Skip to main content
Erschienen in: Endocrine 3/2012

01.12.2012 | New Horizons In

Emerging concepts about prenatal genesis, aberrant metabolism and treatment paradigms in polycystic ovary syndrome

verfasst von: Selma F. Witchel, Sergio E. Recabarren, Frank González, Evanthia Diamanti-Kandarakis, Kai I. Cheang, Antoni J. Duleba, Richard S. Legro, Roy Homburg, Renato Pasquali, Rogerio A. Lobo, Christos C. Zouboulis, Fahrettin Kelestimur, Franca Fruzzetti, Walter Futterweit, Robert J. Norman, David H. Abbott

Erschienen in: Endocrine | Ausgabe 3/2012

Einloggen, um Zugang zu erhalten

Abstract

The interactive nature of the 8th Annual Meeting of the Androgen Excess and PCOS Society Annual Meeting in Munich, Germany (AEPCOS 2010) and subsequent exchanges between speakers led to emerging concepts in PCOS regarding its genesis, metabolic dysfunction, and clinical treatment of inflammation, metabolic dysfunction, anovulation and hirsutism. Transition of care in congenital adrenal hyperplasia from pediatric to adult providers emerged as a potential model for care transition involving PCOS adolescents.
Literatur
1.
Zurück zum Zitat B.C. Fauser, B.C. Tarlatzis, R.W. Rebar, R.S. Legro, A.H. Balen, R. Lobo, E. Carmina, J. Chang, B.O. Yildiz, J.S. Laven, J. Boivin, F. Petraglia, C.N. Wijeyeratne, R.J. Norman, A. Dunaif, S. Franks, R.A. Wild, D. Dumesic, K. Barnhart, 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 (2012) B.C. Fauser, B.C. Tarlatzis, R.W. Rebar, R.S. Legro, A.H. Balen, R. Lobo, E. Carmina, J. Chang, B.O. Yildiz, J.S. Laven, J. Boivin, F. Petraglia, C.N. Wijeyeratne, R.J. Norman, A. Dunaif, S. Franks, R.A. Wild, D. Dumesic, K. Barnhart, 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 (2012)
2.
Zurück zum Zitat D.H. Abbott, A.F. Tarantal, D.A. Dumesic, Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys. Am. J. Primatol. 71, 776–784 (2009)PubMedCrossRef D.H. Abbott, A.F. Tarantal, D.A. Dumesic, Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys. Am. J. Primatol. 71, 776–784 (2009)PubMedCrossRef
4.
Zurück zum Zitat B.O. Yildiz, E.S. Knochenhauer, R. Azziz, Impact of obesity on the risk for polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 93, 162–168 (2008)PubMedCrossRef B.O. Yildiz, E.S. Knochenhauer, R. Azziz, Impact of obesity on the risk for polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 93, 162–168 (2008)PubMedCrossRef
5.
Zurück zum Zitat R. Azziz, C. Marin, L. Hoq, E. Badamgarav, P. Song, Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span. J. Clin. Endocrinol. Metab. 90, 4650–4658 (2005)PubMedCrossRef R. Azziz, C. Marin, L. Hoq, E. Badamgarav, P. Song, Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span. J. Clin. Endocrinol. Metab. 90, 4650–4658 (2005)PubMedCrossRef
6.
Zurück zum Zitat E.O. Talbott, J.V. Zborowski, J.R. Rager, K.E. Kip, X. Xu, T.J. Orchard, Polycystic ovarian syndrome (PCOS): a significant contributor to the overall burden of type 2 diabetes in women. J. Womens Health (Larchmt) 16, 191–197 (2007)CrossRef E.O. Talbott, J.V. Zborowski, J.R. Rager, K.E. Kip, X. Xu, T.J. Orchard, Polycystic ovarian syndrome (PCOS): a significant contributor to the overall burden of type 2 diabetes in women. J. Womens Health (Larchmt) 16, 191–197 (2007)CrossRef
7.
Zurück zum Zitat F. Alvarez-Blasco, J.I. Botella-Carretero, J.L. San Millan, H.F. Escobar-Morreale, Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women. Arch. Intern. Med. 166, 2081–2086 (2006)PubMedCrossRef F. Alvarez-Blasco, J.I. Botella-Carretero, J.L. San Millan, H.F. Escobar-Morreale, Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women. Arch. Intern. Med. 166, 2081–2086 (2006)PubMedCrossRef
8.
Zurück zum Zitat R.A. Wild, E. Carmina, E. Diamanti-Kandarakis, A. Dokras, H.F. Escobar-Morreale, W. Futterweit, R. Lobo, R.J. Norman, E. Talbott, D.A. Dumesic, 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 (2010)PubMedCrossRef R.A. Wild, E. Carmina, E. Diamanti-Kandarakis, A. Dokras, H.F. Escobar-Morreale, W. Futterweit, R. Lobo, R.J. Norman, E. Talbott, D.A. Dumesic, 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 (2010)PubMedCrossRef
9.
Zurück zum Zitat B. Dilbaz, E. Ozkaya, M. Cinar, E. Cakir, S. Dilbaz, Cardiovascular disease risk characteristics of the main polycystic ovary syndrome phenotypes. Endocrine 39, 272–277 (2011)PubMedCrossRef B. Dilbaz, E. Ozkaya, M. Cinar, E. Cakir, S. Dilbaz, Cardiovascular disease risk characteristics of the main polycystic ovary syndrome phenotypes. Endocrine 39, 272–277 (2011)PubMedCrossRef
10.
Zurück zum Zitat Z.J. Chen, H. Zhao, L. He, Y. Shi, Y. Qin, Y. Shi, Z. Li, L. You, J. Zhao, J. Liu, X. Liang, X. Zhao, J. Zhao, Y. Sun, B. Zhang, H. Jiang, D. Zhao, Y. Bian, X. Gao, L. Geng, Y. Li, D. Zhu, X. Sun, J.E. Xu, C. Hao, C.E. Ren, Y. Zhang, S. Chen, W. Zhang, A. Yang, J. Yan, Y. Li, J. Ma, Y. Zhao, Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat. Genet. 43, 55–59 (2011)PubMedCrossRef Z.J. Chen, H. Zhao, L. He, Y. Shi, Y. Qin, Y. Shi, Z. Li, L. You, J. Zhao, J. Liu, X. Liang, X. Zhao, J. Zhao, Y. Sun, B. Zhang, H. Jiang, D. Zhao, Y. Bian, X. Gao, L. Geng, Y. Li, D. Zhu, X. Sun, J.E. Xu, C. Hao, C.E. Ren, Y. Zhang, S. Chen, W. Zhang, A. Yang, J. Yan, Y. Li, J. Ma, Y. Zhao, Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat. Genet. 43, 55–59 (2011)PubMedCrossRef
11.
Zurück zum Zitat M.O. Goodarzi, M.R. Jones, X. Li, A.K. Chua, O.A. Garcia, Y.D. Chen, R.M. Krauss, J.I. Rotter, W. Ankener, R.S. Legro, R. Azziz, J.F. Strauss 3rd, A. Dunaif, M. Urbanek, Replication of association of DENND1A and THADA variants with polycystic ovary syndrome in European cohorts. J. Med. Genet. 49, 90–95 (2012)PubMedCrossRef M.O. Goodarzi, M.R. Jones, X. Li, A.K. Chua, O.A. Garcia, Y.D. Chen, R.M. Krauss, J.I. Rotter, W. Ankener, R.S. Legro, R. Azziz, J.F. Strauss 3rd, A. Dunaif, M. Urbanek, Replication of association of DENND1A and THADA variants with polycystic ovary syndrome in European cohorts. J. Med. Genet. 49, 90–95 (2012)PubMedCrossRef
12.
Zurück zum Zitat H. Zhao, X. Xu, X. Xing, J. Wang, L. He, Y. Shi, Y. Shi, Y. Zhao, Z.J. Chen, Family-based analysis of susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Hum. Reprod. 27, 294–298 (2012)PubMedCrossRef H. Zhao, X. Xu, X. Xing, J. Wang, L. He, Y. Shi, Y. Shi, Y. Zhao, Z.J. Chen, Family-based analysis of susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Hum. Reprod. 27, 294–298 (2012)PubMedCrossRef
13.
Zurück zum Zitat W. Hu, J. Qiao, Expression and regulation of adipocyte fatty acid binding protein in granulosa cells and its relation with clinical characteristics of polycystic ovary syndrome. Endocrine 40, 196–202 (2011)PubMedCrossRef W. Hu, J. Qiao, Expression and regulation of adipocyte fatty acid binding protein in granulosa cells and its relation with clinical characteristics of polycystic ovary syndrome. Endocrine 40, 196–202 (2011)PubMedCrossRef
14.
Zurück zum Zitat H. Jia, L. Yu, X. Guo, W. Gao, Z. Jiang, Associations of adiponectin gene polymorphisms with polycystic ovary syndrome: a meta-analysis. Endocrine (2012). doi:10.1007/s12020-012-9605-3 H. Jia, L. Yu, X. Guo, W. Gao, Z. Jiang, Associations of adiponectin gene polymorphisms with polycystic ovary syndrome: a meta-analysis. Endocrine (2012). doi:10.​1007/​s12020-012-9605-3
15.
Zurück zum Zitat R. Saxena, C.K. Welt, Polycystic ovary syndrome is not associated with genetic variants that mark risk of type 2 diabetes. Acta Diabetol. (2012) [Epub ahead of print] R. Saxena, C.K. Welt, Polycystic ovary syndrome is not associated with genetic variants that mark risk of type 2 diabetes. Acta Diabetol. (2012) [Epub ahead of print]
16.
Zurück zum Zitat R.S. Legro, D. Driscoll, J.F. Strauss 3rd, J. Fox, A. Dunaif, Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc. Natl. Acad. Sci. U.S.A. 95, 14956–14960 (1998)PubMedCrossRef R.S. Legro, D. Driscoll, J.F. Strauss 3rd, J. Fox, A. Dunaif, Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc. Natl. Acad. Sci. U.S.A. 95, 14956–14960 (1998)PubMedCrossRef
17.
Zurück zum Zitat J.M. Vink, S. Sadrzadeh, C.B. Lambalk, D.I. Boomsma, Heritability of polycystic ovary syndrome in a Dutch twin-family study. J. Clin. Endocrinol. Metab. 91, 2100–2104 (2006)PubMedCrossRef J.M. Vink, S. Sadrzadeh, C.B. Lambalk, D.I. Boomsma, Heritability of polycystic ovary syndrome in a Dutch twin-family study. J. Clin. Endocrinol. Metab. 91, 2100–2104 (2006)PubMedCrossRef
18.
Zurück zum Zitat A.D. Coviello, R.S. Legro, A. Dunaif, Adolescent girls with polycystic ovary syndrome have an increased risk of the metabolic syndrome associated with increasing androgen levels independent of obesity and insulin resistance. J. Clin. Endocrinol. Metab. 91, 492–497 (2006)PubMedCrossRef A.D. Coviello, R.S. Legro, A. Dunaif, Adolescent girls with polycystic ovary syndrome have an increased risk of the metabolic syndrome associated with increasing androgen levels independent of obesity and insulin resistance. J. Clin. Endocrinol. Metab. 91, 492–497 (2006)PubMedCrossRef
19.
Zurück zum Zitat J.C. Marshall, Obesity in adolescent girls: is excess androgen the real bad actor? J. Clin. Endocrinol. Metab. 91, 393–395 (2006)PubMedCrossRef J.C. Marshall, Obesity in adolescent girls: is excess androgen the real bad actor? J. Clin. Endocrinol. Metab. 91, 393–395 (2006)PubMedCrossRef
20.
Zurück zum Zitat W.H. Dietz, Health consequences of obesity in youth: childhood predictors of adult disease. Pediatrics 101, 518–525 (1998)PubMed W.H. Dietz, Health consequences of obesity in youth: childhood predictors of adult disease. Pediatrics 101, 518–525 (1998)PubMed
21.
Zurück zum Zitat A.A. Hedley, C.L. Ogden, C.L. Johnson, M.D. Carroll, L.R. Curtin, K.M. Flegal, Prevalence of overweight and obesity among US children, adolescents, and adults, 1999–2002. J. Am. Med. Assoc. 291, 2847–2850 (2004)CrossRef A.A. Hedley, C.L. Ogden, C.L. Johnson, M.D. Carroll, L.R. Curtin, K.M. Flegal, Prevalence of overweight and obesity among US children, adolescents, and adults, 1999–2002. J. Am. Med. Assoc. 291, 2847–2850 (2004)CrossRef
22.
Zurück zum Zitat C.R. McCartney, K.A. Prendergast, S. Chhabra, C.A. Eagleson, R. Yoo, R.J. Chang, C.M. Foster, J.C. Marshall, The association of obesity and hyperandrogenemia during the pubertal transition in girls: obesity as a potential factor in the genesis of postpubertal hyperandrogenism. J. Clin. Endocrinol. Metab. 91, 1714–1722 (2006)PubMedCrossRef C.R. McCartney, K.A. Prendergast, S. Chhabra, C.A. Eagleson, R. Yoo, R.J. Chang, C.M. Foster, J.C. Marshall, The association of obesity and hyperandrogenemia during the pubertal transition in girls: obesity as a potential factor in the genesis of postpubertal hyperandrogenism. J. Clin. Endocrinol. Metab. 91, 1714–1722 (2006)PubMedCrossRef
23.
Zurück zum Zitat C.R. McCartney, Maturation of sleep-wake gonadotrophin-releasing hormone secretion across puberty in girls: potential mechanisms and relevance to the pathogenesis of polycystic ovary syndrome. J. Neuroendocrinol. 22, 701–709 (2010)PubMed C.R. McCartney, Maturation of sleep-wake gonadotrophin-releasing hormone secretion across puberty in girls: potential mechanisms and relevance to the pathogenesis of polycystic ovary syndrome. J. Neuroendocrinol. 22, 701–709 (2010)PubMed
24.
Zurück zum Zitat S.K. Blank, C.R. McCartney, K.D. Helm, J.C. Marshall, Neuroendocrine effects of androgens in adult polycystic ovary syndrome and female puberty. Semin. Reprod. Med. 25, 352–359 (2007)PubMedCrossRef S.K. Blank, C.R. McCartney, K.D. Helm, J.C. Marshall, Neuroendocrine effects of androgens in adult polycystic ovary syndrome and female puberty. Semin. Reprod. Med. 25, 352–359 (2007)PubMedCrossRef
25.
Zurück zum Zitat S.K. Blank, C.R. McCartney, J.C. Marshall, The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome. Hum. Reprod. Update 12, 351–361 (2006)PubMedCrossRef S.K. Blank, C.R. McCartney, J.C. Marshall, The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome. Hum. Reprod. Update 12, 351–361 (2006)PubMedCrossRef
26.
Zurück zum Zitat C.R. McCartney, S.K. Blank, K.A. Prendergast, S. Chhabra, C.A. Eagleson, K.D. Helm, R. Yoo, R.J. Chang, C.M. Foster, S. Caprio, J.C. Marshall, Obesity and sex steroid changes across puberty: evidence for marked hyperandrogenemia in pre- and early pubertal obese girls. J. Clin. Endocrinol. Metab. 92, 430–436 (2007)PubMedCrossRef C.R. McCartney, S.K. Blank, K.A. Prendergast, S. Chhabra, C.A. Eagleson, K.D. Helm, R. Yoo, R.J. Chang, C.M. Foster, S. Caprio, J.C. Marshall, Obesity and sex steroid changes across puberty: evidence for marked hyperandrogenemia in pre- and early pubertal obese girls. J. Clin. Endocrinol. Metab. 92, 430–436 (2007)PubMedCrossRef
27.
Zurück zum Zitat R.L. Rosenfield, Clinical review: identifying children at risk for polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 92, 787–796 (2007)PubMedCrossRef R.L. Rosenfield, Clinical review: identifying children at risk for polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 92, 787–796 (2007)PubMedCrossRef
28.
Zurück zum Zitat D.H. Geller, D. Pacaud, C.M. Gordon, M. Misra, of the Drug and Therapeutics Committee of the Pediatric Endocrine Society, State of the art review: emerging therapies: the use of insulin sensitizers in the treatment of adolescents with polycystic ovary syndrome (PCOS). Int. J. Pediatr. Endocrinol. 2011, 9 (2011)PubMedCrossRef D.H. Geller, D. Pacaud, C.M. Gordon, M. Misra, of the Drug and Therapeutics Committee of the Pediatric Endocrine Society, State of the art review: emerging therapies: the use of insulin sensitizers in the treatment of adolescents with polycystic ovary syndrome (PCOS). Int. J. Pediatr. Endocrinol. 2011, 9 (2011)PubMedCrossRef
29.
Zurück zum Zitat S.F. Witchel, R. Azziz, Congenital adrenal hyperplasia. J. Pediatr. Adolesc. Gynecol. 24, 116–126 (2011)PubMedCrossRef S.F. Witchel, R. Azziz, Congenital adrenal hyperplasia. J. Pediatr. Adolesc. Gynecol. 24, 116–126 (2011)PubMedCrossRef
30.
Zurück zum Zitat R.J. Auchus, S.F. Witchel, K.R. Leight, J. Aisenberg, R. Azziz et al., Guidelines for the development of comprehensive care centers for congenital adrenal hyperplasia: guidance from the CARES foundation initiative. Int. J. Pediatr. Endocrinol. (2011) [Epub 2011 Jan 10] R.J. Auchus, S.F. Witchel, K.R. Leight, J. Aisenberg, R. Azziz et al., Guidelines for the development of comprehensive care centers for congenital adrenal hyperplasia: guidance from the CARES foundation initiative. Int. J. Pediatr. Endocrinol. (2011) [Epub 2011 Jan 10]
31.
Zurück zum Zitat W.C. Chen, C.C. Zouboulis, Hormones and the pilosebaceous unit. Dermatoendocrinology 1, 81–86 (2009)CrossRef W.C. Chen, C.C. Zouboulis, Hormones and the pilosebaceous unit. Dermatoendocrinology 1, 81–86 (2009)CrossRef
32.
Zurück zum Zitat H.J. Teede, M.L. Misso, A.A. Deeks, L.J. Moran, B.G. Stuckey, J.L. Wong, R.J. Norman, Guideline Development Groups, Assessment and management of polycystic ovary syndrome: summary of an evidence-based guideline. Med. J. Aust. 195, S65–S112 (2011)PubMedCrossRef H.J. Teede, M.L. Misso, A.A. Deeks, L.J. Moran, B.G. Stuckey, J.L. Wong, R.J. Norman, Guideline Development Groups, Assessment and management of polycystic ovary syndrome: summary of an evidence-based guideline. Med. J. Aust. 195, S65–S112 (2011)PubMedCrossRef
33.
Zurück zum Zitat D.A. Dumesic, D.H. Abbott, V. Padmanabhan, Polycystic ovary syndrome and its developmental origins. Rev. Endocr. Metab. Disord. 8, 127–141 (2007)PubMedCrossRef D.A. Dumesic, D.H. Abbott, V. Padmanabhan, Polycystic ovary syndrome and its developmental origins. Rev. Endocr. Metab. Disord. 8, 127–141 (2007)PubMedCrossRef
34.
Zurück zum Zitat V. Padmanabhan, A. Veiga-Lopez, D.H. Abbott, S.E. Recabarren, C. Herkimer, Developmental programming: impact of prenatal testosterone excess and postnatal weight gain on insulin sensitivity index and transfer of traits to offspring of overweight females. Endocrinology 151, 595–605 (2010)PubMedCrossRef V. Padmanabhan, A. Veiga-Lopez, D.H. Abbott, S.E. Recabarren, C. Herkimer, Developmental programming: impact of prenatal testosterone excess and postnatal weight gain on insulin sensitivity index and transfer of traits to offspring of overweight females. Endocrinology 151, 595–605 (2010)PubMedCrossRef
35.
Zurück zum Zitat A.V. Roland, C.S. Nunemaker, S.R. Keller, S.M. Moenter, Prenatal androgen exposure programs metabolic dysfunction in female mice. J. Endocrinol. 207, 213–223 (2010)PubMedCrossRef A.V. Roland, C.S. Nunemaker, S.R. Keller, S.M. Moenter, Prenatal androgen exposure programs metabolic dysfunction in female mice. J. Endocrinol. 207, 213–223 (2010)PubMedCrossRef
36.
Zurück zum Zitat A. Veiga-Lopez, T.L. Steckler, D.H. Abbott, K.B. Welch, P.S. MohanKumar, D.J. Phillips, K. Refsal, V. Padmanabhan, Developmental programming: impact of excess prenatal testosterone on intrauterine fetal endocrine milieu and growth in sheep. Biol. Reprod. 84, 87–89 (2011)PubMedCrossRef A. Veiga-Lopez, T.L. Steckler, D.H. Abbott, K.B. Welch, P.S. MohanKumar, D.J. Phillips, K. Refsal, V. Padmanabhan, Developmental programming: impact of excess prenatal testosterone on intrauterine fetal endocrine milieu and growth in sheep. Biol. Reprod. 84, 87–89 (2011)PubMedCrossRef
37.
Zurück zum Zitat C.M. Bruns, S.T. Baum, R.J. Colman, J.R. Eisner, J.W. Kemnitz, R. Weindruch, D.H. Abbott, Insulin resistance and impaired insulin secretion in prenatally androgenized male rhesus monkeys. J. Clin. Endocrinol. Metab. 89, 6218–6223 (2004)PubMedCrossRef C.M. Bruns, S.T. Baum, R.J. Colman, J.R. Eisner, J.W. Kemnitz, R. Weindruch, D.H. Abbott, Insulin resistance and impaired insulin secretion in prenatally androgenized male rhesus monkeys. J. Clin. Endocrinol. Metab. 89, 6218–6223 (2004)PubMedCrossRef
38.
Zurück zum Zitat S.E. Recabarren, P.P. Rojas-García, M.P. Recabarren, V.H. Alfaro, R. Smith, V. Padmanabhan, T. Sir-Petermann, Prenatal testosterone excess reduces sperm count and motility. Endocrinology 149, 6444–6448 (2008)PubMedCrossRef S.E. Recabarren, P.P. Rojas-García, M.P. Recabarren, V.H. Alfaro, R. Smith, V. Padmanabhan, T. Sir-Petermann, Prenatal testosterone excess reduces sperm count and motility. Endocrinology 149, 6444–6448 (2008)PubMedCrossRef
39.
Zurück zum Zitat P.P. Rojas-García, M.P. Recabarren, L. Sarabia, J. Schön, C. Gabler, R. Einspanier, M. Maliqueo, T. Sir-Petermann, R. Rey, S.E. Recabarren, Prenatal testosterone excess alters Sertoli and germ cell number and testicular FSH receptor expression in rams. Am. J. Physiol. Endocrinol. Metab. 299, E998–E1005 (2010)PubMedCrossRef P.P. Rojas-García, M.P. Recabarren, L. Sarabia, J. Schön, C. Gabler, R. Einspanier, M. Maliqueo, T. Sir-Petermann, R. Rey, S.E. Recabarren, Prenatal testosterone excess alters Sertoli and germ cell number and testicular FSH receptor expression in rams. Am. J. Physiol. Endocrinol. Metab. 299, E998–E1005 (2010)PubMedCrossRef
40.
Zurück zum Zitat A.D. Coviello, S. Sam, R.S. Legro, A. Dunaif, High prevalence of metabolic syndrome in first-degree male relatives of women with polycystic ovary syndrome is related to high rates of obesity. J. Clin. Endocrinol. Metab. 94, 4361–4366 (2009)PubMedCrossRef A.D. Coviello, S. Sam, R.S. Legro, A. Dunaif, High prevalence of metabolic syndrome in first-degree male relatives of women with polycystic ovary syndrome is related to high rates of obesity. J. Clin. Endocrinol. Metab. 94, 4361–4366 (2009)PubMedCrossRef
41.
Zurück zum Zitat S. Sam, A.D. Coviello, Y.A. Sung, R.S. Legro, A. Dunaif, Metabolic phenotype in the brothers of women with polycystic ovary syndrome. Diabetes Care 31, 1237–1241 (2008)PubMedCrossRef S. Sam, A.D. Coviello, Y.A. Sung, R.S. Legro, A. Dunaif, Metabolic phenotype in the brothers of women with polycystic ovary syndrome. Diabetes Care 31, 1237–1241 (2008)PubMedCrossRef
42.
Zurück zum Zitat S. Sam, Y.A. Sung, R.S. Legro, A. Dunaif, Evidence for pancreatic beta-cell dysfunction in brothers of women with polycystic ovary syndrome. Metabolism 57, 84–89 (2008)PubMedCrossRef S. Sam, Y.A. Sung, R.S. Legro, A. Dunaif, Evidence for pancreatic beta-cell dysfunction in brothers of women with polycystic ovary syndrome. Metabolism 57, 84–89 (2008)PubMedCrossRef
43.
Zurück zum Zitat R.S. Legro, A.R. Kunselman, L. Demers, S.C. Wang, R. Bentley-Lewis, A. Dunaif, Elevated dehydroepiandrosterone sulfate levels as the reproductive phenotype in the brothers of women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 87, 2134–2138 (2002)PubMedCrossRef R.S. Legro, A.R. Kunselman, L. Demers, S.C. Wang, R. Bentley-Lewis, A. Dunaif, Elevated dehydroepiandrosterone sulfate levels as the reproductive phenotype in the brothers of women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 87, 2134–2138 (2002)PubMedCrossRef
44.
Zurück zum Zitat S.E. Recabarren, R. Smith, R. Rios, M. Maliqueo, B. Echiburú, E. Codner, F. Cassorla, P. Rojas, T. Sir-Petermann, Metabolic profile in sons of women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 93, 1820–1826 (2008)PubMedCrossRef S.E. Recabarren, R. Smith, R. Rios, M. Maliqueo, B. Echiburú, E. Codner, F. Cassorla, P. Rojas, T. Sir-Petermann, Metabolic profile in sons of women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 93, 1820–1826 (2008)PubMedCrossRef
45.
Zurück zum Zitat D.H. Abbott, C.R. Bruns, D.K. Barnett, A. Dunaif, T.L. Goodfriend, D.A. Dumesic, A.F. Tarantal, Experimentally induced gestational androgen excess disrupts glucoregulation in rhesus monkey dams and their female offspring. Am. J. Physiol. Endocrinol. Metab. 299, E741–E751 (2010)PubMedCrossRef D.H. Abbott, C.R. Bruns, D.K. Barnett, A. Dunaif, T.L. Goodfriend, D.A. Dumesic, A.F. Tarantal, Experimentally induced gestational androgen excess disrupts glucoregulation in rhesus monkey dams and their female offspring. Am. J. Physiol. Endocrinol. Metab. 299, E741–E751 (2010)PubMedCrossRef
46.
Zurück zum Zitat S.C. Kent, C.L. Gnatuk, A.R. Kunselman, L.M. Demers, P.A. Lee, R.S. Legro, Hyperandrogenism and hyperinsulinism in children of women with polycystic ovary syndrome: a controlled study. J. Clin. Endocrinol. Metab. 93, 1662–1669 (2008)PubMedCrossRef S.C. Kent, C.L. Gnatuk, A.R. Kunselman, L.M. Demers, P.A. Lee, R.S. Legro, Hyperandrogenism and hyperinsulinism in children of women with polycystic ovary syndrome: a controlled study. J. Clin. Endocrinol. Metab. 93, 1662–1669 (2008)PubMedCrossRef
47.
Zurück zum Zitat T. Sir-Petermann, E. Codner, V. Pérez, B. Echiburú, M. Maliqueo, A. Ladrón de Guevara, J. Preisler, N. Crisosto, F. Sánchez, F. Cassorla, S. Bhasin, Metabolic and reproductive features before and during puberty in daughters of women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 94, 1923–1930 (2009)PubMedCrossRef T. Sir-Petermann, E. Codner, V. Pérez, B. Echiburú, M. Maliqueo, A. Ladrón de Guevara, J. Preisler, N. Crisosto, F. Sánchez, F. Cassorla, S. Bhasin, Metabolic and reproductive features before and during puberty in daughters of women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 94, 1923–1930 (2009)PubMedCrossRef
48.
Zurück zum Zitat J.A. Barry, A.R. Kay, R. Navaratnarajah, S. Iqbal, J.E. Bamfo, A.L. David, M. Hines, P.J. Hardiman, Umbilical vein testosterone in female infants born to mothers with polycystic ovary syndrome is elevated to male levels. J. Obstet. Gynaecol. 30, 444–446 (2010)PubMedCrossRef J.A. Barry, A.R. Kay, R. Navaratnarajah, S. Iqbal, J.E. Bamfo, A.L. David, M. Hines, P.J. Hardiman, Umbilical vein testosterone in female infants born to mothers with polycystic ovary syndrome is elevated to male levels. J. Obstet. Gynaecol. 30, 444–446 (2010)PubMedCrossRef
49.
Zurück zum Zitat H. Anderson, N. Fogel, S.K. Grebe, R.J. Singh, R.L. Taylor, A. Dunaif, Infants of women with polycystic ovary syndrome have lower cord blood androstenedione and estradiol levels. J. Clin. Endocrinol. Metab. 95, 2180–2186 (2010)PubMedCrossRef H. Anderson, N. Fogel, S.K. Grebe, R.J. Singh, R.L. Taylor, A. Dunaif, Infants of women with polycystic ovary syndrome have lower cord blood androstenedione and estradiol levels. J. Clin. Endocrinol. Metab. 95, 2180–2186 (2010)PubMedCrossRef
50.
Zurück zum Zitat N. Xu, S. Kwon, D.H. Abbott, D.H. Geller, D.A. Dumesic, R. Azziz, X. Guo, M.O. Goodarzi, Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS)-like phenotypes in prenatally androgenized rhesus monkeys. PLoS One 6(11), e27286 (2011)PubMedCrossRef N. Xu, S. Kwon, D.H. Abbott, D.H. Geller, D.A. Dumesic, R. Azziz, X. Guo, M.O. Goodarzi, Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS)-like phenotypes in prenatally androgenized rhesus monkeys. PLoS One 6(11), e27286 (2011)PubMedCrossRef
51.
Zurück zum Zitat D.R. Stewart, B.A. Dombroski, M. Urbanek, W. Ankener, K.G. Ewens, J.R. Wood, R.S. Legro, J.F. Strauss 3rd, A. Dunaif, R.S. Spielman, Fine mapping of genetic susceptibility to polycystic ovary syndrome on chromosome 19p13.2 and tests for regulatory activity. J. Clin. Endocrinol. Metab. 91, 4112–4117 (2006)PubMedCrossRef D.R. Stewart, B.A. Dombroski, M. Urbanek, W. Ankener, K.G. Ewens, J.R. Wood, R.S. Legro, J.F. Strauss 3rd, A. Dunaif, R.S. Spielman, Fine mapping of genetic susceptibility to polycystic ovary syndrome on chromosome 19p13.2 and tests for regulatory activity. J. Clin. Endocrinol. Metab. 91, 4112–4117 (2006)PubMedCrossRef
52.
Zurück zum Zitat K.G. Ewens, D.R. Stewart, W. Ankener, M. Urbanek, J.M. McAllister, C. Chen, K.M. Baig, S.C. Parker, E.H. Margulies, R.S. Legro, A. Dunaif, J.F. Strauss 3rd, R.S. Spielman, Family-based analysis of candidate genes for polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 95, 2306–2315 (2010)PubMedCrossRef K.G. Ewens, D.R. Stewart, W. Ankener, M. Urbanek, J.M. McAllister, C. Chen, K.M. Baig, S.C. Parker, E.H. Margulies, R.S. Legro, A. Dunaif, J.F. Strauss 3rd, R.S. Spielman, Family-based analysis of candidate genes for polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 95, 2306–2315 (2010)PubMedCrossRef
53.
Zurück zum Zitat N. Hatzirodos, R.A. Bayne, H.F. Irving-Rodgers, K. Hummitzsch, L. Sabatier, S. Lee, W. Bonner, M.A. Gibson, W.E. Rainey, B.R. Carr, H.D. Mason, D.P. Reinhardt, R.A. Anderson, R.J. Rodgers, Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome. FASEB J. 25, 2256–2265 (2011)PubMedCrossRef N. Hatzirodos, R.A. Bayne, H.F. Irving-Rodgers, K. Hummitzsch, L. Sabatier, S. Lee, W. Bonner, M.A. Gibson, W.E. Rainey, B.R. Carr, H.D. Mason, D.P. Reinhardt, R.A. Anderson, R.J. Rodgers, Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome. FASEB J. 25, 2256–2265 (2011)PubMedCrossRef
54.
Zurück zum Zitat T. Massam-Wu, M. Chiu, R. Choudhury, S.S. Chaudhry, A.K. Baldwin, A. McGovern, C. Baldock, C.A. Shuttleworth, C.M. Klelty, Assembly of fibrillin microfibrils governs extracellular deposition of latent TGF beta. J. Cell Sci. 123(Pt 17), 3006–3018 (2010)PubMedCrossRef T. Massam-Wu, M. Chiu, R. Choudhury, S.S. Chaudhry, A.K. Baldwin, A. McGovern, C. Baldock, C.A. Shuttleworth, C.M. Klelty, Assembly of fibrillin microfibrils governs extracellular deposition of latent TGF beta. J. Cell Sci. 123(Pt 17), 3006–3018 (2010)PubMedCrossRef
55.
Zurück zum Zitat G. Sengle, R.N. Ono, T. Sasaki, L.Y. Sakai, Prodomains of transforming growth factor beta (TGFbeta) superfamily members specify different functions: extracellular matrix interactions and growth factor bioavailability. J. Biol. Chem. 286, 5087–5099 (2011)PubMedCrossRef G. Sengle, R.N. Ono, T. Sasaki, L.Y. Sakai, Prodomains of transforming growth factor beta (TGFbeta) superfamily members specify different functions: extracellular matrix interactions and growth factor bioavailability. J. Biol. Chem. 286, 5087–5099 (2011)PubMedCrossRef
56.
Zurück zum Zitat B. Kruse, F.G. Riepe, N. Krone, H.A.G. Bosinski, S. Kloehn, C.J. Partsch, W.G. Sippell, H. Mönig, Congenital adrenal hyperplasia—how to improve the transition from adolescence to adult life. Exp. Clin. Endocrinol. Diabetes 112, 343–355 (2004)PubMedCrossRef B. Kruse, F.G. Riepe, N. Krone, H.A.G. Bosinski, S. Kloehn, C.J. Partsch, W.G. Sippell, H. Mönig, Congenital adrenal hyperplasia—how to improve the transition from adolescence to adult life. Exp. Clin. Endocrinol. Diabetes 112, 343–355 (2004)PubMedCrossRef
57.
Zurück zum Zitat G.S. Conway, Congenital adrenal hyperplasia: adolescence and transition. Horm. Res. 68(suppl 5), 155–157 (2007)PubMedCrossRef G.S. Conway, Congenital adrenal hyperplasia: adolescence and transition. Horm. Res. 68(suppl 5), 155–157 (2007)PubMedCrossRef
58.
Zurück zum Zitat S.D. Grosse, M.S. Schechter, R. Kulkarni, M.A. Lloyd-Puryear, B. Strickland, E. Trevathan, Models of comprehensive multidisciplinary care for individuals in the United States with genetic disorders. Pediatrics 123, 407–412 (2009)PubMedCrossRef S.D. Grosse, M.S. Schechter, R. Kulkarni, M.A. Lloyd-Puryear, B. Strickland, E. Trevathan, Models of comprehensive multidisciplinary care for individuals in the United States with genetic disorders. Pediatrics 123, 407–412 (2009)PubMedCrossRef
59.
Zurück zum Zitat D. Rosen, Between two worlds: bridging the cultures of child health and adult medicine. J. Adolesc. Health 17, 10–16 (1995)PubMedCrossRef D. Rosen, Between two worlds: bridging the cultures of child health and adult medicine. J. Adolesc. Health 17, 10–16 (1995)PubMedCrossRef
60.
Zurück zum Zitat G.M. Kieckhefer, C.M. Trahms, Supporting development of children with chronic conditions: from compliance toward shared management. Pediatr. Nurs. 26, 354–363 (2000)PubMed G.M. Kieckhefer, C.M. Trahms, Supporting development of children with chronic conditions: from compliance toward shared management. Pediatr. Nurs. 26, 354–363 (2000)PubMed
61.
Zurück zum Zitat E. Carmina, S.E. Oberfield, R.A. Lobo, The diagnosis of polycystic ovary syndrome in adolescents. Am. J. Obstet. Gynecol. 203, 201.e1–5 (2010) E. Carmina, S.E. Oberfield, R.A. Lobo, The diagnosis of polycystic ovary syndrome in adolescents. Am. J. Obstet. Gynecol. 203, 201.e1–5 (2010)
62.
Zurück zum Zitat A. Lindholm, C. Blomquist, M. Bixo, I. Dahlbom, T. Hansson, I. Sundström Poromaa, J. Burén, No difference in markers of adipose tissue inflammation between overweight women with polycystic ovary syndrome and weight-matched controls. Hum. Reprod. 26, 1478–1485 (2011)PubMedCrossRef A. Lindholm, C. Blomquist, M. Bixo, I. Dahlbom, T. Hansson, I. Sundström Poromaa, J. Burén, No difference in markers of adipose tissue inflammation between overweight women with polycystic ovary syndrome and weight-matched controls. Hum. Reprod. 26, 1478–1485 (2011)PubMedCrossRef
63.
Zurück zum Zitat D. Glintborg, M. Andersen, B. Richelsen, J.M. Bruun, Plasma monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha are increased in patients with polycystic ovary syndrome (PCOS) and associated with adiposity, but unaffected by pioglitazone treatment. Clin. Endocrinol. (Oxf) 715, 652–658 (2009)CrossRef D. Glintborg, M. Andersen, B. Richelsen, J.M. Bruun, Plasma monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha are increased in patients with polycystic ovary syndrome (PCOS) and associated with adiposity, but unaffected by pioglitazone treatment. Clin. Endocrinol. (Oxf) 715, 652–658 (2009)CrossRef
64.
Zurück zum Zitat H.F. Escobar-Morreale, M. Luque-Ramírez, F. González, Circulating inflammatory markers in polycystic ovary symdrome: a systematic review and metaanalysis. Fertil. Steril. 95, 1048–1058.e1–2 (2011) H.F. Escobar-Morreale, M. Luque-Ramírez, F. González, Circulating inflammatory markers in polycystic ovary symdrome: a systematic review and metaanalysis. Fertil. Steril. 95, 1048–1058.e1–2 (2011)
65.
Zurück zum Zitat K.A. Toulis, D.G. Goulis, G. Mintziori, E. Kintiraki, E. Eukarpidis, S.A. Mouratoglou, A. Pavlaki, S. Stergianos, M. Poulasouchidou, T.G. Tzellos, A. Makedos, M. Chourdakis, B.C. Tarlatzis, Meta-analysis of cardiovascular disease risk markers in women with polycystic ovary syndrome. Hum. Reprod. Update 17, 741–760 (2011)PubMedCrossRef K.A. Toulis, D.G. Goulis, G. Mintziori, E. Kintiraki, E. Eukarpidis, S.A. Mouratoglou, A. Pavlaki, S. Stergianos, M. Poulasouchidou, T.G. Tzellos, A. Makedos, M. Chourdakis, B.C. Tarlatzis, Meta-analysis of cardiovascular disease risk markers in women with polycystic ovary syndrome. Hum. Reprod. Update 17, 741–760 (2011)PubMedCrossRef
66.
Zurück zum Zitat F. González, Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids 77, 300–305 (2012)PubMedCrossRef F. González, Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids 77, 300–305 (2012)PubMedCrossRef
67.
Zurück zum Zitat F. Gonzalez, K.S. Nair, J.K. Daniels, E. Basal, J.M. Schimke, Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women. Am. J. Physiol. Endocrinol. Metab. 302, E297–E306 (2012)PubMedCrossRef F. Gonzalez, K.S. Nair, J.K. Daniels, E. Basal, J.M. Schimke, Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women. Am. J. Physiol. Endocrinol. Metab. 302, E297–E306 (2012)PubMedCrossRef
68.
Zurück zum Zitat R. Ramasamy, S.J. Vannucci, S.S. Yan, K. Herold, S.F. Yan, A.M. Schmidt, Advanced glycation end products and RAGE: a common threat in aging, diabetes, neurodegeneretion, and inflammation. Glycobiology 15, 16R–28R (2005)PubMedCrossRef R. Ramasamy, S.J. Vannucci, S.S. Yan, K. Herold, S.F. Yan, A.M. Schmidt, Advanced glycation end products and RAGE: a common threat in aging, diabetes, neurodegeneretion, and inflammation. Glycobiology 15, 16R–28R (2005)PubMedCrossRef
69.
Zurück zum Zitat E. Diamanti-Kandarakis, I. Katsikis, C. Piperi, E. Kandaraki, A. Piouka, A.G. Papavassillou, D. Panidis, Increased serum advanced glycation end products is a distinct finding in lean women with PCOS. Clin. Endocrinol. (Oxf) 69, 634–641 (2008)CrossRef E. Diamanti-Kandarakis, I. Katsikis, C. Piperi, E. Kandaraki, A. Piouka, A.G. Papavassillou, D. Panidis, Increased serum advanced glycation end products is a distinct finding in lean women with PCOS. Clin. Endocrinol. (Oxf) 69, 634–641 (2008)CrossRef
70.
Zurück zum Zitat E. Diamanti-Kandarakis, A. Piouka, S. Livadas, C. Piperi, I. Katsikis, A.G. Papavassillou, D. Panidis, Anti-mullerian hormone is associated with advanced glycosylated end products in lean women with polycystic ovary syndrome. Eur. J. Endocrinol. 160, 847–853 (2009)PubMedCrossRef E. Diamanti-Kandarakis, A. Piouka, S. Livadas, C. Piperi, I. Katsikis, A.G. Papavassillou, D. Panidis, Anti-mullerian hormone is associated with advanced glycosylated end products in lean women with polycystic ovary syndrome. Eur. J. Endocrinol. 160, 847–853 (2009)PubMedCrossRef
71.
Zurück zum Zitat E. Diamanti-Kandarakis, C. Piperi, E. Patsouris, P. Korkolopoulou, D. Panidis, L. Pawelczyk, A.G. Papavassiliou, A.J. Duleba, Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries. Histochem. Cell Biol. 127, 581–589 (2007)PubMedCrossRef E. Diamanti-Kandarakis, C. Piperi, E. Patsouris, P. Korkolopoulou, D. Panidis, L. Pawelczyk, A.G. Papavassiliou, A.J. Duleba, Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries. Histochem. Cell Biol. 127, 581–589 (2007)PubMedCrossRef
72.
Zurück zum Zitat K.K. Papachroni, C. Piperi, G. Levidou, P. Korkolopoulou, L. Pawelczyk, E. Diamanti-Kandarakis, A.G. Papavassiliou, Lysyl oxidase interacts with AGE signalling to modulate collagen synthesis in polycystic ovarian tissue. J. Cell Mol. Med. 14, 2460–2469 (2010)PubMedCrossRef K.K. Papachroni, C. Piperi, G. Levidou, P. Korkolopoulou, L. Pawelczyk, E. Diamanti-Kandarakis, A.G. Papavassiliou, Lysyl oxidase interacts with AGE signalling to modulate collagen synthesis in polycystic ovarian tissue. J. Cell Mol. Med. 14, 2460–2469 (2010)PubMedCrossRef
73.
Zurück zum Zitat I.J. Rzepczynska, P.C. Piotrowski, D.H. Wong, A.B. Cress, J. Villanueva, A.J. Duleba, Role of isoprenylation in simvastatin-induced inhibition of ovarian theca-interstitial growth in the rat. Biol. Reprod. 81, 850–855 (2009)PubMedCrossRef I.J. Rzepczynska, P.C. Piotrowski, D.H. Wong, A.B. Cress, J. Villanueva, A.J. Duleba, Role of isoprenylation in simvastatin-induced inhibition of ovarian theca-interstitial growth in the rat. Biol. Reprod. 81, 850–855 (2009)PubMedCrossRef
74.
Zurück zum Zitat D. Izquierdo, N. Foyouzi, J. Kwintkiewicz, A.J. Duleba, Mevastatin inhibits ovarian theca-interstitial cell proliferation and steroidogenesis. Fertil. Steril. 82(Suppl 3), 1193–1197 (2004)PubMedCrossRef D. Izquierdo, N. Foyouzi, J. Kwintkiewicz, A.J. Duleba, Mevastatin inhibits ovarian theca-interstitial cell proliferation and steroidogenesis. Fertil. Steril. 82(Suppl 3), 1193–1197 (2004)PubMedCrossRef
75.
Zurück zum Zitat A. Sokalska, P.C. Piotrowski, I.J. Rzepczynska, A. Cress, A.J. Duleba, Statins inhibit growth of human theca-interstitial cells in PCOS and non-PCOS tissues independently of cholesterol availability. J. Clin. Endocrinol. Metab. 95, 5390–5394 (2010)PubMedCrossRef A. Sokalska, P.C. Piotrowski, I.J. Rzepczynska, A. Cress, A.J. Duleba, Statins inhibit growth of human theca-interstitial cells in PCOS and non-PCOS tissues independently of cholesterol availability. J. Clin. Endocrinol. Metab. 95, 5390–5394 (2010)PubMedCrossRef
76.
Zurück zum Zitat B. Banaszewska, L. Pawelczyk, R.Z. Spaczynski, A.J. Duleba, Effects of simvastatin and metformin on polycystic ovary syndrome after six months of treatment. J. Clin. Endocrinol. Metab. 96, 3493–3501 (2011)PubMedCrossRef B. Banaszewska, L. Pawelczyk, R.Z. Spaczynski, A.J. Duleba, Effects of simvastatin and metformin on polycystic ovary syndrome after six months of treatment. J. Clin. Endocrinol. Metab. 96, 3493–3501 (2011)PubMedCrossRef
77.
Zurück zum Zitat A.J. Duleba, B. Banaszewska, R.Z. Spaczynski, L. Pawelczyk, Simvastatin improves biochemical parameters in women with polycystic ovary syndrome: results of a prospective, randomized trial. Fertil. Steril. 85, 996–1001 (2006)PubMedCrossRef A.J. Duleba, B. Banaszewska, R.Z. Spaczynski, L. Pawelczyk, Simvastatin improves biochemical parameters in women with polycystic ovary syndrome: results of a prospective, randomized trial. Fertil. Steril. 85, 996–1001 (2006)PubMedCrossRef
78.
Zurück zum Zitat C. Kaya, S.D. Cengiz, B. Berker, S. Demirtas, M. Cesur, G. Erdogan, Comparative effects of atorvastatin and simvastatin on the plasma total homocysteine levels in women with polycystic ovary syndrome: a prospective randomized study. Fertil. Steril. 92, 635–642 (2009)PubMedCrossRef C. Kaya, S.D. Cengiz, B. Berker, S. Demirtas, M. Cesur, G. Erdogan, Comparative effects of atorvastatin and simvastatin on the plasma total homocysteine levels in women with polycystic ovary syndrome: a prospective randomized study. Fertil. Steril. 92, 635–642 (2009)PubMedCrossRef
79.
Zurück zum Zitat T. Sathyapalan, E.S. Kilpatrick, A.M. Coady, S.L. Atkin, The effect of atorvastatin in patients with polycystic ovary syndrome: a randomized double-blind placebo-controlled study. J. Clin. Endocrinol. Metab. 94, 103–108 (2009)PubMedCrossRef T. Sathyapalan, E.S. Kilpatrick, A.M. Coady, S.L. Atkin, The effect of atorvastatin in patients with polycystic ovary syndrome: a randomized double-blind placebo-controlled study. J. Clin. Endocrinol. Metab. 94, 103–108 (2009)PubMedCrossRef
80.
Zurück zum Zitat W.C. Knowler, E. Barrett-Connor, S.E. Fowler, R.F. Hamman, J.M. Lachin, E.A. Walker, D.M. Nathan, Diabetes Prevention Program Research Group, Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 346, 393–403 (2002)PubMedCrossRef W.C. Knowler, E. Barrett-Connor, S.E. Fowler, R.F. Hamman, J.M. Lachin, E.A. Walker, D.M. Nathan, Diabetes Prevention Program Research Group, Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 346, 393–403 (2002)PubMedCrossRef
81.
Zurück zum Zitat L.J. Moran, R. Pasquali, H.J. Teede, K.M. Hoeger, R.J. Norman, Treatment of obesity in polycystic ovary syndrome: a position statement of the Androgen Excess and Polycystic Ovary Syndrome Society. Fertil. Steril. 92, 1966–1982 (2009)PubMedCrossRef L.J. Moran, R. Pasquali, H.J. Teede, K.M. Hoeger, R.J. Norman, Treatment of obesity in polycystic ovary syndrome: a position statement of the Androgen Excess and Polycystic Ovary Syndrome Society. Fertil. Steril. 92, 1966–1982 (2009)PubMedCrossRef
82.
Zurück zum Zitat L.J. Moran, M. Noakes, P.M. Clifton, R.J. Norman, The use of anti-mullerian hormone in predicting menstrual response after weight loss in overweight women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 92, 3796–3802 (2007)PubMedCrossRef L.J. Moran, M. Noakes, P.M. Clifton, R.J. Norman, The use of anti-mullerian hormone in predicting menstrual response after weight loss in overweight women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 92, 3796–3802 (2007)PubMedCrossRef
83.
Zurück zum Zitat K.I. Cheang, J.M. Huszar, A.M. Best, S. Sharma, P.A. Essah, J.E. Nestler, Long-term effect of metformin on metabolic parameters in the polycystic ovary syndrome. Diab. Vasc. Dis. Res. 6, 110–119 (2009)PubMedCrossRef K.I. Cheang, J.M. Huszar, A.M. Best, S. Sharma, P.A. Essah, J.E. Nestler, Long-term effect of metformin on metabolic parameters in the polycystic ovary syndrome. Diab. Vasc. Dis. Res. 6, 110–119 (2009)PubMedCrossRef
84.
Zurück zum Zitat K.A. Jablonski, J.B. McAteer, P.I. de Bakker, P.W. Franks, T.I. Pollin, R.L. Hanson, R. Saxena, S. Fowler, A.R. Shuldiner, W.C. Knowler, D. Altshuler, J.C. Florez, Diabetes Prevention Program Research Group, Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program. Diabetes 59, 2672–2681 (2010)PubMedCrossRef K.A. Jablonski, J.B. McAteer, P.I. de Bakker, P.W. Franks, T.I. Pollin, R.L. Hanson, R. Saxena, S. Fowler, A.R. Shuldiner, W.C. Knowler, D. Altshuler, J.C. Florez, Diabetes Prevention Program Research Group, Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program. Diabetes 59, 2672–2681 (2010)PubMedCrossRef
85.
Zurück zum Zitat A. Gambineri, F. Tomassoni, D.I. Gasparini, A. Di Rocco, V. Mantovani, U. Pagotto, P. Altieri, S. Sanna, A.M. Fulghesu, R. Pasquali, Organic cation transporter 1 polymorphisms predict the metabolic response to metformin in women with the polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 95, E204–E208 (2010)PubMedCrossRef A. Gambineri, F. Tomassoni, D.I. Gasparini, A. Di Rocco, V. Mantovani, U. Pagotto, P. Altieri, S. Sanna, A.M. Fulghesu, R. Pasquali, Organic cation transporter 1 polymorphisms predict the metabolic response to metformin in women with the polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 95, E204–E208 (2010)PubMedCrossRef
86.
Zurück zum Zitat T. Sathyapalan, L.W. Cho, E.S. Kilpatrick, A.M. Coady, S.L. Atkin, A comparison between rimonabant and metformin in reducing biochemical hyperandrogenaemia and insulin resistance in patients with polycystic ovary syndrome (PCOS): a randomized open-label parallel study. Clin. Endocrinol. (Oxf) 69, 931–935 (2008)CrossRef T. Sathyapalan, L.W. Cho, E.S. Kilpatrick, A.M. Coady, S.L. Atkin, A comparison between rimonabant and metformin in reducing biochemical hyperandrogenaemia and insulin resistance in patients with polycystic ovary syndrome (PCOS): a randomized open-label parallel study. Clin. Endocrinol. (Oxf) 69, 931–935 (2008)CrossRef
87.
Zurück zum Zitat G.M. Eid, D.R. Cottam, L.M. Velcu, S.G. Mattar, M.T. Korytkowski, G. Gosman, P. Hindi, P.R. Schauer, Effective treatment of polycystic ovarian syndrome with Roux-en-Y gastric bypass. Surg. Obes. Relat. Dis. 1, 77–80 (2005)PubMedCrossRef G.M. Eid, D.R. Cottam, L.M. Velcu, S.G. Mattar, M.T. Korytkowski, G. Gosman, P. Hindi, P.R. Schauer, Effective treatment of polycystic ovarian syndrome with Roux-en-Y gastric bypass. Surg. Obes. Relat. Dis. 1, 77–80 (2005)PubMedCrossRef
88.
Zurück zum Zitat Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, Consensus on infertility treatment related to polycystic ovary syndrome. Fertil. Steril. 89, 505–522 (2008)CrossRef Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, Consensus on infertility treatment related to polycystic ovary syndrome. Fertil. Steril. 89, 505–522 (2008)CrossRef
89.
Zurück zum Zitat H. Abu Hashim, M. El-Shafei, A. Badawy, A. Wafa, H. Zaglol, Does laparoscopic ovarian diathermy change clomiphene-resistant PCOS into clomiphene-sensitive? Arch. Gynecol. Obstet. 284, 503–507 (2011)PubMedCrossRef H. Abu Hashim, M. El-Shafei, A. Badawy, A. Wafa, H. Zaglol, Does laparoscopic ovarian diathermy change clomiphene-resistant PCOS into clomiphene-sensitive? Arch. Gynecol. Obstet. 284, 503–507 (2011)PubMedCrossRef
90.
Zurück zum Zitat N.P. Johnson, A.W. Stewart, J. Falkiner, C.M. Farquhar, S. Milsom, V.P. Singh, Q.L. Okonkwo, K.L. Buckingham, REACT-NZ (REproduction And Collaborative Trials in New Zealand), a multi-centre fertility trials group, PCOSMIC: a multi-centre randomized trial in women with PolyCystic Ovary Syndrome evaluating Metformin for Infertility with Clomiphene. Hum. Reprod. 25, 1675–1683 (2010)PubMedCrossRef N.P. Johnson, A.W. Stewart, J. Falkiner, C.M. Farquhar, S. Milsom, V.P. Singh, Q.L. Okonkwo, K.L. Buckingham, REACT-NZ (REproduction And Collaborative Trials in New Zealand), a multi-centre fertility trials group, PCOSMIC: a multi-centre randomized trial in women with PolyCystic Ovary Syndrome evaluating Metformin for Infertility with Clomiphene. Hum. Reprod. 25, 1675–1683 (2010)PubMedCrossRef
91.
Zurück zum Zitat N.P. Polyzos, S. Tzioras, A.M. Badawy, A. Valachis, C. Dritsas, D. Mauri, Aromatase inhibitors for female infertility: a systematic review of the literature. Reprod. Biomed. Online 19, 456–471 (2009)PubMedCrossRef N.P. Polyzos, S. Tzioras, A.M. Badawy, A. Valachis, C. Dritsas, D. Mauri, Aromatase inhibitors for female infertility: a systematic review of the literature. Reprod. Biomed. Online 19, 456–471 (2009)PubMedCrossRef
92.
Zurück zum Zitat T.D. Vause, A.P. Cheung, S. Sierra, P. Claman, J. Graham, J.A. Guillemin, L. Lapensée, S. Steward, B.C. Wong, Society of Obstetricians and Gynaecologists of Canada, Ovulation induction in polycystic ovary syndrome: No. 242, May 2010. Int. J. Gynaecol. Obstet. 111, 95–100 (2010)PubMedCrossRef T.D. Vause, A.P. Cheung, S. Sierra, P. Claman, J. Graham, J.A. Guillemin, L. Lapensée, S. Steward, B.C. Wong, Society of Obstetricians and Gynaecologists of Canada, Ovulation induction in polycystic ovary syndrome: No. 242, May 2010. Int. J. Gynaecol. Obstet. 111, 95–100 (2010)PubMedCrossRef
93.
Zurück zum Zitat D. Tredway, J.C. Schertz, D. Bock, G. Hemsey, M.P Diamond, Anastrozole vs. clomiphene citrate in infertile women with ovulatory dysfunction: a phase II, randomized, dose-finding study. Fertil. Steril. 95, 1720–4.e1–8 (2011) D. Tredway, J.C. Schertz, D. Bock, G. Hemsey, M.P Diamond, Anastrozole vs. clomiphene citrate in infertile women with ovulatory dysfunction: a phase II, randomized, dose-finding study. Fertil. Steril. 95, 1720–4.e1–8 (2011)
94.
Zurück zum Zitat T. Tulandi, J. Martin, R. Al-Fadhli, N. Kabli, R. Forman, J. Hitkari, C. Librach, E. Greenblatt, R.F. Casper, Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil. Steril. 85, 1761–1765 (2006)PubMedCrossRef T. Tulandi, J. Martin, R. Al-Fadhli, N. Kabli, R. Forman, J. Hitkari, C. Librach, E. Greenblatt, R.F. Casper, Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil. Steril. 85, 1761–1765 (2006)PubMedCrossRef
95.
Zurück zum Zitat S. Palomba, A. Falbo, F. Zullo, F. Orio Jr, Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: a comprehensive review. Endocr. Rev. 30, 1–50 (2009)PubMedCrossRef S. Palomba, A. Falbo, F. Zullo, F. Orio Jr, Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: a comprehensive review. Endocr. Rev. 30, 1–50 (2009)PubMedCrossRef
96.
Zurück zum Zitat R. Pasquali, A. Gambineri, U. Pagotto, The impact of obesity on reproduction in women with polycystic ovary syndrome. Br. J. Obstet. Gynecol. 113, 1148–1159 (2006)CrossRef R. Pasquali, A. Gambineri, U. Pagotto, The impact of obesity on reproduction in women with polycystic ovary syndrome. Br. J. Obstet. Gynecol. 113, 1148–1159 (2006)CrossRef
97.
Zurück zum Zitat E. Diamanti-Kandarakis, C.D. Christakou, E. Kandaraki, F.N. Economou, Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome. Eur. J. Endocrinol. 162, 193–212 (2010)PubMedCrossRef E. Diamanti-Kandarakis, C.D. Christakou, E. Kandaraki, F.N. Economou, Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome. Eur. J. Endocrinol. 162, 193–212 (2010)PubMedCrossRef
98.
Zurück zum Zitat R.S. Legro, H.X. Barnhart, W.D. Schlaff, B.R. Carr, M.P. Diamond, S.A. Carson, M.P. Steinkampf, C. Coutifaris, P.G. McGovern, N.A. Cataldo, G.G. Gosman, J.E. Nestler, L.C. Giudice, P.C. Leppert, E.R. Myers, Cooperative Multicenter Reproductive Medicine Network. Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome. N. Engl. J. Med. 356, 551–566 (2007)PubMedCrossRef R.S. Legro, H.X. Barnhart, W.D. Schlaff, B.R. Carr, M.P. Diamond, S.A. Carson, M.P. Steinkampf, C. Coutifaris, P.G. McGovern, N.A. Cataldo, G.G. Gosman, J.E. Nestler, L.C. Giudice, P.C. Leppert, E.R. Myers, Cooperative Multicenter Reproductive Medicine Network. Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome. N. Engl. J. Med. 356, 551–566 (2007)PubMedCrossRef
99.
Zurück zum Zitat S. Palomba, R. Pasquali, F. Orio Jr, J.E. Nestler, Clomiphene citrate, metformin or both as first-step approach in treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS): a systematic review of head-to-head randomized controlled studies and meta-analysis. Clin. Endocrinol. (Oxf) 70, 311–321 (2009)CrossRef S. Palomba, R. Pasquali, F. Orio Jr, J.E. Nestler, Clomiphene citrate, metformin or both as first-step approach in treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS): a systematic review of head-to-head randomized controlled studies and meta-analysis. Clin. Endocrinol. (Oxf) 70, 311–321 (2009)CrossRef
100.
Zurück zum Zitat A.A. Creanga, H.M. Bradley, C. McCormick, C.T. Witkop, Use of metformin in polycystic ovary syndrome: a meta-analysis. Obstet. Gynecol. 111, 959–968 (2008)PubMedCrossRef A.A. Creanga, H.M. Bradley, C. McCormick, C.T. Witkop, Use of metformin in polycystic ovary syndrome: a meta-analysis. Obstet. Gynecol. 111, 959–968 (2008)PubMedCrossRef
101.
Zurück zum Zitat S. Franks, When should an insulin sensitizing agent used in the treatment of polycystic ovary syndrome? Clin. Endocrinol. (Oxf) 74, 148–151 (2011)CrossRef S. Franks, When should an insulin sensitizing agent used in the treatment of polycystic ovary syndrome? Clin. Endocrinol. (Oxf) 74, 148–151 (2011)CrossRef
102.
Zurück zum Zitat E. Makrantonaki, C.C. Zouboulis, Androgens and ageing of the skin. Curr. Opin. Endocrinol. Diabetes Obes. 16, 240–245 (2009)PubMedCrossRef E. Makrantonaki, C.C. Zouboulis, Androgens and ageing of the skin. Curr. Opin. Endocrinol. Diabetes Obes. 16, 240–245 (2009)PubMedCrossRef
103.
Zurück zum Zitat C.C. Zouboulis, The human skin as a hormone target and an endocrine gland. Hormones (Athens) 3, 9–26 (2004) C.C. Zouboulis, The human skin as a hormone target and an endocrine gland. Hormones (Athens) 3, 9–26 (2004)
104.
Zurück zum Zitat C.C. Zouboulis, The skin as an endocrine organ. Dermatoendocrinology 1, 250–252 (2009)CrossRef C.C. Zouboulis, The skin as an endocrine organ. Dermatoendocrinology 1, 250–252 (2009)CrossRef
105.
Zurück zum Zitat C.C. Zouboulis, W.C. Chen, M.J. Thornton, K. Qin, R. Rosenfield, Sexual hormones in human skin. Horm. Metab. Res. 39, 85–95 (2007)PubMedCrossRef C.C. Zouboulis, W.C. Chen, M.J. Thornton, K. Qin, R. Rosenfield, Sexual hormones in human skin. Horm. Metab. Res. 39, 85–95 (2007)PubMedCrossRef
106.
Zurück zum Zitat A. Drosdzol, V. Skrzypulec, R. Plinta, Quality of life, mental health and self-esteem in hirsute adolescent females. J. Psychosom. Obstet. Gynaecol. 31, 168–175 (2010)PubMedCrossRef A. Drosdzol, V. Skrzypulec, R. Plinta, Quality of life, mental health and self-esteem in hirsute adolescent females. J. Psychosom. Obstet. Gynaecol. 31, 168–175 (2010)PubMedCrossRef
107.
Zurück zum Zitat H.F. Escobar-Morreale, E. Carmina, D. Dewailly, A. Gambineri, F. Kelestimur, P. Moghetti, M. Pugeat, J. Qiao, C.N. Wijeyaratne, S.F. Witchel, R.J. Norman, Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. Hum. Reprod. Update 18, 146–170 (2012) H.F. Escobar-Morreale, E. Carmina, D. Dewailly, A. Gambineri, F. Kelestimur, P. Moghetti, M. Pugeat, J. Qiao, C.N. Wijeyaratne, S.F. Witchel, R.J. Norman, Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. Hum. Reprod. Update 18, 146–170 (2012)
108.
109.
Zurück zum Zitat R. Paparodis, A. Dunaif, The Hirsute woman: challenges in evaluation and management. Endocr. Pract. 17, 807–818 (2011)PubMedCrossRef R. Paparodis, A. Dunaif, The Hirsute woman: challenges in evaluation and management. Endocr. Pract. 17, 807–818 (2011)PubMedCrossRef
110.
Zurück zum Zitat F. Lumachi, S.M. Basso, Medical treatment of hirsutism in women. Curr. Med. Chem. 17, 2530–2538 (2010)PubMedCrossRef F. Lumachi, S.M. Basso, Medical treatment of hirsutism in women. Curr. Med. Chem. 17, 2530–2538 (2010)PubMedCrossRef
111.
Zurück zum Zitat R. Sinclair, M. Patel, T.L. Dawson Jr, A. Yazdabadi, L. Yip, A. Perez, N.W. Rufaut, Hair loss in women: medical and cosmetic approaches to increase scalp hair fullness. Br. J. Dermatol. 165(Suppl 3), 12–18 (2011)PubMedCrossRef R. Sinclair, M. Patel, T.L. Dawson Jr, A. Yazdabadi, L. Yip, A. Perez, N.W. Rufaut, Hair loss in women: medical and cosmetic approaches to increase scalp hair fullness. Br. J. Dermatol. 165(Suppl 3), 12–18 (2011)PubMedCrossRef
112.
Zurück zum Zitat M. Yamaoka, T. Hara, T. Hitaka, T. Kaku, T. Takeuchi, J. Takahashi, S. Asahi, H. Miki, A. Tasaka, M. Kusaka, Orteronel (TAK-700), a novel non-steroidal 17,20-lyase inhibitor: effects on steroid synthesis in human and monkey adrenal cells and serum steroid levels in cynomolgus monkeys. J. Steroid. Biochem. Mol. Biol. 129, 115–128 (2012)PubMedCrossRef M. Yamaoka, T. Hara, T. Hitaka, T. Kaku, T. Takeuchi, J. Takahashi, S. Asahi, H. Miki, A. Tasaka, M. Kusaka, Orteronel (TAK-700), a novel non-steroidal 17,20-lyase inhibitor: effects on steroid synthesis in human and monkey adrenal cells and serum steroid levels in cynomolgus monkeys. J. Steroid. Biochem. Mol. Biol. 129, 115–128 (2012)PubMedCrossRef
Metadaten
Titel
Emerging concepts about prenatal genesis, aberrant metabolism and treatment paradigms in polycystic ovary syndrome
verfasst von
Selma F. Witchel
Sergio E. Recabarren
Frank González
Evanthia Diamanti-Kandarakis
Kai I. Cheang
Antoni J. Duleba
Richard S. Legro
Roy Homburg
Renato Pasquali
Rogerio A. Lobo
Christos C. Zouboulis
Fahrettin Kelestimur
Franca Fruzzetti
Walter Futterweit
Robert J. Norman
David H. Abbott
Publikationsdatum
01.12.2012
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 3/2012
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-012-9701-4

Weitere Artikel der Ausgabe 3/2012

Endocrine 3/2012 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.