Poly Cystic Ovarian Syndrome: An updated overview

Frontiers in Physiology

Volumn 7, Issue APR, 2016, Pages

  El Hayek, Samer ^a   Bitar, Lynn ^a   Hamdar, Layal H ^a   Mirza, Fadi G ^a,b   Daoud, Georges ^a  

^a AMERICAN UNIVERSITY OF BEIRUT   (Lebanon)

^b Columbia University ^*  (United States)

Author keywords

Diabetes; Insulin; Obesity; Ovary; PCOS

Indexed keywords

ANDROGEN; CLOMIFENE CITRATE; D CHIRO INOSITOL; INOSITOL; METFORMIN; MUELLERIAN INHIBITING FACTOR; ORAL CONTRACEPTIVE AGENT; PIOGLITAZONE; ROSIGLITAZONE; SPIRONOLACTONE; TROGLITAZONE; UNCLASSIFIED DRUG;

ACNE; ANOVULATORY INFERTILITY; ANXIETY DISORDER; ATHEROSCLEROSIS; BLADDER CANCER; DEPRESSION; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG SAFETY; EATING DISORDER; ENDOMETRIUM CANCER; FEMALE INFERTILITY; GENE EXPRESSION; GYNECOLOGIC SURGERY; HEART INFARCTION; HIRSUTISM; HUMAN; HYPERANDROGENISM; INSULIN RESISTANCE; INSULIN SENSITIVITY; INTRAUTERINE GROWTH RETARDATION; LAPAROSCOPIC OVARIAN DRILLING; LAPAROSCOPIC SURGERY; MASS SCREENING; MENSTRUAL IRREGULARITY; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; OVARY POLYCYSTIC DISEASE; PATHOGENESIS; PSYCHOLOGICAL WELL BEING; PSYCHOSEXUAL DISORDER; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK FACTOR; SIGNAL TRANSDUCTION; STEROIDOGENESIS; TRANSVAGINAL ECHOGRAPHY;

EID: 84966713311     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2016.00124     Document Type: Review

References (185)

1. Açbay, O., and Gündogdu, S. (1996). Can metformin reduce insulin resistance in polycystic ovary syndrome? Fertil. Steril. 65, 946-949.
2. Anderson, H., Fogel, N., Grebe, S. K., Singh, R. J., Taylor, R. L., and Dunaif, A. (2010). Infants of women with polycystic ovary syndrome have lower cord blood androstenedione and estradiol levels. J. Clin. Endocrinol. Metab. 95, 2180-2186. doi: 10.1210/jc.2009-2651
3. 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. doi: 10.1210/jcem.87.4.8398
4. Azziz, R., Carmina, E., Dewailly, D., Diamanti-Kandarakis, E., Escobar-Morreale, H. F., Futterweit, W., et al. (2006). Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J. Clin. Endocrinol. Metab. 91, 4237-4245. doi: 10.1210/jc.2006-0178
5. Azziz, R., Carmina, E., Dewailly, D., Diamanti-Kandarakis, E., Escobar-Morreale, H. F., Futterweit, W., et al. (2009). The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil. Steril. 91, 456-488. doi: 10.1016/j.fertnstert.2008.06.035
6. Azziz, R., Marin, C., Hoq, L., Badamgarav, E., and Song, P. (2005). Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span. J. Clin. Endocrinol. Metab. 90, 4650-4658. doi: 10.1210/jc.2005-0628
7. Azziz, R., Woods, K. S., Reyna, R., Key, T. J., Knochenhauer, E. S., and Yildiz, B. O. (2004). The prevalence and features of the polycystic ovary syndrome in an unselected population. J. Clin. Endocrinol. Metab. 89, 2745-2749. doi: 10.1210/jc.2003-032046
8. Bahceci, M., Aydemir, M., and Tuzcu, A. (2007). Effects of oral fat and glucose tolerance test on serum lipid profile, apolipoprotein, and CRP concentration, and insulin resistance in patients with polycystic ovary syndrome. Fertil. Steril. 87, 1363-1368. doi: 10.1016/j.fertnstert.2006.11.031
9. Bahceci, M., Tuzcu, A., Canoruc, N., Tuzun, Y., Kidir, V., and Aslan, C. (2004). Serum C-reactive protein (CRP) levels and insulin resistance in non-obese women with polycystic ovarian syndrome, and effect of bicalutamide on hirsutism, CRP levels and insulin resistance. Horm. Res. 62, 283-287. doi: 10.1159/000081973
10. Bailey, C. J., and Turner, R. C. (1996). Metformin. N. Engl. J. Med. 334, 574-579. doi: 10.1056/NEJM199602293340906
11. Baillargeon, J. P., Iuorno, M. J., and Nestler, J. E. (2003). Insulin sensitizers for polycystic ovary syndrome. Clin. Obstet. Gynecol. 46, 325-340. doi: 10.1097/00003081-200306000-00011
12. Baillargeon, J. P., McClish, D. K., Essah, P. A., and Nestler, J. E. (2005). Association between the current use of low-dose oral contraceptives and cardiovascular arterial disease: a meta-analysis. J. Clin. Endocrinol. Metab. 90, 3863-3870. doi: 10.1210/jc.2004-1958
13. Baillargeon, J. P., Nestler, J. E., Ostlund, R. E., Apridonidze, T., and Diamanti-Kandarakis, E. (2008). Greek hyperinsulinemic women, with or without polycystic ovary syndrome, display altered inositols metabolism. Hum. Reprod. 23, 1439-1446. doi: 10.1093/humrep/den097
14. Balen, A. H., Conway, G. S., Kaltsas, G., Techatrasak, K., Manning, P. J., West, C., et al. (1995). Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients. Hum. Reprod. 10, 2107-2111.
15. Balen, A., and Rajkowha, M. (2003). Polycystic ovary syndrome-a systemic disorder? Best Pract. Res. Clin. Obstet. Gynaecol. 17, 263-274. doi: 10.1016/S1521-6934(02)00119-0
16. Balen, A. H., Tan, S. L., MacDougall, J., and Jacobs, H. S. (1993). Miscarriage rates following in vitro fertilization are increased in women with polycystic ovaries and reduced by pituitary desensitization with buserelin. Hum. Reprod. 8, 959-964.
17. Barnard, L., Ferriday, D., Guenther, N., Strauss, B., Balen, A. H., and Dye, L. (2007). Quality of life and psychological well being in polycystic ovary syndrome. Hum. Reprod. 22, 2279-2286. doi: 10.1093/humrep/dem108
18. Berneis, K., Rizzo, M., Hersberger, M., Rini, G. B., Di Fede, G., Pepe, I., et al. (2009). Atherogenic forms of dyslipidaemia in women with polycystic ovary syndrome. Int. J. Clin. Pract. 63, 56-62. doi: 10.1111/j.1742-1241.2008.01897.x
19. Bhattacharya, S. M., and Jha, A. (2011). Prevalence and risk of metabolic syndrome in adolescent Indian girls with polycystic ovary syndrome using the 2009 'joint interim criteria'. J. Obstet. Gynaecol. Res. 37, 1303-1307. doi: 10.1111/j.1447-0756.2010.01516.x
20. Borruel, S., Fernández-Durán, E., Alpañés, M., Martí, D., Álvarez-Blasco, F., Luque-Ramírez, M., et al. (2013). Global adiposity and thickness of intraperitoneal and mesenteric adipose tissue depots are increased in women with polycystic ovary syndrome (PCOS). J. Clin. Endocrinol. Metab. 98, 1254-1263. doi: 10.1210/jc.2012-3698
21. Boudreaux, M. Y., Talbott, E. O., Kip, K. E., Brooks, M. M., and Witchel, S. F. (2006). Risk of T2DM and impaired fasting glucose among PCOS subjects: results of an 8-year follow-up. Curr. Diab. Rep. 6, 77-83. doi: 10.1007/s11892-006-0056-1
22. Brettenthaler, N., De Geyter, C., Huber, P. R., and Keller, U. (2004). Effect of the insulin sensitizer pioglitazone on insulin resistance, hyperandrogenism, and ovulatory dysfunction in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 89, 3835-3840. doi: 10.1210/jc.2003-031737
23. Bruyneel, A., Catteau-Jonard, S., Decanter, C., Clouqueur, E., Tomaszewski, C., Subtil, D., et al. (2014). Polycystic ovary syndrome: what are the obstetrical risks?. Gynecol. Obstet. Fertil. 42, 104-111. doi: 10.1016/j.gyobfe.2014.01.001
24. Burghen, G. A., Givens, J. R., and Kitabchi, A. E. (1980). Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. J. Clin. Endocrinol. Metab. 50, 113-116. doi: 10.1210/jcem-50-1-113
25. Carmina, E., Oberfield, S. E., and Lobo, R. A. (2010). The diagnosis of polycystic ovary syndrome in adolescents. Am. J. Obstet. Gynecol. 203, 201.e201-e205. doi: 10.1016/j.ajog.2010.03.008
26. Cedars, M. I. (2004). Polycystic ovary syndrome: what is it and how should we treat it? J. Pediatr. 144, 4-6. doi: 10.1016/j.jpeds.2003.10.032
27. Chen, Z. J., Zhao, H., He, L., Shi, Y., Qin, Y., Shi, Y., et al. (2011). Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat. Genet. 43, 55-59. doi: 10.1038/ng.732
28. Chhabra, S., McCartney, C. R., Yoo, R. Y., Eagleson, C. A., Chang, R. J., and Marshall, J. C. (2005). Progesterone inhibition of the hypothalamic gonadotropin-releasing hormone pulse generator: evidence for varied effects in hyperandrogenemic adolescent girls. J. Clin. Endocrinol. Metab. 90, 2810-2815. doi: 10.1210/jc.2004-2359
29. Chittenden, B. G., Fullerton, G., Maheshwari, A., and Bhattacharya, S. (2009). Polycystic ovary syndrome and the risk of gynaecological cancer: a systematic review. Reprod. Biomed. Online 19, 398-405. doi: 10.1016/S1472-6483(10)60175-7
30. Clark, A. M., Thornley, B., Tomlinson, L., Galletley, C., and Norman, R. J. (1998). Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum. Reprod. 13, 1502-1505. doi: 10.1093/humrep/13.6.1502
31. Cortón, M., Botella-Carretero, J. I., Benguría, A., Villuendas, G., Zaballos, A., San Millán, J. L., et al. (2007). Differential gene expression profile in omental adipose tissue in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 92, 328-337. doi: 10.1210/jc.2006-1665
32. Cortón, M., Botella-Carretero, J. I., López, J. A., Camafeita, E., San Millán, J. L., Escobar-Morreale, H. F., et al. (2008). Proteomic analysis of human omental adipose tissue in the polycystic ovary syndrome using two-dimensional difference gel electrophoresis and mass spectrometry. Hum. Reprod. 23, 651-661. doi: 10.1093/humrep/dem380
33. Costello, M., Shrestha, B., Eden, J., Sjoblom, P., and Johnson, N. (2007). Insulin-sensitising drugs versus the combined oral contraceptive pill for hirsutism, acne and risk of diabetes, cardiovascular disease, and endometrial cancer in polycystic ovary syndrome. Cochrane Database Syst. Rev. CD005552. doi: 10.1002/14651858.CD005552.pub2
34. Cresswell, J. L., Barker, D. J., Osmond, C., Egger, P., Phillips, D. I., and Fraser, R. B. (1997). Fetal growth, length of gestation, and polycystic ovaries in adult life. Lancet 350, 1131-1135. doi: 10.1016/S0140-6736(97)06062-5
35. Dahlgren, E., Janson, P. O., Johansson, S., Lapidus, L., and Odén, A. (1992). 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. 71, 599-604. doi: 10.3109/00016349209006227
36. Das, M., Djahanbakhch, O., Hacihanefioglu, B., Saridogan, E., Ikram, M., Ghali, L., et al. (2008). Granulosa cell survival and proliferation are altered in polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 93, 881-887. doi: 10.1210/jc.2007-1650
37. Deeks, A. A., Gibson-Helm, M. E., and Teede, H. J. (2010). Anxiety and depression in polycystic ovary syndrome: a comprehensive investigation. Fertil. Steril. 93, 2421-2423. doi: 10.1016/j.fertnstert.2009.09.018
38. De Leo, V., Musacchio, M. C., Morgante, G., Piomboni, P., and Petraglia, F. (2006). Metformin treatment is effective in obese teenage girls with PCOS. Hum. Reprod. 21, 2252-2256. doi: 10.1093/humrep/del185
39. Dewailly, D., Lujan, M. E., Carmina, E., Cedars, M. I., Laven, J., Norman, R. J., et al. (2014). Definition and significance of polycystic ovarian morphology: a task force report from the Androgen Excess and Polycystic Ovary Syndrome Society. Hum. Reprod. Update 20, 334-352. doi: 10.1093/humupd/dmt061
40. de Zegher, F., and Ibáñez, L. (2009). Early Origins of polycystic ovary syndrome: hypotheses may change without notice. J. Clin. Endocrinol. Metab. 94, 3682-3685. doi: 10.1210/jc.2009-1608
41. de Zegher, F., Lopez-Bermejo, A., and Ibáñez, L. (2009). Adipose tissue expandability and the early origins of PCOS. Trends Endocrinol. Metab. 20, 418-423. doi: 10.1016/j.tem.2009.06.003
42. Diabetes Prevention Program (DPP) Research Group (2002). The diabetes prevention program (DPP): description of lifestyle intervention. Diabetes Care 25, 2165-2171.
43. Diamanti-Kandarakis, E. (2010). PCOS in adolescents. Best Pract. Res. Clin. Obstet. Gynaecol. 24, 173-183. doi: 10.1016/j.bpobgyn.2009.09.005
44. Diamanti-Kandarakis, E., and Dunaif, A. (2012). Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr. Rev. 33, 981-1030. doi: 10.1210/er.2011-1034
45. Diamanti-Kandarakis, E., and Panidis, D. (2007). Unravelling the phenotypic map of polycystic ovary syndrome (PCOS): a prospective study of 634 women with PCOS. Clin. Endocrinol. 67, 735-742. doi: 10.1111/j.1365-2265.2007.02954.x
46. Dokras, A., Clifton, S., Futterweit, W., and Wild, R. (2011). Increased risk for abnormal depression scores in women with polycystic ovary syndrome: a systematic review and meta-analysis. Obstet. Gynecol. 117, 145-152. doi: 10.1097/AOG.0b013e318202b0a4
47. Driscoll, D. A. (2003). Polycystic ovary syndrome in adolescence. Semin. Reprod. Med. 21, 301-307. doi: 10.1055/s-2003-43308
48. Dumesic, D. A., and Lobo, R. A. (2013). Cancer risk and PCOS. Steroids 78, 782-785. doi: 10.1016/j.steroids.2013.04.004
49. 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, 33S-39S. doi: 10.1016/s0002-9343(99)80057-6
50. Dunaif, A. (1997). Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr. Rev. 18, 774-800. doi: 10.1210/er.18.6.774
51. Dunaif, A. (1999). Insulin action in the polycystic ovary syndrome. Endocrinol. Metab. Clin. North Am. 28, 341-359. doi: 10.1016/S0889-8529(05)70073-6
52. Dunaif, A., Green, G., Futterweit, W., and Dobrjansky, A. (1990). Suppression of hyperandrogenism does not improve peripheral or hepatic insulin resistance in the polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 70, 699-704. doi: 10.1210/jcem-70-3-699
53. Ehrmann, D. A., Barnes, R. B., and Rosenfield, R. L. (1995). Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion. Endocr. Rev. 16, 322-353. doi: 10.1210/er.16.3.322
54. 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. doi: 10.2337/diacare.22.1.141
55. Ehrmann, D. A., Cavaghan, M. K., Imperial, J., Sturis, J., Rosenfield, R. L., and Polonsky, K. S. (1997). Effects of metformin on insulin secretion, insulin action, and ovarian steroidogenesis in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 82, 524-530. doi: 10.1210/jc.82.2.524
56. Elsenbruch, S., Benson, S., Hahn, S., Tan, S., Mann, K., Pleger, K., et al. (2006). Determinants of emotional distress in women with polycystic ovary syndrome. Hum. Reprod. 21, 1092-1099. doi: 10.1093/humrep/dei409
57. Elsenbruch, S., Hahn, S., Kowalsky, D., Offner, A. H., Schedlowski, M., Mann, K., et al. (2003). Quality of life, psychosocial well-being, and sexual satisfaction in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 88, 5801-5807. doi: 10.1210/jc.2003-030562
58. Escobar-Morreale, H. F., Luque-Ramírez, M., and San Millán, J. L. (2005). The molecular-genetic basis of functional hyperandrogenism and the polycystic ovary syndrome. Endocr. Rev. 26, 251-282. doi: 10.1210/er.2004-0004
59. Escobar-Morreale, H. F., Samino, S., Insenser, M., Vinaixa, M., Luque-Ramírez, M., Lasunción, M. A., et al. (2012). Metabolic heterogeneity in polycystic ovary syndrome is determined by obesity: plasma metabolomic approach using GC-MS. Clin. Chem. 58, 999-1009. doi: 10.1373/clinchem.2011.176396
60. Evans, T. N., and Riley, G. M. (1958). Polycystic ovarian disease (Stein-Leventhal syndrome); etiology and rationale for surgical treatment. Obstet. Gynecol. 12, 168-179.
61. Fauser, B. C., Tarlatzis, B. C., Rebar, R. W., Legro, R. S., Balen, A. H., Lobo, R., et al. (2012). Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil. Steril. 97, 28-38.e25. doi: 10.1016/j.fertnstert.2011.09.024
62. Ferriman, D., and Gallwey, J. D. (1961). Clinical assessment of body hair growth in women. J. Clin. Endocrinol. Metab. 21, 1440-1447. doi: 10.1210/jcem-21-11-1440
63. Formuso, C., Stracquadanio, M., and Ciotta, L. (2015). Myo-inositol vs. D-chiro inositol in PCOS treatment. Minerva Ginecol. 67, 321-325.
64. Franks, S. (2002). Adult polycystic ovary syndrome begins in childhood. Best Pract. Res. Clin. Endocrinol. Metab. 16, 263-272. doi: 10.1053/beem.2002.0203
65. Galazis, N., Galazi, M., and Atiomo, W. (2011). D-Chiro-inositol and its significance in polycystic ovary syndrome: a systematic review. Gynecol. Endocrinol. 27, 256-262. doi: 10.3109/09513590.2010.538099
66. Ganie, M. A., Khurana, M. L., Eunice, M., Gupta, N., Gulati, M., Dwivedi, S. N., et al. (2004). Comparison of efficacy of spironolactone with metformin in the management of polycystic ovary syndrome: an open-labeled study. J. Clin. Endocrinol. Metab. 89, 2756-2762. doi: 10.1210/jc.2003-031780
67. Ganie, M. A., Khurana, M. L., Nisar, S., Shah, P. A., Shah, Z. A., Kulshrestha, B., et al. (2013). Improved efficacy of low-dose spironolactone and metformin combination than either drug alone in the management of women with polycystic ovary syndrome (PCOS): a six-month, open-label randomized study. J. Clin. Endocrinol. Metab. 98, 3599-3607. doi: 10.1210/jc.2013-1040
68. Genazzani, A. D., Prati, A., Santagni, S., Ricchieri, F., Chierchia, E., Rattighieri, E., et al. (2012). Differential insulin response to myo-inositol administration in obese polycystic ovary syndrome patients. Gynecol. Endocrinol. 28, 969-973. doi: 10.3109/09513590.2012.685205
69. Glueck, C. J., Dharashivkar, S., Wang, P., Zhu, B., Gartside, P. S., Tracy, T., et al. (2005). Obesity and extreme obesity, manifest by ages 20-24 years, continuing through 32-41 years in women, should alert physicians to the diagnostic likelihood of polycystic ovary syndrome as a reversible underlying endocrinopathy. Eur. J. Obstet. Gynecol. Reprod. Biol. 122, 206-212. doi: 10.1016/j.ejogrb.2005.03.010
70. Gonzalez, F., Rote, N. S., Minium, J., and Kirwan, J. P. (2006). Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 91, 336-340. doi: 10.1210/jc.2005-1696
71. Goverde, A. J., van Koert, A. J., Eijkemans, M. J., Knauff, E. A., Westerveld, H. E., Fauser, B. C., et al. (2009). Indicators for metabolic disturbances in anovulatory women with polycystic ovary syndrome diagnosed according to the Rotterdam consensus criteria. Hum. Reprod. 24, 710-717. doi: 10.1093/humrep/den433
72. Guttmann-Bauman, I. (2005). Approach to adolescent polycystic ovary syndrome (PCOS) in the pediatric endocrine community in the U.S.A. J. Pediatr. Endocrinol. Metab. 18, 499-506. doi: 10.1515/JPEM.2005.18.5.499
73. Hahn, S., Tan, S., Elsenbruch, S., Quadbeck, B., Herrmann, B. L., Mann, K., et al. (2005). Clinical and biochemical characterization of women with polycystic ovary syndrome in North Rhine-Westphalia. Horm. Metab. Res. 37, 438-444. doi: 10.1055/s-2005-870236
74. Haoula, Z., Salman, M., and Atiomo, W. (2012). Evaluating the association between endometrial cancer and polycystic ovary syndrome. Hum. Reprod. 27, 1327-1331. doi: 10.1093/humrep/des042
75. Hardy, T. S., and Norman, R. J. (2013). Diagnosis of adolescent polycystic ovary syndrome. Steroids 78, 751-754. doi: 10.1016/j.steroids.2013.04.011
76. Hart, R., and Doherty, D. A. (2015). The potential implications of a PCOS diagnosis on a woman's long-term health using data linkage. J. Clin. Endocrinol. Metab. 100, 911-919. doi: 10.1210/jc.2014-3886
77. Hart, R., Doherty, D. A., Mori, T., Huang, R. C., Norman, R. J., Franks, S., et al. (2011). Extent of metabolic risk in adolescent girls with features of polycystic ovary syndrome. Fertil. Steril. 95, 2347-2353, 2353.e2341. doi: 10.1016/j.fertnstert.2011.03.001
78. Hart, R., and Norman, R. (2006). Polycystic ovarian syndrome-prognosis and outcomes. Best Pract. Res. Clin. Obstet. Gynaecol. 20, 751-778. doi: 10.1016/j.bpobgyn.2006.04.006
79. Hashemipour, M., Amini, M., Iranpour, R., Sadri, G. H., Javaheri, N., Haghighi, S., et al. (2004). Prevalence of congenital hypothyroidism in Isfahan, Iran: results of a survey on 20, 000 neonates. Horm. Res. 62, 79-83. doi: 10.1159/000079392
80. Hickey, M., Doherty, D. A., Atkinson, H., Sloboda, D. M., Franks, S., Norman, R. J., et al. (2011). Clinical, ultrasound and biochemical features of polycystic ovary syndrome in adolescents: implications for diagnosis. Hum. Reprod. 26, 1469-1477. doi: 10.1093/humrep/der102
81. Hickey, M., Sloboda, D. M., Atkinson, H. C., Doherty, D. A., Franks, S., Norman, R. J., et al. (2009). The relationship between maternal and umbilical cord androgen levels and polycystic ovary syndrome in adolescence: a prospective cohort study. J. Clin. Endocrinol. Metab. 94, 3714-3720. doi: 10.1210/jc.2009-0544
82. Hillard, P. J. (2005). Oral contraceptives and the management of hyperandrogenism-polycystic ovary syndrome in adolescents. Endocrinol. Metab. Clin. North Am. 34, 707-723, x. doi: 10.1016/j.ecl.2005.04.012
83. Himelein, M. J., and Thatcher, S. S. (2006). Depression and body image among women with polycystic ovary syndrome. J. Health Psychol. 11, 613-625. doi: 10.1177/1359105306065021
84. Homburg, R., and Lambalk, C. B. (2004). Polycystic ovary syndrome in adolescence-a therapeutic conundrum. Hum. Reprod. 19, 1039-1042. doi: 10.1093/humrep/deh207
85. Homburg, R., Levy, T., Berkovitz, D., Farchi, J., Feldberg, D., Ashkenazi, J., et al. (1993). Gonadotropin-releasing hormone agonist reduces the miscarriage rate for pregnancies achieved in women with polycystic ovarian syndrome. Fertil. Steril. 59, 527-531.
86. Hu, S., Leonard, A., Seifalian, A., and Hardiman, P. (2007). Vascular dysfunction during pregnancy in women with polycystic ovary syndrome. Hum. Reprod. 22, 1532-1539. doi: 10.1093/humrep/dem028
87. Huang, R.-C., de Klerk, N. H., Smith, A., Kendall, G. E., Landau, L. I., Mori, T. A., et al. (2011). Lifecourse childhood adiposity trajectories associated with adolescent insulin resistance. Diabetes Care 34, 1019-1025. doi: 10.2337/dc10-1809
88. Hull, M. G. (1987). Epidemiology of infertility and polycystic ovarian disease: endocrinological and demographic studies. Gynecol. Endocrinol. 1, 235-245. doi: 10.3109/09513598709023610
89. Ibanez, L., Díaz, R., López-Bermejo, A., and Marcos, M. V. (2009). Clinical spectrum of premature pubarche: links to metabolic syndrome and ovarian hyperandrogenism. Rev. Endocr. Metab. Disord. 10, 63-76. doi: 10.1007/s11154-008-9096-y
90. Ibáñez, L., Potau, N., Francois, I., and de Zegher, F. (1998). Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls: relation to reduced fetal growth. J. Clin. Endocrinol. Metab. 83, 3558-3562. doi: 10.1210/jcem.83.10.5205
91. Ibáñez, L., Valls, C., Potau, N., Marcos, M. V., and de Zegher, F. (2000). Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious pubarche. J. Clin. Endocrinol. Metab. 85, 3526-3530. doi: 10.1210/jc.85.10.3526
92. Imani, B., Eijkemans, M. J. C., te Velde, E. R., Habbema, J. D. F., and Fauser, B. C. J. M. (1998). Predictors of patients remaining anovulatory during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. J. Clin. Endocrinol. Metab. 83, 2361-2365. doi: 10.1210/jc.83.7.2361
93. Jedel, E., Waern, M., Gustafson, D., Landén, M., Eriksson, E., Holm, G., et al. (2010). Anxiety and depression symptoms in women with polycystic ovary syndrome compared with controls matched for body mass index. Hum. Reprod. 25, 450-456. doi: 10.1093/humrep/dep384
94. Jones, G. L., Hall, J. M., Balen, A. H., and Ledger, W. L. (2008). Health-related quality of life measurement in women with polycystic ovary syndrome: a systematic review. Hum. Reprod. Update 14, 15-25. doi: 10.1093/humupd/dmm030
95. Kahsar-Miller, M. D., Nixon, C., Boots, L. R., Go, R. C., and Azziz, R. (2001). Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS. Fertil. Steril. 75, 53-58. doi: 10.1016/S0015-0282(00)01662-9
96. Kalme, T., Koistinen, H., Loukovaara, M., Koistinen, R., and Leinonen, P. (2003). Comparative studies on the regulation of insulin-like growth factor-binding protein-1 (IGFBP-1) and sex hormone-binding globulin (SHBG) production by insulin and insulin-like growth factors in human hepatoma cells. J. Steroid Biochem. Mol. Biol. 86, 197-200. doi: 10.1016/S0960-0760(03)00268-1
97. Kamangar, F., Okhovat, J. P., Schmidt, T., Beshay, A., Pasch, L., Cedars, M. I., et al. (2015). Polycystic ovary syndrome: special diagnostic and therapeutic considerations for children. Pediatr. Dermatol. 32, 571-578. doi: 10.1111/pde.12566
98. Karabulut, A., Yaylali, G. F., Demirlenk, S., Sevket, O., and Acun, A. (2012). Evaluation of body fat distribution in PCOS and its association with carotid atherosclerosis and insulin resistance. Gynecol. Endocrinol. 28, 111-114. doi: 10.3109/09513590.2011.589929
99. Katulski, K., Czyzyk, A., Podfigurna-Stopa, A., Genazzani, A. R., and Meczekalski, B. (2015). Pregnancy complications in polycystic ovary syndrome patients. Gynecol. Endocrinol. 31, 87-91. doi: 10.3109/09513590.2014.974535
100. Kirschner, M. A., Samojlik, E., Drejka, M., Szmal, E., Schneider, G., and Ertel, N. (1990). Androgen-estrogen metabolism in women with upper body versus lower body obesity. J. Clin. Endocrinol. Metab. 70, 473-479. doi: 10.1210/jcem-70-2-473
101. Knowler, W. C., Barrett-Connor, E., Fowler, S. E., Hamman, R. F., Lachin, J. M., Walker, E. A., et al. (2002). Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 346, 393-403. doi: 10.1056/NEJMoa012512
102. Lass, N., Kleber, M., Winkel, K., Wunsch, R., and Reinehr, T. (2011). Effect of lifestyle intervention on features of polycystic ovarian syndrome, metabolic syndrome, and intima-media thickness in obese adolescent girls. J. Clin. Endocrinol. Metab. 96, 3533-3540. doi: 10.1210/jc.2011-1609
103. Lee, E. J., and Marcy, T. R. (2014). The impact of pioglitazone on bladder cancer and cardiovascular events. Consult. Pharm. 29, 555-558. doi: 10.4140/TCP.n.2014.555
104. Legro, R. (2015). Diagnosis and treatment of polycystic ovary syndrome (PCOS): an interview with Richard Legro. BMC Med. 13:64. doi: 10.1186/s12916-015-0299-2
105. Legro, R. S. (2003). Polycystic ovary syndrome and cardiovascular disease: a premature association? Endocr. Rev. 24, 302-312. doi: 10.1210/er.2003-0004
106. Legro, R. S., Arslanian, S. A., Ehrmann, D. A., Hoeger, K. M., Murad, M. H., Pasquali, R., et al. (2013). Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 98, 4565-4592. doi: 10.1210/jc.2013-2350
107. Legro, R. S., Castracane, V. D., and Kauffman, R. P. (2004). Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls. Obstet. Gynecol. Surv. 59, 141-154. doi: 10.1097/01.OGX.0000109523.25076.E2
108. Legro, R. S., Driscoll, D., Strauss, J. F. III., Fox, J., and Dunaif, A. (1998). Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc. Natl. Acad. Sci. U.S.A. 95, 14956-14960. doi: 10.1073/pnas.95.25.14956
109. Legro, R. S., Gnatuk, C. L., Kunselman, A. R., and Dunaif, A. (2005). Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study. J. Clin. Endocrinol. Metab. 90, 3236-3242. doi: 10.1210/jc.2004-1843
110. 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 affected women. J. Clin. Endocrinol. Metab. 84, 165-169. doi: 10.1097/00006254-199906000-00019
111. Lerchbaum, E., Schwetz, V., Giuliani, A., and Obermayer-Pietsch, B. (2013). Assessment of glucose metabolism in polycystic ovary syndrome: HbA1c or fasting glucose compared with the oral glucose tolerance test as a screening method. Hum. Reprod. 28, 2537-2544. doi: 10.1093/humrep/det255
112. Levin, D., Bell, S., Sund, R., Hartikainen, S. A., Tuomilehto, J., Pukkala, E., et al. (2015). Pioglitazone and bladder cancer risk: a multipopulation pooled, cumulative exposure analysis. Diabetologia 58, 493-504. doi: 10.1007/s00125-014-3456-9
113. Li, Y., Li, Y., Yu Ng, E. H., Stener-Victorin, E., Hou, L., Wu, T., et al. (2011). Polycystic ovary syndrome is associated with negatively variable impacts on domains of health-related quality of life: evidence from a meta-analysis. Fertil. Steril. 96, 452-458. doi: 10.1016/j.fertnstert.2011.05.072
114. Lidegaard, Ø., Løkkegaard, E., Jensen, A., Skovlund, C. W., and Keiding, N. (2012). Thrombotic stroke and myocardial infarction with hormonal contraception. N. Engl. J. Med. 366, 2257-2266. doi: 10.1056/NEJMoa1111840
115. Lungu, A. O., Zadeh, E. S., Goodling, A., Cochran, E., and Gorden, P. (2012). Insulin resistance is a sufficient basis for hyperandrogenism in lipodystrophic women with polycystic ovarian syndrome. J. Clin. Endocrinol. Metab. 97, 563-567. doi: 10.1210/jc.2011-1896
116. Majuri, A., Santaniemi, M., Rautio, K., Kunnari, A., Vartiainen, J., Ruokonen, A., et al. (2007). Rosiglitazone treatment increases plasma levels of adiponectin and decreases levels of resistin in overweight women with PCOS: a randomized placebo-controlled study. Eur. J. Endocrinol. 156, 263-269. doi: 10.1530/eje.1.02331
117. Melo, A. S., Vieira, C. S., Barbieri, M. A., Rosa-E-Silva, A. C., Silva, A. A., Cardoso, V. C., et al. (2010). High prevalence of polycystic ovary syndrome in women born small for gestational age. Hum. Reprod. 25, 2124-2131. doi: 10.1093/humrep/deq162
118. Mendoza, N., Simoncini, T., and Genazzani, A. D. (2014). Hormonal contraceptive choice for women with PCOS: a systematic review of randomized trials and observational studies. Gynecol. Endocrinol. 30, 850-860. doi: 10.3109/09513590.2014.943725
119. Meyer, C., McGrath, B. P., Cameron, J., Kotsopoulos, D., and Teede, H. J. (2005). Vascular dysfunction and metabolic parameters in polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 90, 4630-4635. doi: 10.1210/jc.2004-1487
120. Misso, M., Boyle, J., Norman, R., and Teede, H. (2014). Development of evidenced-based guidelines for PCOS and implications for community health. Semin. Reprod. Med. 32, 230-240. doi: 10.1055/s-0034-1371095
121. Moll, G. W. Jr., and Rosenfield, R. L. (1983). Plasma free testosterone in the diagnosis of adolescent polycystic ovary syndrome. J. Pediatr. 102, 461-464. doi: 10.1016/S0022-3476(83)80678-7
122. Moran, L. J., Hutchison, S. K., Meyer, C., Zoungas, S., and Teede, H. J. (2009). A comprehensive assessment of endothelial function in overweight women with and without polycystic ovary syndrome. Clin. Sci. 116, 761-770. doi: 10.1042/CS20080218
123. Moran, L. J., Misso, M. L., Wild, R. A., and Norman, R. J. (2010). Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum. Reprod. Update 16, 347-363. doi: 10.1093/humupd/dmq001
124. Morgante, G., Cappelli, V., Di Sabatino, A., Massaro, M. G., and De Leo, V. (2015). Polycystic ovary syndrome (PCOS) and hyperandrogenism: the role of a new natural association. Minerva Ginecol. 67, 457-463.
125. Morgante, G., Orvieto, R., Di Sabatino, A., Musacchio, M. C., and De Leo, V. (2011). The role of inositol supplementation in patients with polycystic ovary syndrome, with insulin resistance, undergoing the low-dose gonadotropin ovulation induction regimen. Fertil. Steril. 95, 2642-2644. doi: 10.1016/j.fertnstert.2011.01.035
126. Morin-Papunen, L. C., Koivunen, R. M., Ruokonen, A., and Martikainen, H. K. (1998). Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome. Fertil. Steril. 69, 691-696. doi: 10.1016/S0015-0282(98)00011-9
127. Mortensen, M., Ehrmann, D. A., Littlejohn, E., and Rosenfield, R. L. (2009). Asymptomatic volunteers with a polycystic ovary are a functionally distinct but heterogeneous population. J. Clin. Endocrinol. Metab. 94, 1579-1586. doi: 10.1210/jc.2008-2771
128. Nawrocka-Rutkowska, J., Ciecwiez, S., Marciniak, A., Brodowska, A., Wisniewska, B., Kotlega, D., et al. (2013). Insulin resistance assessment in patients with polycystic ovary syndrome using different diagnostic criteria-impact of metformin treatment. Ann. Agric. Environ. Med. 20, 528-532.
129. Nelson, V. L., Legro, R. S., Strauss, J. F. III., and McAllister, J. M. (1999). Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Mol. Endocrinol. 13, 946-957. doi: 10.1210/mend.13.6.0311
130. Nordio, M., and Proietti, E. (2012). The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone. Eur. Rev. Med. Pharmacol. Sci. 16, 575-581.
131. Norman, R. J., Dewailly, D., Legro, R. S., and Hickey, T. E. (2007). Polycystic ovary syndrome. Lancet 370, 685-697. doi: 10.1016/S0140-6736(07)61345-2
132. Papaleo, E., Unfer, V., Baillargeon, J. P., Fusi, F., Occhi, F., and De Santis, L. (2009). Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertil. Steril. 91, 1750-1754. doi: 10.1016/j.fertnstert.2008.01.088
133. Pasquali, R., Gambineri, A., and Pagotto, U. (2006). The impact of obesity on reproduction in women with polycystic ovary syndrome. BJOG 113, 1148-1159. doi: 10.1111/j.1471-0528.2006.00990.x
134. Pasquali, R., Stener-Victorin, E., Yildiz, B. O., Duleba, A. J., Hoeger, K., Mason, H., et al. (2011). PCOS Forum: research in polycystic ovary syndrome today and tomorrow. Clin. Endocrinol. 74, 424-433. doi: 10.1111/j.1365-2265.2010.03956.x
135. Pau, C. T., Keefe, C., Duran, J., and Welt, C. K. (2014). Metformin improves glucose effectiveness, not insulin sensitivity: predicting treatment response in women with polycystic ovary syndrome in an open-label, interventional study. J. Clin. Endocrinol. Metab. 99, 1870-1878. doi: 10.1210/jc.2013-4021
136. Pellatt, L., Hanna, L., Brincat, M., Galea, R., Brain, H., Whitehead, S., et al. (2007). Granulosa cell production of anti-Mullerian hormone is increased in polycystic ovaries. J. Clin. Endocrinol. Metab. 92, 240-245. doi: 10.1210/jc.2006-1582
137. Pfeifer, S. M., and Dayal, M. (2003). Treatment of the adolescent patient with polycystic ovary syndrome. Obstet. Gynecol. Clin. North Am. 30, 337-352. doi: 10.1016/S0889-8545(03)00028-7
138. Pierpoint, T., McKeigue, P. M., Isaacs, A. J., Wild, S. H., and Jacobs, H. S. (1998). Mortality of women with polycystic ovary syndrome at long-term follow-up. J. Clin. Epidemiol. 51, 581-586. doi: 10.1016/S0895-4356(98)00035-3
139. Powers, S. E., Uliassi, N. W., Sullivan, S. D., Tuchman, L. K., Mehra, R., and Gomez-Lobo, V. (2015). Trends in standard workup performed by pediatric subspecialists for the diagnosis of adolescent polycystic ovary syndrome. J. Pediatr. Adolesc. Gynecol. 28, 43-46. doi: 10.1016/j.jpag.2014.03.002
140. Rago, R., Marcucci, I., Leto, G., Caponecchia, L., Salacone, P., Bonanni, P., et al. (2015). Effect of myo-inositol and alpha-lipoic acid on oocyte quality in polycystic ovary syndrome non-obese women undergoing in vitro fertilization: a pilot study. J. Biol. Regul. Homeost. Agents 29, 913-923.
141. Randeva, H. S., Tan, B. K., Weickert, M. O., Lois, K., Nestler, J. E., Sattar, N., et al. (2012). Cardiometabolic aspects of the polycystic ovary syndrome. Endocr. Rev. 33, 812-841. doi: 10.1210/er.2012-1003
142. Rathsman, B., Rosfors, S., Sjöholm, A., and Nyström, T. (2012). Early signs of atherosclerosis are associated with insulin resistance in non-obese adolescent and young adults with type 1 diabetes. Cardiovasc. Diabetol. 11, 145. doi: 10.1186/1475-2840-11-145
143. Rizzo, M., Berneis, K., Hersberger, M., Pepe, I., Di Fede, G., Rini, G. B., et al. (2009). Milder forms of atherogenic dyslipidemia in ovulatory versus anovulatory polycystic ovary syndrome phenotype. Hum. Reprod. 24, 2286-2292. doi: 10.1093/humrep/dep121
144. Rosenfield, R. L. (2013). Clinical review: adolescent anovulation: maturational mechanisms and implications. J. Clin. Endocrinol. Metab. 98, 3572-3583. doi: 10.1210/jc.2013-1770
145. Rotterdam, E. A.-S. P. C. W. G. (2004). Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum. Reprod. 19, 41-47. doi: 10.1093/humrep/deh098
146. Salley, K. E., Wickham, E. P., Cheang, K. I., Essah, P. A., Karjane, N. W., and Nestler, J. E. (2007). Glucose intolerance in polycystic ovary syndrome-a position statement of the Androgen Excess Society. J. Clin. Endocrinol. Metab. 92, 4546-4556. doi: 10.1210/jc.2007-1549
147. Sathyapalan, T., and Atkin, S. L. (2012). Recent advances in cardiovascular aspects of polycystic ovary syndrome. Eur. J. Endocrinol. 166, 575-583. doi: 10.1530/EJE-11-0755
148. Schmidt, J., Landin-Wilhelmsen, K., Brännström, M., and Dahlgren, E. (2011). Cardiovascular disease and risk factors in PCOS women of postmenopausal age: a 21-year controlled follow-up study. J. Clin. Endocrinol. Metab. 96, 3794-3803. doi: 10.1210/jc.2011-1677
149. Segars, J. H., and Decherney, A. H. (2010). Is there a genetic basis for polycystic ovary syndrome? J. Clin. Endocrinol. Metab. 95, 2058-2060. doi: 10.1210/jc.2010-0518
150. Shaw, L. J., Bairey Merz, C. N., Azziz, R., Stanczyk, F. Z., Sopko, G., Braunstein, G. D., et al. (2008). 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 Institutes of Health-National Heart, Lung, and Blood Institute sponsored Women's Ischemia Syndrome Evaluation. J. Clin. Endocrinol. Metab. 93, 1276-1284. doi: 10.1210/jc.2007-0425
151. Siklar, Z., Berberoglu, M., Çamtosun, E., and Kocaay, P. (2015). Diagnostic characteristics and metabolic risk factors of cases with polycystic ovary syndrome during adolescence. J. Pediatr. Adolesc. Gynecol. 28, 78-83. doi: 10.1016/j.jpag.2014.05.006
152. Sir-Petermann, T., Ladrón de Guevara, A., Villarroel, A. C., Preisler, J., Echiburu, B., and Recabarren, S. (2012). Polycystic ovary syndrome and pregnancy. Rev. Med. Chil. 140, 919-925. doi: 10.4067/S0034-98872012000700015
153. Smith, R. A., von Eschenbach, A. C., Wender, R., Levin, B., Byers, T., Rothenberger, D., et al. (2001). American Cancer Society guidelines for the early detection of cancer: update of early detection guidelines for prostate, colorectal, and endometrial cancers. Also: update 2001-testing for early lung cancer detection. CA Cancer J. Clin. 51, 38-75; quiz 77-80. doi: 10.3322/canjclin.51.1.38
154. Spritzer, P. M., Motta, A. B., Sir-Petermann, T., and Diamanti-Kandarakis, E. (2015). Novel strategies in the management of polycystic ovary syndrome. Minerva Endocrinol. 40, 195-212.
155. Stabile, G., Borrielli, I., Artenisio, A. C., Bruno, L. M., Benvenga, S., Giunta, L., et al. (2014). Effects of the insulin sensitizer pioglitazone on menstrual irregularity, insulin resistance and hyperandrogenism in young women with polycystic ovary syndrome. J. Pediatr. Adolesc. Gynecol. 27, 177-182. doi: 10.1016/j.jpag.2013.09.015
156. Stein, I. F., and Leventhal, M. L. (1935). Amenorrhea associated with bilateral polycystic ovaries. Am. J. Obstet. Gynecol. 29, 181-191. doi: 10.1016/S0002-9378(15)30642-6
157. Stepto, N. K., Cassar, S., Joham, A. E., Hutchison, S. K., Harrison, C. L., Goldstein, R. F., et al. (2013). Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp. Hum. Reprod. 28, 777-784. doi: 10.1093/humrep/des463
158. Talbott, E. O., Zborowski, J. V., Rager, J. R., Kip, K. E., Xu, X., and Orchard, T. J. (2007). Polycystic ovarian syndrome (PCOS): a significant contributor to the overall burden of type 2 diabetes in women. J. Womens Health (Larchmt) 16, 191-197. doi: 10.1089/jwh.2006.0098
159. Tang, T., Glanville, J., Hayden, C. J., White, D., Barth, J. H., and Balen, A. H. (2006). Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome. A randomized, placebo-controlled, double-blind multicentre study. Hum. Reprod. 21, 80-89. doi: 10.1093/humrep/dei311
160. Teede, H., Deeks, A., and Moran, L. (2010). Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med. 8:41. doi: 10.1186/1741-7015-8-41
161. Teede, H. J., Misso, M. L., Deeks, A. A., Moran, L. J., Stuckey, B. G., Wong, J. L., et al. (2011). Assessment and management of polycystic ovary syndrome: summary of an evidence-based guideline. Med. J. Aust. 195, S65-S112. doi: 10.5694/mja11.10915
162. Tfayli, H., and Arslanian, S. (2008). Menstrual health and the metabolic syndrome in adolescents. Ann. N.Y. Acad. Sci. 1135, 85-94. doi: 10.1196/annals.1429.024
163. Urbanek, M., Sam, S., Legro, R. S., and Dunaif, A. (2007). Identification of a polycystic ovary syndrome susceptibility variant in fibrillin-3 and association with a metabolic phenotype. J. Clin. Endocrinol. Metab. 92, 4191-4198. doi: 10.1210/jc.2007-0761
164. Van Hooff, M. H., Voorhorst, F. J., Kaptein, M. B., Hirasing, R. A., Koppenaal, C., and Schoemaker, J. (2000). Insulin, androgen, and gonadotropin concentrations, body mass index, and waist to hip ratio in the first years after menarche in girls with regular menstrual cycles, irregular menstrual cycles, or oligomenorrhea. J. Clin. Endocrinol. Metab. 85, 1394-1400. doi: 10.1210/jc.85.4.1394
165. Velazquez, E. M., Mendoza, S., Hamer, T., Sosa, F., and Glueck, C. J. (1994). Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 43, 647-654. doi: 10.1016/0026-0495(94)90209-7
166. Veltman-Verhulst, S. M., Boivin, J., Eijkemans, M. J., and Fauser, B. J. (2012). Emotional distress is a common risk in women with polycystic ovary syndrome: a systematic review and meta-analysis of 28 studies. Hum. Reprod. Update 18, 638-651. doi: 10.1093/humupd/dms029
167. Venturoli, S., Porcu, E., Fabbri, R., Pluchinotta, V., Ruggeri, S., Macrelli, S., et al. (1995). Longitudinal change of sonographic ovarian aspects and endocrine parameters in irregular cycles of adolescence. Pediatr. Res. 38, 974-980. doi: 10.1203/00006450-199512000-00024
168. Verkauskiene, R., Beltrand, J., Claris, O., Chevenne, D., Deghmoun, S., Dorgeret, S., et al. (2007). Impact of fetal growth restriction on body composition and hormonal status at birth in infants of small and appropriate weight for gestational age. Eur. J. Endocrinol. 157, 605-612. doi: 10.1530/EJE-07-0286
169. Victor, V. M., Rocha, M., Bañuls, C., Sanchez-Serrano, M., Sola, E., Gomez, M., et al. (2009). Mitochondrial complex I impairment in leukocytes from polycystic ovary syndrome patients with insulin resistance. J. Clin. Endocrinol. Metab. 94, 3505-3512. doi: 10.1210/jc.2009-0466
170. Villarroel, C., Merino, P. M., López, P., Eyzaguirre, F. C., Van Velzen, A., Iñiguez, G., et al. (2011). Polycystic ovarian morphology in adolescents with regular menstrual cycles is associated with elevated anti-Mullerian hormone. Hum. Reprod. 26, 2861-2868. doi: 10.1093/humrep/der223
171. Wang, E. T., Cirillo, P. M., Vittinghoff, E., Bibbins-Domingo, K., Cohn, B. A., and Cedars, M. I. (2011). Menstrual irregularity and cardiovascular mortality. J. Clin. Endocrinol. Metab. 96, E114-E118. doi: 10.1210/jc.2010-1709
172. Wang, J. X., Davies, M. J., and Norman, R. J. (2001). Polycystic ovarian syndrome and the risk of spontaneous abortion following assisted reproductive technology treatment. Hum. Reprod. 16, 2606-2609. doi: 10.1093/humrep/16.12.2606
173. Webber, L. J., Stubbs, S., Stark, J., Trew, G. H., Margara, R., Hardy, K., et al. (2003). Formation and early development of follicles in the polycystic ovary. Lancet 362, 1017-1021. doi: 10.1016/S0140-6736(03)14410-8
174. Wedin, W. K., Diaz-Gimenez, L., and Convit, A. J. (2012). Prediction of insulin resistance with anthropometric measures: lessons from a large adolescent population. Diabetes Metab. Syndr. Obes. 5, 219-225. doi: 10.2147/DMSO.S33478
175. Weiner, C. L., Primeau, M., and Ehrmann, D. A. (2004). Androgens and mood dysfunction in women: comparison of women with polycystic ovarian syndrome to healthy controls. Psychosom. Med. 66, 356-362. doi: 10.1097/01.psy.0000127871.46309.fe
176. Wiksten-Almstromer, M., Hirschberg, A. L., and Hagenfeldt, K. (2008). Prospective follow-up of menstrual disorders in adolescence and prognostic factors. Acta Obstet. Gynecol. Scand. 87, 1162-1168. doi: 10.1080/00016340802478166
177. Wild, R. A., Carmina, E., Diamanti-Kandarakis, E., Dokras, A., Escobar-Morreale, H. F., Futterweit, W., et al. (2010). Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J. Clin. Endocrinol. Metab. 95, 2038-2049. doi: 10.1210/jc.2009-2724
178. Winter, E., Wang, J., Davies, M. J., and Norman, R. (2002). Early pregnancy loss following assisted reproductive technology treatment. Hum. Reprod. 17, 3220-3223. doi: 10.1093/humrep/17.12.3220
179. Witchel, S. F., Oberfield, S., Rosenfield, R. L., Codner, E., Bonny, A., Ibáñez, L., et al. (2015). The diagnosis of polycystic ovary syndrome during adolescence. Horm. Res. Paediatr. doi: 10.1159/000375530. [Epub ahead of print].
180. Yildiz, B. O. (2008a). Assessment, diagnosis and treatment of a patient with hirsutism. Nat. Clin. Pract. Endocrinol. Metab. 4, 294-300. doi: 10.1038/ncpendmet0789
181. Yildiz, B. O. (2008b). Oral contraceptives in polycystic ovary syndrome: risk-benefit assessment. Semin. Reprod. Med. 26, 111-120. doi: 10.1055/s-2007-992931
182. Yildiz, B. O. (2015). Approach to the patient: contraception in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 100, 794-802. doi: 10.1210/jc.2014-3196
183. Yildiz, B. O., Goodarzi, M. O., Guo, X., Rotter, J. I., and Azziz, R. (2006). Heritability of dehydroepiandrosterone sulfate in women with polycystic ovary syndrome and their sisters. Fertil. Steril. 86, 1688-1693. doi: 10.1016/j.fertnstert.2006.05.045
184. Yilmaz, M., Bukan, N., Ayvaz, G., Karakoç, A., Törüner, F., Cakir, N., et al. (2005). The effects of rosiglitazone and metformin on oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome. Hum. Reprod. 20, 3333-3340. doi: 10.1093/humrep/dei258
185. Zhang, H. Y., Zhu, F. F., Xiong, J., Shi, X. B., and Fu, S. X. (2009). Characteristics of different phenotypes of polycystic ovary syndrome based on the Rotterdam criteria in a large-scale Chinese population. BJOG 116, 1633-1639. doi: 10.1111/j.1471-0528.2009.02347.x