Endometrial hyperplasia: current approaches to diagnosis and treatment. Literature review and own experience
DOI:
https://doi.org/10.18370/2309-4117.2021.58.18-27Keywords:
endometrial hyperplasia, postmenopause, obesity, metabolic syndrome, immunohistochemical markers, proliferation, apoptosisAbstract
Purpose of the study: to examine the morphological and immunohistochemical features of the endometrium in postmenopausal women with uterine bleeding, depending on body weight and metabolic syndrome.
Materials and methods. The study included 114 women with postmenopausal uterine bleeding. Women were divided into 3 groups. Group I included 41 patients with overweight and obesity class I–II, group II – 43 women with metabolic syndrome, group III (control) consisted of 30 patients with normal body weight. Hysteroscopy with morphological analysis of biopsied material was performed for all patients of groups I and III and 41 patients of group II. Pathohistological and immunohistochemical analysis were used to diagnose endometrial pathology. The level of cell proliferation in the endometrium was assessed by immunohistochemical analysis using monoclonal antibodies for Ki-67 expression; antiapoptotic activity was determined by the Bcl-2 and COX-2 expression.
Results. Endometrial pathology was diagnosed in 94.74% of women. Endometrial polyps in the structure of the identified pathologyprevailed in group I and control group III (82.93% and 83.33%, respectively), while endometrial polyps were detected in 25.59% of women in the group II. Endometrial hyperplasia was diagnosed in the vast majority (69.76%) in group II, hyperplasia without atypia was detected in 51.16% and endometrial hyperplasia with atypia in 18.60%.
Conclusions. Endometrial hyperplasia value was higher in postmenopausal women with metabolic syndrome compared to patients with normal weight, overweight and obesity. There was an increase of Ki-67, Bcl-2 and COX-2 expression in the endometrial glands in women with metabolic syndrome in comparison to patients with normal weight and obesity, for which only increased Bcl-2 expression in the stroma was observed. This confirms the existing data on the predominance of the apoptosis inhibition over proliferation in the formation of endometrial diseases in the postmenopausal period and confirms the combination of hyperproliferative processes and apoptosis inhibition if there is metabolic syndrome.
References
- Cancer in Ukraine, 2018–2019. Morbidity, mortality, indicators of oncology service activity. Kyiv (2020). Available from: [http://www.ncru.inf.ua/publications/BULL_21/index.htm].
- Auclair, M.-H., Yong, P.J., Salvador, S., et al. “Society of Gynecologic Oncology of Canada Guideline No. 390. Classification and Management of Endometrial Hyperplasia.” J Obstet Gynaecol Can 41.12 (2019): 1789–1800. DOI: 10.1016/j.jogc.2019.03.025
- Gallos, I.D., Alazzam, M., Clark, T.J., et al. Royal College of Obstetricians and Gynaecologists. Green-top № 67. Management of Endometrial Hyperplasia (2016). Available from: https://www.rcog.org.uk/globalassets/documents/guidelines/green-top-guidelines/gtg_67_endometrial_hyperplasia.pdf
- Renaud, M.-C., Le, T. “SOGC Clinical Practice Guidelines No. 291. Epidemiology and Investigations for Suspected Endometrial Cancer.” Journal of Obstetrics and Gynaecology Canada 40.9 (2018): e703–e711. DOI: 10.1016/j.jogc.2018.07.005
- Cherniaeva, A.O., Mykytiuk, M.R., Karachentsev, Y.I., Kravchun, N.O. “The level of uricemia in patients with diabetes and anthropometric indices: clinical and biochemical correlations.” Problems of endocrine pathology 2 (2019): 73–80. DOI: 10.21856/j-PEP.2019.2.11
- Smith, R.A., von Eschenbach, A.C., Wender, R., et al. “American Cancer Society guidelines for the early detection of cancer: Update of early detection guidelines for prostate, colorectal, and endometrial cancers”. CA Cancer J Clin 51 (2001): 38.
- Setiawan, V.W., Yang, H.P., Pike, M.C., et al. “Type I and II endometrial cancers: have they different risk factors?” J Clin Oncol 31 (2013): 2607.
- American College of Obstetricians and Gynecologists. “ACOG Committee Opinion No. 793. Hereditary cancer syndromes and risk assessment.” Obstet Gynecol 134 (2019): e143–9.
- Reed, S.D., Urban, R.R. “Classification and diagnosis of endometrial hyperplasia.” Available from: [https://www. uptodate.com/contents/classification-and-diagnosis-of-endometrial-hyperplasia].
- American College of Obstetricians and Gynecologists. “ACOG Committee Opinion № 800. The use of hysteroscopy for the diagnosis and treatment of intrauterine pathology.” Obstet Gynecol 135 (2020): e138–48.
- Leone, F., Timmerman, D., Bourne, T., et al. “Terms, definitions and measurements to describe the sonographic features of the endometrium and intrauterine lesions: a consensus opinion from the International Endometrial Tumor Analysis (IETA) group.” Ultrasound Obstet Gynecol 35 (2010): 103–112. DOI: 10.1002/uog.7487
- American College of Obstetricians and Gynecologists. “ACOG Committee Opinion No. 734. The role of transvaginal ultrasonography in evaluating the endometrium of women with postmenopausal bleeding.” Obstet Gynecol 131 (2018): e124–9.
- Society of Gynecologic Oncology, American College of Obstetricians and Gynecologists. “ACOG Committee Opinion No. 631. Endometrial Intraepithelial Neoplasia (Reaffirmed 2019).” Obstet Gynecol 125 (2015): 1272–8.
- Wolfman, W. “Reaffirmed SOGC Clinical Practice Guidelines No. 249. Asymptomatic Endometrial Thickening.” J Obstet Gynaecol Can 40.5 (2018): e367–e377. DOI: 10.1016/j.jogc.2018.03.005
- Kanzaki, H. Uterine Endometrial Function. Springer, 2016.
- Kalugina, L.V., Tatarchuk, Т. F. “Polycystic ovary syndrome: approach to correction of metabolic disorders.” Reproductive Endocrinology 2.52 (2020): 54–60. DOI: 10.18370/2309-4117.2020.52.54-60
- Troncon, J.K., Meola, J., Candido-dos-Reis, F.J., et al. “Analysis of differential genetic expression in endometrial polyps of postmenopausal women.” Climacteric 20.5 (2017): 462–6. DOI: 10.1080/13697137.2017.1335701
- Zanko, O.V. Diagnosis, treatment and prevention of hyperproliferative diseases of the endometrium in postmenopausal women. Thesis abstract for PhD degree. Kyiv (2018).
- Pereira, A.K.C., Garcia, M.T., Pinheiro, W., et al. “What is the influence of cyclooxygenase-2 on postmenopausal endometrial polyps?” Climacteric 18.4 (2014): 498–502. DOI: 10.3109/13697137.2014.966240
- Pinheiro, A., Antunes А., Andrade, L., et al. “Expression of hormone receptors, Bcl-2, Cox-2 and Ki67 in benign endometrial polyps and their association with obesity.” Molecular Medicine Reports 9.6 (2014): 2335–41. DOI: 10.3892/Mmr.2014.2125
- Saraiva, A.L.R., Payan-Carreira, F., Gärtner, I., et al. “Immunohistochemical expression of cyclooxygenase-2 (COX- 2) in feline endometrial adenocarcinoma and in normal and hyperplastic endometria.” Reproduction in Domestic Animals 50.2 (2015): 333–40. DOI: 10.1111/rda.12497
- Sanderson, P.A., Critchley, H.O.D., et al. “New concepts for an old problem: the diagnosis of endometrial hyperplasia.” Human Reproduction Update 23 (2017): 232–54. DOI: 10.1093/humupd/dmw042
- Jacobs, I., Gentry-Maharaj, A., Burnell, M., et al. “Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal women: a case-control study within the UKCTOCS cohort.” Lancet Oncol 12 (2011): 38–48.
- Furness, S., Roberts, H., Marjoribanks, J., et al. “Hormone therapy in postmenopausal women and risk of endometrial hyperplasia.” Cochrane Database Syst Rev 8 (2012): CD000402.
- Royal College of Obstetricians and Gynaecologists. Long-term Consequences of Polycystic Ovary Syndrome. Green-top Guideline No. 33. London. RCOG (2014).
- Antypkin, Y.G., Vdovychenko, Y.P., Graziottin, A., et al. “Uterine bleeding and quality of life of a woman. Resolution of the expert council.” Reproductive Endocrinology 3.47 (2019): 8–12. DOI: 10.18370/2309-4117.2019.47.8-12
- Argenta, P.A., Kassing, M., Truskinovsky, A.M., et al. “Bariatric surgery and endometrial pathology in asymptomatic morbidly obese women: a prospective, pilot study.” BJOG 120 (2013): 795–800.
- Modesitt, S.C., Hallowell, P.T., Slack-Davis, J.K., et al. “Women at extreme risk for obesity-related carcinogenesis: Baseline endometrial pathology and impact of bariatric surgery on weight, metabolic profiles and quality of life.” Gynecol Oncol 138 (2015): 238–45.
- Jernigan, A.M., Maurer, K.A., Cooper, K., et al. “Referring survivors of endometrial cancer and complex atypical hyperplasia to bariatric specialists: a prospective cohort study.” Am J Obstet Gynecol 213 (2015): 350.e1–10.
- Royal College of Obstetricians and Gynaecologists, British Society of Gynaecological Endoscopy. Management of Suspected Ovarian Masses in Premenopausal Women. Green-top Guideline No. 62. London. RCOG (2011).
- Gallos, I.D., Krishan, P., Shehmar, M., et al. “LNG-IUS versus oral progestogen treatment for endometrial hyperplasia: a long-term comparative cohort study.” Hum Reprod 28 (2013): 2966–71.
- Ismail, M.T., Fahmy, D.M., Elshmaa, N.S. “Efficacy of levonorgestrel-releasing intrauterine system versus oral progestins in treatment of simple endometrial hyperplasia without atypia.” Reprod Sci 20 (2013): 45–50.
- Behnamfar, F., Ghahiri, A., Tavakoli, M. “Levonorgestrel-releasing intrauterine system (Mirena) in compare to medroxyprogesterone acetate as a therapy for endometrial hyperplasia.” J Res Med Sci 19 (2014): 686–90.
- Gallos, I.D., Yap, J., Rajkhowa, M., et al. “Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis.” Am J Obstet Gynecol 207 (2012): 266.e1–12.
- National Institute for Health and Care Excellence. Fertility problems: assessment and treatment. NICE clinical guideline 156. Manchester. NICE (2013).
- Emons, G., Beckmann, M.W., Schmidt, D., et al. “New WHO classification of endometrial hyperplasias.” Geburtshilfe Frauenheilkd 75 (2015): 135–6.
- Zaino, R., Carinelli, S.G., Ellenson, L.H., et al. WHO Classification of Tumours of Female Reproductive Organs. 4th edition ed. Lyon, France. WHO Press (2014).
- Beavis, A.L., Cheema, S., Holschneider, C.H., et al. “Almost half of women with endometrial cancer or hyperplasia do not know that obesity affects their cancer risk.” Gynecol Oncol Rep 13 (2015): 71–5.
- Gunderson, C.C., Fader, A.N., Carson, K.A., et al. “Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review.” Gynecol Oncol 125 (2012): 477–82.
- Armstrong, A.J., Hurd, W.W., Elguero, S., et al. “Diagnosis and management of endometrial hyperplasia.” J Minim Invasive Gynecol 19 (2012): 562–71.
- Shan, W., Wang, C., Zhang, Z., et al. “Conservative therapy with metformin plus megestrol acetate for endometrial atypical hyperplasia.” J Gynecol Oncol 25 (2014): 214–20.
- Mitsuhashi, A., Sato, Y., Kiyokawa, T., et al. “Phase II study of medroxyprogesterone acetate plus metformin as a fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer.” Ann Oncol 27 (2016): 262–6.
- Ørbo, A., Arnes, M., Vereide, A.B., et al. “Relapse risk of endometrial hyperplasia after treatment with the levonorgestrel-impregnated intrauterine system or oral progestogens.” BJOG 123 (2016): 1512–9.
- Gonthier, C., Piel, B., Touboul, C., et al. “Cancer incidence in patients with atypical endometrial hyperplasia managed by primary hysterectomy or fertility-sparing treatment.” Anticancer Res 35 (2015): 6799–804.
- Tatarchuk, T.F., Kalugina, L.V., Tutchenko, T.N.“Endometrial hyperplastic processes: what's new?” Reproductive endocrinology 5 (2015): 7–13. DOI: 10.18370/2309-4117.2015.25.7-13
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Т.Ф. Татарчук, Ю.О. Дубоссарська, З.М. Дубоссарська, С.І. Регеда, О.В. Занько
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.