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Does endometriosis increase the risks of endometrial hyperplasia and endometrial cancer?

  • Hoon Kim
    Affiliations
    Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea

    Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
    Search for articles by this author
  • Author Footnotes
    1 Both authors equally contributed to this work.
    Hyun Jung Kim
    Correspondence
    Corresponding authors at: Department of Preventive Medicine, Korea University College of Medicine, 126-1, 5-ga, Inchon-ro, Seoul, Republic of Korea.
    Footnotes
    1 Both authors equally contributed to this work.
    Affiliations
    Department of Preventive Medicine, Korea University College of Medicine, Seoul, Republic of Korea
    Search for articles by this author
  • Author Footnotes
    1 Both authors equally contributed to this work.
    Hyeong Sik Ahn
    Correspondence
    Corresponding authors at: Department of Preventive Medicine, Korea University College of Medicine, 126-1, 5-ga, Inchon-ro, Seoul, Republic of Korea.
    Footnotes
    1 Both authors equally contributed to this work.
    Affiliations
    Department of Preventive Medicine, Korea University College of Medicine, Seoul, Republic of Korea
    Search for articles by this author
  • Author Footnotes
    1 Both authors equally contributed to this work.
Published:November 07, 2022DOI:https://doi.org/10.1016/j.ygyno.2022.06.021

      Highlights

      • The risks of endometrial hyperplasia and cancer were found to be higher in women with than without endometriosis.
      • The risks of endometrial hyperplasia and cancer were greater in women diagnosed with endometriosis before age 45 years.
      • The risks of endometrial hyperplasia and cancer were more significant in women with endometriosis with BMI < 23 kg/m2.
      • The risks of endometrial hyperplasia and cancer were greater in women with endometriosis with menarcheal age < 15 years.
      • The presence of endometriosis did not affect overall survival in women with endometrial cancer.

      Abstract

      Objective

      The risk of developing endometrial hyperplasia after diagnosis of endometriosis has not been determined. Moreover, the risk of endometrial cancer associated with endometriosis is unclear. This nationwide population-based study investigated the associations of endometrial hyperplasia and endometrial cancer with endometriosis, after adjusting for covariates.

      Methods

      This population-based observational study analyzed data from the Korean National Health Insurance (NHI) database, including 147,869 women who were diagnosed with endometriosis from 2002 to 2017, with each patient matched to 20 control women without endometriosis. Cox proportional hazard regression analyses were performed to estimate the hazard ratios (HRs) of endometrial hyperplasia, endometrial cancer, and mortality from endometrial cancer.

      Results

      Among three million women in this population, 16,377 women were diagnosed with endometrial hyperplasia, and 1795 women were diagnosed with endometrial cancer over 19,931,794 person-years of follow-up. Women with endometriosis were at significantly higher risks of endometrial hyperplasia (adjusted hazard ratio [aHR] 1.85, 95% confidence interval [CI] 1.75–1.95), and endometrial cancer (aHR 1.35, 95% CI 1.12–1.63) were compared with control women after adjustment for covariates. A diagnosis of endometriosis did not affect survival in patients with endometrial cancer.

      Conclusion

      The risks of endometrial hyperplasia and endometrial cancer were found to be significantly higher in women with than without endometriosis. The presence of endometriosis did not affect overall survival in women with endometrial cancer. Additional long-term prospective studies with adequate control of confounders are needed.

      Keywords

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      References

        • Eisenberg V.H.
        • Weil C.
        • Chodick G.
        • Shalev V.
        Epidemiology of endometriosis: a large population-based database study from a healthcare provider with 2 million members.
        BJOG. 2018; 125: 55-62
        • Mirkin D.
        • Murphy-Barron C.
        • Iwasaki K.
        Actuarial analysis of private payer administrative claims data for women with endometriosis.
        J. Manag. Care Pharm. 2007; 13: 262-272
        • Morassutto C.
        • Monasta L.
        • Ricci G.
        • Barbone F.
        • Ronfani L.
        Incidence and estimated prevalence of endometriosis and Adenomyosis in Northeast Italy: a data linkage study.
        PLoS One. 2016; 11e0154227
        • Krawczyk N.
        • Banys-Paluchowski M.
        • Schmidt D.
        • Ulrich U.
        • Fehm T.
        Endometriosis-associated malignancy.
        Geburtshilfe Frauenheilkd. 2016; 76: 176-181
        • Swiersz L.M.
        Role of endometriosis in cancer and tumor development.
        Ann N Y Acad Sci. 2002; 955 (discussion 93–5, 396–406): 281-292
        • Kok V.C.
        • Tsai H.J.
        • Su C.F.
        • Lee C.K.
        The risks for ovarian, endometrial, breast, colorectal, and other cancers in women with newly diagnosed endometriosis or Adenomyosis: a population-based study.
        Int. J. Gynecol. Cancer. 2015; 25: 968-976
        • Mogensen J.B.
        • Kjaer S.K.
        • Mellemkjaer L.
        • Jensen A.
        Endometriosis and risks for ovarian, endometrial and breast cancers: a nationwide cohort study.
        Gynecol. Oncol. 2016; 143: 87-92
        • Surrey E.S.
        • Soliman A.M.
        • Johnson S.J.
        • Davis M.
        • Castelli-Haley J.
        • Snabes M.C.
        Risk of developing comorbidities among women with endometriosis: a retrospective matched cohort study.
        J Womens Health (Larchmt). 2018; 27: 1114-1123
        • Lundberg F.E.
        • Iliadou A.N.
        • Rodriguez-Wallberg K.
        • Gemzell-Danielsson K.
        • Johansson A.L.V.
        The risk of breast and gynecological cancer in women with a diagnosis of infertility: a nationwide population-based study.
        Eur. J. Epidemiol. 2019; 34: 499-507
        • Poole E.M.
        • Lin W.T.
        • Kvaskoff M.
        • De Vivo I.
        • Terry K.L.
        • Missmer S.A.
        Endometriosis and risk of ovarian and endometrial cancers in a large prospective cohort of U.S. nurses.
        Cancer Causes Control. 2017; 28: 437-445
        • Saavalainen L.
        • Lassus H.
        • But A.
        • Tiitinen A.
        • Harkki P.
        • Gissler M.
        • et al.
        Risk of gynecologic Cancer according to the type of endometriosis.
        Obstet. Gynecol. 2018; 131: 1095-1102
        • Saraswat L.
        • Ayansina D.
        • Cooper K.G.
        • Bhattacharya S.
        • Horne A.W.
        • Bhattacharya S.
        Impact of endometriosis on risk of further gynaecological surgery and cancer: a national cohort study.
        BJOG. 2018; 125: 64-72
        • Williams C.L.
        • Jones M.E.
        • Swerdlow A.J.
        • Botting B.J.
        • Davies M.C.
        • Jacobs I.
        • et al.
        Risks of ovarian, breast, and corpus uteri cancer in women treated with assisted reproductive technology in Great Britain, 1991–2010: data linkage study including 2.2 million person years of observation.
        BMJ. 2018; 362: k2644
        • Jenabi E.
        • Poorolajal J.
        The effect of body mass index on endometrial cancer: a meta-analysis.
        Public Health. 2015; 129: 872-880
        • Gong T.T.
        • Wang Y.L.
        • Ma X.X.
        Age at menarche and endometrial cancer risk: a dose-response meta-analysis of prospective studies.
        Sci. Rep. 2015; 5: 14051
        • Kim H.K.
        • Song S.O.
        • Noh J.
        • Jeong I.K.
        • Lee B.W.
        Data configuration and publication trends for the Korean National Health Insurance and Health Insurance Review & Assessment Database.
        Diabetes Metab. J. 2020; 44: 671-678
        • Shin J.W.
        • Kang T.
        • Lee J.S.
        • Kang M.J.
        • Huh C.H.
        • Kim M.S.
        • et al.
        Time-dependent risk of acute myocardial infarction in patients with alopecia Areata in Korea.
        JAMA Dermatol. 2020; 156: 763-771
        • Wise M.R.
        • Jordan V.
        • Lagas A.
        • Showell M.
        • Wong N.
        • Lensen S.
        • et al.
        Obesity and endometrial hyperplasia and cancer in premenopausal women: A systematic review.
        Am J Obstet Gynecol. 2016; 214 (689 e1- e17)
        • Liu Y.
        • Zhang W.
        Association between body mass index and endometriosis risk: a meta-analysis.
        Oncotarget. 2017; 8: 46928-46936
        • Nnoaham K.E.
        • Webster P.
        • Kumbang J.
        • Kennedy S.H.
        • Zondervan K.T.
        Is early age at menarche a risk factor for endometriosis? A systematic review and meta-analysis of case-control studies.
        Fertil. Steril. 2012; 98 (e6): 702-712
        • Kim H.J.
        • Shah S.C.
        • Hann H.J.
        • Kazmi S.Z.
        • Kang T.
        • Lee J.H.
        • et al.
        Familial risk of inflammatory bowel disease: a population-based cohort study in South Korea.
        Clin Gastroenterol Hepatol. 2021; 19 (In this issue): 2128-2137https://doi.org/10.1016/j.cgh.2020.09.054
        • Melin A.
        • Lundholm C.
        • Malki N.
        • Swahn M.L.
        • Sparen P.
        • Bergqvist A.
        Endometriosis as a prognostic factor for cancer survival.
        Int. J. Cancer. 2011; 129: 948-955
        • Bulun S.E.
        • Cheng Y.H.
        • Yin P.
        • Imir G.
        • Utsunomiya H.
        • Attar E.
        • et al.
        Progesterone resistance in endometriosis: link to failure to metabolize estradiol.
        Mol. Cell. Endocrinol. 2006; 248: 94-103
        • Vazquez-Martinez E.R.
        • Bello-Alvarez C.
        • Hermenegildo-Molina A.L.
        • Solis-Paredes M.
        • Parra-Hernandez S.
        • Cruz-Orozco O.
        • et al.
        Expression of membrane progesterone receptors in Eutopic and ectopic endometrium of women with endometriosis.
        Biomed. Res. Int. 2020; 2020: 2196024
        • Flores V.A.
        • Vanhie A.
        • Dang T.
        • Taylor H.S.
        Progesterone receptor status predicts response to progestin therapy in endometriosis.
        J. Clin. Endocrinol. Metab. 2018; 103: 4561-4568
        • Perez-Medina T.
        • Bajo J.
        • Folgueira G.
        • Haya J.
        • Ortega P.
        Atypical endometrial hyperplasia treatment with progestogens and gonadotropin-releasing hormone analogues: long-term follow-up.
        Gynecol. Oncol. 1999; 73: 299-304
        • Upson K.
        • Allison K.H.
        • Reed S.D.
        • Jordan C.D.
        • Newton K.M.
        • Swisher E.M.
        • et al.
        Biomarkers of progestin therapy resistance and endometrial hyperplasia progression.
        Am J Obstet Gynecol. 2012; 207 (36 e1–8)
        • Aghajanova L.
        • Velarde M.C.
        • Giudice L.C.
        Altered gene expression profiling in endometrium: evidence for progesterone resistance.
        Semin. Reprod. Med. 2010; 28: 51-58
        • Orejuela F.J.
        • Ramondetta L.M.
        • Smith J.
        • Brown J.
        • Lemos L.B.
        • Li Y.
        • et al.
        Estrogen and progesterone receptors and cyclooxygenase-2 expression in endometrial cancer, endometrial hyperplasia, and normal endometrium.
        Gynecol. Oncol. 2005; 97: 483-488
        • Bulun S.E.
        • Zeitoun K.M.
        • Takayama K.
        • Sasano H.
        Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance.
        J. Mol. Endocrinol. 2000; 25: 35-42
        • Fowler J.M.
        • Ramirez N.
        • Cohn D.E.
        • Kelbick N.
        • Pavelka J.
        • Ben-Shachar I.
        • et al.
        Correlation of cyclooxygenase-2 (COX-2) and aromatase expression in human endometrial cancer: tissue microarray analysis.
        Am. J. Obstet. Gynecol. 2005; 192 (discussion 71-3): 1262-1271
        • Painter J.N.
        • O’Mara T.A.
        • Morris A.P.
        • Cheng T.H.T.
        • Gorman M.
        • Martin L.
        • et al.
        Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses.
        Cancer Med. 2018; 7: 1978-1987
        • Bianchini F.
        • Kaaks R.
        • Vainio H.
        Weight control and physical activity in cancer prevention.
        Obes. Rev. 2002; 3: 5-8
        • Kaaks R.
        • Lukanova A.
        • Kurzer M.S.
        Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review.
        Cancer Epidemiol. Biomark. Prev. 2002; 11: 1531-1543
        • Miyata H.
        • Shirai K.
        • Muraki I.
        • Iso H.
        • Tamakoshi A.
        Associations of body mass index, weight change, physical activity, and sedentary behavior with endometrial Cancer risk among Japanese women: the Japan collaborative cohort study.
        J Epidemiol. 2021; 31: 621-627
        • Peevey J.F.
        • Seagle B.L.
        • Maniar K.P.
        • Kim J.J.
        Association of body mass index with ER, PR and 14-3-3sigma expression in tumor and stroma of type I and type II endometrial carcinoma.
        Oncotarget. 2017; 8: 42548-42559
        • Ha H.I.
        • Chang H.K.
        • Park S.J.
        • Lim J.
        • Won Y.J.
        • Lim M.C.
        The incidence and survival of cervical, ovarian, and endometrial cancer in Korea, 1999-2017: Korea central Cancer registry.
        Obstet Gynecol Sci. 2021; 64: 444-453
        • Bozdag G.
        Recurrence of endometriosis: risk factors, mechanisms and biomarkers.
        Womens Health (Lond). 2015; 11: 693-699
        • Seo S.H.
        Low fertility trend in the Republic of Korea and the problems of its family and demographic policy implementation.
        Population Econ. 2019; 3: 29-35
        • Gandini S.
        • Lazzeroni M.
        • Peccatori F.A.
        • Bendinelli B.
        • Saieva C.
        • Palli D.
        • et al.
        The risk of extra-ovarian malignancies among women with endometriosis: a systematic literature review and meta-analysis.
        Crit Rev Oncol Hematol. 2019; 134: 72-81
        • Kvaskoff M.
        • Mahamat-Saleh Y.
        • Farland L.V.
        • Shigesi N.
        • Terry K.L.
        • Harris H.R.
        • et al.
        Endometriosis and cancer: a systematic review and meta-analysis.
        Hum. Reprod. Update. 2021; 27: 393-420