Endometrial hyperplasia: search for optimal solutions and strategies

DOI

https://dx.doi.org/10.18565/aig.2021.4.23-31

Dumanovskaya M.R., Chernukha G.E., Tabeeva G.I., Asaturova A.V.
Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, Moscow, Russia

Endometrial hyperplasia (EH) is one of the main causes of abnormal uterine bleeding (AUB), which reduces quality of life in women and is a significant risk factor for malignant transformation of the endometrium, which together determines the importance of the problem, especially in developing cancer prevention programs. The current issue is to standardize morphological classifications to level the subjectivity of making histological diagnoses and to search for biomarkers that can predict the pathological process. The literature review discusses treatment options for EH, in particular the principles of hormone therapy that remains a generally recognized treatment option aimed at reversing the pathological process, preventing AUB and disease progression to endometrioid adenocarcinoma (EA), and restoring normal endometrial function and fertility. Worthy of separate attention is the management tactics for reproductive-aged patients with atypical EH, especially with unrealized generating function.
Conclusion. The clinical protocols for the management tactics in patients with EH, which have been proposed to clinicians over the past 5 years, can standardize approaches to solving the problem. However, despite the substantial recent progress in the development of the discussed problem, there remain unresolved problems, one of the main ones is to search for reliable predictors for EH, its possible progression in EA, and to predict disease relapses and therapy response.

endometrial hyperplasia

levonorgestrel intrauterine system

progestogens

cancer prevention

marker

Full text (in Russian)

Kurman R., Carcangiu M., Herrington C., Young R. World Health Organisation Classification of tumors of female reproductive organs. 4th ed. Lyon, France: IARC Press; 2014.
Думановская М.Р., Чернуха Г.Е., Асатурова А.В., Коган Е.А. Частота выявления и структура гиперплазии эндометрия в различные возрастные периоды. Акушерство и гинекология. 2015; 3: 40-4. [Dumanovskaya M.R., Chernukha G.E., Asaturova A.V., Kogan E.A. The frequency of detection and structure of endometrial hyperplasia at different age periods. Obstetrics and Gynecology. 2015; 3: 40-4 (in Russian)].
Чернуха Г.Е., Асатурова А.В., Иванов И.А., Думановская М.Р. Структура патологии эндометрия в различные возрастные периоды. Акушерство и гинекология. 2018; 8: 129-34. [Chernukha G.E., Asaturova A.V., Ivanov I.A., Dumanovskaya M.R. The structure of endometrial pathology at different age periods. Obstetrics and Gynecology. 2018; 8: 129-34. (in Russian)]. https://dx.doi.org/10.18565/aig.2018.8.129-134.
Tian Y., Liu Y., Wang G., Lv Y., Zhang J., Bai X. et al. Endometrial hyperplasia in infertile women undergoing IVF/ICSI: A retrospective cross-sectional study. J. Gynecol. Obstet. Hum. Reprod. 2020; 49(9): 101780. https://dx.doi.org/110.1016/j.jogoh.2020.101780.
Sattanakho P., Kleebkaow P., Sangkomkumhang U., Booranabunyat S., Buppasiri P. Rate of significant endometrial pathology in women at low risk for endometrial hyperplasia or cancer presenting with abnormal uterine bleeding. Pragmat. Obs. Res. 2020; 11: 13-8. https://dx.doi.org/110.2147/POR.S240930.
Giannella L., Cerami L.B., Setti T., Bergamini E., Boselli F. Prediction of endometrial hyperplasia and cancer among premenopausal women with abnormal uterine bleeding. Biomed. Res. Int. 2019; 2019: 8598152. https://dx.doi.org/10.1155/2019/8598152.
Sanderson P.A., Critchley H.O., Williams A.R., Arends M.J., Saunders P.T. New concepts for an old problem: the diagnosis of endometrial hyperplasia. Hum. Reprod. Update. 2017; 23(2): 232-54. https://dx.doi.org/10.1093/humupd/dmw042.
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. https://dx.doi.org/10.1200/JCO.2009.24.1315.
Hutt S., Tailor A., Ellis P., Michael A., Butler-Manuel S., Chatterjee J. The role of biomarkers in endometrial cancer and hyperplasia: a literature review. Acta Oncol. 2019; 58(3): 342-52. https://dx.doi.org/10.1080/0284186X.2018.1540886.
Ferlay J., Colombet M., Soerjomataram I., Mathers C., Parkin D.M., Piñeros M. et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int. J. Cancer. 2019; 144(8): 1941-53. https://dx.doi.org/10.1002/ijc.31937.
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. e1-689. e17.
https://seer.cancer.gov/statfacts/html/corp.html
Rahib L., Smith B.D., Aizenberg R., Rosenzweig A.B., Fleshman J.M., Matrisian L.M. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014; 74(11): 2913-21. https://dx.doi.org/10.1158/0008-5472.CAN-14-0155.
Каприн А.Д., Старинский В.В., Петрова Г.В., ред. Злокачественные новообразования в России в 2018 году (заболеваемость и смертность). М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России; 2019. [Kaprin A.D., Starinskij V.V., Petrova G.V., red. Malignant tumors in Russian in 2018 (morbidity and mortality). Moscow, 2019. (in Russian)].
Uterine cancer statistics. 2018. Available at: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-bycancer-type/uterine-cancer/incidence#ref-1 Accessed 03.07.2018.
Noone A.M., Howlader N., Krapcho M., Miller D., Brest A., Yu M. et al. SEER сancer ыtatistics кeview, 1975–2015. Bethesda, MD: National Cancer Institute; 2018.
Rosen M.W., Tasset J., Kobernik E.K., Smith Y.R., Johnston C., Quint E.H. Risk factors for endometrial cancer or hyperplasia in adolescents and women 25 years old or younger. J. Pediatr. Adolesc. Gynecol. 2019; 32(5): 546-9. https://dx.doi.org/10.1016/j.jpag.2019.06.004.
Tavassoli F., Devilee P., eds. World Health Organization Classification of tumours. Pathology and genetics. Tumours of the breast and female genital organs. Lyon, France: IARC Press; 2003: 217-28.
Scully R.E., Bonfiglio T.A., Kurman R.J., Silverberg S.G., Wilkinson E.J., eds. Histological typing of female genital tract tumours. 2nd ed. New York: Springer-Verlag; 1994: 13.
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. https://dx.doi.org/10.1038/modpathol.3800328.
Кондриков Н.И., Асатурова А.В., Могиревская О.А., Баринова И.В., Андреев А.И., Нажимов В.П. Воспроизводимость диагнозов гиперплазии эндометрия по классификации ВОЗ и по модифицированной (бинарной) классификации. Акушерство и гинекология. 2011; 3: 42-6. [Kondrikov N.I., Asaturova A.V., Mogirevskaya O.A., Barinova I.V., Andreev A.I., Nazhimov V.P. Reproducibility of diagnoses of endometrial hyperplasia according to the WHO classification and to the modified (binary) classification. Obstetrics and Gynecology. 2011; 3: 42-6. (in Russian)].
Cree I.A., White V.A., Indave B.I., Lokuhetty D. Revising the WHO classification: female genital tract tumours. Histopathology. 2020; 76(1): 151-6. https://dx.doi.org/10.1111/his.13977.
Mutter G.L. Endometrial intraepithelial neoplasia (EIN): will it bring order to chaos? The Endometrial Collaborative Group. Gynecol. Oncol. 2000; 76(3): 287-90. https://dx.doi.org/10.1006/gyno.1999.5580.
Committee on Gynecologic Practice, Society of Gynecologic Oncology. The American College of Obstetricians and Gynecologists Committee Opinion no. 631. Endometrial intraepithelial neoplasia. Obstet. Gynecol. 2015; 125(5): 1272-8. https://dx.doi.org/10.1097/01.AOG.0000465189.50026.20.
Raffone A., Travaglino A., Saccone G., Insabato L., Mollo A., De Placido G. et al. Endometrial hyperplasia and progression to cancer: which classification system stratifies the risk better? A systematic review and meta-analysis. Arch. Gynecol. Obstet. 2019; 299(5): 1233-42. https://dx.doi.org/10.1007/s00404-019-05103-1.
Cancer Genome Atlas Research Network; Kandoth C., Schultz N., Cherniack A.D., Akbani R., Liu Y., Shen H. et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013; 497(7447): 67-73. https://dx.doi.org/10.1038/nature12113.
https://www.cancer.gov/search/results?swKeyword=biomarker
Russo M., Newell J.M., Budurlean L., Houser K.R., Sheldon K., Kesterson J. et al. Mutational profile of endometrial hyperplasia and risk of progression to endometrioid adenocarcinoma. Cancer. 2020; 126(12): 2775-83. https://dx.doi.org/10.1002/cncr.32822.
Думановская М.Р., Чернуха Г.Е., Бурменская О.В., Донников А.Е., Трофимов Д.Ю. Вероятность неопластической трансформации при различных типах гиперплазии эндометрия. Акушерство и гинекология. 2013; 8: 56-62. [Dumanovskaya M.R., Chernukha G.E., Burmenskaya O.V., Donnikov A.E., Trofimov D.Yu. The probability of neoplastic transformation in different types of endometrial hyperplasia. Obstetrics and Gynecology. 2013; 8: 56-62. (in Russian)].
Multinu F., Chen J., Madison J.D., Torres M., Casarin J., Visscher D. et al. Analysis of DNA methylation in endometrial biopsies to predict risk of endometrial cancer. Gynecol. Oncol. 2020; 156(3): 682-8. https://dx.doi.org/10.1016/j.ygyno.2019.12.023.
Chen C., Song X., Wei W., Zhong H., Dai J., Lan Z. et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat. Commun. 2017; 8(1): 875. https://dx.doi.org/10.1038/s41467-017-00901-0.
Łaniewski P., Ilhan Z.E., Herbst-Kralovetz M.M. The microbiome and gynaecological cancer development, prevention and therapy. Nat. Rev. Urol. 2020; 17(4): 232-50. https://dx.doi.org/10.1038/s41585-020-0286-z.
Walther-António M.R., Chen J., Multinu F., Hokenstad A., Distad T.J., Cheek E.H. et al. Potential contribution of the uterine microbiome in the development of endometrial cancer. Genome Med. 2016; 8(1): 122. https://dx.doi.org/10.1186/s13073-016-0368-y.
Walsh D.M., Hokenstad A.N., Chen J., Sung J., Jenkins G.D., Chia N. et al. Postmenopause as a key factor in the composition of the Endometrial Cancer Microbiome (ECbiome). Sci. Rep. 2019; 9(1): 19213. https://dx.doi.org/10.1038/s41598-019-55720-8.
Gallos I.D., Alazzam M., Clark T.J., Faraj R., RosenthaA., Smith P.P., Gupta J.K. Management of endometrial hyperplasia. Green-top Guideline No. 67. RCOG/BSGE Joint Guideline; 2016. Available at: https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg67
Sharifzadeh F., Aminimoghaddam S., Kashanian M., Fazaeli M., Sheikhansari N. A comparison between the effects of metformin and megestrol on simple endometrial hyperplasia. Gynecol. Endocrinol. 2017; 33(2): 152-5. https://dx.doi.org/10.1080/09513590.2016.1223285.
Clement N.S., Oliver T.R., Shiwani H., Sanner J.R., Mulvaney C.A., Atiomo W. Metformin for endometrial hyperplasia. Cochrane Database Syst. Rev. 2017; 10(10): CD012214. https://dx.doi.org/10.1002/14651858.CD012214.pub2.
Acosta-Torres S., Murdock T., Matsuno R., Beavis A.L., Stone R.L., Wethington S.L. et al. The addition of metformin to progestin therapy in the fertility-sparing treatment of women with atypical hyperplasia/endometrial intraepithelial neoplasia or endometrial cancer: Little impact on response and low live-birth rates. Gynecol. Oncol. 2020; 157(2): 348-56. https://dx.doi.org/10.1016/j.ygyno.2020.02.008.
Ozdemir Kutbay N., Biray Avci C., Sarer Yurekli B., Caliskan Kurt C., Shademan B., Gunduz C. et al. Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells. J. Biochem. Mol. Toxicol. 2020; 34(10): e22547. https://dx.doi.org/10.1002/jbt.22547.
Hampsch R.A., Wells J.D., Traphagen N.A., McCleery C.F., Fields J.L., Shee K. et al. AMPK activation by metformin promotes survival of dormant ER+ breast cancer cells. Clin. Cancer Res. 2020; 26(14): 3707-19. https://dx.doi.org/10.1158/1078-0432.CCR-20-0269.
Lv Z., Guo Y. Metformin and its benefits for various Ddiseases. Front. Endocrinol. (Lausanne). 2020; 11: 191. https://dx.doi.org/10.3389/fendo.2020.00191.
HKCOG Gudelines number 16 September 2015. Guidelines on clinical management of endometrial hyperplasia. Publ. The Hong Kong College of Obstetricians and Gynaecologists, A Foundation College of Hong Kong Academy of Medicine.
Auclair M.H., Yong P.J., Salvador S., Thurston J., Colgan T.T.J., Sebastianelli A. Guideline No. 392 – Classification and management of endometrial hyperplasia. J. Obstet. Gynaecol. Can. 2019; 41(12): 1789-800. https://dx.doi.org/10.1016/j.jogc.2019.03.025.
Committee Opinion No. 734: The role of transvaginal ultrasonography in evaluating the endometrium of women with postmenopausal bleeding. Obstet. Gynecol. 2018; 131(5): e124-9. https://dx.doi.org/10.1097/AOG.0000000000002631.
Schmidt T., Breidenbach M., Nawroth F., Mallmann P., Beyer I.M., Fleisch M.C. et al. Hysteroscopy for asymptomatic postmenopausal women with sonographically thickened endometrium. Maturitas. 2009; 62(2): 176-8. https://dx.doi.org/10.1016/j.jmig.2010.09.014.
Smith-Bindman R., Weiss E., Feldstein V. How thick is too thick? When endometrial thickness should prompt biopsy in postmenopausal women without vaginal bleeding. Ultrasound Obstet. Gynecol. 2004; 24(5): 558-65. https://dx.doi.org/10.1097/AOG.0b013e3181b48feb.
American College of Obstetricians and Gynecologists (ACOG). ACOG Committee Opinion No. 440: The role of transvaginal ultrasonography in the evaluation of postmenopausal bleeding. Obstet. Gynecol. 2009; 114(2, Pt. 1): 409-11. https://dx.doi.org/10.1097/AOG.0b013e3181b48feb.
Bachmann L.M., ter Riet G., Clark T.J., Gupta J.K., Khan K.S. Probability analysis for diagnosis of endometrial hyperplasia and cancer in postmenopausal bleeding: an approach for a rational diagnostic workup. Acta Obstet. Gynecol. Scand. 2003; 82(6): 564-9. https://dx.doi.org/10.1034/j.1600-0412.2003.00176.x.
National Institutes of Health (NIH) National Cancer Institute (NCI). Surveillance, Epidemiology, and End Results Program (SEER). Bethesda, MD; 2000. Available at: https://seer.cancer.gov/ Accessed 05 December 2017.
Natarajan P., Vinturache A., Hutson R., Nugent D., Broadhead T. The value of MRI in management of endometrial hyperplasia with atypia. World J. Surg. Oncol. 2020; 18(1): 34. https://dx.doi.org/10.1186/s12957-020-1811-5.
Landrum L.M., Zuna R.E., Walker J.L. Endometrial hyperplasia, estrogen therapy, and the prevention of endometrial cancer. In: Di Saia P.J., Creasman W.T., Mannel R.S., McMeekin D.S., Mutch D.G., eds. Clinical gynecologic oncology. 8th ed. Elsevier Saunders; 2012: 121-39.
Ørbo 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. https://dx.doi.org/10.1016/j.ygyno.2008.06.014.
Mittermeier T., Farrant C., Wise M.R. Levonorgestrel-releasing intrauterine system for endometrial hyperplasia. Cochrane Database Syst. Rev. 2020; (9): CD012658. https://dx.doi.org/10.1002/14651858.CD012658.
Gompel A. Progesterone and endometrial cancer. Best Pract. Res. Clin. Obstet. Gynaecol. 2020; 69: 95-107. https://dx.doi.org/10.1016/j.bpobgyn.2020.05.003.
Uysal G., Acmaz G., Madendag Y., Cagli F., Akkaya H., Madendag I. et al. The efficacy of dienogest in the treatment of simple endometrial hyperplasia without atypia. Gynecol. Obstet. Invest. 2018; 83(2): 151-5. https://dx.doi.org/10.1159/000477618.
Marra C., Penati C., Ferrari L., Cantù M.G., Bargossi L., Fruscio R. Treatment of simple and complex endometrial non-atypical hyperplasia with natural progesterone: response rate to different doses. Gynecol. Endocrinol. 2014; 30(12): 899-901. https://dx.doi.org/10.3109/09513590.2014.945904.
Чернуха Г.Е., Думановская М.Р., Коган Е.А., Асатурова А.В., Файзуллина Н.М. Новые возможности лечения гиперплазии эндометрия натуральным микронизированным прогестероном. Акушерство и гинекология. 2013; 10: 51-8. [Chernukha G.E., Dumanovskaya M.R., Kogan E.A., Asaturova A.V., Faĭzullina N.M. New possibilities for the treatment of endometrial hyperplasia with natural micronized progesterone. Obstetrics and Gynecology. 2013; 10: 51-8. (in Russian)].
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. https://dx.doi.org/10.1016/j.maturitas.2003.08.008.
Agorastos T., Bontis J., Vakiani A., Vavilis D., Constantinidis T. Treatment of endometrial hyperplasias with gonadotropin-releasing hormone agonists: pathological, clinical, morphometric, and DNA-cytometric data. Gynecol. Oncol. 1997; 65(1): 102-14. https://dx.doi.org/10.1006/gyno.1997.4639.
Адамян Л.В., ред. Сочетанные доброкачественные опухоли и гиперпластические процессы матки (миома, аденомиоз, гиперплазия эндометрия). Проект клинических рекомендаций по ведению больных. М.; 2015. [Adamyan L.V., ed. Combined benign tumors and hyperplastic processes of the uterus (myoma, adenomyosis, endometrial hyperplasia). Draft Clinical Practice Guidelines for Patient Management. 2015. (in Russian)].
Ørbo A., Arnes M., Vereide A.B., Straume B. Relapse risk of endometrial hyperplasia after treatment with the levonorgestrel-impregnated intrauterine system or oral progestogens. BJOG. 2016; 123(9): 1512-9. https://dx.doi.org/10.1111/1471-0528.13763.
Sletten E.T., Arnes M., Lyså L.M., Larsen M., Ørbo A. Significance of progesterone receptors (PR-A and PR-B) expression as predictors for relapse after successful therapy of endometrial hyperplasia: a retrospective cohort study. BJOG. 2019; 126(7): 936-43. https://dx.doi.org/10.1111/1471-0528.15579.
Sletten E.T., Smaglyukova N., Ørbo A., Sager G. Expression of nuclear progesterone receptors (nPRs), membrane progesterone receptors (mPRs) and progesterone receptor membrane components (PGRMCs) in the human endometrium after 6 months levonorgestrel low dose intrauterine therapy. J. Steroid Biochem. Mol. Biol. 2020; 202: 105701. https://dx.doi.org/10.1016/j.jsbmb.2020.105701.
Vilos G.A., Oraif A., Vilos A.G., Ettler H., Edris F., Abu-Rafea B. Long-term clinical outcomes after resectoscopic endometrial ablation of nonatypical endometrial hyperplasia in women with abnormal uterine bleeding. J. Minim. Invasive Gynecol. 2015; 22(4): 704. https://dx.doi.org/10.1016/j.jmig.2015.02.017.
Avci M.E., Sadik S., Uçar M.G. A prospective study of rollerball endometrial ablation in the management of refractory recurrent symptomatic endometrial hyperplasia without atypia. Gynecol. Obstet. Invest. 2012; 74(4): 282-7. https://dx.doi.org/10.1159/000341708.
Vetter M.H., Smith B., Benedict J., Hade E.M., Bixel K., Copeland L.J. et al. Preoperative predictors of endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia or complex atypical hyperplasia. Am. J. Obstet. Gynecol. 2020; 222(1): 60. e1-60. e7. https://dx.doi.org/10.1016/j.ajog.2019.08.002.
Doherty M.T., Sanni O.B., Coleman H.G., Cardwell C.R., McCluggage W.G., Quinn D. et al. Concurrent and future risk of endometrial cancer in women with endometrial hyperplasia: A systematic review and meta-analysis. PLoS One. 2020; 15(4): e0232231. https://dx.doi.org/10.1371/journal.pone.023223.
Parker W.H. Ovarian conservation versus bilateral oophorectomy at the time of hysterectomy for benign disease. Menopause. 2014; 21(2): 192-4. https://dx.doi.org/10.1097/GME.0b013e31829be0a0.
Evans E.C., Matteson K.A., Orejuela F.J., Alperin M., Balk E.M., El-Nashar S. et al. Society of Gynecologic Surgeons Systematic Review Group. Salpingo-oophorectomy at the time of benign hysterectomy: A systematic review. Obstet. Gynecol. 2016; 128(3): 476-85. https://dx.doi.org/10.1097/AOG.0000000000001592.
Чернуха Г.Е., Могиревская О.А., Шигорева Т.В., Силакова А.В. Внутриматочная левоноргестрел-рилизинг система: альтернативный подход к терапии различных форм гиперплазии эндометрия. Сибирский онкологический журнал. 2007; Приложение 1: 110-5. [Chernukha G.E., Mogirevskaya O.A., Shigoreva T.V., Silakova A.V. The intrauterine levonorgestrel-releasing system: an alternative approach to the treatment of various forms of endometrial hyperplasia. Siberian Journal of Oncology. 2007; Suppl 1: 110-5. (in Russian)].
Новикова О.В., Новикова Е.Г., Волченко Н.Н., Лозовая Ю.А., Авасова Ч.А., Скрепцова Н.С., Чархифалакян А.В. Лечение рецидивов атипической гиперплазии и начального рака эндометрия после самостоятельной гормонотерапии. Акушерство и гинекология: новости, мнения, обучение. 2018; 1: 68-76. [Novikova O.V., Novikova E.G., Volchenko N.N., Lozovaya Yu.A., Avasova C.A. et al. Treatment of recurrences of atypical hyperplasia and early endometrial cancer after prior conservative treatment. Obstetrics and Gynecology: News, Opinions, Training. 2018; 1: 68-76. (in Russian)].
Gallos I.D., Yap J., Rajkhowa M., Luesley D.M., Coomarasamy A., Gupta J.K. Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: A systematic review and meta-analysis. Am. J. Obstet. Gynecol. 2012; 207(4): 266. e1-12. https://dx.doi.org/10.1016/j.ajog.2012.08.011.
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 metaanalysis. Am. J. Obstet. Gynecol. 2010; 203(6): 547. e1-10. https://dx.doi.org/10.1016/j.ajog.2010.07.037.

Received 24.11.2020

Accepted 07.12.2020

Madina R. Dumanovskaya, Cand. Sci. (Med.), Researcher, Department of Gynecological Endocrinology, V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. E-mail: dumanovskaya@gmail.com. ORCID: 0000-0001-7286-6047.
117997, Russia, Moscow, Oparina str., 4.
Galina E. Chernukha, Dr. Med. Sci., Professor, Chief Researcher of the Department of Gynecological Endocrinology, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. ORCID: 0000-0002-9065-5689. 117997, Russia, Moscow, Oparina str., 4.
Gyuzyal I. Tabeeva, Cand. Sci. (Med.), senior researcher, Department of Gynecological Endocrinology, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. ORCID: 0000-0003-1498-6520. 117997, Russia, Moscow, Oparina str., 4.
Alexandra V. Asaturova, Cand. Sci. (Med.), Head of the 1st Pathology Department, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. ORCID: 0000-0001-8739-5209. 117997, Russia, Moscow, Oparina str., 4.

For citation: Dumanovskaya M.R., Chernukha G.E., Tabeeva G.I., Asaturova A.V. Endometrial hyperplasia: search for optimal solutions and strategies.
Akusherstvo i Ginekologiya /Obstetrics and Gynecology. 2021; 4: 23-31 (in Russian)
https://dx.doi.org/10.18565/aig.2021.4.23-31

Endometrial hyperplasia: search for optimal solutions and strategies

Dumanovskaya M.R., Chernukha G.E., Tabeeva G.I., Asaturova A.V.

Keywords

References

About the Authors

Similar Articles