CoChat
Sign Up
Cited by 25Ovarian function and disordersDiabetes, Cardiovascular Risks, and LipoproteinsGenetic and Kidney Cyst Diseases

Natural history of polycystic ovary syndrome: A systematic review of cardiometabolic outcomes from longitudinal cohort studies

Open access
Kiconco, Sylvia, Tay, Chau T., Rassie, Kate L., Azziz, Ricardo, Teede, Helena J., Joham, Anju E.·2022·Clinical Endocrinology
DOI 10.1111/cen.14647
Open this paper in CoChat — free accountOpen PDF

Abstract

Objective: Women with polycystic ovary syndrome (PCOS) have a worsened metabolic profile but the progression of cardiometabolic features over time is unclear. Understanding this natural history is a key priority in PCOS research and vital for guiding the prevention and management of this common condition. We explored cardiometabolic changes that are observed in women with PCOS compared to those without PCOS across the life course. Design, Patients and Measurements: A systematic review of longitudinal cohort studies was conducted across MEDLINE, EMBASE, Ovid PsycInfo, CINAHL PLUS and EBM reviews between 15 January 2020 and 11 February 2021. Eligible studies included participants with or without PCOS diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health (NIH) criteria. We included studies that were published from the year 1990 to 2021 with data on cardiometabolic outcomes as per the PCOS core outcomes set. Results: There were 31 longitudinal studies with 28,316 participants from four continents. At the start of follow up, participants were aged between 1 year and 49 years with a follow‐up period ranging from 2 to 32 years. Changes in BMI and the risk of coronary heart disease were similar in adult women with and without PCOS. Women with PCOS had a higher risk of Type 2 diabetes than their non‐PCOS counterparts. Evidence for the majority of all other outcomes was conflicting and with inadequate data. Conclusion: Understanding the natural history of PCOS and particularly changes in cardiometabolic features remains challenging. Existing literature is extensive but heterogeneous and inconsistent. Longitudinal studies in unselected populations are needed to provide high‐quality data in this area.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/cen.14647

Cites

13 of 13 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 55

  1. Umland EM, Weinstein LC, EM B Menstruation related disorders. In: DiPiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy: A Pa- thophysiologic Approach. 8th ed. McGraw-Hill; 2011
  2. Azziz R, Carmina E, Chen Z, et al. Polycystic ovary syndrome. Nat Rev Dis Primers. 2016;2:16057.
  3. Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod. 2016;31(12): 2841-2855.
  4. 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):544-551.
  5. Apridonidze T, Essah PA, Iuorno MJ, Nestler JE. Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005;90(4):1929-1935.
  6. Deeks AA, Gibson-Helm ME, Paul E, Teede HJ. Is having polycystic ovary syndrome a predictor of poor psychological function including anxiety and depression? Hum Reprod. 2011;26(6):1399-1407.
  7. Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifes- tations that impacts on health across the lifespan. BMC Med. 2010; 8(1):41.
  8. Azziz R, Marin C, Hoq L, Badamgarav E, Song P. Health care-related economic burden of the polycystic ovary syndrome during the re- productive life span. J Clin Endocrinol Metab. 2005;90(8):4650-4658.
  9. Teede HJ, Misso ML, Costello MF, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018; 33(9):1602-1618.
  10. The Rotterdam ESHRE/ASM-Sponsored PCOS Consensus Work- shop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19-25.
  11. Glintborg D, Rubin KH, Nybo M, Abrahamsen B, Andersen M. Car- diovascular disease in a nationwide population of Danish women with polycystic ovary syndrome. Cardiovasc Diabetol. 2018;17(1):37.
  12. Dokras A. Cardiovascular disease risk in women with PCOS. Steroids. 2013;78(8):773-776.
  13. Al Wattar BH, Teede H, Garad R, et al. Harmonising research out- comes for polycystic ovary syndrome: an international multi- stakeholder core outcome set. Hum Reprod. 2020;35(2):404-412.
  14. Monash Centre for Health Research and Implementation. Evidence Synthesis Program template for critical appraisal of a cohort study 2014. MCHRI-Monash University and Monash Health, Melbourne, Australia (adapted from Critical Appraisal Templates (2010) Centre for Clinical Effectiveness, Southern Health, Melbourne, Australia AND Wells G, Shea B, O'Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Paper presented at: 3rd Symposium on Systematic Reviews Beyond the Basics: Improving Quality and Impact. 2003; Oxford.
  15. Behboudi-Gandevani S, Ramezani Tehrani F, Hosseinpanah F, et al. Cardiometabolic risks in polycystic ovary syndrome: long-term population-based follow-up study. Fertil Steril. 2018;110(7): 1377-1386.
  16. 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.
  17. Brown ZA, Louwers YV, Fong SL, et al. The phenotype of polycystic ovary syndrome ameliorates with aging. Fertil Steril. 2011;96(5): 1259-1265.
  18. Carmina E, Campagna AM, Lobo RA. Emergence of ovulatory cycles with aging in women with polycystic ovary syndrome (PCOS) alters the trajectory of cardiovascular and metabolic risk factors. Hum Reprod. 2013;28(8):2245-2252.
  19. Carmina E, Campagna AM, Mansuet P, Vitale G, Kort D, Lobo R. Does the level of serum antimüllerian hormone predict ovulatory function in women with polycystic ovary syndrome with aging? Fertil Steril. 2012;98(4):1043-1046.
  20. Celik C, Tasdemir N, Abali R, Bastu E, Yilmaz M. Progression to impaired glucose tolerance or type 2 diabetes mellitus in polycystic ovary syndrome: a controlled follow-up study. Fertil Steril. 2014; 101(4):1123-1128.
  21. Choi YM, Hwang KR, Oh SH, et al. Progression to prediabetes or diabetes in young Korean women with polycystic ovary syndrome: a longitudinal observational study. Clin Endocrinol (Oxf). 2021;94(5): 837-844.
  22. Crumbach ME, Skrgatic L, Goluza T, Baldani DP. Long-term con- sequences of polycystic ovary syndrome. Gynaecologia et Perinatologia. 2016;25(2):53-58.
  23. Forslund M, Schmidt J, Brännström M, Landin-Wilhelmsen K, Dahlgren E. Reproductive hormones and anthropometry: a follow- up of PCOS and controls from perimenopause to older than 80 years. J Clin Endocrinol Metab. 2021;106(2):421-430.
  24. Gambineri A, Patton L, Altieri P, et al. Polycystic ovary syndrome is a risk factor for type 2 diabetes: results from a long-term prospective study. Diabetes. 2012;61(9):2369-2374.
  25. Greenwood EA, Pasch LA, Shinkai K, Cedars MI, Huddleston HG. Clinical course of depression symptoms and predictors of enduring depression risk in women with polycystic ovary syndrome: results of a longitudinal study. Fertil Steril. 2019;111(1):147-156.
  26. Huddleston HG, Quinn MM, Kao CN, Lenhart N, Rosen MP, Cedars MI. Women with polycystic ovary syndrome demonstrate worsening markers of cardiovascular risk over the short-term despite declining hyperandrogenaemia: results of a longitudinal study with community controls. Clin Endocrinol. 2017;87(6): 775-782.
  27. Iftikhar S, Collazo-Clavell ML, Roger VL, et al. Risk of cardiovascular events in patients with polycystic ovary syndrome. Neth J Med. 2012;70(2):74-80.
  28. Jacewicz-Święcka M, Kowalska I. Changes in metabolic profile in the women with a history of pcos-a long-term follow-up study. J Clin Med. 2020;9:10.
  29. Jakubowicz DJ, Iuorno MJ, Jakubowicz S, Roberts KA, Nestler JE. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87(2):524-529.
  30. Javed A, Lteif AN, Kumar S, Simmons PS, Chang AY. Fasting glucose changes in adolescents with polycystic ovary syndrome compared with obese controls: a retrospective cohort study. J Pediatr Adolesc Gynecol. 2015;28(6):451-456.
  31. Kazemi Jaliseh H, Ramezani Tehrani F, Behboudi-Gandevani S, et al. Polycystic ovary syndrome is a risk factor for diabetes and prediabetes in middle-aged but not elderly women: a long-term population-based follow-up study. Fertil Steril. 2017;108(6):1078-1084.
  32. Leelaphiwat S, Munkrut N, Weerakiet S, Tingthanatikul Y. Incidence of diabetes mellitus in Thai women with polycystic ovary syndrome. J Med Assoc Thai. 2019;102(8):853-860.
  33. Ng NYH, Jiang G, Cheung LP, et al. Progression of glucose intoler- ance and cardiometabolic risk factors over a decade in Chinese women with polycystic ovary syndrome: a case-control study. PLOS Med. 2019;16(10):e1002953.
  34. Palomba S, Falbo A, Chiossi G, et al. Lipid profile in nonobese pregnant women with polycystic ovary syndrome: a prospective controlled clinical study. Steroids. 2014;88:36-43.
  35. Palomba S, Falbo A, Russo T, et al. Insulin sensitivity after metformin suspension in normal-weight women with polycystic ovary syn- drome. J Clin Endocrinol Metab. 2007;92(8):3128-3135.
  36. Ramezani Tehrani F, Montazeri SA, Hosseinpanah F, et al. Trend of cardio-metabolic risk factors in polycystic ovary syndrome: a population-based prospective cohort study. PLOS One. 2015;10(9): e0137609.
  37. Schmidt J, Brannstrom M, Landin-Wilhelmsen K, Dahlgren E. Re- productive hormone levels and anthropometry in postmenopausal wo- men with polycystic ovary syndrome (PCOS): a 21-year follow-up study of women diagnosed with PCOS around 50 years ago and their age- matched controls. J Clin Endocrinol Metab. 2011;96(7):2178-2185.
  38. Schmidt J, Landin-Wilhelmsen K, Brannstrom M, Dahlgren E. Car- diovascular disease and risk factors in PCOS women of post- menopausal age: a 21-year controlled follow-up study. J Clin Endocrinol Metab. 2011;96(12):3794-3803.
  39. Tay CT, Hart RJ, Hickey M, et al. Updated adolescent diagnostic criteria for polycystic ovary syndrome: impact on prevalence and longitudinal body mass index trajectories from birth to adulthood. BMC Med. 2020;18(1):389.
  40. Udesen PB, Sørensen AE, Joglekar MV, et al. Levels of circulating insulin cell-free DNA in women with polycystic ovary syndrome-a longitudinal cohort study. Reprod Biol Endocrinol. 2019;17(1):34.
  41. Velija-Asimi Z, Burekovic A, Dujic T, Dizdarevic-Bostandzic A, Semiz S. Incidence of prediabetes and risk of developing cardio- vascular disease in women with polycystic ovary syndrome. Bosn J Basic Med Sci. 2016;16(4):298-306. https://pubmed.ncbi.nlm.nih. gov/27648989/
  42. Wang ET, Calderon-Margalit R, Cedars MI, et al. Polycystic ovary syndrome and risk for long-term diabetes and dyslipidemia. Obstet Gynecol. 2011;117(1):6-13.
  43. Cheng-Che S, Albert CY, Jeng-Hsiu H, Li-Yu H, Shih-Jen T. A na- tionwide population-based retrospective cohort study of the risk of uterine, ovarian and breast cancer in women with polycystic ovary syndrome. Oncologist. 2015;20(1):45-49. https://pubmed.ncbi.nlm. nih.gov/25410097/
  44. Borruel S, Moltó JF, Alpañés M, et al. Surrogate markers of visceral adiposity in young adults: waist circumference and body mass index are more accurate than waist hip ratio, model of adipose distribution and visceral adiposity index. PLOS One. 2014;9(12):e114112.
  45. Lord J, Thomas R, Fox B, Acharya U, Wilkin T. The central issue? Visceral fat mass is a good marker of insulin resistance and metabolic disturbance in women with polycystic ovary syndrome. Int J Gynecol Obstet 2006;113(10):1203-1209.
  46. Stepto NK, Cassar S, Joham AE, et al. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic- hyperinsulaemic clamp. Hum Reprod. 2013;28:777-784.
  47. Kakoly NS, Khomami MB, Joham AE, et al. Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS: A systematic review and meta-regression. Human Reproduction Update. 2018;24:455-467.
  48. Arslanian SA, Lewy VD, Danadian K. Glucose intolerance in obese adolescents with polycystic ovary syndrome: roles of insulin re- sistance and beta-cell dysfunction and risk of cardiovascular disease. J Clin Endocrinol Metab. 2001;86(1):66-71.
  49. Wekker V, van Dammen L, Koning A, et al. Long-term cardiometa- bolic disease risk in women with PCOS: a systematic review and meta-analysis. Hum Reprod Update. 2020;26(6):942-960.
  50. Zheng SH, Li XL. Visceral adiposity index as a predictor of clinical severity and therapeutic outcome of PCOS. Gynecol Endocrinol. 2016;32(3):177-183.
  51. El Khoudary SR, Aggarwal B, Beckie TM, et al. Menopause transition and cardiovascular disease risk: implications for timing of early prevention: a scientific statement from the american heart associa- tion. Circulation. 2020;142(25):e506-e532.
  52. Cho L, Davis M, Elgendy I, et al. Summary of updated re- commendations for primary prevention of cardiovascular disease in women: JACC state-of-the-art review. J Am Coll Cardiol. 2020; 75(20):2602-2618.
  53. Gariani K, Hugon-Rodin J, Philippe J, Righini M, Blondon M. Asso- ciation between polycystic ovary syndrome and venous throm- boembolism: a systematic review and meta-analysis. Thromb Res. 2020;185:102-108.
  54. Bird ST, Hartzema AG, Brophy JM, Etminan M, Delaney JA. Risk of venous thromboembolism in women with polycystic ovary syn- drome: a population-based matched cohort analysis. Can Med Assoc J. 2013;185(2):E115-E120.
  55. Jones H, Sprung VS, Pugh CJ, et al. Polycystic ovary syndrome with hyperandrogenism is characterized by an increased risk of hepatic steatosis compared to nonhyperandrogenic PCOS phenotypes and healthy controls, independent of obesity and insulin resistance. J Clin Endocrinol Metab. 2012;97(10):3709-3716.

Cited by

Sorted by citations

Authors
Kiconco, S., Tay, C. T., Rassie, K. L., Azziz, R., Teede, H. J., & Joham, A. E.
Affiliations
  • Monash University (AU)
  • Monash Medical Centre (AU)
  • University of Alabama at Birmingham (US)
Corresponding author
Joham, Anju E.
ORCID
Venue
Clinical Endocrinology
Publisher
Wiley
Published
2021-12-11
Volume
96
Issue
4
Pages
475-498
ISSN
  • 0300-0664 (ISSN-L)
  • 1365-2265
DOI
10.1111/cen.14647
OpenAlex
W4200488340
Cited by
25
References
13
Citations by year
2026: 7 · 2025: 2 · 2024: 2 · 2023: 8 · 2022: 6
FWCI
0.66
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Clinical Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
Keywords
polycystic ovary syndrome, cardiometabolic outcomes, natural history (disease), type 2 diabetes, coronary artery disease, body mass index, Rotterdam criteria, NIH criteria
MeSH terms
Adult, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Humans, Infant, Longitudinal Studies, Polycystic Ovary Syndrome, Cohort Studies

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review