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El síndrome de ovario poliquístico (SOP) es un trastorno endocrinometabólico de etiología compleja. En su fenotipo coinciden pacientes con mecanismos etiopatogénicos diferentes.
El defecto primario del SOP parece residir en una capacidad aumentada de secretar andrógenos en el ovario y, posiblemente, la glándula suprarrenal, de etiología aún desconocida. Sobre éste actúan diversos factores desencadenantes, entre los que destacan el hiperinsulinismo endógeno derivado de la resistencia insulínica y la obesidad. Dependiendo de la gravedad del defecto esteroidogénico, los factores desencadenantes tendrán un peso mayor o menor en la aparición del síndrome, como se ejemplifica en las diferencias fenotípicas marcadas entre pacientes delgadas y obesas con SOP.
La etiología del SOP es multifactorial y compleja, y en su aparición y desarrollo influyen factores genéticos y ambientales, cuya interrelación es aún objeto de estudio. El escenario más probable es una herencia poligénica sujeta a una influencia ambiental marcada, derivada de factores como la dieta, el sedentarismo y el estilo de vida, sujetos a una marcada variabilidad étnica y geográfica.
Palabras clave:
Síndrome de ovario poliquístico
Resistencia insulínica
Obesidad
Etiología
Fisiopatología
The polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder, in which patients with different etiopathogenic mechanisms show the same phenotype.
The primary defect in PCOS consists of an exaggerated synthesis and secretion of androgens by the ovary and, possibly, by the adrenal gland. The etiology remains unknown.
This primary defect is triggered by several factors, of which the endogenous hyperinsulinism secondary to insulin resistance and obesity is the best known.
Depending on the severity of the steroidogenic defect, the triggering factors play a greater or lesser role in the development of the disorder, as exemplified by the marked phenotypic differences among lean and obese PCOS patients.
The etiology of PCOS is complex and multifactorial and involves interaction among genetic and environmental factors. This interaction is currently under study. The most probable scenario involves a complex inheritance combined with a strong environmental influence. The latter derives from factors such as diet, exercise, and lifestyle, which are heavily dependent on ethnic and geographic variability.
Key words:
Polycystic ovary syndrome
Insulin resistance
Obesity
Etiology
Physiopathology
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Bibliografía
[1.]
V.L. Nelson, R.S. Legro, J.F. Strauss 3rd, J.M. McAllister.
Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries.
Mol Endocrinol, 13 (1999), pp. 946-957
[2.]
J.K. Wickenheisser, P.G. Quinn, V.L. Nelson, R.S. Legro, J.F. Strauss 3rd, J.M. McAllister.
Differential activity of the cytochrome P450 17alphahydroxylase and steroidogenic acute regulatory protein gene promoters in normal and polycystic ovary syndrome theca cells.
J Clin Endocrinol Metab, 85 (2000), pp. 2304-2311
[3.]
V.L. Nelson, K.N. Qin, R.L. Rosenfield, J.R. Wood, T.M. Penning, R.S. Legro, et al.
The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome.
J Clin Endocrinol Metab, 86 (2001), pp. 5925-5933
[4.]
J.K. Wickenheisser, V.L. Nelson-DeGrave, P.G. Quinn, J.M. McAllister.
Increased cytochrome P450 17alpha-hydroxylase promoter function in theca cells isolated from patients with polycystic ovary syndrome involves nuclear factor-1.
Mol Endocrinol, 18 (2004), pp. 588-605
[5.]
J.K. Wickenheisser, V.L. Nelson-Degrave, J.M. McAllister.
Dysregulation of cytochrome P450 17alpha-hydroxylase messenger ribonucleic acid stability in theca cells isolated from women with polycystic ovary syndrome.
J Clin Endocrinol Metab, 90 (2005), pp. 1720-1727
[6.]
J.R. Wood, C.K. Ho, V.L. Nelson-Degrave, J.M. McAllister, J.F. Strauss 3rd.
The molecular signature of polycystic ovary syndrome (PCOS) theca cells defined by gene expression profiling.
J Reprod Immunol, 63 (2004), pp. 51-60
[7.]
V.L. Nelson-Degrave, J.K. Wickenheisser, K.L. Hendricks, T. Asano, M. Fujishiro, R.S. Legro, et al.
Alterations in mitogen-activated protein kinase kinase and extracellular regulated kinase signaling in theca cells contribute to excessive androgen production in polycystic ovary syndrome.
Mol Endocrinol, 19 (2005), pp. 379-390
[8.]
A. Dunaif.
Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis.
Endocr Rev, 18 (1997), pp. 774-800
[9.]
R.D. Murray, R.M. Davison, R.C. Russell, G.S. Conway.
Clinical presentation of PCOS following development of an insulinoma: case report.
Hum Reprod, 15 (2000), pp. 86-88
[10.]
H.F. Escobar-Morreale, B. Roldán, R. Barrio, M. Alonso, J. Sancho, H. De la Calle, et al.
High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus.
J Clin Endocrinol Metab, 85 (2000), pp. 4182-4187
[11.]
B. Roldán, H.F. Escobar-Morreale, R. Barrio, H. De la Calle, M. Alonso, R. García-Robles, et al.
Identification of the source of androgen excess in hyperandrogenic type 1 diabetic patients.
Diabetes Care, 24 (2001), pp. 1297-1299
[12.]
E. Codner, N. Soto, P. López, L. Trejo, A. Ávila, F.C. Eyzaguirre, et al.
Diagnostic criteria for polycystic ovary syndrome and ovarian morphology in women with type 1 diabetes mellitus.
J Clin Endocrinol Metab, 91 (2006), pp. 2250-2256
[13.]
B. Klinger, S. Anin, A. Silbergeld, R. Eshet, Z. Laron.
Development of hyperandrogenism during treatment with insulin-like growth factor-I (IGF-I) in female patients with Laron syndrome.
Clin Endocrinol, 48 (1998), pp. 81-87
[14.]
G.S. Hotamisligil, N.S. Shargill, B.M. Spiegelman.
Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.
Science, 259 (1993), pp. 87-91
[15.]
K.F. Roby, P.F. Terranova.
Effects of tumor necrosis factor-alpha in vitro on steroidogenesis of healthy and atretic follicles of the rat: theca as a target.
Endocrinology, 126 (1990), pp. 2711-2718
[16.]
R.Z. Spaczynski, A. Arici, A.J. Duleba.
Tumor necrosis factor-alpha stimulates proliferation of rat ovarian theca-interstitial cells.
Biol Reprod, 61 (1999), pp. 993-998
[17.]
A.J. Morales, G.A. Laughlin, T. Butzow, H. Maheshwari, G. Baumann, S.S. Yen.
Insulin, somatotropic, and luteinizing hormone axes in lean and obese women with polycystic ovary syndrome: common and distinct features.
J Clin Endocrinol Metab, 81 (1996), pp. 2854-2864
[18.]
G.A. Burghen, J.R. Givens, A.E. Kitabchi.
Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease.
J Clin Endocrinol Metab, 50 (1980), pp. 113-116
[19.]
C.M. DeUgarte, A.A. Bartolucci, R. Azziz.
Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment.
Fertil Steril, 83 (2005), pp. 1454-1460
[20.]
H.F. Escobar-Morreale, J.I. Botella-Carretero, F. Álvarez-Blasco, J. Sancho, J.L. San Millán.
The polycystic ovary syndrome associated with morbid obesity may resolve after weight loss induced by bariatric surgery.
J Clin Endocrinol Metab, 90 (2005), pp. 6364-6369
[21.]
J.C. Lovejoy, G.A. Bray, M.O. Bourgeois, R. Macchiavelli, J.C. Rood, C. Greeson, et al.
Exogenous androgens influence body composition and regional body fat distribution in obese postmenopausal women—a clinical research center study.
J Clin Endocrinol Metab, 81 (1996), pp. 2198-2203
[22.]
J.M. Elbers, H. Asscheman, J.C. Seidell, J.A. Megens, L.J. Gooren.
Long-term testosterone administration increases visceral fat in female to male transsexuals.
J Clin Endocrinol Metab, 82 (1997), pp. 2044-2047
[23.]
C. Nilsson, M. Niklasson, E. Eriksson, P. Bjorntorp, A. Holmang.
Imprinting of female offspring with testosterone results in insulin resistance and changes in body fat distribution at adult age in rats.
J Clin Invest, 101 (1998), pp. 74-78
[24.]
J.R. Eisner, D.A. Dumesic, J.W. Kemnitz, R.J. Colman, D.H. Abbott.
Increased adiposity in female rhesus monkeys exposed to androgen excess during early gestation.
Obes Res, 11 (2003), pp. 279-286
[25.]
S.E. Recabarren, V. Padmanabhan, E. Codner, A. Lobos, C. Durán, M. Vidal, et al.
Postnatal developmental consequences of altered insulin sensitivity in female sheep treated prenatally with testosterone.
Am J Physiol-Endocrinol Metabol, 289 (2005), pp. E801-E806
[26.]
C.M. Bruns, S.T. Baum, R.J. Colman, J.R. Eisner, J.W. Kemnitz, R. Weindruch, et al.
Insulin resistance and impaired insulin secretion in prenatally androgenized male rhesus monkeys.
J Clin Endocrinol Metab, 89 (2004), pp. 6218-6223
[27.]
N. Xita, A. Tsatsoulis.
Fetal programming of polycystic ovary syndrome by androgen excess: evidence from experimental, clinical and genetic association studies.
J Clin Endocrinol Metab, 91 (2006), pp. 1660-1669
[28.]
S. Franks, M.I. McCarthy, K. Hardy.
Development of polycystic ovary syndrome: involvement of genetic and environmental factors.
Int J Androl, 29 (2006), pp. 278-285
[29.]
H.F. Escobar-Morreale, G. Villuendas, J.I. Botella-Carretero, F. Álvarez-Blasco, R. Sanchón, M. Luque-Ramírez, et al.
Adiponectin and resistin in PCOS: a clinical, biochemical and molecular genetic study.
Hum Reprod, (2006),
[30.]
A. Gambineri, C. Pelusi, S. Genghini, A.M. Morselli-Labate, M. Cacciari, U. Pagotto, et al.
Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome.
Clin Endocrinol (Oxf), 60 (2004), pp. 241-249
[31.]
L. Ibánez, C. Valls, A. Ferrer, K. Ong, D.B. Dunger, F. De Zegher.
Additive effects of insulin-sensitizing and anti-androgen treatment in young, nonobese women with hyperinsulinism, hyperandrogenism, dyslipidemia, and anovulation.
J Clin Endocrinol Metab, 87 (2002), pp. 2870-2874
[32.]
H.E. Cooper, W.N. Spellacy, K.A. Prem, W.D. Cohen.
Hereditary factors in the Stein-Leventhal syndrome.
Am J Obstet Gynecol, 100 (1968), pp. 371-387
[33.]
R.S. Wilroy Jr, J.R. Givens, W.L. Wiser, S.A. Coleman, R.N. Andersen, R.L. Summitt.
Hyperthecosis: an inheritable form of polycystic ovarian disease.
Birth Defects Orig Artic Ser, 11 (1975), pp. 81-85
[35.]
J.R. Givens.
Familial polycystic ovarian disease.
Endocrinol Metab Clin North Am, 17 (1988), pp. 771-783
[36.]
D. Ferriman, A.W. Purdie.
The inheritance of polycystic ovarian disease and a possible relationship to premature balding.
Clin Endocrinol (Oxf), 11 (1979), pp. 291-300
[37.]
W.M. Hague, J. Adams, S.T. Reeders, T.E. Peto, HS. Jacobs.
Familial polycystic ovaries: a genetic disease?.
Clin Endocrinol (Oxf), 29 (1988), pp. 593-605
[38.]
O. Lundle, P. Magnus, L. Sandvik, S. Hoglo.
Familial clustering in the polycystic ovarian syndrome.
Gynecol Obstet Invest, 28 (1989), pp. 23-30
[39.]
A.H. Carey, K.L. Chan, F. Short, D. White, R. Williamson, S. Franks.
Evidence for a single gene effect causing polycystic ovaries and male pattern baldness.
Clin Endocrinol (Oxf), 38 (1993), pp. 653-658
[40.]
S. Jahanfar, J.A. Eden, P. Warren, M. Seppala, T.V. Nguyen.
A twin study of polycystic ovary syndrome.
Fertil Steril, 63 (1995), pp. 478-486
[41.]
S. Jahanfar, J.A. Eden, T. Nguyen, X.L. Wang, D.E. Wilcken.
A twin study of polycystic ovary syndrome and lipids.
Gynecol Endocrinol, 11 (1997), pp. 111-117
[42.]
R.J. Norman, S. Masters, W. Hague.
Hyperinsulinemia is common in family members of women with polycystic ovary syndrome.
Fertil Steril, 66 (1996), pp. 942-947
[43.]
R.S. Legro, D. Driscoll, J.F. Strauss, J. Fox, A. Dunaif.
Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome.
Proc Natl Acad Sci USA, 95 (1998), pp. 14956-14960
[44.]
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 (2002), pp. 2134-2138
[45.]
R.S. Legro, R. Bentley-Lewis, D. Driscoll, S.C. Wang, A. Dunaif.
Insulin resistance in the sisters of women with polycystic ovary syndrome: association with hyperandrogenemia rather than menstrual irregularity.
J Clin Endocrinol Metab, 87 (2002), pp. 2128-2133
[46.]
R. Azziz, M.D. Kashar-Miller.
Family history as a risk factor for the polycystic ovary syndrome.
J Pediatr Endocrinol Metab, 13 (2000), pp. 1303-1306
[47.]
M.D. Kahsar-Miller, C. Nixon, L.R. Boots, R.C. Go, R. Azziz.
Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS.
Fertil Steril, 75 (2001), pp. 53-58
[48.]
W. Mao, M. Li, Y. Zhao.
Study on parents phenotypes in women with polycystic ovary syndrome.
Zhonghua Fu Chan Ke Za Zhi, 35 (2000), pp. 583-585
[49.]
B.O. Yildiz, H. Yarali, H. Oguz, M. Bayraktar.
Glucose intolerance, insulin resistance, and hyperandrogenemia in first degree relatives of women with polycystic ovary syndrome.
J Clin Endocrinol Metab, 88 (2003), pp. 2031-2036
[50.]
H.F. Escobar-Morreale, M. Luque-Ramírez, J.L. San Millán.
The moleculargenetic basis of functional hyperandrogenism and the polycystic ovary syndrome.
Endocr Rev, 26 (2005), pp. 251-282
[51.]
R.S. Legro, R. Spielman, M. Urbanek, D. Driscoll, J.F. Strauss 3rd, A. Dunaif.
Phenotype and genotype in polycystic ovary syndrome.
Recent Prog Horm Res, 53 (1998), pp. 217-256
[53.]
L. Ibánez, F. De Zegher, N. Potau.
Premature pubarche, ovarian hyperandrogenism, hyperinsulinism and the polycystic ovary syndrome: from a complex constellation to a simple sequence of prenatal onset.
J Endocrinol Invest, 21 (1998), pp. 558-566
[54.]
T. Sir-Petermann, C. Hitchsfeld, M. Maliqueo, E. Codner, B. Echiburu, R. Gazitua, et al.
Birth weight in offspring of mothers with polycystic ovarian syndrome.
Hum Reprod, 20 (2005), pp. 2122-2126
[55.]
M. Hara, S.Y. Alcoser, A. Qaadir, K.K. Beiswenger, N.J. Cox, D.A. Ehrmann.
Insulin resistance is attenuated in women with polycystic ovary syndrome with the Pro(12)Ala polymorphism in the PPARgamma gene.
J Clin Endocrinol Metab, 87 (2002), pp. 772-775
[56.]
D.A. Ehrmann, X. Tang, I. Yoshiuchi, N.J. Cox, G.I. Bell.
Relationship of insulin receptor substrate-1 and -2 genotypes to phenotypic features of polycystic ovary syndrome.
J Clin Endocrinol Metab, 87 (2002), pp. 4297-4300
[57.]
S.A. El Mkadem, C. Lautier, F. Macari, N. Molinari, P. Lefèbvre, E. Renard, et al.
Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome.
Diabetes, 50 (2001), pp. 2164-2168
[58.]
G. Villuendas, J.I. Botella-Carretero, B. Roldán, J. Sancho, H.F. Escobar-Morreale, J.L. San Millán.
Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls.
Hum Reprod, 20 (2005), pp. 3184-3191
[60.]
D.J. Barker, C. Osmond, J. Golding, D. Kuh, M.E. Wadsworth.
Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease.
BMJ, 298 (1989), pp. 564-567
[61.]
D.J. Barker, A.R. Bull, C. Osmond, S.J. Simmonds.
Fetal and placental size and risk of hypertension in adult life.
BMJ, 301 (1990), pp. 259-262
[62.]
A. Gambineri, C. Pelusi, V. Vicennati, U. Pagotto, R. Pasquali.
Obesity and the polycystic ovary syndrome.
Int J Obes Relat Metab Disord, 26 (2002), pp. 883-896
[63.]
Álvarez-Blasco F, Botella-Carretero JI, Luque-Ramírez M, Sanchón R, San Millán JL, Sancho J, et al. Estudio prospectivo de la prevalencia del síndrome de ovario poliquístico en mujeres premenopáusicas con sobrepeso u obesidad. En: 48.° Congreso de la Sociedad Española de Endocrinología y Nutrición; 2006; Sevilla. Endocrinol Nutr. 2006;76.
[64.]
J.I. Isojarvi, T.J. Laatikainen, A.J. Pakarinen, K.T. Juntunen, V.V. Myllyla.
Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy.
N Engl J Med, 329 (1993), pp. 1383-1388
[65.]
M.J. Morrell, J. Isojarvi, A.E. Taylor, M. Dam, R. Ayala, G. Gómez, et al.
Higher androgens and weight gain with valproate compared with lamotrigine for epilepsy.
Epilepsy Res, 54 (2003), pp. 189-199
[66.]
L. Bilo, R. Meo, R. Valentino, C. Di Carlo, S. Striano, C. Nappi.
Characterization of reproductive endocrine disorders in women with epilepsy. [see comment].
J Clin Endocrinol Metab, 86 (2001), pp. 2950-2956
[67.]
V.L. Nelson-DeGrave, J.K. Wickenheisser, J.E. Cockrell, J.R. Wood, R.S. Legro, J.F. Strauss 3rd, et al.
Valproate potentiates androgen biosynthesis in human ovarian theca cells.
Endocrinology, 145 (2004), pp. 799-808
[68.]
J.R. Wood, V.L. Nelson-Degrave, E. Jansen, J.M. McAllister, S. Mosselman, J.F. Strauss 3rd.
Valproate-induced alterations in human theca cell gene expression: clues to the association between valproate use and metabolic side effects.
Physiol Genomics, 20 (2005), pp. 233-243
[69.]
E. Codner, D. Mook-Kanamori, R.A. Bazaes, N. Unanue, H. Sovino, F. Ugarte, et al.
Ovarian function during puberty in girls with type 1 diabetes mellitus: response to leuprolide.
J Clin Endocrinol Metab, 90 (2005), pp. 3939-3945
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