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A Síndrome do Ovário Policístico e as Doenças Cardiovasculares: Uma Porta Ainda Aberta

Palavras-chave
Síndrome do Ovário Policístico; Doenças Cardiovasculares/fisiopatologia; Obesidade/metabolismo; Sistema Nervoso Autônomo/anormalidades; Barorreflexo

Esta edição dos Arquivos Brasileiros de Cardiologia (ABC Cardiol) traz o artigo “Mulheres com Síndrome do Ovário Policístico Apresentam menor Sensibilidade Barorreflexa, a Qual Pode Estar Associada ao Aumento da Gordura Corporal”, de Philbois, SV et al., que nos desperta para essa condição clínica tão prevalente em nosso meio e seus muitos aspectos relacionados ao cardiometabolismo, à neuroregulação e ao risco cardiovascular.11 Philbois SV, Gastaldi AC, Facioli TP, Felix ACS, Reis RM, Fares TH, et al. Women with polycystic ovarian syndrome exhibit reduced baroreflex sensitivity that may be associated with increased body fat. Arq Bras Cardiol. 2019; 112(4):424-429.

A síndrome do ovário policístico (SOP) é o distúrbio endócrino mais comum entre as mulheres em idade reprodutiva,22 Yau TT, Ng NY, Cheung LP, Ma RC. Polycystic ovary syndrome: a common reproductive syndrome with long-term metabolic consequences. Hong Kong Med J. 2017;23(6):622-34. com prevalência estimada entre 6 e 10% desta população.33 Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745-9.) De acordo com os Critérios de Rotterdam, a SOP é diagnosticada na presença de pelo menos dois dos três critérios: distúrbios menstruais ou amenorréia com falta crônica de ovulação, características clínicas e/ou bioquímicas do hiperandrogenismo e a presença de ovários policísticos na ultrassonografia após a exclusão de outras desordens endócrinas.44 Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. The androgen excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009;91(2):456-88. Geralmente, a SOP tem sido considerada como um distúrbio reprodutivo, contudo, é também uma condição de risco significativamente aumentado para distúrbios cardiometabólicos.22 Yau TT, Ng NY, Cheung LP, Ma RC. Polycystic ovary syndrome: a common reproductive syndrome with long-term metabolic consequences. Hong Kong Med J. 2017;23(6):622-34. O impacto sobre a reprodução é predominante durante os anos reprodutivos, enquanto as alterações cardiometabólicas tornam-se preponderantes nos estágios posteriores da vida da mulher.22 Yau TT, Ng NY, Cheung LP, Ma RC. Polycystic ovary syndrome: a common reproductive syndrome with long-term metabolic consequences. Hong Kong Med J. 2017;23(6):622-34.

As mulheres com SOP apresentam maior risco de ocorrência de obesidade, hipertensão arterial, intolerância à glicose, dislipidemia e apneia obstrutiva do sono.55 Sartor BM, Dickey RP. Polycystic ovarian syndrome and the metabolic syndrome. Am J Med Sci. 2005;330(6):336-42. A obesidade está presente em cerca de 50%,44 Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. The androgen excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009;91(2):456-88. a resistência à insulina ocorre em 60% a 95%,66 Colilla S, Cox NJ, Ehrmann DA. Heritability of insulin secretion and insulin action in women with polycystic ovary syndrome and their first degree relatives. J Clin Endocrinol Metab. 2001;86(5):2027-31. levando à intolerância à glicose em 31% a 35%77 Legro RS, Gnatuk CL, Kunselman AR, Dunaif A. Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study. J Clin Endocrinol Metab. 2005;90(6):3236-42. e diabetes melito tipo 2 em 7,5% a 20%88 Boudreaux MY, Talbott EO, Kip KE, Brooks MM, Witchel SF. Risk of T2DM and impaired fasting glucose among PCOS subjects: results of an 8-year follow-up. Curr Diab Rep. 2006;6(1):77-83. dessas mulheres. Contudo, a dislipidemia é a anormalidade metabólica mais comum na SOP, apresentando-se geralmente com o fenótipo de baixos níveis de lipoproteína de alta densidade (HDL) e altas concentrações de triglicérides, consistente com a resistência à insulina, podendo também cursar com aumento da lipoproteína de baixa densidade (LDL).77 Legro RS, Gnatuk CL, Kunselman AR, Dunaif A. Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study. J Clin Endocrinol Metab. 2005;90(6):3236-42.,88 Boudreaux MY, Talbott EO, Kip KE, Brooks MM, Witchel SF. Risk of T2DM and impaired fasting glucose among PCOS subjects: results of an 8-year follow-up. Curr Diab Rep. 2006;6(1):77-83.

A prevalência de doença hepática gordurosa não alcoólica e a apneia obstrutiva do sono estão também elevadas em mulheres com SOP. Mesmo depois de controlar o índice de massa corporal (IMC), as mulheres com SOP ainda são trinta vezes mais propensas a ter distúrbios respiratórios do sono.99 Vgontzas AN, Legro RS, Bixler EO, Grayev A, Kales A, Chrousos GP. Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance. J Clin Endocrinol Metab. 2001;86(2):517-20.,1010 Gopal M, Duntley S, Uhles M, Attarian H. The role of obesity in the increased prevalence of obstructive sleep apnea syndrome in patients with polycystic ovarian syndrome. Sleep Med. 2002;3(5):401-4. Marcadores sub-clínicos de doença cardiovascular, como o aumento da espessura íntima-média da carótida,1111 Luque-Ramirez M, Mendieta-Azcona C, Alvarez-Blasco F, Escobar-Morreale HF. Androgen excess is associated with the increased carotid intima-media thickness observed in young women with polycystic ovary syndrome. Hum Reprod. 2007;22(12):3197-203. maior calcificação das artérias coronárias,1212 Talbott EO, Zborowski JV, Rager JR, Boudreaux MY, Edmundowicz DA, Guzick DS. Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004;89(11):5454-61. e mais elevadas concentrações séricas de proteína C-reativa1313 Boulman N, Levy Y, Leiba R, Shachar S, Linn R, Zinder O, et al. Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease. J Clin Endocrinol Metab. 2004;89(5):2160-5. têm sido também associados à SOP.

Há evidências de que o sistema nervoso autônomo (SNA) desempenha um papel importante na regulação da fisiologia ovariana.1414 Aguado LI. Role of the central and peripheral nervous system in the ovarian function. J Microsc Res Tech. 2002;59(6):462-73. Estima-se que uma maior atividade simpática em mulheres com SOP possa estar associada às suas características hormonais e metabólicas.1515 Sverrisdottir YB, Mogren T, Kataoka J, Janson PO, Stener-Victorin E. Is polycystic ovary syndrome associated with high sympathetic nerve activity and size at birth? Am J Physiol Endocrinol Metab. 2008;294(3):E576-81. Embora a disfunção autonômica seja considerada um preditor de eventos cardiovasculares e mortalidade,1616 Tsuji H, Larson MG, Venditti Jr FJ, Manders ES, Evans JC, Feldman CL, et al. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation. 1996;94(11):2850-5. há limitadas evidências sobre alterações neste parâmetro fisiopatológico entre mulheres com SOP.

Um estudo demonstrou que ratos com ovários policísticos induzidos por estrogênio tiveram uma alta captação de norepinefrina, e um alto grau de liberação do neurotransmissor com a estimulação elétrica ovariana.1717 Lara HE, Ferruz JL, Luza S, Bustamante DA, Borges Y, Ojeda SR. Activation of ovarian sympathetic nerves in polycystic ovary syndrome. Endocrinology. 1993;133(6):2690-5. Yildirir et al. analisaram as variações da frequência cardíaca (VFC) em mulheres com SOP demonstrando um aumento significativo no componente de baixa frequência do espectro e uma diminuição no componente de alta frequência em relação ao grupo controle.1818 Yildirir A, Aybar F, Kabakci G, Yarali H, Oto A. Heart rate variability in young women with polycystic ovary syndrome. Ann Noninvasive Electrocardiol. 2006;11(4):306-12. Tekin et al. mostraram uma diminuição na recuperação da frequência cardíaca e da pressão arterial após esforço em comparação com controles.1919 Tekin G, Tekin A, Kilicarslan EB, Haydardedeoglu B, Katircibasi T, Kocum T, et al. Altered autonomic neural control of the cardiovascular system in patients with polycystic ovary syndrome. Int J Cardiol. 2008;130(1):49-55. Drag et al. demonstraram disfunção dos componentes simpático e parassimpático do SNA em mulheres com SOP utilizando eletromiografia.2020 Dag ZO, Alpua M, Turkel Y, Isik Y Autonomic dysfunction in patients with polycystic ovary syndrome. Taiwan J Obstet Gynecol. 2015;54(4):381-4. Os autores não encontraram associação entre o aumento de peso, avaliado pelo IMC, e as alterações nos testes de resposta simpática da pele e a variação do intervalo R-R, parâmetro da resposta parassimpática, atribuindo ao hiperandrogenismo e à resistência à insulina a provável causa da disfunção.2020 Dag ZO, Alpua M, Turkel Y, Isik Y Autonomic dysfunction in patients with polycystic ovary syndrome. Taiwan J Obstet Gynecol. 2015;54(4):381-4. Utilizando a análise espectral da VFC, o estudo de Philbois SV et al., publicado neste número dos ABC Cardiol, não encontrou alterações no controle autonômico cardiovascular em mulheres com SOP.11 Philbois SV, Gastaldi AC, Facioli TP, Felix ACS, Reis RM, Fares TH, et al. Women with polycystic ovarian syndrome exhibit reduced baroreflex sensitivity that may be associated with increased body fat. Arq Bras Cardiol. 2019; 112(4):424-429. Contudo, os autores correlacionam a dimunição da sensibilidade do barorreflexo, uma importante medida da função autonômica cardiovascular, assim como a atenuação dos valores da VFC, com o aumento da gordura corporal em mulheres com SOP.11 Philbois SV, Gastaldi AC, Facioli TP, Felix ACS, Reis RM, Fares TH, et al. Women with polycystic ovarian syndrome exhibit reduced baroreflex sensitivity that may be associated with increased body fat. Arq Bras Cardiol. 2019; 112(4):424-429.

Embora os resultados dos estudos sejam conflitantes, conclui-se que a resistência à insulina, o hiperandrogenismo e a obesidade possam resultar em disfunção autonômica na SOP.11 Philbois SV, Gastaldi AC, Facioli TP, Felix ACS, Reis RM, Fares TH, et al. Women with polycystic ovarian syndrome exhibit reduced baroreflex sensitivity that may be associated with increased body fat. Arq Bras Cardiol. 2019; 112(4):424-429.,1717 Lara HE, Ferruz JL, Luza S, Bustamante DA, Borges Y, Ojeda SR. Activation of ovarian sympathetic nerves in polycystic ovary syndrome. Endocrinology. 1993;133(6):2690-5.

18 Yildirir A, Aybar F, Kabakci G, Yarali H, Oto A. Heart rate variability in young women with polycystic ovary syndrome. Ann Noninvasive Electrocardiol. 2006;11(4):306-12.

19 Tekin G, Tekin A, Kilicarslan EB, Haydardedeoglu B, Katircibasi T, Kocum T, et al. Altered autonomic neural control of the cardiovascular system in patients with polycystic ovary syndrome. Int J Cardiol. 2008;130(1):49-55.

20 Dag ZO, Alpua M, Turkel Y, Isik Y Autonomic dysfunction in patients with polycystic ovary syndrome. Taiwan J Obstet Gynecol. 2015;54(4):381-4.
-2121 Di Domenico K, Wiltgen D, Nickel FJ, Magalhães JA, Moraes RS, Spritzer PM. Cardiac autonomic modulation in polycystic ovary syndrome: does the phenotype matter? Fertil Steril. 2013;99(1):286-92. Essa desregulação autonômica é reconhecida como fator de pior prognóstico,1616 Tsuji H, Larson MG, Venditti Jr FJ, Manders ES, Evans JC, Feldman CL, et al. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation. 1996;94(11):2850-5.,2222 Thayer JF, Yamamoto SS, Brosschot JF. The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. Int J Cardiol. 2010;141(2):122-31. podendo se somar à plêiade de alterações metabólicas,55 Sartor BM, Dickey RP. Polycystic ovarian syndrome and the metabolic syndrome. Am J Med Sci. 2005;330(6):336-42.

6 Colilla S, Cox NJ, Ehrmann DA. Heritability of insulin secretion and insulin action in women with polycystic ovary syndrome and their first degree relatives. J Clin Endocrinol Metab. 2001;86(5):2027-31.

7 Legro RS, Gnatuk CL, Kunselman AR, Dunaif A. Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study. J Clin Endocrinol Metab. 2005;90(6):3236-42.
-88 Boudreaux MY, Talbott EO, Kip KE, Brooks MM, Witchel SF. Risk of T2DM and impaired fasting glucose among PCOS subjects: results of an 8-year follow-up. Curr Diab Rep. 2006;6(1):77-83. clínicas99 Vgontzas AN, Legro RS, Bixler EO, Grayev A, Kales A, Chrousos GP. Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance. J Clin Endocrinol Metab. 2001;86(2):517-20.,1010 Gopal M, Duntley S, Uhles M, Attarian H. The role of obesity in the increased prevalence of obstructive sleep apnea syndrome in patients with polycystic ovarian syndrome. Sleep Med. 2002;3(5):401-4. e estruturais1111 Luque-Ramirez M, Mendieta-Azcona C, Alvarez-Blasco F, Escobar-Morreale HF. Androgen excess is associated with the increased carotid intima-media thickness observed in young women with polycystic ovary syndrome. Hum Reprod. 2007;22(12):3197-203.

12 Talbott EO, Zborowski JV, Rager JR, Boudreaux MY, Edmundowicz DA, Guzick DS. Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004;89(11):5454-61.
-1313 Boulman N, Levy Y, Leiba R, Shachar S, Linn R, Zinder O, et al. Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease. J Clin Endocrinol Metab. 2004;89(5):2160-5. relacionadas à síndrome na determinação de um maior risco cardiovascular. Apesar de todas essas demonstrações de disfunções subclínicas, faltam ainda estudos conclusivos de acompanhamento dessas mulheres em longo prazo para demonstrar evidências definitivas do aumento de desfechos clínicos cardiovasculares associados à SOP.2323 Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E, et al. American Association Of Clinical Endocrinologists, American College Of Endocrinology, and Androgen Excess and Pcos Society Disease State Clinical Review: guide to the best practices in the evaluation and treatment of Polycystic Ovary Syndrome - part 2. Endocr Pract. 2015;21(12):1415-26.

  • Minieditorial referente ao artigo: Mulheres com Síndrome do Ovário Policístico Apresentam menor Sensibilidade Barorreflexa, a Qual Pode Estar Associada ao Aumento da Gordura Corporal

References

  • 1
    Philbois SV, Gastaldi AC, Facioli TP, Felix ACS, Reis RM, Fares TH, et al. Women with polycystic ovarian syndrome exhibit reduced baroreflex sensitivity that may be associated with increased body fat. Arq Bras Cardiol. 2019; 112(4):424-429.
  • 2
    Yau TT, Ng NY, Cheung LP, Ma RC. Polycystic ovary syndrome: a common reproductive syndrome with long-term metabolic consequences. Hong Kong Med J. 2017;23(6):622-34.
  • 3
    Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745-9.
  • 4
    Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. The androgen excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009;91(2):456-88.
  • 5
    Sartor BM, Dickey RP. Polycystic ovarian syndrome and the metabolic syndrome. Am J Med Sci. 2005;330(6):336-42.
  • 6
    Colilla S, Cox NJ, Ehrmann DA. Heritability of insulin secretion and insulin action in women with polycystic ovary syndrome and their first degree relatives. J Clin Endocrinol Metab. 2001;86(5):2027-31.
  • 7
    Legro RS, Gnatuk CL, Kunselman AR, Dunaif A. Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study. J Clin Endocrinol Metab. 2005;90(6):3236-42.
  • 8
    Boudreaux MY, Talbott EO, Kip KE, Brooks MM, Witchel SF. Risk of T2DM and impaired fasting glucose among PCOS subjects: results of an 8-year follow-up. Curr Diab Rep. 2006;6(1):77-83.
  • 9
    Vgontzas AN, Legro RS, Bixler EO, Grayev A, Kales A, Chrousos GP. Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance. J Clin Endocrinol Metab. 2001;86(2):517-20.
  • 10
    Gopal M, Duntley S, Uhles M, Attarian H. The role of obesity in the increased prevalence of obstructive sleep apnea syndrome in patients with polycystic ovarian syndrome. Sleep Med. 2002;3(5):401-4.
  • 11
    Luque-Ramirez M, Mendieta-Azcona C, Alvarez-Blasco F, Escobar-Morreale HF. Androgen excess is associated with the increased carotid intima-media thickness observed in young women with polycystic ovary syndrome. Hum Reprod. 2007;22(12):3197-203.
  • 12
    Talbott EO, Zborowski JV, Rager JR, Boudreaux MY, Edmundowicz DA, Guzick DS. Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004;89(11):5454-61.
  • 13
    Boulman N, Levy Y, Leiba R, Shachar S, Linn R, Zinder O, et al. Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease. J Clin Endocrinol Metab. 2004;89(5):2160-5.
  • 14
    Aguado LI. Role of the central and peripheral nervous system in the ovarian function. J Microsc Res Tech. 2002;59(6):462-73.
  • 15
    Sverrisdottir YB, Mogren T, Kataoka J, Janson PO, Stener-Victorin E. Is polycystic ovary syndrome associated with high sympathetic nerve activity and size at birth? Am J Physiol Endocrinol Metab. 2008;294(3):E576-81.
  • 16
    Tsuji H, Larson MG, Venditti Jr FJ, Manders ES, Evans JC, Feldman CL, et al. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation. 1996;94(11):2850-5.
  • 17
    Lara HE, Ferruz JL, Luza S, Bustamante DA, Borges Y, Ojeda SR. Activation of ovarian sympathetic nerves in polycystic ovary syndrome. Endocrinology. 1993;133(6):2690-5.
  • 18
    Yildirir A, Aybar F, Kabakci G, Yarali H, Oto A. Heart rate variability in young women with polycystic ovary syndrome. Ann Noninvasive Electrocardiol. 2006;11(4):306-12.
  • 19
    Tekin G, Tekin A, Kilicarslan EB, Haydardedeoglu B, Katircibasi T, Kocum T, et al. Altered autonomic neural control of the cardiovascular system in patients with polycystic ovary syndrome. Int J Cardiol. 2008;130(1):49-55.
  • 20
    Dag ZO, Alpua M, Turkel Y, Isik Y Autonomic dysfunction in patients with polycystic ovary syndrome. Taiwan J Obstet Gynecol. 2015;54(4):381-4.
  • 21
    Di Domenico K, Wiltgen D, Nickel FJ, Magalhães JA, Moraes RS, Spritzer PM. Cardiac autonomic modulation in polycystic ovary syndrome: does the phenotype matter? Fertil Steril. 2013;99(1):286-92.
  • 22
    Thayer JF, Yamamoto SS, Brosschot JF. The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. Int J Cardiol. 2010;141(2):122-31.
  • 23
    Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E, et al. American Association Of Clinical Endocrinologists, American College Of Endocrinology, and Androgen Excess and Pcos Society Disease State Clinical Review: guide to the best practices in the evaluation and treatment of Polycystic Ovary Syndrome - part 2. Endocr Pract. 2015;21(12):1415-26.

Datas de Publicação

  • Publicação nesta coleção
    15 Abr 2019
  • Data do Fascículo
    Abr 2019
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