95. Martens J.W., Geller D. H., Arlt W., et al. (2000) Enzymatic activities of P450c17 stably expressed in fibroblasts from patiens with the polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 85:4338-4346.
96. Mauras N., Welch S., Rini A., and Haymond M. (1998) Ovarian hyperandrogenism is associated with insulin resistance to both peripheral carbohydrate and whole-body protein metabolism in postpubertal young females: a metabolic study. J. Clin. Endocrinol. Metab. 83:1900-1905.
97. Metcalf M. G., Skidmore D. S., Lowry G. P. and Mackenzie J. A. (1983) Incidence of ovulation in the years after the menarche. J. Endocrinol. 97:213-219.
98. Miller D., Emans S. J., and Kohane I. (1996) Follow-up study of adolescent girls with a history of premature pubarche. J. Adolesc. Health 18:301-305.
99. Miller J., Rosenbloom A., and Silverstein J. (2004) Childhood obesity. J. Clin. Endocrinol. Metab. 89:4211-4218.
100. Miller W. L. (1997) Pathophysiology, genetics and treatment of hyperandrogenism. Pediatr. Clin. North. Am. 44:375-395.
101. Moghetti P., Castello R., Negri C., et al. (2000) Metformin eVects 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. 85:139-146.
102. Nestler J. E., Powers L. P., Matt D.W., et al. (1991) A direct eVect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 72:83-89.
103. Nobels F. and Dewailly D. (1992) Puberty and polycystic ovarian syndrome: the insulin/insulin-like growth factor I hypothesis. Fertil. Steril. 58:655-666.
104. Norman R. J., Masters S., and Hague W. (1996) Hyperinsulinemia is common in family members of women with polycystic ovary syndrome. Fertil. Steril. 66:942-947.
105. Oppenheimer E., Linder B., and DiMartino-Nardi A. (1995) Decreased insulin sensitivity in prepubertal girls with premature adrenarche and acanthosis nigricans. J. Clin. Endocrinol. Metab. 80:614-618.
106. Palmert M. R., Gordon C. M., Kartashov A. I., et al. (2002) Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 87:1017-1023.
107. Pang S. (1984) Premature adrenarche. Pediatr. Adolesc. Endocrinol. 13:173-184.
108. Pasquali R., Antenucci D., Casimirri F., et al. (1989) Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss. J. Clin. Endocrinol. Metab. 68:173-179.
109. Penhoat A., Jaillard C., and Saez J. M. (1989) Synergistic eVects of corticotropin and insulinlike growth factor 1 on corticotropin receptors and corticotropin responsiveness in cultured bovine adrenocortical cells. Biochem. Biophys. Res. Commun. 165:355-359.
110. Penny R., Olambiwonnu O. N., and Fraiser S.D. (1977) Episodic fluctuations of serum gonadotropins in pre-and postpubertal girls and boys. J. Clin. Endocrinol. Metab. 45:307-344.
111. Phillips D. I. and Barker D. J. (1997) Association between low birthweight and high resting pulse in adult life: is the sympathetic nervous system involved in programming the insulin resistance syndrome? Diabet. Med. 14:673-677.
112. Polson D.W., Adams J., Wadsworth J., and Franks S. (1988) Polycystic ovaries: a common finding in normal women. Lancet i:870-872.
113. Raitakari O. T., Juonala M., Kahonen M., et al. (2003) Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. Am. Med. Assoc. 290:2277-2283.
114. Ravussin E. and Smith S. R. (2002) Increased fat intake, impaired fat oxidation, and failure of fat cell proliferation result in ectopic fat storage, insulin resistance, and type 2 diabetes mellitus. Ann. N.Y. Acad. Sci. 967:363-378.
115. Remer T. and Marz F. (1999) Role of nutritional status in the regulation of adrenarche. J. Clin. Endocrinol. Metab. 84:3936-3944.
116. Roldán B., San Millán J. L., and Escobar-Morreale H. F. (2004) Genetic basis of metabolic abnormalities in polycystic ovary syndrome. Am. J. Pharmacogenomics, 4:93-107.
117. Rosenbaum M. and Leibel R. L. (1989) Obesity in childhood. Pediatr. Rev. 11:43-55.
118. SchaVer J. E. (2003) Lipotoxicity: when tissues overeat. Curr. Opin. Lipidol. 14:281-287.
119. Schmitz-PeiVer C. (2000) Signalling aspects of insulin resistance in skeletal muscle: mechanisms induced by lipid oversupply. Cell Signal 12:583-594.
120. Silfen M. E., Manibo A. M., Ferin M., et al. (2002) Elevated free IGF-1 levels in prepubertal Hispanic girls with premature adrenarche: relationship with hyperandrogenism and insulin sensitivity. J. Clin. Endocrinol. Metab. 87:398-403.
121. Silfen M. E., Denburg M. R., Manibo A. M., et al. (2003) Early endocrine, metabolic, and sonographic characteristics of polycystic ovary syndrome (PCOS): comparison between nonobese and obese adolescents. J. Clin. Endocrinol. Metab. 88:4682-4688.
122. Sorbara L., Weiss D., Delson R., et al. (1991). Polycystic ovary syndrome, ethnicity and insulin action. 14th IDF Congress Satellite on Epidemiology of Diabetes, Williamsburg, VA, Abstr. 93.
123. Southam A. L. and Richart R. M. (1996) The prognosis for adolescents with menstrual abnormalities. Am. J. Obstet. Gynecol. 94:637-645.
124. Teixeira R. J., Ginzbarg D., Rodrigues Freitas J., et al. (2004) Serum leptin levels in premature pubarche and prepubertal girls with and without obesity. J. Pediatr. Endocrinol. Metab. 17:1393-1398.
125. Tounian P., Aggoun Y., Dubern B., et al. (2001) Presence of increased stiVness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study. Lancet 358:1400-1404.
126. Urbanek M. and Spielman R. S. (2002) Genetic analysis of candidate genes for the polycystic ovary syndrome. Curr. Opin. Endocrinol. Metab. 9:492-501.
127. Van HooV M. H., Voorhorst F. J., Kaptein M. B., et al. (2001) Polycystic ovaries in adolescents and the relationship with menstrual cycle patterns, luteinizing hormone, androgens, and insulin. Fertil. Steril. 75:642-644.
128. Van Lente F. (2000) Markers of inflammation as predictors in cardiovascular disease. Clin. Chim. Acta 293:31-52.
129. Venturoli S., Porcu E., Fabbri R., et al. (1992) Longitudinal evaluation of the diVerent gonadotropin pulsatile patterns in anovulatory cycles of young girls. J. Clin. Endocrinol. Metab. 74:836-841.
130. Venturoli S., Porcu E., and Flamigni C. (1994) Polycystic ovary syndrome. Curr. Opin. Pediatr. 6:388-396.
131. Vuguin P., Linder B., Rosenfeld R. G., Saenger P., and DiMartino-Nardi J. (1999) The roles of insulin sensitivity, insulin-like growth factor 1 (IGF-1), and IGF-binding protein-1 and-3 in the hyperandrogenism of African-American and Caribbean Hispanic girls with premature adrenarche. J. Clin. Endocrinol. Metab. 84:2037-2042.
132. Witchel S. F. and Aston C. E. (2000) The role of heterozygosity for CYP21 in the polycystic ovary syndrome. J. Pediatr. Endocrinol. Metab. 13(Suppl. 5):1315-1317.
133. Witchel S. F., Lee P. A., Suda-Hartman M., and HoVman E. P. (1997) Hyperandrogenism and manifesting heterozygotes for 21-hydroxylase deficiency. Biochem. Mol. Med. 62:151-158.
134. Witchel S. F., Smith R., Tomboc M., and Aston C. E. (2001) Candidate gene analysis in premature pubarche and adolescent hyperandrogenism. Fertil. Steril. 75:724-730.
135. Yen S. S. C. (1986) Chronic anovulation caused by peripheral endocrine disorders. In Yen S. S. C. and JaVe R.B. (eds.) Reproductive Endocrinology, pp. 441-499. Philadelphia, PA:W. B. Saunders.
136. Yildiz B.O., Yarali H., Oguz H., and Bayraktar M. (2003) Glucose intolerance, insulin resistance, and hyperandrogenemia in first degree relatives of women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 88:2031-2036.
137. Zawadski J. K. and Dunaif A. (1992) Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In Dunaif A., Givens J. R., Haseltime F., and Merriam G. R. (eds.) Polycystic Ovary Syndrome, pp. 377-384. Boston, MA: Blackwell.
138. Zhang L., Rodríguez H., Ohno S., and Miller W. L. (1995) Serine phosphorylation of human P450c17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome. Proc. Natl. Acad. Sci. U.S.A. 92:10619-10623.
139. Zumoff B., Freeman R., Coupey S., et al. (1983) A chronobiologic abnormality in luteinizing hormone secretion in teenage girls with the polycystic ovary syndrome. N. Engl. J. Med. 309:1206-1209.