Premature pubarche, ovarian hyperandrogenism, hyperinsulinism and the polycystic ovary syndrome: From a complex constellation to a simple sequence of prenatal onset

Journal of Endocrinological Investigation

Volumn 21, Issue 9, 1998, Pages 558-566

  Ibanez L ^a   De Zegher, F ^b   Potau, N ^a  

^a HOSPITAL MATERNO INFANTIL VALL D HEBRON   (Spain)

^b UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

Adrenal hyperandrogenism; Hyperinsulinemia; Intrauterine growth retardation; Ovarian hyperandrogenism; PCOS; Premature pubarche

Indexed keywords

ANDROGEN; INSULIN; LIPID;

ADOLESCENT; ANDROGEN SYNTHESIS; ARTICLE; BIRTH WEIGHT; DYSLIPIDEMIA; FEMALE; HUMAN; HYPERANDROGENISM; HYPERINSULINEMIA; HYPERINSULINISM; OVARY POLYCYSTIC DISEASE; PRECOCIOUS PUBERTY; PREMATURITY; PREPUBERTY; PUBERTY; SCHOOL CHILD;

EID: 0031751850     PISSN: 03914097     EISSN: None     Source Type: Journal    
DOI: 10.1007/BF03350781     Document Type: Article

References (88)

1. Ibáñez L., Virdis R., Potau N., Zampolli M., Ghizonni L., Albisu M.A., Carrascosa A., Bernasconi S., Vicens-Calvet E. Natural history of premature pubarche: An auxological study. J. Clin. Endocrinol. Metab. 74: 254, 1992.
2. Reiter E.O., Saenger P. Premature adrenarche. The Endocrinologist 7: 85, 1997.
3. Korth-Schutz S., Levine L.S., New M.I. Evidence for the adrenal source of androgens in precocious adrenarche. Acta Endocrinol. (Copenh). 82: 242, 1976.
4. Rosenfield R.L. Plasma 17-ketosteroids and 17β-hydroxysteroids in girls with premature development of sexual hair. J. Pediatr. 79: 260, 1971.
5. Rosenfield R.L, Rich B.H., Lucky A.W. Adrenarche as a cause of benign pseudopuberty in boys. J. Pediatr. 101: 1005, 1982.
6. Pang S. Premature pubarche. Pediatr. Adolesc. Endocrinol. 13: 173, 1984.
7. Voutilainen R., Perheentupa J., Apter D. Benign premature adrenarche: clinical features and serum steroid levels. Acta Paediatr. Scand. 72: 707, 1983.
8. Ibáñez L., Bonnin M.R., Zampolli M., Prat N., Alia P.J., Navarro M.A. Usefulness of an ACTH test in the diagnosis of nonclassical 21-hydroxylase deficiency among children presenting with premature pubarche. Horm. Res. 44: 51, 1995.
9. Rosenfield R.L, Lucky A.W. Acne, hirsutism, and alopecia in adolescent girls. Endocrinol. Metab. Clin. North Am. 22: 507, 1993.
10. Rosenfield R.L. Normal and almost normal variations in pubertal development. Premature pubarche and premature thelarche revisited. Horm. Res. 41 (Suppl. 2): 7, 1994.
11. Temeck J.M., Pang S., Nelson C., New M.I. Genetic defects in steroidogenesis in premature pubarche. J. Clin. Endocrinol. Metab. 64: 609, 1987.
12. New M.I., Lorenzen F., Lerner A.J., Kohn B., Oberfield S.E., Pollack M.S., Dupont B., Stoner E., Levy D.J., Pang S., Levine L.S. Genotyping steroid 21-hydroxylase deficiency: hormonal reference data. J. Clin. Endocrinol. Metab. 57: 320, 1983.
13. 5-steroid levels. J. Clin. Endocrinol. Metab. 81: 3961, 1996.
14. Siegel S.F., Finegold D.N., Urban M.D., McVie R., Lee P.A. Premature pubarche: Etiological heterogeneity? J. Clin. Endocrinol. Metab. 74: 239, 1992.
15. Joehrer K., Geley S., Strasser-Wozak E.M.C., Azziz R., Wollmann H.A., Schmitt K., Kofler R., White P.C. CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11β-hydroxylase deficiency. Hum. Mol. Genet. 6: 1829, 1997.
16. Balducci R., Boscherini B., Mangiantini A., Morelli M., Toscano V. Isolated precocious pubarche: An approach. J. Clin. Endocrinol. Metab. 79: 582, 1994.
17. Ibáñez L., Potau N., Zampolli M., Marcos M.V., Carrascosa A. Functional adrenal hyperandrogenism is a common feature in postpubertal girls with a history of premature pubarche: relationship to hyperinsulinemia and ovarian androgen excess. Horm. Res. 48 (Suppl. 2): 110, 1997 (Abstract).
18. Lucky A.W., Rosenfield R.L., McGuire J., Rudy S., Heike J. Adrenal androgen hyperresponsiveness to adrenocorticotropin in women with acne and/or hirsutism: adrenal enzyme defects and exaggerated adrenarche. J. Clin. Endocrinol. Metab. 62: 840, 1986.
19. Barnes R.B., Ehrmann D.E., Brigell D.F., Rosenfield R.L Ovarian steroidogenic responses to gonadotropin-releasing hormone agonist testing with nafarelin in hirsute women with adrenal responses to adrenocorticotropin suggestive of 3β-hydroxysteroid dehydrogenase deficiency. J. Clin. Endocrinol. Metab. 76: 450, 1993.
20. Rosenfield R.L. Editorial: Evidence that idiopathic functional adrenal hyperandrogenism is caused by dysregulation of adrenal steroidogenesis and that hyperinsulinemia may be involved. J. Clin. Endocrinol. Metab. 81: 878, 1996.
21. Rao J.K., Chihal H.J., Johnson C.M. Primary polycystic ovary syndrome in a premenarcheal girl. A case report. J. Reprod. Med. 30: 361, 1985.
22. Ibáñez L., Potau N., Albisu M.A., Enríquez G., Gussinyé M., Carrascosa A., Vicens-Calvet E. Post-puberal assessment in girls with premature pubarche: clinical, biochemical, and echographic findings. Horm. Res. 33 (Suppl. 3): 37, 1990 [Abstract].
23. Yen S.S.C. Chronic anovulation caused by peripheral endocrine disorders. In: Yen S.S.C., Jaffe R.B. (Eds.), Reproductive Endocrinology. Saunders, Philadelphia, 1980, p. 441.
24. Bridges N.A., Cooke A., Healy M.J.R., Hindmarsh P.C., Brook C.G.D. Ovaries in sexual precocity. Clin. Endocrinol. (Oxf). 42: 135, 1995.
25. Ibáñez L., Potau N., Zampolli M., Prat N., Gussinyé M., Saenger P., Vicens-Calvet E., Carrascosa A. Source localization of androgen excess in adolescent girls. J. Clin. Endocrinol. Metab. 79: 1778, 1994.
26. Franks S. Polycystic ovary syndrome. N. Engl. J. Med. 333: 853, 1995.
27. Ehrmann D.A., Rosenfield R.L, Barnes R.B., Brigell D.F., Sheikh Z. Detection of functional ovarian hyperandrogenism in women with androgen excess. N. Engl. J. Med. 327: 157, 1992.
28. Ehrmann D.A., Barnes R.B., Rosenfield R.L. Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion. Endocr. Rev. 16: 322, 1995.
29. Legro R.S., Muhleman D.R., Comings D.E., Lobo R.A., Kovacs B.W. A dopamine D3 receptor genotype is associated with hyperandrogenic chronic anovulation and resistant to ovulation induction with clomiphene citrate in female Hispanics. Fertil. Steril. 63: 779, 1995.
30. Lanzone A., Fulghesu A.M., Cucinelli F., Ciampelli M., Caruso A., Mancuso S. Evidence of a distinct derangement of opioid tone in hyperinsulinemic patients with polycystic ovarian syndrome: relationship with insulin and lutenizing hormone secretion. J. Clin. Endocrinol. Metab. 80: 3501, 1995.
31. Barnes R.B., Rosenfield R.L, Burstein S., Ehrmann D.A. Pituitary-ovarian responses to nafarelin testing in the polycystic ovary syndrome. N. Engl. J. Med. 320: 559, 1989.
32. Rosenfield R.L. Current concepts of polycystic ovary syndrome. Baillières Clin. Obstet. Gynecol. 11: 307, 1997.
33. Rosenfield R.L. Is polycystic ovary syndrome a neuroendocrine or an ovarian disorder? Clin. Endocrinol. (Oxf.) 47: 423, 1997.
34. Gilling-Smith C., Story H., Rogers V., Franks S. Evidence for a primary abnormality of thecal cell steroidogenesis in the polycystic ovary syndrome. Clin. Endocrinol. (Oxf.) 47: 93, 1997.
35. Ibáñez L, Hall J.E., Potau N., Carrascosa A., Prat N., Taylor A.E. Ovarian 17-hydroxyprogesterone hyperresponsiveness to gonadotropin-releasing hormone (GnRH) agonist challenge in women with polycystic ovary syndrome is not mediated by luteinizing hormone hypersecretion: Evidence from GnRH agonist and human chorionic gonadotropin stimulation testing. J. Clin. Endocrinol. Metab. 81: 4103, 1996.
36. Nestler J.E., Jakubowicz D.J. Decreases in ovarian cytochrome P450c17α activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N. Engl. J. Med. 335: 617, 1996.
37. Nestler J.E., Jakubowicz D.J. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17α activity and serum androgens. J. Clin. Endocrinol. Metab. 82: 4075, 1997.
38. Morales A.J., Laughlin G.A., Bützow T., Maheshwari H., Baumann G., Yen S.S.C. Insulin, somatotropic, and luteinizing hormone axes in lean and obese women with polycystic ovary syndrome: Common and distinct features. J. Clin. Endocrinol. Metab. 81: 2854, 1996.
39. Mastorakos G., Scopa C.D., Vryonidu A., Friedman T.C., Kattis D., Phenekos C., Merino M. J., Chrousos G.P. Presence of immunoreactive corticotropin-releasing hormone in normal and polycystic human ovaries. J. Clin. Endocrinol. Metab. 79: 1191, 1994.
40. Erden H.F., Zwain I.H., Yen S.S.C. Corticotropin-releasing factor inhibits luteinizing hormone-stimulated P450c17 gene expression and androgen production by isolated thecal cells of human ovarian follicles. J. Clin. Endocrinol. Metab. 83: 448, 1998.
41. Ibáñez L., Potau N., Virdis R., Zampolli M., Terzi C., Gussinyé M., Carrascosa A., Vicens-Calvet E. Postpubertal outcome in girls diagnosed of premature pubarche during childhood: Increased frequency of functional ovarian hyperandrogenism. J. Clin. Endocrinol. Metab. 76: 1599, 1993.
42. Ibáñez L., Potau N., Zampolli M., Street M.E., Carrascosa A. 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, 1997.
43. Miller W.L. Molecular biology of steroid hormone synthesis. Endocr. Rev. 9: 295, 1988.
44. Miller W.L, Auchus R.J., Geller D.H. The regulation of 17,20 lyase activity. Steroids 62: 133, 1997.
45. Ibáñez L., Potau N., Francois L, de Zegher F. Precocious pubarche, hyperinsulinism and ovarian hyperandrogenism in girls: relation to reduced fetal growth. J. Clin. Endocrinol. Metab. 1998 (in press).
46. Auchus R.J., Geller D. H., Lee T. C., Miller W.L. The regulation of human P450c17 activity: relationship to premature adrenarche, insulin resistance and the polycystic ovary syndrome. TEM 9: 47, 1998.
47. Ibáñez L., Potau N., Georgopoulos N., Prat N., Gussinyé M., Carrascosa A. Growth hormone, insulin-like growth factor-l axis, and insulin secretion in hyperandrogenic adolescents. Fertil. Steril. 64: 1113, 1995.
48. Jialal I., Naiker P., Reddi K., Moodley J., Joubert SM. Evidence for insulin resistance in nonobese patients with polycystic ovarian disease. J. Clin. Endocrinol. Metab. 64: 1066, 1987.
49. Apter D., Bützow T., Laughlin G.A., Yen S.S.C. Metabolic features of polycystic ovary syndrome are found in adolescent girls with hyperandrogenism. J. Clin. Endocrinol. Metab. 80: 2966, 1995.
50. Nestler J.E., Clore J.N., Blackard W.G. The central role of obesity (hyperinsulinemia) in the pathogenesis of polycystic ovary syndrome. Am. J. Obstet. Gynecol. 161: 1095, 1989.
51. Dunaif A., Segal K.R., Futterweit W., Dobransky A. Profound peripheral insulin resistance, independent of obesity, in the polycystic ovary syndrome. Diabetes 38: 1165, 1989.
52. O'Meara N.M., Blackman J.D., Ehrmann D.A., Barnes R.B., Jaspan J.B., Rosenfield R.L. Defects in β-cell function in functional ovarian hyperandrogenism. J. Clin. Endocrinol. Metab. 76: 1241, 1993.
53. Rittmaster R.S., Deshwasl N., Lehman L. The role of adrenal hyperandrogenism, insulin resistance, and obesity in the pathogenesis of polycystic ovarian syndrome. J. Clin. Endocrinol. Metab. 76: 1295, 1993.
54. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr. Rev. 18: 774, 1997.
55. Barbieri R.L., Makris A., Randall R.W., Daniels G., Kistner R.W, Ryan K.J. Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J. Clin. Endocrinol. Metab. 62: 904, 1986.
56. Cara J.F., Rosenfield R.L. Insulin-like growth factor I and insulin potentiate luteinizing hormone-induced androgen synthesis by rat ovarian thecal-interstitial cells. Endocrinology 123: 733, 1988.
57. L'Allemand D., Penhoat A., Lebrethon M.C., Ardèvol R., Baehr V., Oelkers W., Saez J.M. 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, 1996.
58. Mesiano S., Katz L.S., Lee J.Y., Jaffe R.B. Insulin-like growth factors augment steroid production and expression of steroidogenic enzymes in human fetal adrenal cortical cells: implications for adrenal androgen production. J. Clin. Endocrinol. Metab. 82: 1390, 1997.
59. Duleba A.J., Spacynski R.Z., Olive D.L. Insulin and insulin-like growth factor I stimulate the proliferation of human ovarian theca-interstitial cells. Fertil. Steril. 69: 335, 1998.
60. Nestler J.E. Editorial: sex hormone-binding globulin: a marker for hyperinsulinemia and/or insulin resistance? J. Clin. Endocrinol. Metab. 76: 273, 1993.
61. Suikkari A.M., Koivisto V.A., Rutanen E.M., Yki-Järvinen H., Karonen S.L., Seppäla M. Insulin regulates the serum levels of low molecular weight insulin-like growth factor binding protein. J. Clin. Endocrinol. Metab. 66: 266, 1988.
62. Jakubowicz D.J., Beer N.A., Beer R.M., Nestler J.E. Disparate effects of weight reduction by diet on serum dehydroepiandrosterone-sulfate levels in obese men and women. J. Clin. Endocrinol. Metab. 80: 3373, 1995.
63. Moghetti P., Castello R., Negri C., Tosi F., Spiazzi G., Brun E., Balducci R., Toscano V., Muggeo M. Insulin infusion amplifies 17α-hydroxycorticosteroid intermediates response to adrenocorticotropin in hyperandrogenic women: apparent relative impairment of 17,20 lyase activity. J. Clin. Endocrinol. Metab. 81: 881, 1996.
64. Amiel S.A., Caprio S., Sherwin R.S., Plewe G., Haymond M.W., Tamborlane W.V. Insulin resistance of puberty: a defect restricted to peripheral glucose metabolism. J. Clin. Endocrinol. Metab. 72: 277, 1991.
65. Caprio S., Plewe G., Diamond M.P., Simonson D.C., Boulware S.D., Sherwin R.S., Tamborlane W.V. Increased insulin secretion in puberty: a compensatory response to reductions in insulin sensitivity. J. Pediatr. 114: 963, 1989.
66. Potau N., Ibáñez L., Riqué S., Carrascosa A. Pubertal changes in insulin secretion and peripheral insulin sensitivity. Horm. Res. 48: 219, 1997.
67. Holly J.M.P., Smith C.P., Dunger D.B., Howell R.J.S., Chard T., Perry L.A., Savage M.O., Cianfarani S., Rees L.H., Wass J.A.H. Relationship between the pubertal fall in sex hormone binding globulin and insulin-like growth factor binding protein-1. A synchronized approach to pubertal development? Clin. Endocrinol. (Oxf.) 31: 277, 1989.
68. Argente J., Barrios V., Pozo J., Munoz M.T., Hervás F., Stene M., Hernandez M. Normative data for insulin-like growth factors (IGFs), IGF-binding proteins, and growth hormone-binding protein in healthy Spanish pediatric population: ageand sex-related changes. J. Clin. Endocrinol. Metab. 77: 1522, 1993.
69. Nobels F., Dewailly D. Puberty and polycystic ovary syndrome: the insulin/insulin-like growth factor I hypothesis. Fertil. Steril. 58: 655, 1992.
70. Ibáñez L., Potau N., Carrascosa A. Possible genesis of polycystic ovary syndrome in the periadolescent girl. Current Opinion in endocrinology and Diabetes. 5: 19, 1998.
71. 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. 82: 2283, 1997.
72. Ibáñez L, Potau N., Chacón P., Pascual C., Carrascosa A. Hyperinsulinemia, dyslipemia and cardiovascular risk in girls with a history of premature pubarche. Diabetologia 1998 (in press).
73. Wild R.A., Alaupovic P., Parker I.J. Lipid and lipoprotein abnormalities in hirsute women. I. The association with insulin resistance. Am. J. Obstetr. Gynecol. 166: 1191, 1992.
74. Robinson S., Henderson A.D., Gelding S.V., Kiddy D., Niththyananthan R., Bush A., Richmond W., Johnston D.G., Franks S. Dyslipemia is associated with insulin resistance in women with polycystic ovaries. Clin. Endocrinol. (Oxf.) 44: 277, 1996.
75. Arslanian S., Suprasongsin C. Insulin sensitivity, lipids, and body composition in childhood: Is "Syndrome X" present? J. Clin. Endocrinol. Metab. 87: 1058, 1996.
76. Primrose D.E., Savage J.M., Boreham C.A., Cran G.W., Strain J.J. Cholesterol screening and family history of vascular disease. Arch. Dis. Child. 71: 239, 1994.
77. 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. 81: 1237, 1996.
78. Ibáñez L., Potau N., Carrascosa A. Androgens in adrenarche and pubarche. In: Azziz R., Nestler J.E., Dewailly D. (Eds.), Androgen excess disorders in women. Lippincott-Raven, Philadelphia, 1997, p. 73.
79. Barker D.J.P., Hales C.H.D., Osmond C., Clark P.M.S. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 36: 62, 1993.
80. Hofman P.L, Cutfield W.S., Robinson E.M., Bergman R.N., Menon R.K., Sperling M.A., Gluckman P.D. Insulin resistance in short children with intrauterine growth retardation. J. Clin. Endocrinol. Metab. 82: 402, 1997.
81. François I., de Zegher F. Adrenarche and fetal growth. Pediatr. Res. 47: 440, 1997.
82. François I., de Zegher F., Spiessens C., D'Hooghe T., Vanderschueren D. Low birth weight and subsequent male subfertility. Pediatr. Res. 42: 899, 1997.
83. Zhang L., Rodriguez H., Ohno S., Miller W.L. Serine phosphorylation of human P450c17 increases 17,20 lyase activity: implications for adrenarche and the polycystic ovary syndrome. Proc. Natl. Acad. Sci. USA. 92: 10619, 1995.
84. Grunberger G. Interplay between insulin signaling and protein kinase C. Cellular Signaling 3: 171, 1991.
85. Miller W.L. Pathophysiology, genetics and treatment of hyper-androgenism. Pediatr. Clin. North Am. 44: 375, 1997.
86. Ibáñez L, Potau N. Carrascosa A. Insulin resistance, premature adrenarche, and a risk of the polycystic ovary syndrome (POS). TEM 9: 72, 1998.
87. Gluckman, P.D., Harding J.E. The physiology and pathophysiology of intrauterine growth retardation. Horm. Res. 48 (Suppl. 1): 11, 1997.
88. Barker D.J.P., Gluckman P.D., Godrey K.M., Harding J.E., Owens J.A., Robinson J.S. Fetal nutrition and cardiovascular disease in adult life. Lancet 341: 938, 1993.