The effects of metformin and rosiglitazone, alone and in combination, on the ovary and endometrium in polycystic ovary syndrome

American Journal of Obstetrics and Gynecology

Volumn 196, Issue 4, 2007, Pages 402.e1-402.e11

  Legro, Richard S ^a   Zaino, Richard J ^a   Demers, Laurence M ^a   Kunselman, Allen R ^a   Gnatuk, Carol L ^a   Williams, Nancy I ^b   Dodson, William C ^a  

^a PENN STATE COLLEGE OF MEDICINE   (United States)

^b PENNSYLVANIA STATE UNIVERSITY   (United States)

Author keywords

endometrial histology; endometrial hyperplasia; hyperandrogenism; insulin resistance; urine

Indexed keywords

ESTRONE GLUCURONIDE; GLUCOSE; INSULIN; METFORMIN; PREGNANEDIOL; ROSIGLITAZONE; TESTOSTERONE;

ADULT; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE TIME EFFECT RELATION; DRUG MECHANISM; ENDOMETRIUM CARCINOMA; ENDOMETRIUM HYPERPLASIA; FEMALE; GLUCOSE BLOOD LEVEL; HISTOPATHOLOGY; HUMAN; HUMAN CELL; HUMAN TISSUE; INSULIN BLOOD LEVEL; OVARY POLYCYSTIC DISEASE; PRIORITY JOURNAL; STEROID BLOOD LEVEL; TESTOSTERONE BLOOD LEVEL;

EID: 33947705624     PISSN: 00029378     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ajog.2006.12.025     Document Type: Article

References (49)

1. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 81 (2004) 19-25
2. Dunaif A., Segal K.R., Shelley D.R., Green G., Dobrjansky A., and Licholai T. Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes 41 (1992) 1257-1266
3. Lord J.M., Flight I.H., and Norman R.J. Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, d-chiro-inositol) for polycystic ovary syndrome. Cochrane Database Syst Rev 3 (2003) CD003053
4. 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 86 (2001) 1626-1632
5. Moghetti P., Tosi F., Tosti A., et al. Comparison of spironolactone, flutamide, and finasteride efficacy in the treatment of hirsutism: a randomized, double blind, placebo-controlled trial. J Clin Endocrinol Metab 85 (2000) 89-94
6. Baillargeon J.P., Jakubowicz D.J., Iuorno M.J., Jakubowicz S., and Nestler J.E. Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. Fertil Steril 82 (2004) 893-902
7. Moghetti P., Castello R., Negri C., et al. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab 85 (2000) 139-146
8. Nestler J.E., Jakubowicz D.J., Evans W.S., and Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 338 (1998) 1876-1880
9. Vandermolen D.T., Ratts V.S., Evans W.S., Stovall D.W., Kauma S.W., and Nestler J.E. Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone. Fertil Steril 75 (2001) 310-315
10. Inzucchi S.E., Maggs D.G., Spollett G.R., et al. Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N Engl J Med 338 (1998) 867-872
11. Dunaif A., Segal K.R., Futterweit W., and Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 38 (1989) 1165-1174
12. Homburg R., Armar N.A., Eshel A., Adams J., and Jacobs H.S. Influence of serum luteinising hormone concentrations on ovulation, conception, and early pregnancy loss in polycystic ovary syndrome. BMJ 297 (1988) 1024-1026
13. Cheung A.P. Ultrasound and menstrual history in predicting endometrial hyperplasia in polycystic ovary syndrome. Obstet Gynecol 98 (2001) 325-331
14. Hardiman P., Pillay O.C., and Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet 361 (2003) 1810-1812 [Erratum in: Lancet 2003;362:1082]
15. Legro R.S., Driscoll D., Strauss III J.F., Fox J., and Dunaif A. Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc Natl Acad Sci U S A 95 (1998) 14956-14960
16. Hatch R., Rosenfield R.L., Kim M.H., and Tredway D. Hirsutism: implications, etiology, and management. Am J Obstet Gynecol 140 (1981) 815-830
17. 0,120): comparison with other measures. Diabetes Res Clin Pract 47 (2000) 177-184
18. Adams J., Franks S., Polson D.W., et al. Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotropin releasing hormone. Lancet 2 (1985) 1375-1379
19. Pache T.D., Hop W.C., Wladimiroff J.W., Schipper J., and Fauser B.C. Transvaginal sonography and abnormal ovarian appearance in menstrual cycle disturbances. Ultrasound Med Biol 17 (1991) 589-593
20. Legro R.S., Chiu P., Kunselman A.R., Bentley C.M., Dodson W.C., and Dunaif A. Polycystic ovaries are common in women with hyperandrogenic chronic anovulation but do not predict metabolic or reproductive phenotype. J Clin Endocrinol Metab 90 (2005) 2571-2579
21. Legro R.S., Kunselman A.R., and Dunaif A. Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med 111 (2001) 607-613
22. O'Connor K.A., Brindle E., Holman D.J., et al. Urinary estrone conjugate and pregnanediol 3-glucuronide enzyme immunoassays for population research. Clin Chem 49 (2003) 1139-1148
23. Jordan J., Craig K., Clifton D.K., and Soules M.R. Luteal phase defect: the sensitivity and specificity of diagnostic methods in common clinical use. Fertil Steril 62 (1994) 54-62
24. Winters K.M., Adams W.C., Meredith C.N., Loan M.D., and Lasley B.L. Bone density and cyclic ovarian function in trained runners and active controls. Med Sci Sports Exerc 28 (1996) 776-785
25. Munro C.J., Stabenfeldt G.H., Cragun J.R., Addiego L.A., Overstreet J.W., and Lasley B.L. Relationship of serum estradiol and progesterone concentrations to the excretion profiles of their major urinary metabolites as measured by enzyme immunoassay and radioimmunoassay. Clin Chem 37 (1991) 838-844
26. McConnell H.J., O'Connor K.A., Brindle E., and Williams N.I. Validity of methods for analyzing urinary steroid data to detect ovulation in athletes. Med Sci Sports Exerc 34 (2002) 1836-1844
27. Murray M.J., Meyer W.R., Zaino R.J., et al. A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women. Fertil Steril 81 (2004) 1333-1343
28. Noyes R.W., Hertig A.T., and Rock J. Dating the endometrial biopsy. Fertil Steril 1 (1950) 3-25
29. Kassam A., Overstreet J.W., Snow-Harter C., De Souza M.J., Gold E.B., and Lasley B.L. Identification of anovulation and transient luteal function using a urinary pregnanediol-3-glucuronide ratio algorithm. Environment Health Perspect 104 (1996) 408-413
30. Field A.E., Coakley E.H., Must A., et al. Impact of overweight on the risk of developing common chronic diseases during a 10-year period. Arch Intern Med 161 (2001) 1581-1586
31. Ehrmann D.A., Cavaghan M.K., Imperial J., Sturis J., Rosenfield R.L., and Polonsky K.S. Effects of metformin on insulin secretion, insulin action, and ovarian steroidogenesis in women with polycystic ovary syndrome. J Clin Endocrinol Metab 82 (1997) 524-530
32. Yilmaz M., Biri A., Karakoc A., et al. The effects of rosiglitazone and metformin on insulin resistance and serum androgen levels in obese and lean patients with polycystic ovary syndrome. J Endocrinol Invest 28 (2005) 1003-1008
33. Yilmaz M., Karakoc A., Toruner F.B., et al. The effects of rosiglitazone and metformin on menstrual cyclicity and hirsutism in polycystic ovary syndrome. Gynecol Endocrinol 21 (2005) 154-160
34. Mitkov M., Pehlivanov B., and Terzieva D. Metformin versus rosiglitazone in the treatment of polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 126 (2006) 93-98
35. Legro R.S., and Myers E. Surrogate end-points or primary outcomes in clinical trials in women with polycystic ovary syndrome?. Hum Reprod 19 (2004) 1697-1704
36. Jakubowicz D.J., Seppala M., Jakubowicz S., et al. Insulin reduction with metformin increases luteal phase serum glycodelin and insulin-like growth factor-binding protein 1 concentrations and enhances uterine vascularity and blood flow in the polycystic ovary syndrome. J Clin Endocrinol Metab 86 (2001) 1126-1133
37. Seppala M., Mandelin E., Koistinen R., Bergholm R., Tiikkainen M., and Yki-Jarvinen H. Glycodelin responses to hyperinsulinaemic clamp vary according to basal serum glycodelin concentration. Clin Endocrinol (Oxf) 62 (2005) 611-615
38. Palomba S., Russo T., Orio Jr. F., et al. Uterine effects of metformin administration in anovulatory women with polycystic ovary syndrome. Hum Reprod 21 (2006) 457-465
39. Session D.R., Kalli K.R., Tummon I.S., Damario M.A., and Dumesic D.A. Treatment of atypical endometrial hyperplasia with an insulin-sensitizing agent. Gynecol Endocrinol 17 (2003) 405-407
40. Pritts E.A., Zhao D., Ricke E., Waite L., and Taylor R.N. PPAR-γ decreases endometrial stromal cell transcription and translation of RANTES in vitro. J Clin Endocrinol Metab 87 (2002) 1841-1844
41. Lebovic D.I., Kir M., and Casey C.L. Peroxisome proliferator-activated receptor-gamma induces regression of endometrial explants in a rat model of endometriosis. Fertil Steril 82 Suppl 3 (2004) 1008-1013
42. Inzucchi S.E., Maggs D.G., Spollett G.R., et al. Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N Engl J Med 338 (1998) 867-872
43. Ehrmann D.A., Cavaghan M.K., Imperial J., Sturis J., Rosenfield R.L., and Polonsky K.S. Effects of metformin on insulin secretion, insulin action, and ovarian steroidogenesis in women with polycystic ovary syndrome. J Clin Endocrinol Metab 82 (1997) 524-530
44. Dunaif A., Scott D., Finegood D., Quintana B., and Whitcomb R. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J Clin Endocrinol Metab 81 (1996) 3299-3306
45. Ehrmann D.A., Schneider D.J., Sobel B.E., Cavaghan M.K., Imperial J., and 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 82 (1997) 2108-2116
46. Stovall T.G., Photopulos G.J., Poston W.M., Ling F.W., and Sandles L.G. Pipelle endometrial sampling in patients with known endometrial carcinoma. Obstet Gynecol 77 (1991) 954-956
47. Fothergill D.J., Brown V.A., and Hill A.S. Histological sampling of the endometrium: a comparison between formal curettage and the Pipelle sampler. Br J Obstet Gynaecol 99 (1992) 779-780
48. Coutifaris C., Myers E.R., Guzick D.S., et al. Histological dating of timed endometrial biopsy tissue is not related to fertility status. Fertil Steril 82 (2004) 1264-1272
49. Loi C.M., Stern R., Koup J.R., Vassos A.B., Knowlton P., and Sedman A.J. Effect of troglitazone on the pharmacokinetics of an oral contraceptive agent. J Clin Pharmacol 39 (1999) 410-417