Obstetrics and GynecologyObstetrics and GynecologyАкушерство и гинекология0300-90922412-5679Bionika Media246895ArticlesСтатьиReview ArticleCURRENT VIEWS ON ENDOMETRIAL HYPERPLASIAСОВРЕМЕННЫЕ ПРЕДСТАВЛЕНИЯ О ГИПЕРПЛАЗИИ ЭНДОМЕТРИЯCHERNUKHAG. EЧЕРНУХАГалина Евгеньевна

доктор медицинских наук, профессор, руководитель отделения гинекологической эндокринологии

g_chernukha@oparina4.ruDUMANOVSKAYAM. RДУМАНОВСКАЯМадина Равилевна

аспирант отделения гинекологической эндокринологии

m_dumanovskaya@oparina4.ruAcademician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of RussiaФГБУ Научный центр акушерства, гинекологии и перинатологии им. академика В.И. Кулакова Минздрава России150320133NO3 (2013)№3 (2013)263217022023Copyright ©; 2013, Bionika MediaCopyright ©; 2013, ООО «Бионика Медиа»2013Bionika MediaООО «Бионика Медиа»https://journals.eco-vector.com/0300-9092/article/view/246895

The review gives literature update on different aspects of hyper- and neoplastic processes in the endometrium. The results of investigations into the prevalence, risk factors, and diagnosis of endometrial hyperplasia, including the possibilities of using immunohistochemical and molecular genetic studies, are presented. The efficiency of different hormone therapy options is shown.

В обзоре представлены современные данные литературы, касающиеся различных аспектов проблемы гипер- и неопластических процессов эндометрия. Приведены результаты исследований по распространенности, факторам риска, диагностике гиперплазии эндометрия, включая возможности применения иммуногистохимических и молекулярно-генетических методов. Представлены результаты эффективности различных видов гормонотерапии.

endometrial hyperplasiatreatmentimmunohistochemistryгиперплазия эндометриялечениеиммуногистохимияMills A.M., Longacre T.A. Endometrial hyperplasia. Semin. Diagn. Pathol. 2010; 27(4): 199-214.Silverberg S.G., Mutter G.L., Kurman R.J., Kubik-Huch R.A., Nogales F, Tavassoli F.A. Tumours of the uterine corpus: epithelial tumours and related lesions. In: Tavassoli F.A., Devilee P., eds. Pathology and genetics: tumours of the breast and female genital organs. Lyon, France: IARC Press; 2003: 221-32.Silverberg S.G. Problems in the differential diagnosis of endometrial hyperplasia and carcinoma. Mod. Pathol. 2000, 13: 309-27.Zaino R.J., Kauderer J., Trimble C.L., Silverberg S.G., Curtin J.P., Lim P.C. et al. Reproducibility of the diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer. 2006; 106(4): 804-11.Sherman M.E., Ronnett B.M., Ioffe O.B., Richesson D.A., Rush B.B., Glass A.G. et al. Reproducibility of biopsy diagnoses of endometrial hyperplasia: evidence supporting a simplified classification. Int. J. Gynecol. Pathol. 2008; 27(3): 318-25.Mutter G.L. Endometrial intraepithelial neoplasia (EIN): will it bring order to chaos? The Endometrial Collaborative Group. Gynecol. Oncol. 2000; 76(3): 287-90.Mutter G.L., Zaino R.J., Baak J.P., Bentley R.C., Robboy S.J. Benign endometrial hyperplasia sequence and endometrial intraepithelial neoplasia. Int. J. Gynecol. Pathol. 2007; 26(2): 103-14.Hecht J.L., Ince T.A., Baak J.P., Baker H.E., Ogden M.W., Mutter G.L. Prediction of endometrial carcinoma by subjective endometrial intraepithelial neoplasia diagnosis. Mod. Pathol. 2005; 18(3): 324-30.Baak J.P., Mutter G.L. EIN and WHO94. J. Clin. Pathol. 2005; 58(1): 1-6.Reed S.D., Newton K.M., Clinton W.L., Epplein M., Garcia R, Allison K. et al. Incidence of endometrial hyperplasia. Am. J. Obstet. Gynecol. 2009; 200(6): 678; e1-6.Iram S., Musonda P., Ewies A.A. Premenopausal bleeding: When should the endometrium be investigated? A retrospective non-comparative study of 3006 women. Eur. J. Obstet. Gynecol. Reprod. Biol. 2010; 148(1): 86-9.Gol K., Saracoglu F, Ekici A., Sahin I. Endometrial patterns and endocrinologic characteristics of asymptomatic menopausal women. Gynecol. Endocrinol. 2001; 15: 63-7.Ewies A.A., Musonda P. Managing postmenopausal bleeding revisited: what is the best first line investigation and who should be seen within 2 weeks? A cross-sectional study of 326 women. Eur. J. Obstet. Gynecol. Reprod. Biol. 2010; 153(1): 67-71.Park J.C., Lim S.Y., Jang T.K., Bae J.G., Kim J.I., Rhee J.H. Endometrial histology and predictable clinical factors for endometrial disease in women with polycystic ovary syndrome. Clin. Exp. Reprod. Med. 2011; 38: 42-6.Holm N.S., Glintborg D., Andersen M.S., Schledermann D., Ravn P. The prevalence of endometrial hyperplasia and endometrial cancer in women with polycystic ovary syndrome or hyperandrogenism. Acta Obstet. Gynecol. Scand. 2012; 91: 1173-6.Kurman R.J., Kaminski P.F., Norris H.J The behavior of endometrial hyperplasia. A long-term study of “untreated” hyperplasia in 170 patients. Cancer. 1985; 56(2): 403-12.Ivanov S. Clinicopathological analysis in cases with glandular and atypical glandular hyperplasia treated with gestagens. Akush. Ginekol. (Sofiia). 2005; 44(4): 18-20.Baak J.P., Mutter G.L., Robboy S., van Diest P.J., Uyterlinde A.M., Orbo A. et al. The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system. Cancer. 2005; 103(11): 2304-12.Lacey J.V.Jr., Ioffe O.B., Ronnett B.M., Rush B.B., Richesson D.A., Chatterjee N. et al. Endometrial carcinoma risk among women diagnosed with endometrial hyperplasia: the 34-year experience in a large health plan. Br. J. Cancer. 2008; 98(1): 45-53.Lacey J.V.Jr., Sherman M.E., Rush B.B., Ronnett B.M., Ioffe O.B., Duggan M.A. et al. Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia. J. Clin. Oncol. 2010; 28(5): 788-92.Jabbour H.N., Kelly R.W., Fraser H.M., Critchley H.O. Endocrine regulation of menstruation. Endocr. Rev. 2006; 27(1): 17-46.Erkanli S., Bolat F., Kayaselcuk F., Demirhan B., Kuscu E. COX2 and survivin are overexpressed and positively correlated in endometrial carcinoma. Gynecol. Oncol. 2007; 104: 320-5.Kapucuoglu N., Aktepe F., Kaya H., Bircan S., Karahan N., Ciri$ M. Immunohistochemical expression of PTEN in normal, hyperplastic and malignant endometrium and its correlation with hormone receptors, bcl-2, bax, and apoptotic index. Pathol. Res. Pract. 2007; 203(3): 153-62.Hongying Dai, Shuping Zhao, Lin Xu, Aiping Chen, Shuzhen Da. Expression of Efp, VEGF and bFGF in normal, hyperplastic and malignant endometrial tissue. Oncol. Rep. 2010; 23: 795-9.Steinbakk A., Gudlaugsson E., Aasprong O.G., Skaland I., Malpica A., Feng W. et al. Molecular biomarkers in endometrial hyperplasias predict cancer progression. Am. J. Obstet. Gynecol. 2011; 204(4): 357; e1-12.Writing Group for the PEPI Trial. Effects ofhormone replacement therapy on endometrial histology in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA. 1996; 275: 370-5.MacDonald P.C., Edman C.D., Hemsell D.L., Porter J.C., Siiteri P.K. Effect of obesity on conversion of plasma androstenedione to estrone in postmenopausal women with and without endometrial cancer. Am. J. Obstet. Gynecol. 1978; 130: 448-55.Epplein M., Reed S.D., Voigt L.F., Newton K.W., Holt V.L., Weiss N.S. Risk of complex and atypical endometrial hyperplasia in relation to anthropometric measures and reproductive history. Am. J. Epidemiol. 2008; 168(6): 563-70.Gallagher E.J., LeRoith D. Diabetes, cancer, and metformin: connections of metabolism and cell proliferation. Ann. N. Y. Acad. Sci. 2011; 1243: 54-68.Friberg E., Orsini N., Mantzoros C.S., Wolk A. Diabetes mellitus and risk of endometrial cancer: a meta-analysis. Diabetologia. 2007; 50(7): 1365-74.Zhang Z.H., Su P.Y., Hao J.H., Sun Y.H. The role of preexisting diabetes mellitus on incidence and mortality of endometrial cancer: a meta-analysis of prospective cohort studies. Int. J. Gynecol. Cancer. 2013; 23(2): 294-303.American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 108. Polycystic ovary syndrome. Obstet. Gynecol. 2009; 114: 936-49.Atiomo W., Read A., Golding M., Silcocks P., Razali N., Sarkar S. et al. Local recruitment experience in a study comparing the effectiveness of a low glycaemic index diet with a low calorie healthy eating approach at achieving weight loss and reducing the risk of endometrial cancer in women with polycystic ovary syndrome (PCOS). Contemp. Clin. Trials. 2009; 30: 451-6.Farquhar C.M., Lethaby A., Sowter M., Verry J., Baranyai J. An evaluation of risk factors for endometrial hyperplasia in premenopausal women with abnormal menstrual bleeding. Am. J. Obstet. Gynecol. 1999; 181: 525-9.Runowicz C.D., Costantino J.P., Wickerham D.L., Cecchini R.S., Cronin W.M., Ford L.G. et al. Gynecologic conditions in participants in the NSABP breast cancer prevention study of tamoxifen and raloxifene (STAR). Am. J. Obstet. Gynecol. 2011; 205: 535; e1-5.Taranger-Charpin C., Carpentier S., Dales J.P., Garcia S., Djemli A., Andrac L. et al. Immunohistochemical expression of PTEN antigen: a new tool for diagnosis of early endometrial neoplasia. Bull. Acad. Natl. Med. 2004; 188: 415-27.Matias-Guiu X., Catasus L., Bussaglia E., Lagarda H., Garcia A., Pons C. et al. Molecular pathology of endometrial hyperplasia and carcinoma. Hum. Pathol. 2001; 32: 569-77.Moreno-Bueno G., Hardisson D., Sarrio D., Sanchez C., Cassia R., Prat J. et al. Abnormalities of E- and P-cadherin and catenin (beta-, gamma-catenin, and p120ctn) expression in endometrial cancer and endometrial atypical hyperplasia. J. Pathol. 2003; 199: 471-8.Allison K.H., Tenpenny E., Reed S.D., Swisher E.M., Garica R.L. Immunohistochemical markers in endometrial hyperplasia: is there a panel with promise? A review. Appl. Immunohistochem. Mol. Morphol. 2008; 16(4): 329-43.Orbo A., Nilsen M.N., Arnes M.S., Pettersen I., Larsen K. Loss of expression of MLH1, MSH2, MSH6, and PTEN related to endometrial cancer in 68 patients with endometrial hyperplasia. Int. J. Gynecol. Pathol. 2003; 22(2): 141-8.Lacey J.V.Jr., Chia V.M. Endometrial hyperplasia and the risk of progression to carcinoma. Review. Maturitas. 2009; 63: 39-44.Clark T.J., Neelakantan D., Gupta J.K. The management of endometrial hyperplasia: an evaluation of current practice. Eur. J. Obstet. Gynecol. Reprod. Biol. 2006; 125(2): 259-64.American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 440. The role of transvaginal ultrasonography in the evaluation of postmenopausal bleeding. Obstet. Gynecol. 2009; 114: 409-11.Jacobs I., Gentry-Maharaj A., Burnell M., Manchanda R., Singh N., Sharma A. et al. Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal women: a case-control study within the UKCTOCS cohort. Lancet Oncol. 2011; 12: 38-48.Schnatz P.F., Guile M., O’Sullivan D.M., Sorosky J.I. Clinical significance of atypical glandular cells on cervical cytology. Obstet. Gynecol. 2006; 107: 701-8.Goldstein S.R. Modern evaluation of the endometrium. Obstet. Gynecol. 2010; 116: 168-76.Daud S., Jalil S.S., Griffin M., Ewies A.A. Endometrial hyperplasia - the dilemma of management remains: a retrospective observational study of 280 women. Eur. J. Obstet. Gynecol. Reprod. Biol. 201; 159(1): 172-5.Kazandi M., Okmen F., Ergenoglu A.M., Yeniel A.O., Zeybek B., Zekioglu O., Ozdemir N. Comparison of the success of histopathological diagnosis with dilatation-curettage and Pipelle endometrial sampling. J. Obstet. Gynaecol. 2012; 32(8): 790-4.Pennant S., Manek S., Kehoe S. Endometrial atypical hyperplasia and subsequent diagnosis of endometrial cancer: a retrospective audit and literature review. J. Obstet. Gynaecol. 2008; 28(6): 632-3.Trimble C.L., Kauderer J., Zaino R., Silverberg S., Lim P.C., Burke J.J. 2nd et al. Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer. 2006; 106(4): 812-9.Robbe E.J., van Kuijk S.M., de Boed E.M., Smits L.J., van der Wurff A.A., Kruitwagen R.F. et al. Predicting the coexistence of an endometrial adenocarcinoma in the presence of atypical complex hyperplasia: immunohistochemical analysis of endometrial samples. Int. J. Gynecol. Cancer. 2012; 22(7): 1264-72.Polyzos N.P., Mauri D., Tsioras S., Messini C.I., Valachis A., Messinis I.E. Intraperitoneal dissemination of endometrial cancer cells after hysteroscopy: a systematic review and metaanalysis. Int. J. Gynecol. Cancer. 2010; 20: 261-7.Reed S.D., Newton K.M., Garcia R.L., Allison K.H., Voigt L.F., Jordan C.D. et al. Complex hyperplasia with and without atypia clinical outcomes and implications of progestin therapy. Obstet. Gynecol. 2010; 116(2, Pt 1): 365-73.Marsden D.E., Hacker N.F. Optimal management of endometrial hyperplasia. Best Pract. Res. Clin. Obstet. Gynaecol. 2001; 15: 393-405.Grimbizis G., Tsalikis T., Tzioufa V., Kasapis M., Mantalenakis S. Regression of endometrial hyperplasia after treatment with the gonadotrophin-releasing hormone analogue triptorelin: a prospective study. Hum. Reprod. 1999; 14(2): 479-84.Radowicki S., Skorzewska K. Treatment of hyperplasia endometrium with GNRH agonists. Ginekol. Pol. 2003; 74(9): 836-9.Agorastos T., Vaitsi V., Paschopoulos M., Vakiani A., Zournatzi-Koiou V., Saravelos H. et al. Prolonged use of gonadotropin-releasing hormone agonist and tibolone as add-back therapy for the treatment of endometrial hyperplasia. Maturitas. 2004; 48(2): 125-32.Agorastos T., Vaitsi V., Pantazis K., Efstathiadis E., Vavilis D., Bontis J.N. Aromatase inhibitor anastrozole for treating endometrial hyperplasia in obese postmenopausal women. Eur. J. Obstet. Gynecol Reprod. Biol. 2005; 118(2): 239-40.Barker L.C., Brand I.R., Crawford S.M. Sustained effect of the aromatase inhibitors anastrozole and letrozole on endometrial thickness in patients with endometrial hyperplasia and endometrial carcinoma. Curr. Med. Res. Opin. 2009; 25(5): 1105-9.Li H.Z., Chen X.N., Qiao J. Letrozole as primary therapy for endometrial hyperplasia in young women. Int. J. Gynaecol. Obstet. 2008; 100(1): 10-2.Kim J.J., Chapman-Davis E. Role of progesterone in endometrial cancer Semin. Reprod. Med. 2010; 28(1):81-90.Davies S., Dai D., Feldman I., Pickett G., Leslie K.K. Identification of a novel mechanism of NF-kappaB inactivation by progesterone through progesterone receptors in Hec50co poorly differentiated endometrial cancer cells: induction of A20 and ABIN-2. Gynecol. Oncol. 2004; 94(2): 463-70.Zheng W., Baker H.E., Mutter G.L. Involution of PTEN-null endometrial glands with progestin therapy. Gynecol. Oncol. 2004; 92(3): 1008-13.Eichner E., Abellera M. Endometrial hyperplasia treated by progestins. Obstet. Gynecol. 1971; 38: 739-42.0rbo A., Arnes M., Hancke C., Vereide A.B., Pettersen I., Larsen K. Treatment results of endometrial hyperplasia after prospective D-score classification: a follow-up study comparing effect of LNG-IUD and oral progestins versus observation only. Gynecol. Oncol. 2008; 111(1): 68-73.Vereide A.B., Arnes M., Straume B., Maltau J.M., Orbo A. Nuclear morphometric changes and therapy monitoring in patients with endometrial hyperplasia: a study comparing effects of intrauterine levonorgestrel and systemic medroxyprogesterone. Gynecol. Oncol. 2003; 91(3): 526-33.Signorelli M., Caspani G., Bonazzi C., Chiappa V., Perego P., Mangioni C. Fertility-sparing treatment in young women with endometrial cancer or atypical complex hyperplasia: a prospective single-institution experience of 21 cases. Br. J. Obstet. Gynaecol. 2009; 116(1): 114-8.Banno K., Kisu I., Yanokura M., Tsuji K., Masuda K., Ueki A. et al. Progestin therapy for endometrial cancer: the potential of fourth-generation progestin (review). Int. J. Oncol. 2012; 40(6): 1755-62.Gallos I.D., Shehmar M., Thangaratinam S., Papapostolou T.K., Coomarasamy A., Gupta J.K. Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and meta-analysis. Am. J. Obstet. Gynecol. 2010; 203: 547; e1-10.Gallos I.D., Ofinran O., Shehmar M., Coomarasamy A., Gupta J.K. Current management of endometrial hyperplasia - a survey of United Kingdom consultant gynaecologists. Eur. J. Obstet. Gynecol. 2011; 158(2): 305-7.Linkov F., Edwards R., Balk J., Yurkovetsky Z., Stadterman B., Lokshin A., Taioli E. Endometrial hyperplasia, endometrial cancer and prevention: gaps in existing research of modifiable risk factors. Eur. J. Cancer. 2008; 44: 1632-44.Tan B.K., Adya R., Chen J., Lehnert H., Sant Cassia L.J., Randeva H.S. Metformin treatment exerts antiinvasive and antimetastatic effects in human endometrial carcinoma cells. J. Clin. Endocrinol. Metab. 2011; 96(3): 808-16.Mueck A.O., Seeger H., Rabe T. Hormonal contraception and risk of endometrial cancer: a systematic review. Endocr. Relat. Cancer. 2010; 17: 263-71.