PCOS: An ovarian disorder that leads to dysregulation in the hypothalamic-pituitary-adrenal axis?

European Journal of Obstetrics and Gynecology and Reproductive Biology

Volumn 118, Issue 1, 2005, Pages 4-16

  Doi, Suhail A R ^a,b   Towers, Philip A ^b   Scott, Christopher J ^b   Al Shoumer, Kamal A S ^a  

^a KUWAIT UNIVERSITY   (Kuwait)

^b CHARLES STURT UNIVERSITY   (Australia)

Author keywords

Hypothalamic pituitary adrenal axis; Ovarian disorder; Polycystic ovary syndrome

Indexed keywords

CORTICOSTEROID; FOLLITROPIN; INHIBIN; INSULIN; LUTEINIZING HORMONE; SEX HORMONE; SOMATOMEDIN C;

ADRENAL GLAND; DISEASE ASSOCIATION; ENDOCRINE DISEASE; HUMAN; HYPERANDROGENISM; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; HYPOTHALAMUS HYPOPHYSIS SYSTEM; OBESITY; OVARY; OVARY FOLLICLE DEVELOPMENT; OVARY POLYCYSTIC DISEASE; PRIORITY JOURNAL; REVIEW;

EID: 10644293299     PISSN: 03012115     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejogrb.2004.06.024     Document Type: Review

References (134)

1. S. Franks Adult polycystic ovary syndrome begins in childhood Best Pract Res Clin Endocrinol Metab 16 2 2002 263 272
2. R. Fox, and A. Ryan Polycystic ovary syndrome: not ovarian, not simple, unkind Hum Fertil (Camb) 5 1 2002 S28 S32
3. R. Barnes, and R.L. Rosenfield The polycystic ovary syndrome: pathogenesis and treatment Ann Intern Med 110 5 1989 386 399
4. R.B. Barnes, R.L. Rosenfield, S. Burstein, and D.A. Ehrmann Pituitary-ovarian responses to nafarelin testing in the polycystic ovary syndrome N Engl J Med. 320 9 1989 559 565
5. R.L. Rosenfield Current concepts of polycystic ovary syndrome Baillieres Clin Obstet Gynaecol 11 2 1997 307 333
6. D.A. Ehrmann, R.L. Rosenfield, R.B. Barnes, D.F. Brigell, and Z. Sheikh Detection of functional ovarian hyperandrogenism in women with androgen excess N Engl J Med 327 3 1992 157 162
7. E. Carmina, and R.A. Lobo Do hyperandrogenic women with normal menses have polycystic ovary syndrome? Fertil Steril 71 2 1999 319 322
8. E. Carmina, L. Wong, and L. Chang Endocrine abnormalities in ovulatory women with polycystic ovaries on ultrasound Hum Reprod 12 5 1997 905 909
9. P.L. Chang, S.R. Lindheim, and C. Lowre Normal ovulatory women with polycystic ovaries have hyperandrogenic pituitary-ovarian responses to gonadotropin-releasing hormone-agonist testing J Clin Endocrinol Metab 85 3 2000 995 1000
10. R.S. Legro, D. Driscoll, J.F. Strauss 3rd, J. Fox, and A. Dunaif Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome Proc Natl Acad Sci USA 95 25 1998 14956 14960
11. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome Fertil Steril 81 1 2004 19 25
12. M.A. Kirschner, I.R. Zucker, and D. Jespersen Idiopathic hirsutism - an ovarian abnormality N Engl J Med 294 12 1976 637 640
13. M. Barontini, M.C. Garcia-Rudaz, and J.D. Veldhuis Mechanisms of hypothalamic-pituitary-gonadal disruption in polycystic ovarian syndrome Arch Med Res 32 6 2001 544 552
14. T.D. Pache, W.C. Hop, and F.H. de Jong 17beta-Oestradiol, androstenedione and inhibin levels in fluid from individual follicles of normal and polycystic ovaries, and in ovaries from androgen treated female to male transsexuals Clin Endocrinol (Oxf) 36 6 1992 565 571
15. R.A. Anderson, N.P. Groome, and D.T. Baird Inhibin A and inhibin B in women with polycystic ovarian syndrome during treatment with FSH to induce mono-ovulation Clin Endocrinol (Oxf) 48 5 1998 577 584
16. D.T. Baird, C.S. Corker, and D.W. Davidson Pituitary-ovarian relationships in polycystic ovary syndrome J Clin Endocrinol Metab 45 4 1977 798 801
17. M.M. Seibel, M.M. Kamrava, C. McArdle, and M.L. Taymor Treatment of polycystic ovary disease with chronic low-dose follicle stimulating hormone: biochemical changes and ultrasound correlation Int J Fertil 29 1 1984 39 43
18. Z. Shoham, A. Patel, and H.S. Jacobs Polycystic ovarian syndrome: safety and effectiveness of stepwise and low-dose administration of purified follicle-stimulating hormone Fertil Steril 55 6 1991 1051 1056
19. D. Hamilton-Fairley, D. Kiddy, H. Watson, M. Sagle, and S. Franks Low-dose gonadotrophin therapy for induction of ovulation in 100 women with polycystic ovary syndrome Hum Reprod 6 8 1991 1095 1099
20. N.A. Klein, P.J. Illingworth, and N.P. Groome Decreased inhibin B secretion is associated with the monotropic FSH rise in older, ovulatory women: a study of serum and follicular fluid levels of dimeric inhibin A and B in spontaneous menstrual cycles J Clin Endocrinol Metab 81 7 1996 2742 2745
21. C.K. Welt, D.J. McNicholl, A.E. Taylor, and J.E. Hall Female reproductive aging is marked by decreased secretion of dimeric inhibin J Clin Endocrinol Metab 84 1 1999 105 111
22. D.R. Danforth, L.K. Arbogast, and J. Mroueh Dimeric inhibin: a direct marker of ovarian aging Fertil Steril 70 1 1998 119 123
23. V.T. Goudas, and D.A. Dumesic Polycystic ovary syndrome Endocrinol Metab Clin North Am 26 4 1997 893 912
24. H.M. Buckler, R.I. McLachlan, V.B. MacLachlan, D.L. Healy, and H.G. Burger Serum inhibin levels in polycystic ovary syndrome: basal levels and response to luteinizing hormone-releasing hormone agonist and exogenous gonadotropin administration J Clin Endocrinol Metab 66 4 1988 798 803
25. D. Robertson, H.G. Burger, and J. Sullivan Biological and immunological characterization of inhibin forms in human plasma J Clin Endocrinol Metab 81 2 1996 669 676
26. D.M. Robertson, J. Sullivan, M. Watson, and N. Cahir Inhibin forms in human plasma J Endocrinol 144 2 1995 261 269
27. R.J. Norman, C.R. Milner, N.P. Groome, and D.M. Robertson Circulating follistatin concentrations are higher and activin concentrations are lower in polycystic ovarian syndrome Hum Reprod 16 4 2001 668 672
28. P. Pigny, C. Cortet-Rudelli, and C. Decanter Serum levels of inhibins are differentially altered in patients with polycystic ovary syndrome: effects of being overweight and relevance to hyperandrogenism Fertil Steril 73 5 2000 972 977
29. J.S. Laven, B. Imani, M.J. Eijkemans, F.H. de Jong, and B.C. Fauser Absent biologically relevant associations between serum inhibin B concentrations and characteristics of polycystic ovary syndrome in normogonadotrophic anovulatory infertility Hum Reprod 16 7 2001 1359 1364
30. C. Cortet-Rudelli, P. Pigny, and C. Decanter Obesity and serum luteinizing hormone level have an independent and opposite effect on the serum inhibin B level in patients with polycystic ovary syndrome Fertil Steril 77 2 2002 281 287
31. M.W. Elting, J. Kwee, R. Schats, L.T. Rekers-Mombarg, and J. Schoemaker The rise of estradiol and inhibin B after acute stimulation with follicle-stimulating hormone predict the follicle cohort size in women with polycystic ovary syndrome, regularly menstruating women with polycystic ovaries, and regularly menstruating women with normal ovaries J Clin Endocrinol Metab 86 4 2001 1589 1595
32. S. Muttukrishna, and P.G. Knight Inverse effects of activin and inhibin on the synthesis and secretion of FSH and LH by ovine pituitary cells in vitro J Mol Endocrinol 6 2 1991 171 178
33. K.D. Dahl, C.A. Campen, D.M. McGuinness, and W. Vale Differential regulation in the release of bioactive versus immunoactive gonadotropins from cultured rat pituitary cells by inhibin and androgens J Androl 13 6 1992 526 533
34. F.J. Hayes, N. Pitteloud, S. DeCruz, W.F. Crowley Jr., and P.A. Boepple Importance of inhibin B in the regulation of FSH secretion in the human male J Clin Endocrinol Metab 86 11 2001 5541 5546
35. F.A. Conte, M.M. Grumbach, Y. Ito, C.R. Fisher, and E.R. Simpson A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom) J Clin Endocrinol Metab 78 6 1994 1287 1292
36. A. Di Cerbo, A. Biason-Lauber, and M. Savino Combined 17alpha-Hydroxylase/17,20-lyase deficiency caused by Phe93Cys mutation in the CYP17 gene J Clin Endocrinol Metab 87 2 2002 898 905
37. D. Meirow, J.G. Schenker, and A. Rosler Ovarian hyperstimulation syndrome with low oestradiol in non-classical 17-alpha-hydroxylase, 17,20-lyase deficiency: what is the role of oestrogens? Hum Reprod 11 10 1996 2119 2121
38. S.A. Fisher, R.L. Reid, D.A. Van Vugt, and R.F. Casper A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women Fertil Steril 78 2 2002 280 285
39. M.F. Mitwally, and R.F. Casper Aromatase inhibition for ovarian stimulation: future avenues for infertility management Curr Opin Obstet Gynecol 14 3 2002 255 263
40. M.F. Mitwally, and R.F. Casper Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate Fertil Steril 75 2 2001 305 309
41. H. Ali Hassan, D. El-Gezeiry, T.M. Nafaa, and I. Baghdady Improved responsiveness of PCOS patients to clomiphene after CYP17a inhibitor J Assist Reprod Genet 18 11 2001 608 611
42. C. Gilling-Smith, D.S. Willis, R.W. Beard, and S. Franks Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries J Clin Endocrinol Metab 79 4 1994 1158 1165
43. L. Ibanez, J.E. Hall, and N. Potau 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 11 1996 4103 4107
44. S.G. Levrant, R.B. Barnes, and R.L. Rosenfield A pilot study of the human chorionic gonadotrophin test for ovarian hyperandrogenism Hum Reprod 12 7 1997 1416 1420
45. C. Gilling-Smith, H. Story, V. Rogers, and S. Franks Evidence for a primary abnormality of thecal cell steroidogenesis in the polycystic ovary syndrome Clin Endocrinol (Oxf) 47 1 1997 93 99
46. C.R. McCartney, A.B. Bellows, and M.B. Gingrich Exaggerated 17-hydroxyprogesterone response to intravenous infusions of recombinant human LH in women with polycystic ovary syndrome Am J Physiol Endocrinol Metab 286 6 2004 E902 E908 Epub 2004, Jan 21
47. D.A. Ehrmann, R.B. Barnes, and R.L. Rosenfield Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion Endocr Rev 16 3 1995 322 353
48. A. Morishima, M.M. Grumbach, E.R. Simpson, C. Fisher, and K. Qin Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens J Clin Endocrinol Metab 80 12 1995 3689 3698
49. L.C. Layman, E.J. Lee, and D.B. Peak Delayed puberty and hypogonadism caused by mutations in the follicle-stimulating hormone beta-subunit gene N Engl J Med 337 9 1997 607 611
50. D. Rabin, I. Spitz, and B. Bercovici Isolated deficiency of follicle-stimulating hormone. Clinical and laboratory features N Engl J Med 287 26 1972 1313 1317
51. C.H. Matthews, S. Borgato, and P. Beck-Peccoz Primary amenorrhoea and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone Nat Genet 5 1 1993 83 86
52. R.B. Barnes, A.B. Namnoum, R.L. Rosenfield, and L.C. Layman The role of LH and FSH in ovarian androgen secretion and ovarian follicular development: clinical studies in a patient with isolated FSH deficiency and multicystic ovaries Hum Reprod 17 1 2002 88 91
53. M.S. Coffler, K. Patel, and M.H. Dahan Evidence for abnormal granulosa cell responsiveness to follicle-stimulating hormone in women with polycystic ovary syndrome J Clin Endocrinol Metab 88 4 2003 1742 1747
54. J.C. Marshall, C.A. Eagleson, and C.R. McCartney Hypothalamic dysfunction Mol Cell Endocrinol 183 1-2 2001 29 32
55. S.E. Kirk, A.C. Dalkin, M. Yasin, D.J. Haisenleder, and J.C. Marshall Gonadotropin-releasing hormone pulse frequency regulates expression of pituitary follistatin messenger ribonucleic acid: a mechanism for differential gonadotrope function Endocrinology 135 3 1994 876 880
56. W.L. Miller, F. Shafiee-Kermani, B.D. Strahl, and H.J. Huang The nature of FSH induction by GnRH Trends Endocrinol Metab 13 6 2002 257 263
57. T. Eldar-Geva, I.M. Spitz, N.P. Groome, E.J. Margalioth, and R. Homburg Follistatin and activin A serum concentrations in obese and non-obese patients with polycystic ovary syndrome Hum Reprod 16 12 2001 2552 2556
58. F.J. Hayes, A.E. Taylor, K.A. Martin, and J.E. Hall Use of a gonadotropin-releasing hormone antagonist as a physiologic probe in polycystic ovary syndrome: assessment of neuroendocrine and androgen dynamics J Clin Endocrinol Metab 83 7 1998 2343 2349
59. C.L. Pastor, M.L. Griffin-Korf, J.A. Aloi, W.S. Evans, and J.C. Marshall Polycystic ovary syndrome: evidence for reduced sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone J Clin Endocrinol Metab 83 2 1998 582 590
60. C.A. Eagleson, M.B. Gingrich, and C.L. Pastor 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 85 11 2000 4047 4052
61. K. Patel, M.S. Coffler, and M.H. Dahan Relationship of GnRH-stimulated LH release to episodic LH secretion and baseline endocrine-metabolic measures in women with polycystic ovary syndrome Clin Endocrinol (Oxf) 60 1 2004 67 74
62. N.C. Buffet, and P. Bouchard The neuroendocrine regulation of the human ovarian cycle Chronobiol Int 18 6 2001 893 919
63. D.S. McConnell, Q. Wang, and P.M. Sluss A two-site chemiluminescent assay for activin-free follistatin reveals that most follistatin circulating in men and normal cycling women is in an activin-bound state J Clin Endocrinol Metab 83 3 1998 851 858
64. H.F. Escobar-Morreale, M. Asuncion, R.M. Calvo, J. Sancho, and J.L. San Millan Receiver operating characteristic analysis of the performance of basal serum hormone profiles for the diagnosis of polycystic ovary syndrome in epidemiological studies Eur J Endocrinol 145 5 2001 619 624
65. E. Vanky, K.A. Salvesen, and S.M. Carlsen Six-month treatment with low-dose dexamethasone further reduces androgen levels in PCOS women treated with diet and lifestyle advice, and metformin Hum Reprod 19 3 2004 529 533
66. B. Couzinet, G. Meduri, and M.G. Lecce The postmenopausal ovary is not a major androgen-producing gland J Clin Endocrinol Metab 86 10 2001 5060 5066
67. G. Gebre-Medhin, E.S. Husebye, and H. Mallmin Oral dehydroepiandrosterone (DHEA) replacement therapy in women with Addison's disease Clin Endocrinol (Oxf) 52 6 2000 775 780
68. T. Piltonen, R. Koivunen, and L. Morin-Papunen Ovarian and adrenal steroid production: regulatory role of LH/HCG Hum Reprod 17 3 2002 620 624
69. J.A. Bermudez, C. Moran, and J. Herrera Determination of the steroidogenic capacity in premature ovarian failure Fertil Steril 60 4 1993 668 671
70. C. De Geyter, M. De Geyter, P.R. Huber, E. Nieschlag, and W. Holzgreve Progesterone serum levels during the follicular phase of the menstrual cycle originate from the crosstalk between the ovaries and the adrenal cortex Hum Reprod 17 4 2002 933 939
71. H.L. Judd, W.E. Lucas, and S.S. Yen Effect of oophorectomy on circulating testosterone and androstenedione levels in patients with endometrial cancer Am J Obstet Gynecol 118 6 1974 793 798
72. N.E. Reame, R.P. Kelche, and I.Z. Beitins Age effects of follicle-stimulating hormone and pulsatile luteinizing hormone secretion across the menstrual cycle of premenopausal women J Clin Endocrinol Metab 81 4 1996 1512 1518
73. N. Santoro, T. Banwell, and D. Tortoriello Effects of aging and gonadal failure on the hypothalamic-pituitary axis in women Am J Obstet Gynecol 178 4 1998 732 741
74. S. Muttukrishna, S. Sharma, and D.H. Barlow Serum inhibins, estradiol, progesterone and FSH in surgical menopause: a demonstration of ovarian pituitary feedback loop in women Hum Reprod 17 10 2002 2535 2539
75. A.P. Cheung, S.M. Pride, B.H. Yuen, and L. Sy In-vivo ovarian androgen responses to recombinant FSH with and without recombinant LH in polycystic ovarian syndrome Hum Reprod 17 10 2002 2540 2547
76. A.J. Hsueh, K.D. Dahl, and J. Vaughan Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis Proc Natl Acad Sci USA 84 14 1987 5082 5086
77. C.D. Smyth, F. Miro, P.F. Whitelaw, C.M. Howles, and S.G. Hillier Ovarian thecal/interstitial androgen synthesis is enhanced by a follicle-stimulating hormone-stimulated paracrine mechanism Endocrinology 133 4 1993 1532 1538
78. R.B. Barnes, R.L. Rosenfield, A. Namnoum, and L.C. Layman Effect of follicle-stimulating hormone on ovarian androgen production in a woman with isolated follicle-stimulating hormone deficiency N Engl J Med 343 16 2000 1197 1198
79. M.E. Parsanezhad, M.H. Bagheri, S. Alborzi, and E.H. Schmidt Ovarian stromal blood flow changes after laparoscopic ovarian cauterization in women with polycystic ovary syndrome Hum Reprod 18 7 2003 1432 1437
80. E. Carmina, A. Longo, and R.A. Lobo Does ovarian blood flow distinguish between ovulatory and anovulatory patients with polycystic ovary syndrome? Am J Obstet Gynecol 189 5 2003 1283 1286
81. X.K. Wu, S.Y. Zhou, K. Sallinen, P. Pollanen, and R. Erkkola Ovarian-adrenal cross-talk in polycystic ovary syndrome: evidence from wedge resection Eur J Endocrinol 143 3 2000 383 388
82. F. Khamsi, S. Roberge, and Y. Yavas Recent discoveries in physiology of insulin-like growth factor-1 and its interaction with gonadotropins in folliculogenesis Endocrine 16 3 2001 151 165
83. J.F. Cara, J. Fan, J. Azzarello, and R.L. Rosenfield Insulin-like growth factor-I enhances luteinizing hormone binding to rat ovarian theca-interstitial cells J Clin Invest 86 2 1990 560 565
84. A. Dunaif, G. Green, and R.G. Phelps Acanthosis Nigricans, insulin action, and hyperandrogenism: clinical, histological, and biochemical findings J Clin Endocrinol Metab 73 3 1991 590 595
85. R.S. Legro, V.D. Castracane, and R.P. Kauffman Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls Obstet Gynecol Surv 59 2 2004 141 154
86. A. Gambineri, C. Pelusi, and S. Genghini Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome Clin Endocrinol (Oxf) 60 2 2004 241 249
87. N. Sattar, Z.E. Hopkinson, and I.A. Greer Insulin-sensitising agents in polycystic ovary syndrome Lancet 351 9099 1998 305 307
88. E. Seli, and A.J. Duleba Should patients with polycystic ovarian syndrome be treated with metformin? Hum Reprod 17 9 2002 2230 2236
89. G. Loverro, F. Lorusso, and G. De Pergola Clinical and endocrinological effects of 6 months of metformin treatment in young hyperinsulinemic patients affected by polycystic ovary syndrome Gynecol Endocrinol 16 3 2002 217 224
90. D.A. Ehrmann, D.J. Schneider, and B.E. Sobel Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome J Clin Endocrinol Metab 82 7 1997 2108 2116
91. I. Hasegawa, H. Murakawa, and M. Suzuki Effect of troglitazone on endocrine and ovulatory performance in women with insulin resistance-related polycystic ovary syndrome Fertil Steril 71 2 1999 323 327
92. M.E. Geffner, S.A. Kaplan, and N. Bersch Persistence of insulin resistance in polycystic ovarian disease after inhibition of ovarian steroid secretion Fertil Steril 45 3 1986 327 333
93. F. Singer, G. Bhargava, and L. Poretsky Persistent insulin resistance after normalization of androgen levels in a woman with congenital adrenal hyperplasia. A case report J Reprod Med 34 11 1989 921 922
94. R. Azziz, C.L. Deal, H.D. Potter, S.E. Gargosky, and R.G. Rosenfeld Regulation of extragonadal insulin-like growth factor-binding protein-3 by testosterone in oophorectomized women J Clin Endocrinol Metab 79 6 1994 1747 1751
95. J.E. Nestler, C.O. Barlascini, and D.W. Matt Suppression of serum insulin by diazoxide reduces serum testosterone levels in obese women with polycystic ovary syndrome J Clin Endocrinol Metab 68 6 1989 1027 1032
96. A. Dunaif, D. Scott, D. Finegood, B. Quintana, and R. Whitcomb The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome J Clin Endocrinol Metab 81 9 1996 3299 3306
97. M. Li, J.F. Youngren, and A. Dunaif Decreased insulin receptor (IR) autophosphorylation in fibroblasts from patients with PCOS: effects of serine kinase inhibitors and IR activators J Clin Endocrinol Metab 87 9 2002 4088 4093
98. A. Dunaif Insulin action in the polycystic ovary syndrome Endocrinol Metab Clin North Am 28 2 1999 341 359
99. R.S. Legro Insulin resistance in polycystic ovary syndrome: treating a phenotype without a genotype Mol Cell Endocrinol 145 1-2 1998 103 110
100. J.E. Nestler, L.P. Powers, and D.W. Matt A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome J Clin Endocrinol Metab 72 1 1991 83 89
101. J.G. Rheinwald, and H. Green Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes Nature 265 5593 1977 421 424
102. M.P. Diamond, D.A. Grainger, A.J. Laudano, K. Starick-Zych, and R.A. DeFronzo Effect of acute physiological elevations of insulin on circulating androgen levels in nonobese women J Clin Endocrinol Metab 72 4 1991 883 887
103. J.E. Nestler, J.N. Clore, J.F. Strauss 3rd, and W.G. Blackard The effects of hyperinsulinemia on serum testosterone, progesterone, dehydroepiandrosterone sulfate, and cortisol levels in normal women and in a woman with hyperandrogenism, insulin resistance, and acanthosis nigricans J Clin Endocrinol Metab 64 1 1987 180 184
104. L. Poretsky On the paradox of insulin-induced hyperandrogenism in insulin-resistant states Endocr Rev 12 1 1991 3 13
105. R.L. Barbieri, A. Makris, and K.J. Ryan Effects of insulin on steroidogenesis in cultured porcine ovarian theca Fertil Steril 40 2 1983 237 241
106. X.K. Wu, S.Y. Zhou, and J.X. Liu Selective ovary resistance to insulin signaling in women with polycystic ovary syndrome Fertil Steril 80 4 2003 954 965
107. S.G. Hillier Gonadotropic control of ovarian follicular growth and development Mol Cell Endocrinol 179 1-2 2001 39 46
108. C.I. Pao, P.K. Farmer, and S. Begovic Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding protein 1 gene transcription by hormones and provision of amino acids in rat hepatocytes Mol Endocrinol 7 12 1993 1561 1568
109. L. Poretsky, B. Glover, V. Laumas, M. Kalin, and A. Dunaif The effects of experimental hyperinsulinemia on steroid secretion, ovarian Endocrinology 122 2 1988 581 585
110. V. De Leo, A. La Marca, R. Orvieto, and G. Morgante Effect of metformin on insulin-like growth factor (IGF) I and IGF- binding protein I in polycystic ovary syndrome J Clin Endocrinol Metab 85 4 2000 1598 1600
111. S.G. Hillier, E.L. Yong, and P.J. Illingworth Effect of recombinant inhibin on androgen synthesis in cultured human thecal cells Mol Cell Endocrinol 75 2 1991 R1 R6
112. C.K. Welt, and A.L. Schneyer Differential regulation of inhibin B and inhibin a by follicle- stimulating hormone and local growth factors in human granulosa cells from small antral follicles J Clin Endocrinol Metab 86 1 2001 330 336
113. L.C. Giudice Insulin-like growth factors and ovarian follicular development Endocr Rev 13 4 1992 641 669
114. A. el-Roeiy, X. Chen, and V.J. Roberts Expression of insulin-like growth factor-I (IGF-I) and IGF-II and the IGF-I, IGF-II, and insulin receptor genes and localization of the gene products in the human ovary J Clin Endocrinol Metab 77 5 1993 1411 1418
115. M.E. Silfen, A.M. Manibo, and M. Ferin Elevated free IGF-I levels in prepubertal Hispanic girls with premature adrenarche: relationship with hyperandrogenism and insulin sensitivity J Clin Endocrinol Metab 87 1 2002 398 403
116. R. Homburg, C. Pariente, B. Lunenfeld, and H.S. Jacobs The role of insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 (IGFBP-1) in the pathogenesis of polycystic ovary syndrome Hum Reprod 7 10 1992 1379 1383
117. A.E. Tiitinen, T.J. Laatikainen, and M.T. Seppala Serum levels of insulin-like growth factor binding protein-1 and ovulatory responses to clomiphene citrate in women with polycystic ovarian disease Fertil Steril 60 1 1993 58 62
118. A.J. Morales, G.A. Laughlin, and T. Butzow Insulin, somatotropic, and luteinizing hormone axes in lean and obese women with polycystic ovary syndrome: common and distinct features J Clin Endocrinol Metab 81 8 1996 2854 2864
119. L.C. Giudice Growth factor action on ovarian function in polycystic ovary syndrome Endocrinol Metab Clin North Am 28 2 1999 325 339 vi
120. V.L. Nelson, K.N. Qin Kn, and R.L. Rosenfield The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome J Clin Endocrinol Metab 86 12 2001 5925 5933
121. G. Carbunaru, P. Prasad, and B. Scoccia The hormonal phenotype of nonclassic 3 beta-hydroxysteroid dehydrogenase (HSD3B) deficiency in hyperandrogenic females is associated with insulin-resistant polycystic ovary syndrome and is not a variant of inherited HSD3B2 deficiency J Clin Endocrinol Metab 89 2 2004 783 794
122. C.E. Fluck, W.L. Miller, and R.J. Auchus The 17,20-lyase activity of cytochrome p450c17 from human fetal testis favors the delta5 steroidogenic pathway J Clin Endocrinol Metab 88 8 2003 3762 3766
123. A.C. Swart, N.W. Kolar, N. Lombard, J.I. Mason, and P. Swart Baboon cytochrome P45017alpha-hydroxylase/17,20-lyase (CYP17) Eur J Biochem 269 22 2002 5608 5616
124. K. Remsberg, E. Talbott, J. Zborowski, R. Evans, and K. McHugh-Pemu Evidence for competing effects of body mass, hyperinsulinemia, insulin resistance, and androgens on leptin levels among lean, overweight, and obese women with polycystic ovary syndrome Fertil Steril 78 3 2002 479
125. A. Arroyo, G.A. Laughlin, A.J. Morales, and S.S. Yen Inappropriate gonadotropin secretion in polycystic ovary syndrome: influence of adiposity J Clin Endocrinol Metab 82 11 1997 3728 3733
126. H. Grulet, A.C. Hecart, and B. Delemer Roles of LH and insulin resistance in lean and obese polycystic ovary syndrome Clin Endocrinol (Oxf) 38 6 1993 621 626
127. P.O. Dale, T. Tanbo, S. Vaaler, and T. Abyholm Body weight, hyperinsulinemia, and gonadotropin levels in the polycystic ovarian syndrome: evidence of two distinct populations Fertil Steril 58 3 1992 487 491
128. W.X. Ke, G.Q. Shan, and S.Y. Hua Different responses of insulin, C-peptide, and testosterone to an oral glucose tolerance test in two groups of women with polycystic ovarian syndrome Acta Obstet Gynecol Scand 75 2 1996 166 169
129. B. Banaszewska, R.Z. Spaczynski, M. Pelesz, and L. Pawelczyk Incidence of elevated LH/FSH ratio in polycystic ovary syndrome women with normo- and hyperinsulinemia Rocz Akad Med Bialymst 48 2003 131 134
130. S. Toprak, A. Yonem, and B. Cakir Insulin resistance in nonobese patients with polycystic ovary syndrome Horm Res 55 2 2001 65 70
131. G. Tropeano, I.P. Vuolo, and A. Lucisano Gonadotropin levels in women with polycystic ovary syndrome: their relationship to body weight and insulin levels J Endocrinol Invest 19 3 1996 139 145
132. D.J. Jakubowicz, and J.E. Nestler 17 alpha-Hydroxyprogesterone responses to leuprolide and serum androgens in obese women with and without polycystic ovary syndrome offer dietary weight loss J Clin Endocrinol Metab 82 2 1997 556 560
133. F.V. Comim, and P.M. Spritzer Increased growth hormone response to clonidine in nonobese normoinsulinemic patients with polycystic ovary syndrome Fertil Steril 81 1 2004 108 113
134. S. Hashimoto, J. Yatabe, S. Midorikawa, H. Sanada, and T. Watanabe Inhibition of growth hormone excess reduces insulin resistance and ovarian dysfunction in a lean case of polycystic ovary syndrome with a growth-hormone-producing pituitary adenoma Horm Res 59 3 2003 149 155