Endometrial hyperplastic processes: modern approaches to diagnosis and treatment

An issue of endometrial hyperplastic processes in the reproductive period is one of the pressing problems of gynecology due to their high prevalence in this age group. The continuing interest in this issue is determined by the data that endometrial hyperplastic processes tend to have a long, relapsing course, the lack of specific, pathognomonic symptoms as well as the complexity in differential diagnosis and choice of methods for prevention and treatment. Unfortunately, the problem of treating such patients remains far from being solved, which dictates a need to optimize patient management tactics, which should be aimed not only at creating proper integrated approaches to predicting development and recurrence of endometrial hyperplastic processes, but also developing a differentiated approach to management patients with this pathology in order to reduce gynecological and oncological morbidity as well as increase reproductive potential in this patient cohort. About the Authors N. I. SviridovaRussian Federation Natalia I. Sviridova – MD, Dr Sci Med, Associate Professor, Head of the Department of Obstetrics and Gynecology, Institute of Continuing Medical and Pharmaceutical Education 1 Pavshikh Bortsov Square, Volgograd 400131 L. V. Tkachenko Russian Federation Lyudmila V. Tkachenko – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Institute of Continuing Medical and Pharmaceutical Education 1 Pavshikh Bortsov Square, Volgograd 400131 M. A. Yakhontova Russian Federation Mariya A. Yakhontova – MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Institute of Continuing Medical and Pharmaceutical Education 1 Pavshikh Bortsov Square, Volgograd 400131 I. A. Gritsenko Russian Federation Irina A. Gritsenko – MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Institute of Continuing Medical and Pharmaceutical Education 1 Pavshikh Bortsov Square, Volgograd 400131 S. N. Maximov Russian Federation Sergey N. Maximov – MD, Postgraduate Student, Department of Obstetrics and Gynecology, Institute of Continuing Medical and Pharmaceutical Education 1 Pavshikh Bortsov Square, Volgograd 400131 K. A. Puryaseva Russian Federation Kseniya A. Puryaseva – MD, Postgraduate Student, Department of Obstetrics and Gynecology, Institute of Continuing Medical and Pharmaceutical Education 1 Pavshikh Bortsov Square, Volgograd 400131

1. Dumanovskaya M.R., Chernukha G.E., Tabeeva G.I., Asaturova A.V. Endometrial hyperplasia: search for optimal solutions and strategies. [Giperplaziya endometriya: poisk optimal'nyh reshenij i strategij]. Akusherstvo i ginekologiya. 2021;(4):23–31. (In Russ.). https://doi.org/10.18565/aig.2021.4.23-31. 2. Podzolkova N.M., Korennaya V.V. Modern ideas about the etiology, pathogenesis and principles of treatment of endometrial hyperplasia. [Sovremennye predstavleniya ob etiologii, patogeneze i principah lecheniya giperplazii endometriya]. Akusherstvo i ginekologiya. 2021;(8):192–9. (In Russ.). https://doi.org/10.18565/aig.2021.8.192-199. 3. Clinical guidelines. Endometrial hyperplasia. [Klinicheskie rekomendacii. Giperplaziya endometriya]. Moscow: Ministerstvo zdravoohraneniya Rossijskoj Federacii, 2021. 45 p. (In Russ.). Available at: https://www.rzn8gb.ru/pub/att/9_1344_482.pdf. [Accessed: 10.11.2023]. 4. Gabidullina R.I., Smirnova G.A., Nuhbala F.R. et al. Hyperplastic processes of the endometrium: modern tactics of patient management. [Giperplasticheskie process endometriya: sovremennaya taktika vedeniya pacientok]. Ginekologiya. 2019;21(6):53–8. (In Russ.). https://doi.org/10.26442/20795696.2019.6.190472. 5. Bagdasaryan L.Yu., Ponomarev V.V., Karakhalis L.Yu. et al. Factors influencing the development of endometrial polyps. [Faktory, vliyayushchie na razvitie polipov endometriya]. Kubanskij nauchnyj medicinskij vestnik. 2018;25(2):25–8. (In Russ.). https://doi.org/10.25207/1608-6228-2018-25-2-25-28. 6. Andrews W.W., Hauth J.C., Cliver S.P. et al. Association of asymptomatic bacterial vaginosis with endometrial microbial colonization and plasma cell endometritis in nonpregnant women. Am J Obstet Gynecol. 2006;195(6):1611–6. https://doi.org/10.1016/j.ajog.2006.04.010. 7. De Marchi F., Fabris A.M., Tommasi L. et al. Accuracy of hysteroscopy made by young residents in detecting endometrial pathologies in postmenopausal women. Eur J Gynaecol Oncol. 2014;35(3):219–23. 8. Asaturova A.V., Chernukha G.E., Ivanov I.A., Kuzemin A.A. Clinical and morphometric characteristics features of endometrial polyps and underlying mechanisms of abnormal uterine bleeding. [Kliniko-morfometricheskie osobennosti polipov endometriya i mekhanizmy vozniknoveniya anomal'nyh matochnyh krovotechenij]. Akusherstvo i ginekologiya. 2019;(7):64–70. (In Russ.). https://doi.org/10.18565/aig.2019.7.64-70. 9. Clevenger-Hoeft M., Syrop C.H., Stovall D.W., Van Voorhis B.J. Sonohysterography in premenopausal women with and with-out abnormal bleeding. Obstet Gynecol. 1999;94(4):516–20. https://doi.org/10.1016/s0029-7844(99)00345-2. 10. Clark T.J., Stevenson H. Endometrial polyps and abnormal uterine bleeding (AUB-P): what is the relationship, how are they diagnosed and how are they treated? Best Pract Res Clin Obstet Gynaecol. 2017;40:89–104.https://doi.org/10.1016/j.bpobgyn.2016.09.005. 11. Cohen M.A., Sauer M.V., Keltz M., Lindheim R. Utilizing routine sonohysterography to detect intrauterine pathology before initiating hormone replacement therapy. Menopause. 1999;6(1):68–70. 12. Cakmak H., Taylor H.S. Implantation failure: molecular mechanisms and clinical treatment. Hum Reprod Update. 2011;17(2):242–53. https://doi.org/10.1093.humupd/dmq037. 13. Tanos V., Berry K.E., Seikkula J. et al. The management of polyps in femalereproductiveorgans. Int J Surg. 2017;43:7–16. https://doi.org/10.1016/j.ijsu.2017.05.012. 14. Capmas P., Pourcelot A.G., Giral E. et al. Office hysteroscopy: a report of 2402 cases. J Gynecol Obstet Biol Reprod (Paris). 2016;45(5):445–50. https://doi.org/10.1016/j.jgyn.2016.02.007 15. Chernukha G.E., Asaturova A.V., Ivanov I.A., Dumanovskaya M.R. Endometrial lesion’s pattern in different age groups. [Struktura patologii endometriya v razlichnye vozrastnye periody]. Akusherstvo i ginekologiya. 2018;(8):129–34. (In Russ.). https://doi.org/10.18565/aig.2018.8.129-134. 16. Sattarov Sh.N., Kogan E.A., Sarkisov S.E. et al. Molecular mechanisms of the pathogenesis of postmenopausal endometrial polyps. [Molekulyarnye mekhanizmy patogeneza polipov endometriya v postmenopauze]. Akusherstvo i ginekologiya. 2013;(6):17–22. (In Russ.). 17. Xuebing P., TinChiu L., Enlan X. et al. Is endometrial polyp formation associated with increased expression of vascular endothelial growth factor and transforming growth factor-beta1? Eur J Obstet Gynecol Reprod Biol. 2011;159(1):198–203. https://doi.org/10.1016/j.ejogrb.2011.06.036. 18. Gentry-Maharaj A., Karpinskyj C. Current and future approaches to screening for endometrial cancer. Best Pract Res Clin Obstet Gynaecol. 2020;65:79–97. https://doi.org/10.1016/j.bpobgyn.2019.12.006. 19. Clarke M.A., Long B.J., Del Mar Morillo A. et al. Association of endometrial cancer risk with postmenopausal bleeding in women: a systematic review and meta-analysis. JAMA Int Med. 2018;178(9):1210–22. https://doi.org/10.1001/jamainternmed.2018.2820. 20. Parazzini F., Viganò P., Candiani M., Fedele L. Diet and endometriosis risk: a literature review. Reprod Biomed Online. 2013;26(4):323–36. https://doi.org/10.1016/j.rbmo.2012.12.011. 21. Vercellini P., Viganò P., Somigliana E., Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10(5):261–75. https://doi.org/10.1038/nren-do.2013.255. 22. Giannella L., Carpini G.D., Sopracordevole F. et al. Atypical endometrial hyperplasia and unexpected cancers at final histology: a study on endometrial sampling methods and risk factors. Diagnostics (Basel). 2020;10(7):474. https://doi.org/10.3390/diagnostics10070474. 23. Shan M., Carlson K.E., Bujotzek A.et al. Nonsteroidal bivalent estrogen ligands: an application of the bivalent concept to the estrogen receptor. ACS Chem Biol. 2013;8(4):707–15. https://doi.org/10.1021/cb3006243. 24. Wise L.A., Radin R.G., Kumanyika S.K. et al Prospective study of dietary fat and risk of uterine leiomyomata. Am J ClinNutr. 2014;99(5):1105–16. https://doi.org/10.3945/ajcn.113.073635. 25. Bakour S., Gupta J., Khan K. Risk factors associated with endometrial polyps in abnormal uterine bleeding. Int J Gynaecol Obstet. 2002;76(2):165–8. https://doi.org/10.1016/s0020-7292(01)00548-3. 26. Ismail S.M. Pathology of endometrium treated with tamoxifen. J Clin Pathol. 1994;47(9):827–33. https://doi.org/10.1136/jcp.47.9.827. 27. Saccardi C., Gizzo S., Patrelli T.S. et al. Endometrial surveillance in tamoxifen users: role, timing and accuracy of hysteroscopic investigation: observational longitudinal cohort study. Endocr Relat Cancer. 2013;20(4):455–62. https://doi.org/10.1530/erc-13-0020. 28. Dibi R.P., Zettler C.G., Pessini S.A. et al. Tamoxifen use and endometrial lesions: hysteroscopic, histological, and immunohistochemical findings in postmenopausal women with breast cancer. Menopause. 2009;16(2):293–300. https://doi.org/10.1097/gme.0b013e31818af10a. 29. American Association of Gynecologic Laparoscopists. AAGL practice report: practice guidelines for the diagnosis and management of endometrial polyps. J Minim Invasive Gynecol. 2012;19(1):3–10. https://doi.org/10.1016/j.jmig.2011.09.003. 30. Nordengren J., Pilka R., Noskova V. et al. Differential localization and expression of urokinase plasminogen activator (uPA), its receptor (uPAR), and its inhibitor (PAI-1) mRNA and protein in endometrial tissue during the menstrual cycle. Mol Hum Reprod. 2004;10(9):655–63. https://doi.org/10.1093/molehr/gah081. 31. WHO Classification of Tumours of Female Reproductive Organs. Eds. R.J. Kurman, M.L. Carcangiu, C.S. Herrington, R.H. Young. WHO Classification of Tumours, 4th Edition. Lyon: International Agency for Research on Cancer, 2014. 307 p. 32. Mulac-Jericevic B., Mullinax R.A., DeMayo F.J. et al. Subgroup of reproductive functions of progesterone mediated by progesterone receptor-B isoform. Science. 2000;289(5485):1751–4. https://doi.org/10.1126/science.289.5485.1751. 33. Grimm S.L., Hartig S.M., Edwards D.P. Progesterone receptor signaling mechanisms. J Mol Biol. 2016;428(19):3831–49. https://doi.org/10.1016/j.jmb.2016.06.020. 34. Rojas P.A., May M., Sequeira G.R. et al. Progesterone receptor isoform ratio: a breast cancer prognostic and predictive factor for antiprogestin responsiveness. J Natl Cancer Inst. 2017;109(7):djw317. https://doi.org/10.1093/jnci/djw317. 35. Miyamoto T., Watanabe J., Hata H. et al. Significance of progesterone receptor-A and -B expressions in endometrial adenocarcinoma. J Steroid Biochem Mol Biol. 2004;92(3):111–8. https://doi.org/10.1016/j.jsbmb.2004.07.007. 36. Han A.R., Lee T.H., Kim S., Lee H.Y. Risk factors and biomarkers for the recurrence of ovarian endometrioma: about the immunoreactivity of progesterone receptor isoform B and nuclear factor kappa B. Gynecol Endocrinol. 2017;33(1):70–4. https://doi.org/10.1080/09513590.2016.1205580. 37. Kaya H.S., Hantak A.M., Stubbs L.J. et al. Roles of progesterone receptor A and B isoforms during human endometrial decidualization. Mol Endocrinol. 2015;29(6):882–95. https://doi.org/10.1210/me.2014-1363. 38. Mylonas I., Jeschke U., Shabani N. et al. Steroid receptors ERalpha, ERbeta, PR-A and PR-B are differentially expressed in normal and atrophic human endometrium. Histol Histopathol. 2007;22(2):169–76. https://doi.org/10.14670/hh-22.169. 39. Ryan A.J., Susil B., Jobling T.W., Oehler M.K. Endometrial cancer. Cell Tissue Res. 2002;322(1):53–61. https://doi.org/10.1007/s00441-005-1109-5. 40. Arakelov S.E., Prudnikova N.Yu., Ordiyatsn I.M., Zhilina N.V. The role of immunoreactivity and lysosomal hydrolases ACE and GLU in the endometrium and blood plasma during the recurrence of endometrial hyperplastic processes in pre- and postmenopausal women. [Rol' immunoreaktivnosti i lizosomal'nyh gidrolaz ASE i GLU v endometriii i plazme krovi pri recidivirovaniigiperlasticheskih processov enndometriya u zhen'shchin v pre i postmenopauzal'nom periode]. Vestnik Rossijskogo universiteta druzhby narodov. Seriya Medicina. 2008;(6):149–58. (In Russ.). 41. Polina M.L., Arakelov S.E., Radzinskiy V.E., Ordiyants I.M. Genetic determinants of gynecological and mammological diseases in women of reproductive age. [Geneticheskie determinanty ginekologicheskih i mammologicheskih zabolevanij u zhenshchin reproduktivnogo vozrasta]. Vestnik Rossijskogo universiteta druzhby narodov. Seriya Medicina. 2008;(5):250–60. (In Russ.). 42. Zitao L., Kuokkanen S., Pal L. Steroid hormone receptor profile of premenopausal endometrial polyps. Reprod Sci. 2010;17(4):377–83. https://doi.org/10.1177/1933719109356803. 43. Antunes A., Vassallo J., Pinheiro A. et al. Immunohistochemical expression of estrogen and progesterone receptors in endometrial polyps: A comparison between benign and malignant polyps in postmenopausal patients. Oncol Lett. 2014;7(6):1944–50. https://doi.org/10.3892/ol.2014.2004. 44. Giordano G., Gnetti L., Merisio C., Melpignano M. Postmenopausal status, hypertension and obesity as risk factors for malignant transformation in endometrial polyps. Maturitas. 2007;56(2):190–7. https://doi.org/10.1016/j.maturitas.2006.08.002 45. Topcu H.O., Erkaya S., Guzel A.I. et al. Risk factors for endometrial hyperplasia concomitant endometrial polyps in pre- and post-menopausal women. Asian Pac J Cancer Prev. 2014;15(13):5423–5. https://doi.org/10.7314/apjcp.2014.15.13.5423. 46. Costa-Paiva L., Godoy C.E., Antunes A. et al. Risk of malignancy in endometrial polyps in premenopausal and postmenopausal women according to clinico-pathologic characteristics. Menopause. 2011;18(12):1278–82. https://doi.org/10.1097/gme.0b013e.31821e23a1. 47. Kogan E.A., Stanoevich I.V., Kudrina E.A., Ishchenko A.I. Morphological and immunohistochemical parallels in endometrial hyperplasia. [Morfologicheskie i immunogistohimicheske paralleli pri giperplaziyah endometriya]. Arhiv patologii. 2007;(6):21–4. (In Russ.). 48. Akhmetova E.S., Belokrinitskaya T.E., Vitkovsky Yu.A. Inflammatory cytokines in endometrial dysplastic processes. [Vospalitel'nye citokiny pri displasticheskih processah endometri. Materialy 9-go Vserossijskogo nauchnogo foruma «Mat' i ditya»]. Moscow, 2007. 328–9. (In Russ.). 49. Ishchenko A.I., Kudrina E.A., Stanoevich I.V. Benign uterine diseases: social aspects of the problem. [Dobrokachestvennye zabolevaniya matki: social'nye aspekty problem]. Vrach. 2008;(8):14–6. (In Russ.). 50. Bzhalava D., Muhr L.S., Lagheden C. et al. Deep sequencing extends the diversity of human papillomaviruses in human skin. Sci Rep. 2014;4:5807. https://doi.org/10.1038/srep05807. 51. Nagai Y. Persistence of human papillomavirus infection after therapeutic conization for CIN III: is it an alarm for disease recurrence? Gynecol Oncol. 2000;79(2):294–9. https://doi.org/10.1006/gyno.2000.5952. 52. Breusenko V.G., Savelyeva G.M., Golova Yu.A., Mishieva O.I. Treatment of endometrial hyperplastic processes in the postmenopausal period. [Lechenie giperplasticheskih processov endometriya v periode postmenopauzy]. Akusherstvo i ginekologiya. 2009;(4):19–23. (In Russ.). 53. Salamova K.K., Saprykina L.V., Ramazanova A.M. et al. Clinical characteristics of women with endometrial hyperplasia. [Klinicheskie osobennosti pacientok s giperplasticheskimi processami endometriya]. RMZh. Mat' i ditya. 2021;4(2):124–9. (In Russ.). DOI: 10.32364/2618-8430-2021-4-2-124-129. 54. Kondrikov N.I., Barinova I.V. Uterine pathology. Guide for physicians. [Patologiya matki. Rukovodstvo dlya vrachej]. Moscow: Prakticheskaya medicina, 2019. 352 p. (In Russ.). 55. Pathology and genetics of tumours of the breast and female genital organs. Eds. F.A. Tavassoli, P. Devilee. WHO classification of tumours, 3rd edition. Lyon: IARC Press, 2003. 432 р. https://doi.org/10.1111/j.1365-2559.2004.02026.x. 56. Pushkarev V.A., Mustafina G.T., Khusnutdinov S.M., Mazitov I.M. Endometrial polyps (diagnosis, clinic, treatment). [Polipy endometriya (diagnostika, klinika, lechenie)]. Kreativnaya hirurgiya i onkologiya. 2010;(1):43–8. (In Russ.). 57. Yarin G.Yu., Luft E.V., Wilhelmi I.A. Experience of a differentiated approach to surgical treatment of endometrial polyps. [Opyt differencirovannogo podhoda k hirurgicheskomu lecheniyu polipov endometriya]. Sibirskoe medicinskoe obozrenie. 2020;(1):78–83. (In Russ.). https://doi.org/10.20333/2500136-2020-1-78-83. 58. The American College of Obstetricians and Gynecologists Committee Opinion no. 631. Endometrial intraepithelial neoplasia. Obstet Gynecol. 2015;125(5):1272–8. https://doi.org/10.1097/01.AOG.0000465189.50026.20. 59. Ma T., Readman E., Hicks L. et al. Is outpatient hysteroscopy the new gold standard? Results from an 11year prospective observational study. Aust N Z J Obstet Gynaecol. 2017;57(1):7480. https://doi.org/10.1111/ajo.12560. 60. Elgina S.I., Zolotorevskaya O.S., Burova O.S. et al. Office hysteroscopy in the outpatient practice of an obstetrician-gynecologist. [Ofisnaya gisteroskopiya v ambulatornoj praktike vracha akushera-ginekologa]. Mat' i ditya v Kuzbasse. 2018;(4):21–4. (In Russ.). 61. Sarkisov S.E., Khitrykh O.V., Kukovenko E.M. Long-term results and optimization of treatment tactics for endometrial polyps in postmenopause. [Otdalennye rezul'taty i optimizaciya taktiki lecheniya polipov endometriya v postmenopauze]. Akusherstvo i ginekologiya. 2009;(5):44–8. (In Russ.). 62. Venturella R., Miele G., Cefalì K. et al. Subcutaneous progesterone for endometrial polyps in premenopausal women: a preliminary retrospective analysis. J Minim Invasive Gynecol. 2019;26(1):143–7. https://doi.org/10.1016/j.jmig.2018.04.023. 63. Kanthi J.M., Remadevi C., Sumathy S. et al. Clinical study of endometrial polyp and role of diagnostic hysteroscopy and blind avulsion of polyp. J Clin Diagn Res. 2016;10(6):QC01-4. https://doi.org/10.7860/JCDR/2016/18173.7983. 64. AlHilli M.M., Nixon K.E., Hopkins M.R. et al. Long-term out comes after intrauterine morcellation vs hysteroscopic resection of endometrial polyps. J Minim Invasive Gynecol. 2013;20(2):215–21. https://doi.org/10.1016/j.jmig.2012.10.013. 65. Gao W., Zhang L., Li W. et al. Three-year follow-up results of polypectomy with endometrial ablation in the management of endometrial polyps associated with tamoxifen in Chinese women. Eur J Obstet Gynecol Reprod Biol. 2012;161(1):62–5. https://doi.org/10.1016/j.ejogrb.2011.10.014. Review For citations: Sviridova N.I., Tkachenko L.V., Yakhontova M.A., Gritsenko I.A., Maximov S.N., Puryaseva K.A. Endometrial hyperplastic processes: modern approaches to diagnosis and treatment. Obstetrics, Gynecology and Reproduction. 2024;18(1):83-95. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2023.464 JATS XML This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.