Advertisement

Polycystic Ovary Syndrome-Related Risks in Postmenopausal Women

  • Panagiotis Anagnostis
  • Stavroula A. Paschou
  • Irene Lambrinoudaki
  • Dimitrios G. Goulis
Chapter

Abstract

Polycystic ovarian syndrome (PCOS) is associated with cardiovascular disease (CVD) risk factors, such as impaired glucose metabolism dyslipidaemia and arterial hypertension, predisposing to CVD in post-reproductive life. Despite the clustering of these risk factors, an association between PCOS and CVD has not been established in postmenopausal women. Relevant studies are characterized by methodological factors, such as heterogeneity in both PCOS and CVD definitions in postmenopausal women, study design, small sample size, amelioration of menstruation with ageing, and insufficient follow-up duration. Well-designed, high-quality prospective studies are needed to establish or exclude an effect of PCOS on type 2 diabetes mellitus (T2DM) and CVD risk in postmenopausal women, irrespective of obesity, ageing or menopause per se. Finally, PCOS may be associated with an increased risk of endometrial cancer; such an association has not been shown with other types of gynaecological cancer, such as breast or ovarian cancer.

Keywords

Polycystic ovarian syndrome (PCOS) Postmenopausal women Diabetes Cardiovascular disease Cancer 

Notes

Competing Interest

None to declare.

Funding: None.

References

  1. 1.
    Anagnostis P, Tarlatzis BC, Kauffman RP. Polycystic ovarian syndrome (PCOS): long-term metabolic consequences. Metabolism. 2018;86:33–43.PubMedCrossRefGoogle Scholar
  2. 2.
    March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2010;25(2):544–51.PubMedCrossRefGoogle Scholar
  3. 3.
    Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, Welt CK, Endocrine S. Diagnosis and treatment of polycystic ovary syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(12):4565–92.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Paschou SA, Anagnostis P, Goulis DG, Lambrinoudaki I. Androgen excess and post-reproductive health. Maturitas. 2018;115:115–6.CrossRefGoogle Scholar
  5. 5.
    Randeva HS, Tan BK, Weickert MO, Lois K, Nestler JE, Sattar N, Lehnert H. Cardiometabolic aspects of the polycystic ovary syndrome. Endocr Rev. 2012;33(5):812–41.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Livadas S, Kollias A, Panidis D, Diamanti-Kandarakis E. Diverse impacts of aging on insulin resistance in lean and obese women with polycystic ovary syndrome: evidence from 1345 women with the syndrome. Eur J Endocrinol. 2014;171(3):301–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2010;16(4):347–63.PubMedCrossRefGoogle Scholar
  8. 8.
    Cibula D, Cifkova R, Fanta M, Poledne R, Zivny J, Skibova J. Increased risk of non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease in perimenopausal women with a history of the polycystic ovary syndrome. Hum Reprod. 2000;15(4):785–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Shaw LJ, Bairey Merz CN, Azziz R, Stanczyk FZ, Sopko G, Braunstein GD, Kelsey SF, Kip KE, Cooper-Dehoff RM, Johnson BD, Vaccarino V, Reis SE, Bittner V, Hodgson TK, Rogers W, Pepine CJ. Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from the National Institutes of Health—National Heart, Lung, and Blood Institute sponsored Women’s ischemia syndrome evaluation. J Clin Endocrinol Metab. 2008;93(4):1276–84.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Mani H, Levy MJ, Davies MJ, Morris DH, Gray LJ, Bankart J, Blackledge H, Khunti K, Howlett TA. Diabetes and cardiovascular events in women with polycystic ovary syndrome: a 20-year retrospective cohort study. Clin Endocrinol. 2013;78(6):926–34.CrossRefGoogle Scholar
  11. 11.
    Merz CN, Shaw LJ, Azziz R, Stanczyk FZ, Sopko G, Braunstein GD, Kelsey SF, Kip KE, Cooper-DeHoff RM, Johnson BD, Vaccarino V, Reis SE, Bittner V, Hodgson TK, Rogers W, Pepine CJ. Cardiovascular disease and 10-year mortality in postmenopausal women with clinical features of polycystic ovary syndrome. J Womens Health (Larchmt). 2016;25(9):875–81.CrossRefGoogle Scholar
  12. 12.
    Meun C, Franco OH, Dhana K, Jaspers L, Muka T, Louwers Y, Ikram MA, Fauser B, Kavousi M, Laven JSE. High androgens in postmenopausal women and the risk for atherosclerosis and cardiovascular disease: the Rotterdam study. J Clin Endocrinol Metab. 2018;103(4):1622–30.PubMedCrossRefGoogle Scholar
  13. 13.
    Paschou SA, Anagnostis P, Pavlou DI, Vryonidou A, Goulis DG, Lambrinoudaki I. Diabetes in menopause: risks and management. Curr Vasc Pharmacol. 2018 Jun 25.  https://doi.org/10.2174/157016111666180625124405.
  14. 14.
    Amiri M, Ramezani Tehrani F, Nahidi F, Kabir A, Azizi F, Carmina E. Effects of oral contraceptives on metabolic profile in women with polycystic ovary syndrome: a meta-analysis comparing products containing cyproterone acetate with third generation progestins. Metabolism. 2017;73:22–35.PubMedCrossRefGoogle Scholar
  15. 15.
    Fruzzetti F, Perini D, Lazzarini V, Parrini D, Gambacciani M, Genazzani AR. Comparison of effects of 3 mg drospirenone plus 20 mug ethinyl estradiol alone or combined with metformin or cyproterone acetate on classic metabolic cardiovascular risk factors in nonobese women with polycystic ovary syndrome. Fertil Steril. 2010;94(5):1793–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Komukai K, Mochizuki S, Yoshimura M. Gender and the renin-angiotensin-aldosterone system. Fundam Clin Pharmacol. 2010;24(6):687–98.PubMedCrossRefGoogle Scholar
  17. 17.
    Pinola P, Puukka K, Piltonen TT, Puurunen J, Vanky E, Sundstrom-Poromaa I, Stener-Victorin E, Linden Hirschberg A, Ravn P, Skovsager Andersen M, Glintborg D, Mellembakken JR, Ruokonen A, Tapanainen JS, Morin-Papunen LC. Normo- and hyperandrogenic women with polycystic ovary syndrome exhibit an adverse metabolic profile through life. Fertil Steril. 2017;107(3):788–795.e2.PubMedCrossRefGoogle Scholar
  18. 18.
    Schmidt J, Landin-Wilhelmsen K, Brannstrom M, Dahlgren E. Cardiovascular disease and risk factors in PCOS women of postmenopausal age: a 21-year controlled follow-up study. J Clin Endocrinol Metab. 2011;96(12):3794–803.PubMedCrossRefGoogle Scholar
  19. 19.
    Armeni E, Stamatelopoulos K, Rizos D, Georgiopoulos G, Kazani M, Kazani A, Kolyviras A, Stellos K, Panoulis K, Alexandrou A, Creatsa M, Papamichael C, Lambrinoudaki I. Arterial stiffness is increased in asymptomatic nondiabetic postmenopausal women with a polycystic ovary syndrome phenotype. J Hypertens. 2013;31(10):1998–2004.PubMedCrossRefGoogle Scholar
  20. 20.
    Tremollieres FA, Pouilles JM, Cauneille C, Ribot C. Coronary heart disease risk factors and menopause: a study in 1684 French women. Atherosclerosis. 1999;142(2):415–23.PubMedCrossRefGoogle Scholar
  21. 21.
    Dallongeville J, Marecaux N, Isorez D, Zylbergberg G, Fruchart JC, Amouyel P. Multiple coronary heart disease risk factors are associated with menopause and influenced by substitutive hormonal therapy in a cohort of French women. Atherosclerosis. 1995;118(1):123–33.PubMedCrossRefGoogle Scholar
  22. 22.
    Maas AH, Franke HR. Women’s health in menopause with a focus on hypertension. Neth Heart J. 2009;17(2):68–72.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Anagnostis P, Stevenson JC, Crook D, Johnston DG, Godsland IF. Effects of menopause, gender and age on lipids and high-density lipoprotein cholesterol subfractions. Maturitas. 2015;81(1):62–8.CrossRefGoogle Scholar
  24. 24.
    Anagnostis P, Stevenson JC, Crook D, Johnston DG, Godsland IF. Effects of gender, age and menopausal status on serum apolipoprotein concentrations. Clin Endocrinol. 2016;85(5):733–40.CrossRefGoogle Scholar
  25. 25.
    Anagnostis P, Karras S, Lambrinoudaki I, Stevenson JC, Goulis DG. Lipoprotein(a) in postmenopausal women: assessment of cardiovascular risk and therapeutic options. Int J Clin Pract. 2016;70(12):967–77.CrossRefGoogle Scholar
  26. 26.
    Lambrinoudaki I. Cardiovascular risk in postmenopausal women with the polycystic ovary syndrome. Maturitas. 2011;68(1):13–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Iftikhar S, Collazo-Clavell ML, Roger VL, St Sauver J, Brown RD Jr, Cha S, Rhodes DJ. Risk of cardiovascular events in patients with polycystic ovary syndrome. Neth J Med. 2012;70(2):74–80.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Lovejoy JC, Champagne CM, de Jonge L, Xie H, Smith SR. Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes. 2008;32(6):949–58.CrossRefGoogle Scholar
  29. 29.
    Nadal A, Alonso-Magdalena P, Soriano S, Quesada I, Ropero AB. The pancreatic beta-cell as a target of estrogens and xenoestrogens: implications for blood glucose homeostasis and diabetes. Mol Cell Endocrinol. 2009;304(1–2):63–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Lee JS, Hayashi K, Mishra G, Yasui T, Kubota T, Mizunuma H. Independent association between age at natural menopause and hypercholesterolemia, hypertension, and diabetes mellitus: Japan nurses’ health study. J Atheroscler Thromb. 2013;20(2):161–9.PubMedCrossRefGoogle Scholar
  31. 31.
    de Groot PC, Dekkers OM, Romijn JA, Dieben SW, Helmerhorst FM. PCOS, coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysis. Hum Reprod Update. 2011;17(4):495–500.PubMedCrossRefGoogle Scholar
  32. 32.
    Anderson SA, Barry JA, Hardiman PJ. Risk of coronary heart disease and risk of stroke in women with polycystic ovary syndrome: a systematic review and meta-analysis. Int J Cardiol. 2014;176(2):486–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Zhao L, Zhu Z, Lou H, Zhu G, Huang W, Zhang S, Liu F. Polycystic ovary syndrome (PCOS) and the risk of coronary heart disease (CHD): a meta-analysis. Oncotarget. 2016;7(23):33715–21.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Wild S, Pierpoint T, McKeigue P, Jacobs H. Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study. Clin Endocrinol. 2000;52(5):595–600.CrossRefGoogle Scholar
  35. 35.
    Wang ET, Cirillo PM, Vittinghoff E, Bibbins-Domingo K, Cohn BA, Cedars MI. Menstrual irregularity and cardiovascular mortality. J Clin Endocrinol Metab. 2011;96(1):E114–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Solomon CG, Hu FB, Dunaif A, Rich-Edwards JE, Stampfer MJ, Willett WC, Speizer FE, Manson JE. Menstrual cycle irregularity and risk for future cardiovascular disease. J Clin Endocrinol Metab. 2002;87(5):2013–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Krentz AJ, von Muhlen D, Barrett-Connor E. Searching for polycystic ovary syndrome in postmenopausal women: evidence of a dose-effect association with prevalent cardiovascular disease. Menopause. 2007;14(2):284–92.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Glintborg D, Rubin KH, Nybo M, Abrahamsen B, Andersen M. Cardiovascular disease in a nationwide population of Danish women with polycystic ovary syndrome. Cardiovasc Diabetol. 2018;17(1):37.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Paschou SA, Palioura E, Ioannidis D, Anagnostis P, Panagiotakou A, Loi V, Karageorgos G, Goulis DG, Vryonidou A. Adrenal hyperandrogenism does not deteriorate insulin resistance and lipid profile in women with PCOS. Endocr Connect. 2017;6(8):601–6.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Vryonidou A, Papatheodorou A, Tavridou A, Terzi T, Loi V, Vatalas IA, Batakis N, Phenekos C, Dionyssiou-Asteriou A. Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005;90(5):2740–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Meyer ML, Malek AM, Wild RA, Korytkowski MT, Talbott EO. Carotid artery intima-media thickness in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2012;18(2):112–26.PubMedCrossRefGoogle Scholar
  42. 42.
    Sprung VS, Atkinson G, Cuthbertson DJ, Pugh CJ, Aziz N, Green DJ, Cable NT, Jones H. Endothelial function measured using flow-mediated dilation in polycystic ovary syndrome: a meta-analysis of the observational studies. Clin Endocrinol. 2013;78(3):438–46.CrossRefGoogle Scholar
  43. 43.
    Calderon-Margalit R, Siscovick D, Merkin SS, Wang E, Daviglus ML, Schreiner PJ, Sternfeld B, Williams OD, Lewis CE, Azziz R, Schwartz SM, Wellons MF. Prospective association of polycystic ovary syndrome with coronary artery calcification and carotid-intima-media thickness: the coronary artery risk development in young adults Women’s study. Arterioscler Thromb Vasc Biol. 2014;34(12):2688–94.PubMedCrossRefGoogle Scholar
  44. 44.
    Barry JA, Azizia MM, Hardiman PJ. Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2014;20(5):748–58.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Harris HR, Terry KL. Polycystic ovary syndrome and risk of endometrial, ovarian, and breast cancer: a systematic review. Fertil Res Pract. 2016;2:14.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Shobeiri F, Jenabi E. The association between polycystic ovary syndrome and breast cancer: a meta-analysis. Obstet Gynecol Sci. 2016;59(5):367–72.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Harris HR, Babic A, Webb PM, Nagle CM, Jordan SJ, Risch HA, Rossing MA, Doherty JA, Goodman MT, Modugno F, Ness RB, Moysich KB, Kjaer SK, Hogdall E, Jensen A, Schildkraut JM, Berchuck A, Cramer DW, Bandera EV, Wentzensen N, Kotsopoulos J, Narod SA, Phelan CM, JR ML, Anton-Culver H, Ziogas A, Pearce CL, Wu AH, Terry KL, Ovarian Cancer Association Consortium; Australian Ovarian Cancer Study Group. Polycystic ovary syndrome, oligomenorrhea, and risk of ovarian cancer histotypes: evidence from the Ovarian Cancer Association Consortium. Cancer Epidemiol Biomark Prev. 2018;27(2):174–82.CrossRefGoogle Scholar
  48. 48.
    Kyrgiou M, Kalliala I, Markozannes G, Gunter MJ, Paraskevaidis E, Gabra H, Martin-Hirsch P, Tsilidis KK. Adiposity and cancer at major anatomical sites: umbrella review of the literature. BMJ. 2017;356:j477.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Morch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard O. Contemporary hormonal contraception and the risk of breast cancer. N Engl J Med. 2017;377(23):2228–39.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Panagiotis Anagnostis
    • 1
  • Stavroula A. Paschou
    • 2
  • Irene Lambrinoudaki
    • 3
  • Dimitrios G. Goulis
    • 4
  1. 1.Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynaecology, Medical SchoolAristotle University of Thessaloniki, “Papageorgiou” General HospitalThessalonikiGreece
  2. 2.Division of Endocrinology and Diabetes, “Aghia Sophia” Hospital, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  3. 3.Division of Endocrinology and Diabetes, Second Department of Obstetrics and GynaecologyMedical School, National and Kapodistrian University of AthensAthensGreece
  4. 4.Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynaecology, Medical SchoolAristotle University of ThessalonikiThessalonikiGreece

Personalised recommendations