Polycystic ovary syndrome and metabolic comorbidities: Therapeutic options

Drugs of Today

Volumn 45, Issue 10, 2009, Pages 763-775

  De Leo, Vincenzo ^a   Musacchio, M C ^a   Palermo, V ^b   Di Sabatino, A ^a   Morgante, G ^a   Petraglia, F ^a  

^a UNIVERSITY OF SIENA   (Italy)

^b UNIVERSITY OF CATANIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ACARBOSE; ANTIDIABETIC AGENT; CHLORPROPAMIDE; CIGLITAZONE; CLOMIFENE CITRATE; CONTRACEPTIVE AGENT; DEXTRO INOSITOL; DIAZOXIDE; FLUTAMIDE; METFORMIN; PHENFORMIN; PIOGLITAZONE; ROSIGLITAZONE; SOMATOSTATIN; TOLBUTAMIDE; TROGLITAZONE; UNCLASSIFIED DRUG;

ABDOMINAL DISCOMFORT; ADD ON THERAPY; ANOREXIA; CARDIOVASCULAR RISK; CHOLESTEROL BLOOD LEVEL; CLINICAL TRIAL; COMORBIDITY; DIARRHEA; DRUG MEGADOSE; DRUG WITHDRAWAL; ENDOTHELIAL DYSFUNCTION; GROWTH RETARDATION; HEART PALPITATION; HIGH RISK POPULATION; HOT FLUSH; HUMAN; HYPERGLYCEMIA; HYPERINSULINEMIA; HYPERLIPIDEMIA; HYPERTENSION; HYPERURICEMIA; IN VITRO STUDY; INSULIN RESISTANCE; LACTIC ACIDOSIS; LIFESTYLE MODIFICATION; LIVER TOXICITY; LOW DRUG DOSE; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OVARY POLYCYSTIC DISEASE; REVIEW; SIDE EFFECT; SODIUM RETENTION; TREATMENT WITHDRAWAL; TRIACYLGLYCEROL BLOOD LEVEL; WEIGHT GAIN; WEIGHT REDUCTION;

COMORBIDITY; DIABETES MELLITUS, TYPE 2; FEMALE; HUMANS; HYPERLIPIDEMIAS; HYPOGLYCEMIC AGENTS; INSULIN RESISTANCE; METFORMIN; OBESITY; POLYCYSTIC OVARY SYNDROME; WEIGHT LOSS;

EID: 76749118966     PISSN: 16993993     EISSN: 16994019     Source Type: Journal    
DOI: 10.1358/dot.2009.45.10.1429463     Document Type: Review

References (103)

1. De Leo, V., La Marca, A., Petraglia, F. Insulin-lowering agents in the management of polycystic ovary syndrome. Endocr Rev 2003, 24(5): 633-67.
2. Dunaif, A., Givens, J.R., Haseltine, F.R., Merriam, G.R. (Eds.). Polycystic ovary syndrome. Blackwell Scientific Publications: Boston 1992, 377-84.
3. The Rotterdam ESRHE/ASRM-sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and lond-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004, 19: 41-7.
4. Amer, S.A., Li, T.C., Baygrave, C, Sprigg, A., Sravelos, H., Cookie, I.D. An evaluation of inter-observer and intra-observer variability of ultrasound diagnosis of polycystic ovaries. Hum Reprod 2002, 17(6): 1616-22.
5. Azziz, R., Carmina, E., Dewailly, D. et al. Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: An Androgen Excess guideline. J Clin Endocrinol Metab 2006, 91(11): 4237-45.
6. Salley, K.E.S., Wickham, E.P., Chenag, K.L., Essah, P.A., Karjane, N.W., Nestler, J.E. Position statement: Glucose intolerance in polycystic ovary syndrome- a position statement of the androgen excess society. J Clin Endocrinol Metab 2007, 92(812). 4546-56.
7. Chou, K.H., Von Eye Corleta, H., Capp, E., Spritzer, P.M. Clinical, metabolic and endocrine parameters in response to metformin in obese women with polycystic ovary syndrome: A randomized, double-blind and placebo-controlled trial. Horm Metab Res 2003, 35: 86-91.
8. Lord, J.M., Flight, I.H., Norman, R.J. Metformin in polycystic ovary syndrome: Systematic review and meta-analysis. BMJ 2003, 327(7421): 951-7.
9. Ibáñez, L., Valls, C, Potau, N., Marcos, M.V., De Zegher, F. Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious pubarche. J Clin Endocrinol Metab 2000, 85(10): 3526-30.
10. Mantzoros, C.S., Flier, J.S. Insulin resistance: The clinical spectrum. Adv Endocrinol Metab 1995, 6: 193-232.
11. Ciaraldi, T.R., Et-Roeiy, A., Madar, Z., Reichart, D., Olefsky, J.M., Yen, S.S.C. Cellular mechanisms of insulin resistance in polycystic ovarian syndrome. J Clin Endocrinol Metab 1992, 75(2): 577-83.
12. Marsden, P.J., Murdoch, A., Taylor, R. Severe impairment of insulin action in adipocytes from amenorrhoeic subjects with polycystic ovary syndrome. Metabolism 1994, 43(12): 1536-42.
13. Morales, A.J., Laughlin, G.A., Butzow, 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 distinct features. J Clin Endocrinol Metab 1996, 81(8): 2854-9.
14. Achard, M., Thiers, M.J. Le virilisme plaire et son association a l'insuffisance glycolytique (diabete des femmes a barbe). Bull Acad Natl Med 1921, 86: 51-64.
15. Kahn, C.R., Flier, J.S., Bar, R.S., Archer, J.A., Gorden, P., Martin, M.M., Roth, J. The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. N Engl J Med 1976, 294(14): 739-45.
16. Dunaif, A. Hyperandrogenic anovulation (PCOS): A unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus. Am J Med 1995, 98(1A): 33S-9S.
17. Zhang, L.H., Rodriguez, H., Ohno, S., Milter, 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 1995, 92(23): 10619-23.
18. Nestler, J.E., Jakubowicz, D.J., De Vargas, A.F., Brik, C., Quintero, N., Medina, R Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system. J Clin Endocrinol Metab 1998, 83(6): 2001-5.
19. Franks, S., McCarthy, M.I., Hardy, K. Development of polycystic ovary syndrome: involvement of genetic and environmental factors, lnt J Androl 2006, 29(1): 278-85.
20. Poretsky, L., Cataldo, N.A., Rosenwaks, Z., Giudice, LC The insulin-related ovarian regulatory system in health and disease. Endocr Rev 1999, 20(4): 535-82.
21. Duleba, A.J., Spaczynski, R.Z., Olive, D.L. Insulin and Insulin-like growth factor I stimulate the proliferation of human ovarian theca-interstitial cells. Fertil Steril 1998, 69(2): 335-40.
22. Wrathall, J.H., Knigh, P.G. Effects of inhibin-related peptides and oestradiol on androstenedione and progesterone secretion by bovine theca cells in vitro. J Endocrinol 1995, 145(3): 491-500.
23. Kristiansen, S.B., Endoh, A., Casson, P.R., Buster, J.E., Hornsby, P.J. Induction of steroidogenic enzyme genes by insulin and IGF-I in cultured adult human adrenocortical cells. Steroids 1997, 62(2): 258-65.
24. Adashi, E.Y., Resnick, C.E., D'Ercole, A.J., Svoboda, M.E., Van Wyk, J.J. Insulin-like growth factors as intraovarian regulators of granulosa cell growth and function. Endocr Rev 1985, 6(3): 400-20.
25. Unger, J.W., Livingston, J.N., Moss, A.M. Insulin receptors in the central nervous system: Localization, signalling mechanisms and functional aspects. Prog Neurobiol 1991, 36(5): 343-62.
26. Yamashita, S., Melmed, S. Insulin regulation of rat growth hormone gene transcription. J Clin Invest 1986, 78(4): 1008-14.
27. Dunaif, A., Scott, D., Finegood, D., Quintana, B., Whitcomb, R. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J Clin Endocrinol Metab 1996, 81(9): 3299-306.
28. Ehrmann, D.A., Schneider, D.J., Sobel, B.E., Cavaghan, M.K., lmperia, J,. Rosenfield, R.L., Polonsky, K.S. Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1997, 82(7): 2108-16.
29. Erickson. G.R., Magoffin, D.A., Cragun, J.R,. Chang, R.J. The effects of insulin and insulin-like growth factors-l and -II on estradiol production by granulosa cells of polycystic ovaries. J Clin Endocrinol Metab 1990, 70(4): 894-902.
30. Bergh, C, Carlsson, B., Olsson, J.H., Selleskog, U., Hillensjo, T. Regulation of androgen production in cultured human theca cells by insulin-like growth factor I and insulin. Fertil Steril 1993, 59(2): 323-31.
31. Hosker, J.P., Matthews, D.R., Rudenski, A.S., Burnett, M.A., Darling, P., Bown, E.G., Turner, R.C Continuous infusion of glucose with model assessment: Measurement of insulin resistance and β-cell function in man. Diabetologia 1985, 28(7): 401-11.
32. Katz, A., Nambi, S.S., Mather, K., Baron, A.D., Follmann, D.A., Sullivan, C, Quon, M.J. Quantitative insulin sensitivity check index: A simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000, 85(7): 2402-10.
33. King, H., Rewers, M. Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults. WHO Ad Hoc Diabetes Reporting Group. Diabetes Care 1993, 16(1): 157-77.
34. Wild, S., Pierpoint, T., McKeigue, P., Jacobs, H. Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: A retrospective cohort study. Clin Endocrinol 2000, 52: 595-600.
35. Legro, R.S., Kunselman, A.R., Dodson, W.C, Dunaif, A. Prevalence and predictors of 7isk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: A prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 1999, 84(1): 165-9.
36. Palmert, M.R., Gordon, C.M., Kartashov, A,I., Legro, R.S., Emans, S.J., Dunaif, A. Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome. J Clin Endocrinol Metab 2002, 87(3): 1017-23
37. Kousta, E., Cela, E., Lawrence, N.J. et al. The prevalence of polycystic ovaries in women with a history of gestational diabetes. Clin Endocrinol 2000, 53: 501-7.
38. Talbott, E., Guzick, D., Clerici, A. et al. Coronary heart disease risk factors in women with polycystic ovary syndrome. Arterioscler Thromb Vase Biol 1995, 15: 821-6.
39. Laitinen, J., Taponen, S., Martikainen, H. et al. Body size from birth to adulthood as a predictor of self-reported polycystic ovary syndrome symptoms. lnt J Obes Relat Metab Disord 2003, 27(6): 710-5.
40. Kiddy, D.S., Hamilton-Fairley, D., Bush, A. et al. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol 1992, 36: 105-111.
41. Andersen, P., Seljeflot, L, Abdelnoor, M., et al. Increased insulin sensitivity and fibrinolytic capacity after dietary intervention in obese women with polycystic ovary syndrome. Metabolism 1995, 44(5): 611-6.
42. Wild, S., Pierpoint, T., McKeigue, P., Jacobs, H. Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: A retrospective cohort study. Clin Endocrinol 2000, 52: 595-600.
43. Pirwany, LR., Fleming, R., Greer, I.A., Packard, C.J., Sattar, N. Lipids and lipoprotein subfractions in women with PCOS: Relationship to metabolic and endocrine parameters. Clin Endocrinol 2001, 54: 447-53.
44. Taponen, S., Martikainen, H., Jarvelin, M.R. et al. Northern Finland Birth Cohort 1966 Study. Metabolic cardiovascular disease risk factors In women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland Birth Cohort 1966 Study. Clin Endocrinol Metab 2004, 89: 2114-2118.
45. Mather, K.J., Kwan, F., Corenblum, B. Hyperinsulinemia in polycystic ovary syndrome correlates with increased cardiovascular risk independent of obesity. Fertil Steril 2000, 73(1): 150-6.
46. Cussons, AJ., Stuckey, B.G., Watts, G.F. Cardiovascular disease in the polycystic ovary syndrome: New insights and perspectives. Atherosclerosis 2006, 185(2): 227-39.
47. Orio, F. Jr, Palomba, S., Cascella, T. et al. Early impairment of endothelial structure and function in young normal-weight women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004, 89(9): 4588-93.
48. Tarkun, I, Arslan, B.C., Canturk, Z., Turemen, E., Sahin, T., Duman, C. Endothelial dysfunction in young women with polycystic ovary syndrome: relationship with insulin resistance and low-grade chronic inflammation. J Clin Endocrinol Metab 2004, 89(11): 5592-6.
49. Lerman, A., Edwards, B.S., Hallett, J.W., Heublein, D.M., Sandberg, S.M., Burnett, J.C. Jr. Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis. N Engl J Med 1991, 325(14): 997-1001.
50. Ferri, C., Pittoni, V., Piccoli, A. et al. Insulin stimulates endothelin-1 secretion from human endothelial cells and modulates its circulating levels in vivo. J Clin Endocrinol Metab 1995, 80(3): 829-35.
51. Ridker, P.M., Hennekens, C.H., Buring, J.E., Rifai, N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000, 342(12): 836-43.
52. Dahlgreen, E., Janson, P.O., Johansson, S., Lapidus, L,. Oden, A. polycystic ovary syndrome and risk for myocardial infarction. Evaluated from a risk factor model based on a prospective population study of women. Acta Obstet Gynecol Scand 1992, 71(8): 599-604.
53. Pierpoint, T., McKeigue, P.M., Isaacs, A.J., Wild, S.H., Jacobs, H.S. Mortality of women with polycystic ovary syndrome at long-term follow-up. J Clin Epidemiol 1998, 51(7): 581-6.
54. Talbott, E.O., Zborowski, J.V., Rager, J.R. et al. Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004, 89(11): 5454-61.
55. Shaw, L.J., Merz, C.N., Azziz, R. et al. Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival. Results from the National Institute of Health National Heart, Lung, and Blood Institute (NHLBI) sponsored women's ischemia syndrome evaluation (WISE). J Clin Endocrinol Metab 2008, 93(4): 1276-84.
56. Clark, A.M. Ledger, W., Galletly, C, Tomlinson, L., Blaney, F., Wang, X., Norman, R.J. Weight loss results in siqnificant improvement in pregnancy and ovulation rates in anovulatory obese women. Hum Reprod 1995, 10(10): 2705-12.
57. De Leo, V., Lanzetta, D., D'Antona, D., la Marca, A., Morgante, G. Hormonal effects of flutamide in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998, 83(1): 99-102.
58. De Leo, V., La Marca, A., Lanzetta, D., Cariello, P.L., D'Antona, D., Morgante, G. Effects of flutamide on pituitary and adrenal responsiveness to corticotrophin releasing factor (CRF). Clin Endocrinol (Oxford) 1998, 49: 85-9.
59. Jensen, J.T., Speroff, L. Health benefits of oral contraceptives. Obstet Gynecol Clin North Am 2000, 27(4): 705-21.
60. Mastorakos, G, Koliopoulos, C, Creatsas, G. Androgen and lipid profiles in adolescents with polycystic ovary syndrome who were treated with two forms of combined oral contraceptives. Fertil Steril 2002, 77(5): 919-27.
61. Huber-Bucholz, M.M., Carey, D.G., Norman. R.J. Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome. J Clin Endocrinol Metab 1999, 84(4): 1470-4.
62. Diamanti-Kandarakis, E., Kouli, C, Tsianateli, T., Bergiele, A. Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome. Eur J Endocrinol 1998, 138(3): 269-74.
63. Katsiki, N., Georgiadou, E., Hatzitolios, A.I. The role of insulin-sensitizing agents in the treatment of polycystic ovary syndrome. Drugs 2009, 69(11): 1417-31.
64. Fulgencio, J.P., Kohl, C, Girard, J., Pegorier, J.P. Effect of metformin on fatty acid and glucose metabolism in freshly isolated hepatocytes and on specific gene expression in cultured hepatocytes. Biochem Pharmacol 2001, 62(4): 439-46.
65. Widen, E.I., Eriksson, J.G., Groop, L.C. Metformin normalizes nonoxidative glucose metabolism in insulin-resistant normoglycemic first-degree relatives of patients with NIDDM. Diabetes 1992, 41(3): 354-8.
66. Landin, K., Tengbom, L., Smith, U. Metformin and metoprolol CR treatment in non-obese men. J Intern Med 1994, 235(4): 335-41.
67. Stith, B.J., Woronoff, K., Wiernsperger, N. Stimulation of the intracellular portion of the human insulin receptor by the antidiabetic drug metformin. Biochem Pharmacol 1998, 55(4): 533-6.
68. DeFronzo, R.A., Barzilai, N., Simonson, D.C Mechanism of metformin action in obese and lean noninsulin-dependent diabetic subjects. J Clin Endocrinol Metab 1991, 73(6): 1294-301.
69. Matthaei, S., Stumvoli, M., Kellerer, M., Haring, H.U. Pathophysiology and pharmacological treatment of insulin resistance. Endocr Rev 2000, 21(6): 585-618.
70. Stepensky, D., Friedman, M., Srour, W., Raz, I., Hoffman, A. Preclinical evaluation of pharmacokinetic-pharmacodynamic rationale for oral CR metformin formulation. J Control Release 2001, 71(1): 107-15.
71. Morin-Papunen, L.C, Vauhkonen, I., Koivunen, R.M., Ruokonen, A., Martikainen, H.K., Tapanainen, J.S. Endocrine and metabolic effects of metformin vs. ethinyl estradiol-cyproterone acetate in obese women with polycystic ovary syndrome: a randomized study. J Clin Endocrinol Metab 2000, 85(9): 3161-8.
72. De Leo, V, La Marca, A., Orvieto, R., Morgante, G. Effect of metformin on insulin-like growth factor (IGF) I and IGF-binding protein I in polycystic ovary syndrome. J Clin Endocrinol Metab 2000, 85(4): 1598-600.
73. La Marca, A., Morgante, G., Paglia, T., Ciotta, L., Cianci, A., De Leo, V. Effects of metformin on adrenal steroidogenesis in women with polycystic ovary syndrome. Fertil Steril 1999, 72(6): 985-9.
74. Velazquez, E., Acosta, A., Mendoza, S.G. Menstrual cyclicity after metformin therapy in polycystic ovary syndrome. Obstet Gynecol 1997, 90(3): 392-5.
75. De Leo, V, Musacchio, M.C., Morgante, G., Piomboni, P., Petraglia, F. Metformin treatment is effective in obese teenage girls with PCOS. Hum Reprod 2006, 21(9): 2252-6.
76. Nestler, J.E., Jakubowicz, D.J., Evans, W.S., Pasquali, R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 1998, 338(26): 1876-80.
77. De Leo, V., La Marca, A., Ditto, A., Morgante, G., Cianci, A. Effects of metformin on gonadotropin-induced ovulation in women with polycystic ovary syndrome. Fertil Steril 1999, 72(2): 282-5.
78. Lord, J.M., Flight, I.H., Norman, R.J. Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, ploglitazone, D-chiro-inositol) for polycystic ovary syndrome. Cochrane Database Syst Rev. 2003, (3): CD003053.
79. Neveu, N., Granger, L., St-Michel, P., Lavoie, H.B. Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction and achievement of pregnancy in 154 women with polycystic ovary syndrome. Fertil Steril. 2007, 87(1): 113-20.
80. Palomba, S., Orio, F. Jr., Falbo, A. et al. Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005, 90(7): 4068-74.
81. Moll, E., Bossuyt, P.M., Korevaar, J.C., Lambalk, C.B., van der Veen, F. Effect of Clomifene citrate plus metformin and Clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial. BMJ 2006, 332(7556): 1485.
82. Legro, R.S., Barnhart, H.X., Schtaff, W.D. et aL. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007, 356(6): 551-66.
83. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. 2008, 23(3): 462-77.
84. McCarthy, E.A., Walker, S.P., McLachlan, K., Boyle, J., Permezel, M. Metformin in obstetric and gynecologic practice: A review. Obstet Gynecol Surv 2004, 59(2): 118-27.
85. Glueck, C.J., Bornovali, S., Pranikoff, J., Goldenberg, N., Dharashivkar, S., Wang, P. Metformin, pre-eclampsia, and pregnancy outcomes in women with polycystic ovary syndrome. Diabet Med 2004, 21(8): 829-36.
86. Heard, MJ., Pierce, A., Carson, S.A., Buster, J.E. Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome. Fertil Steril 2002, 7: 890-1.
87. Gilbert, C., Valois, M., Koren, G. Pregnancy outcome after first-trimester exposure to metformin: A meta-analysis. Fertil Steril 2006, 86(3): 658-63.
88. Jakubowicz, D.J., luorno, M.J., Jakubowicz, S., Roberts, K.A., Nestler, J.E. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab 2002, 87(2): 524-9.
89. Glueck, C.J., Wang, P., Goldenberg, N., Sieve-Smith, L. Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin. Hum Reprod 2002, 17(11): 2858-64.
90. Glueck, C.J., Wang, P., Kobayashi, S., Phillips, H., Sieve-Smith, L. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Fertil Steril 2002, 77(3): 520-5.
91. Ehrmann, D.A., Schneider, D.J., Sobel, B.E., Cavaghan, M.K., Imperial, J., Rosenfield, R.L., Polonsky, K.S. Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1997, 82(7): 2108-16.
92. Lehmann, J.M., Moore, L.B., Smith-Oliver, T.A., Wilkison, W.O., Willson, T.M., Kliewer, S.A. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ(PPARγ). J Biol Chem 1995, 270(22): 12953-6.
93. Azziz, R., Ehrmann, D., Legro, R.S. et al. Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: A multicenter, double blind, placebo-controlled trial. J Clin Endocrinol Metab 2001, 86(4): 1626-32.
94. Ehrmann, D.A., Schneider, D.J., Sobel, B.E., Cavaghan, M.K., Imperial, J., Rosenfield, R.L., Polonsky, K.S. Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1997, 82(7): 2108-16.
95. Baillargeon, J.P., Jakubowicz, D.J., luorno, M.J. et al. Effects of metformin and rosiglitazone, atone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. Fertil Steril 2004, 82(4): 893-902.
96. Tarkun, I., Cetinarslan, B., Tureman, E. et al. Effect of rosiglitazone on insulin resistance, C-reactive protein and endothelial function in non-obese young women with polycystic ovary syndrome. Eur J Endocrinol 2005, 153(1): 115-21.
97. Brettenthaler, N., De Gaytor, C, Huber, P.R. & Keller, U. Effect of the insulin sensitizer pioglitazone on insulin resistance, hyperandrogenism, and ovulatory dysfunction in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004, 89(8): 3835-40.
98. Aroda, V.R., Ciaraldi, T.P., Burke, P. et al. Metabolic and hormonal changes induced by pioglitazone in polycystic ovary syndrome: A randomized, placebo-controlled clinical trial. J Clin Endocrinol Metab 2009, 94(2): 469-76.
99. Shokeir, T., El-Kannishy, G. Rosiglitazone as treatment for clomiphene citrate-resistant polycystic ovary syndrome: Factors associated with clinical response. J Womens Health 2008, 17(9): 1445-52.
100. l00. Ortega-Gonzalez, C., Luna, S., Hernandez, L. et al. Responses of serum androgen and insulin resistance to metformin and pioglitazone in obese, insulin-resistant women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005, 90(3): 1360-5.
101. Krassas, G,E., Kaltsas, T,.T Pontikides, N., Jacobs, H., Blum, W., Messinis, I. Leptin levels in women with polycystic ovary syndrome before a treatment with diazoxide. Eur J Endocrinol 1998, 39(2): 184-9.
102. Ciotta, L., Catogero, A.E., Farina, M., De Leo, V., La Marca, A., Cianci, A. Clinical, endocrine and metabolic effects of acarbose, an α-glucosidase inhibitor, in PCOS patients with increased insulin response and normal glucose tolerance. Hum Reprod 2001, 16(10): 2066-72.
103. Nestler, J.E., Jakubowicz, D.J., Reamer, P., Gunn, R.D., Allan, G. Ovulatory and metabolic effects of o-chiro-inositol in the polycystic ovary syndrome. N Engl J Med 1999, 340(17): 1314-20.