AccScience Publishing / TD / Volume 2 / Issue 1 / DOI: 10.36922/td.328
Cite this article
Journal Browser
Volume | Year
News and Announcements
View All

An overview of the risk, underlying factors, and mechanism of cancer progression in polycystic ovary syndrome

Rubiat Afrin Ayon1 Md. Azmain Faike1 Sumiya Zaman Ononna1 Aminul Hassan1 Shoumik Kundu1 Farhana Akhter2 Mohammad Mahfuz Ali Khan Shawan1 Md. Mozammel Hossain1 Md. Ibrahim Khalil1* Md. Ashraful Hasan1*
Show Less
1 Laboratory of Preventive and Integrative Biomedicine, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh
2 Government Unani and Ayurvedic Medical College Hospital, Mirpur-13, Dhaka 1221, Bangladesh
Tumor Discovery 2023, 2(1), 328
Submitted: 16 January 2023 | Accepted: 3 March 2023 | Published: 17 March 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder among women of reproductive age. PCOS is characterized by ovulatory dysfunction, clinical or biochemical features of hyperandrogenism, and polycystic ovaries. The risk of cancer among PCOS patients has been a topic of discussion for decades due to the overlapping metabolic and endocrine abnormalities. This review article focuses on the association of PCOS with various types of reproductive (such as endometrial cancer, ovarian cancer, and breast cancer) and non-reproductive cancers, considering different aspects, such as the risk of cancer progression in PCOS patients, the underlying factors, and the mechanism through which PCOS might progress to cancer. The information provided in this article would help create awareness among PCOS patients about the need to take risk-reducing measures. This article might also aid in the effort of identifying novel therapeutic targets to counteract the progression of cancer in PCOS.

Polycystic ovary syndrome

Shermin S, Noor A, Jahan S, 2019, Polycystic ovary syndrome: A brief review with recent updates. Delta Med Coll J, 7(2): 84–99.


Hasan M, Sultana S, Sohan M, et al., 2022, Prevalence and associated risk factors for mental health problems among patients with polycystic ovary syndrome in Bangladesh: A nationwide cross-sectional study. PLoS One, 17(6): e0270102. https://10.1371/journal.pone.0270102


Guzick DS, 2004, Polycystic ovary syndrome. Obstet Gynecol, 103(1): 181–193. 


Lim JJ, Lima PD, Salehi R, et al., 2017, Regulation of androgen receptor signaling by ubiquitination during folliculogenesis and its possible dysregulation in polycystic ovarian syndrome. Sci Rep, 7(1): 10272.


Ruan X, Kubba A, Aguilar A, et al., 2017, Use of cyproterone acetate/ethinylestradiol in polycystic ovary syndrome: Rationale and practical aspects. Eur J Contracept Reprod Health Care, 22(3): 183–190.


Kamrul-Hasan AB, Aalpona FT, Mustari M, et al., 2020, Divergences in clinical, anthropometric, metabolic, and hormonal parameters among different phenotypes of polycystic ovary syndrome presenting at endocrinology outpatient departments: A multicenter study from Bangladesh. J Hum Reprod Sci, 13(4): 277–284.


Fauser BC, Tarlatzis BC, Rebar RW, et al., 2012, Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): The Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus workshop Group. Fertil Steril, 97(1): 28–38.e25. 


Corbould A, Kim YB, Youngren JF, et al., 2005, Insulin resistance in the skeletal muscle of women with PCOS involves intrinsic and acquired defects in insulin signaling. Am J Physiol Endocrinol Metab, 288(5): E1047–E1054.


Balen A, 2001, Polycystic ovary syndrome and cancer. Hum Reprod Update, 7(6): 522–525.


Siegel RL, Miller KD, Jemal A, 2016, Cancer statistics, 2016. CA Cancer J Clin, 66(1): 7–30.


Stein IF, Leventhal ML, 1935, Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol, 29(2): 181–191. 


Speert H, 1949, Carcinoma of the endometrium in young women. Surg Gynecol Obstet, 88(3): 332–336. 


Harris HR, Terry KL, 2016, Polycystic ovary syndrome and risk of endometrial, ovarian, and breast cancer: A systematic review. Fertil Res Pract, 2(1): 1–9.


Cirillo PM, Wang ET, Cedars MI, et al., 2016, Irregular menses predicts ovarian cancer: Prospective evidence from the child health and development studies. Int J Cancer, 139(5): 1009–1017.


Li Y, Chen C, Ma Y, et al., 2019, Multi-system reproductive metabolic disorder: Signifcance for the pathogenesis and therapy of polycystic ovary syndrome (PCOS). Life Sci, 228: 167–175.


Gadducci A, Gargini A, Palla E, et al., 2005, Polycystic ovary syndrome and gynecological cancers: Is there a link? J Gynaecol Endocrinol, 20(4): 200–208.


Syed V, Ulinski G, Mok SC, et al., 2001, Expression of gonadotropin receptor and growth responses to key reproductive hormones in normal and malignant human ovarian surface epithelial cells. Cancer Res, 61(18): 6768–6776. 


Modugno F, 2004, Ovarian cancer and polymorphisms in the androgen and progesterone receptor genes: A HuGE review. Am J Epidemiol, 159(4): 319–335. 


Ding DC, Chen W, Wang JH, et al., 2018, Association between polycystic ovarian syndrome and endometrial, ovarian, and breast cancer: A population-based cohort study in Taiwan. Medicine (Baltimore), 97(39): e12608.


Beral V, Doll R, Hermon C, et al., 2008, Ovarian cancer and oral contraceptives: Collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet, 371(9609): 303–314.


Anderson KE, Sellers TA, Chen PL, et al., 1997, Association of Stein Leventhal syndrome with the incidence of postmenopausal breast carcinoma in a large prospective study of women in Iowa. Cancer, 79(3): 494–499.


Shobeiri F, Jenabi E, 2016, The association between polycystic ovary syndrome and breast cancer: A meta-analysis. Obstet Gynecol Sci, 59(5): 367–372.


Fanta M, 2013, Is polycystic ovary syndrome, a state of relative estrogen excess, a real risk factor for estrogen-dependant malignancies? Gynecol Endocrinol, 29(2): 145–147.


Urbanek M, Legro Driscoll DA, et al., 1999, Thirty-seven candidate genes for polycystic ovary syndrome: Strongest evidence for linkage is with follistatin. Proc Natl Acad Sci U S A, 96(15): 8573–8578. 


Liu Y, Gold EB, Lasley BL, et al., 2004, Factors affecting menstrual cycle characteristics. Am J Epidemiol, 160(2): 131–140.


Rani R, Hajam YA, Kumar R, et al., 2022, A landscape analysis of the potential role of polyphenols for the treatment of Polycystic Ovarian Syndrome (PCOS). Phytomed Plus, 2(1): 100161.


Bulsara J, Patel P, Soni A, et al., 2021, A review: Brief insight into polycystic ovarian syndrome. Endocrinol Metab Sci, 3: 100085.


Ibáñez L, Oberfield SE, Witchel S, et al., 2017, An international consortium update: Pathophysiology, diagnosis, and treatment of polycystic ovarian syndrome in adolescence. Horm Res Paediatr, 88(6): 371–395.


Dumesic DA, Oberfield SE, Stener-Victorin E, et al., 2015, Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocr Rev, 36(5): 487–525.


Kanbour SA, Dobs AS, 2022, Hyperandrogenism in women with polycystic ovarian syndrome: Pathophysiology and controversies. Androgens Clin Res Ther, 3(1): 22–30.


Cheung AP, Cog F, 2010, Polycystic ovary syndrome: A contemporary view. J Obstet Gynaecol Can, 32(5): 423–425. 


Walters KA, Gilchrist RB, Ledger WL, et al., 2018, New perspectives on the pathogenesis of PCOS: Neuroendocrine origins. Trends Endocrinol Metab, 29(12): 841–852.


Lv PP, Jin M, Rao JP, et al., 2020, Role of anti-Müllerian hormone and testosterone in follicular growth: A cross-sectional study. BMC Endocr Disord, 20(1): 101.


Ashraf S, Nabi M, Rashid F, et al., 2019, Hyperandrogenism in polycystic ovarian syndrome and role of CYP gene variants: A review. Egypt J Med Hum Genet, 20(1): 25.


Yau TT, Ng NY, Cheung LP, et al., 2017, Polycystic ovary syndrome: A common reproductive syndrome with long-term metabolic consequences. Hong Kong Med J, 23(6): 622–634.


Yilmaz M, Bukan N, Ayvaz G, et al., 2005, The effects of rosiglitazone and metformin on oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome. Hum Reprod, 20(12): 3333–3340.


Moller DE, Flier JS, 1988, Detection of an alteration in the insulin-receptor gene in a patient with insulin resistance, acanthosis nigricans, and the polycystic ovary syndrome (Type A insulin resistance). N Engl J Med, 319(23): 1526–1529.


Diamanti-Kandarakis E, Papavassiliou AG, 2006, Molecular mechanisms of insulin resistance in polycystic ovary syndrome. Trends Mol Med, 12(7): 324–332.


Burghen GA, Givens JR, Kitabchi AE, 1980, Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. J Clin Endocrinol Metab, 50(1): 113–116. 


Armanini D, Boscaro M, Bordin L, et al., 2022, Controversies in the pathogenesis, diagnosis and treatment of PCOS: Focus on insulin resistance, inflammation, and hyperandrogenism. Int J Mol Sci, 23(8): 4110.


Willis D, Franks S, 1995, Insulin action in human granulosa cells from normal and polycystic ovaries is mediated by the insulin receptor and not the Type-I insulin-like growth factor receptor. J Clin Endocrinol Metab, 80(12): 3788–3790. 


Azziz R, Carmina E, Dewailly D, et al., 2009, The androgen excess and PCOS society criteria for the polycystic ovary syndrome: The complete task force report. Fertil Steril, 91(2): 456–488.


Gambineri A, Patton L, Altieri P, et al., 2012, Polycystic ovary syndrome is a risk factor for Type 2 diabetes: Results from a long-term prospective study. Diabetes, 61(9): 2369–2374.


Bremer AA, Miller WL, 2008, The serine phosphorylation hypothesis of polycystic ovary syndrome: A unifying mechanism for hyperandrogenemia and insulin resistance. Fertil Steril, 89(5): 1039–1048.


Siddiqui S, Mateen S, Ahmad R, et al., 2022, A brief insight into the etiology, genetics, and immunology of polycystic ovarian syndrome (PCOS). J Assist Reprod Genet, 39(11): 2439–2473.


Moll GW Jr., Rosenfield RL, 1983, Plasma free testosterone in the diagnosis of adolescent polycystic ovary syndrome. J Pediatr, 102(3): 461–464.


Van Hooff MH, Voorhorst FJ, Kaptein MB, et al., 2000, Polycystic ovaries in adolescents and the relationship with menstrual cycle patterns, luteinizing hormone, androgens, and insulin. Fertil Steril, 74(1): 49–58.


Diamanti-Kandarakis E, Dunaif A, 2012, Insulin resistance and the polycystic ovary syndrome revisited: An update on mechanisms and implications. Endocr Rev, 33(6): 981–1030.


Zuo T, Zhu M, Xu W, 2016, Roles of oxidative stress in polycystic ovary syndrome and cancers. Oxid Med Cell Longev, 2016: 8589318.


Sabuncu T, Vural H, Harma M, et al., 2001, Oxidative stress in polycystic ovary syndrome and its contribution to the risk of cardiovascular disease. Clin Biochem, 34(5): 407–413. 


Patel S, 2018, Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy. J Steroid Biochem Mol Biol, 182: 27–36. 


Xue Z, Li J, Feng J, et al., 2021, Research progress on the mechanism between polycystic ovary syndrome and abnormal endometrium. Front Physiol, 12: 788772.


Yang Y, Qiao J, Li R, et al., 2011, Is interleukin-18 associated with polycystic ovary syndrome? Reprod Biol Endocrinol, 9(1): 7.


González F, Nair KS, Daniels JK, et al., 2012, Hyperandrogenism sensitizes leukocytes to hyperglycemia to promote oxidative stress in lean reproductive-age women. J Clin Endocrinol Metab, 97(8): 2836–2843. 


Rosenfield RL, Ehrmann DA, 2016, The pathogenesis of polycystic ovary syndrome (PCOS): The hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev, 37(5): 467–520.


Day F, Karaderi T, Jones MR, et al., 2018, Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria. PLoS Genet, 14(12): e1007813.


Escobar-Morreale HF, 2018, Polycystic ovary syndrome: Definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol, 14(5): 270–284.


Aziz R, Carmina E, Chen Z, et al., 2016, Polycystic ovary syndrome. Nat Rev Dis Primers, 2(1): 16057.


Lizneva D, Suturina L, Walker W, et al., 2016, Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril, 106(1): 6–15. 


Meczekalski B, Pérez-Roncero GR, López-Baena MT, et al., 2020, The polycystic ovary syndrome and gynecological cancer risk. J Gynaecol Endocrinol, 36(4): 289–293.


Barry JA, Azizia MM, Hardiman PJ, 2014, Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: A systematic review and meta-analysis. Hum Reprod Update, 20(5): 748–758.


de França Neto AH, Rogatto S, Do Amorim MM, et al., 2010, Oncological repercussions of polycystic ovary syndrome. J Gynaecol Endocrinol, 26(10): 708–711.


Parker SL, 1997, Cancer statistics, 1997. CA Cancer J Clin, 47: 5–27.


National Cancer Institute of Canada, 2003, Canadian Cancer Statistics. Toronto, Canada: National Cancer Institute.


Daniilidis A, Dinas K, 2009, Long term health consequences of polycystic ovarian syndrome: A review analysis. Hippokratia, 13(2): 90–92.


Hardiman P, Pillay OS, Atiomo W, 2003, Polycystic ovary syndrome and endometrial carcinoma. Lancet, 361(9371): 1810–1812.


Pillay OC, Te Fong, LW, Crow JC, et al., 2006, The association between polycystic ovaries and endometrial cancer. Hum Reprod, 21(4): 924–929.


Atiomo W, Khalid S, Parameshweran S, et al., 2009, Proteomic biomarkers for the diagnosis and risk stratification of polycystic ovary syndrome: A systematic review. BJOG, 116(2): 137–143.


Gottschau M, Kjaer SK, Jensen A, et al., 2015, Risk of cancer among women with polycystic ovary syndrome: A Danish cohort study. Gynecol Oncol, 136(1): 99–103.


Shen CC, Yang AC, Hung JH, et al., 2015, A nationwide population-based retrospective cohort study of the risk of uterine, ovarian and breast cancer in women with polycystic ovary syndrome. Oncologist, 20(1): 45–49.


Haoula Z, Salman M, Atiomo W, 2012, Evaluating the association between endometrial cancer and polycystic ovary syndrome. Hum Reprod, 27(5): 1327–1331.


Fearnley EJ, Marquart L, Spurdle AB, et al., 2010, Polycystic ovary syndrome increases the risk of endometrial cancer in women aged less than 50 years: An Australian case-control study. Cancer Causes Control, 21(12): 2303–2308.


Reid BM, Permuth JB, Sellers TA, 2017, Epidemiology of ovarian cancer: A review. Cancer Biol Med, 14(1): 9–32.


Risch HA, 1998, Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst, 90(23): 1774–1786. 


Hunn J, Rodriguez GC, 2012, Ovarian cancer: Etiology, risk factors, and epidemiology. Clin Obstet Gynecol, 55(1), 3–23.


Ali AT, 2014, Reproductive factors and the risk of endometrial cancer. Int J Gynecol Cancer, 24(3): 384–393.


Rojas K, Stuckey A, 2016, Breast cancer epidemiology and risk factors. Clin Obstet Gynecol, 59(4): 651–672.


Pérez-López FR, 2019, Sporadic ovarian and fallopian tube cancer in postmenopausal women. In: Postmenopausal Diseases and Disorders. Cham: Springer. p79–100.


Brinton LA, Moghissi KS, Westhoff CL, et al., 2010, Cancer risk among infertile women with androgen excess or menstrual disorders (including polycystic ovary syndrome). Fertil Steril, 94(5): 1787–1792.


Bray F, Ferlay J, Soerjomataram I, et al., 2018, Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 68(6): 394–424.


Xu H, Han Y, Lou J, et al., 2017, PDGFRA, HSD17B4 and HMGB2 are potential therapeutic targets in polycystic ovarian syndrome and breast cancer. Oncotarget, 8(41): 69520–69526. 


Cooney LG, Dokras A, 2018, Beyond fertility: Polycystic ovary syndrome and long-term health. Fertil Steril, 110(5): 794–809. 


Terry KL, Willett WC, Rich-Edwards JW, et al., 2006, A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer. Arch Intern Med, 166(22): 2484–2489.


LedgerWL, 2003, Non-reproductiveconsequencesofpolycystic ovary syndrome. Curr Obstet Gynecol, 13(6): 350–354. 


Mravec B, Tibensky M, 2020, Increased cancer risk in polycystic ovary syndrome: An (un) sympathetic connection? Med Hypotheses, 134: 109437.


Shafiee MN, Chapman C, Barrett D, et al., 2013, Reviewing the molecular mechanisms which increase endometrial cancer (EC) risk in women with polycystic ovarian syndrome (PCOS): Time for paradigm shift? Gynecol Oncol, 131(2): 489–492.


Arcidiacono B, Iiritano S, Nocera A, et al., 2012, Insulin resistance and cancer risk: An overview of the pathogenetic mechanisms. Exp Diabetes Res, 2012: 789174.


Grivennikov SI, Greten FR, Karin M, 2010, Immunity, inflammation, and cancer. Cell J, 140(6): 883–899.


Zahalka AH, Arnal-Estapé A, Maryanovich M, et al., 2017, Adrenergic nerves activate an angio-metabolic switch in prostate cancer. Science, 358(6361): 321–326. 


Hara MR, Kovacs JJ, Whalen EJ, et al., 2011, A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1. Nature, 477(7364): 349–353.


Magnon C, Hall SJ, Lin J, et al., 2013, Autonomic nerve development contributes to prostate cancer progression. Science, 341(6142): 1236361.


Papaioannou S, Tzafettas J, 2010, Anovulation with or without PCO, hyperandrogenaemia and hyperinsulinaemia as promoters of endometrial and breast cancer. Best Pract Res Clin Obstet Gynaecol, 24(1): 19–27.


Dumesic DA, Lobo RA, 2013, Cancer risk and PCOS. Steroids, 78(8): 782–785. 


Yumiceba V, López-Cortés A, Pérez-Villa A, et al., 2020, Oncology and pharmacogenomics insights in polycystic ovary syndrome: An integrative analysis. Front Endocrinol (Lausanne), 11: 585130.


Setiawan VW, Yang HP, Pike MC, et al., 2013, Type I and II endometrial cancers: Have they different risk factors? Clin Oncol, 31(20): 2607–2018.


Samarnthai N, Hall K, Yeh IT, 2010, Molecular profiling of endometrial malignancies. Obstet Gynecol, 2010: 162363.


Zou J, Li Y, Liao N, et al., 2022, Identification of key genes associated with polycystic ovary syndrome (PCOS) and ovarian cancer using an integrated bioinformatics analysis. J Ovarian Res, 15(1): 1–16.


Toss A, Tomasello C, Razzaboni E, et al., 2015, Hereditary ovarian cancer: Not only BRCA 1 and 2 genes. Biomed Res Int, 2015: 341723.


Perets R, Wyant GA, Muto KW, et al., 2013, Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca; Tp53; Pten models. Cancer Cell, 24(6): 751–765.

Conflict of interest
The authors declare that they have no competing interests.
Back to top
Tumor Discovery, Electronic ISSN: 2810-9775 Published by AccScience Publishing