Therapeutic options of endometrial hyperplasia management. Current recommendations and prospective directions of treatment

Literature review

Authors

DOI:

https://doi.org/10.18370/2309-4117.2021.60.86-90

Keywords:

endometrial hyperplasia with atypia, endometrial cancer, progesterone receptors, conservative treatment, cridanimod, progestins

Abstract

Endometrial hyperplasia (EH) is a pathological condition characterized by proliferation of the endometrial glands with an increase in the glands/stroma ratio compared to normal proliferative endometrium. EH is a precursor to the development of one of the most common gynecological malignancies – endometrial cancer. There are EH without atypia and with atypia.
Total hysterectomy with bilateral salpingo-oophorectomy is the method of choice in the treatment of atypical EH. It is important to eliminate risk factors – overweight patients should lose weight by adjusting diet, increase physical activity. Recently, aromatase inhibitors have also proven to be an effective treatment option for EH with atypia. Oral progestogens and the levonorgestrel-releasing intrauterine device are methods of choice for conservative treatment of premenopausal and postmenopausal women with atypical EH.
However, not all patients can use progestins for a long time due to possible side effects. Failure of progestin treatment may depend on various factors, such as the patient’s age, health status, other conditions, and the degree or type of hyperplasia. So it is important to look for new methods of EH management and adjuvant drugs that will potentiate the effectiveness of basic treatment, as well as opportunities to reduce the risks of progesterone receptor resistance and potentiation of progestins. Cridanimod is a new small molecule that has been shown in studies to increase the progesterone receptors expression in the endometrium. It has been suggested that in combination with progestin therapy it increases the progesterone receptors expression and thus improves the effectiveness of treatment. Research results allows to consider the possibility of using cridanimod in complex EH therapy, especially against the background of viral infection. Cridanimod reduces the risk of resistance to progestogen therapy in EH, provides the best result after conservative treatment and reduces the number of relapses.

Author Biographies

T.F. Tatarchuk, SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”; State Scientific Institution “Center for Innovative Medical Technologies of the NAS of Ukraine”, Kyiv

MD, professor, corresponding member of the NAMS of Ukraine, deputy director for research work, head of the Endocrine Gynecology Department;
Head of Department of Reproductive Health

T.I. Kvasha, SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”, Kyiv

PhD, senior researcher, Endocrine Gynecology Department

N.F. Zakharenko, SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”; Institute for Planning Family Clinic, Kyiv

MD, senior researcher, Endocrine Gynecology Department;
Chairman of the Academic Council

N.V. Kosei, SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”; SSI “Center for Innovative Medical Technologies of the NAS of Ukraine, Kyiv

MD, professor, chief researcher, Endocrine Gynecology Department;
Head of Department of Reproductive Health

V.S. Solskyy, SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”, Kyiv

PhD, senior researcher, Endocrine Gynecology Department

I.V. Shmulian, Clinic “Verum”, Kyiv

Obstetrician-gynecologist

References

  1. Tatarchuk, T.F., Dubossarska, Y.O., Dubossarska, Z.М., et al. “Endometrial hyperplasia: modern approaches to diagnosis and treatment.” Reproductive endocrinology 2.58 (2021): 18–27. DOI: 10.18370/2309-4117.2021.58.18-27
  2. American College of Obstetricians and Gynecologists. ACOG Committee Opinion № 631. Endometrial Intraepithelial Neoplasia. Reaffirmed 2019.
  3. 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
  4. American College of Obstetricians and Gynecologists. “ACOG Committee Opinion No. 793. Hereditary cancer syndromes and risk assessment.” Obstet Gynecol 134 (2019): e143–9.
  5. Royal College of Obstetricians and Gynaecologists. Management of Endometrial Hyperplasia (2016).
  6. 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].
  7. Society of Gynecologic Oncology of Canada, Committee and the Society of Obstetricians and Gynaecologists of Canada. Guideline № 390. Classification and Management of Endometrial Hyperplasia (2019).
  8. Emons, G., Beckmann, M.W., Schmidt, D., et al. “New WHO classification of endometrial hyperplasias.” Geburtshilfe Frauenheilkd 75 (2015): 135–6.
  9. 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).
  10. Royal College of Obstetricians and Gynaecologists. Long-term Consequences of Polycystic Ovary Syndrome. Green-top Guideline No. 33. London. RCOG (2014).
  11. 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
  12. 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.
  13. 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.
  14. 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).
  15. 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. 16. American College of Obstetricians and Gynecologists. “ACOG Committee Opinion No. 793. Hereditary cancer syndromes and risk assessment.” Obstet Gynecol 134 (2019): e143–9.
  16. 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.
  17. 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].
  18. 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
  19. 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.
  20. 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.
  21. 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.
  22. Reed, S.D., Urban, R.R. “Classification and diagnosis of endometrial hyperplasia. ”Availablefrom:https://www.uptodate.com/contents/classification-and-diagnosis-of-endometrial-hyperplasia].
  23. 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].
  24. 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.
  25. Orbo, 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.
  26. 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.
  27. Armstrong, A.J., Hurd, W.W., Elguero, S., et al. “Diagnosis and management of endometrial hyperplasia.” J Minim Invasive Gynecol 19 (2012): 562–71.
  28. Gunderson, C.C., Fader, A.N., Carson, K.A., Bristow, R.E. “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.
  29. Orbo, A., Vereide, A., Arnes, M., et al. “Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial.” BJOG 121 (2014): 477–86.
  30. 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.
  31. Ushijima, K., Yahata, H., Yoshikawa, H., et al. “Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women.” J Clin Oncol 25 (2017): 2798–803.
  32. Emarh, M. “Cyclic versus continuous medroxyprogesterone acetate for treatment of endometrial hyperplasia without atypia: a 2-year observational study.” Arch Gynecol Obstet 292 (2015): 1339–43.
  33. Vishal Chandra, Jong Joo Kim, Doris Mangiaracina Benbrook, et al. “Therapeutic options for management of endometrial hyperplasia.” J Gynecol Oncol 27.1 (2016): e8. DOI: 10.3802/jgo.2016.27.e8
  34. Pennant, M.E., Mehta, R., Moody, P., et al. “Premenopausal abnormal uterine bleeding and risk of endometrial cancer.” BJOG 124 (2017): 404–11.
  35. Vishal Chandra, Jong Joo Kim, Doris Mangiaracina Benbrook, et al. “Therapeutic options for management of endometrial hyperplasia.” J Gynecol Oncol 27.1 (2016): e8. DOI: 10.3802/jgo.2016.27.e8
  36. Carlson, M.J., De Geest, K., Wang, X., et al. “Cridanimod and progestin therapy in hormone-resistant endometrial cancer.” Journal of Clinical Oncology 31.15 (2013). Available from: [https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.5597]. 10.1200/jco.2013.31.15_suppl.5597
  37. Gunderson, C.C., Fader, A.N., Carson, K.A., Bristow, R.E. “Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review.” Gynecol Oncol 2012; 125: 477-82.
  38. Timotheadou, E. “Emerging targeted agents in endometrial cancer treatment.” OA Cancer 1.1 (2013): 9.
  39. Lee, Y.C., Lheureux, S., Mirza, M.R., Oza, A.M. “Targeted Therapy in Management of Endometrial Cancer.” In: Management of Endometrial Cancer. Springer, Cham (2020).
  40. Mutch, D. “The New FIGO Staging System for Cancers of the Vulva, Cervix, Endometrium, and Sarcomas.” Gynecologic Oncology 115 (2009): 325–8. DOI: 10.1016/j.ygyno.2009.10.050
  41. Jerzaka, K.J., Duskab, L., MacKay, H.J. “Endocrine therapy in endometrial cancer: An old dog with new tricks.” Gynecologic Oncology 153.1 (2019): 175–83.
  42. Genkin, D., Surkov, K. Method of treatment of primary hormone resistant endometrial cancer. United States Patent Publication, March 31, 2017.
  43. Tatarchuk, T.F., Herman, D.G. “Endometrial polyp: new strategies for effective treatment.” Reproductive Endocrinology 4.36 (2017): 14–22. DOI: 10.18370/2309-4117.2017.36.14-22
  44. Kotelnikov S.N., Pelevin M.A., Volkova A.T., Tsyrlina E.V. “Open comparative study of changes in morphological and receptor status of tumor tissue during a course of neoadjuvant therapy with neovir and provera in patients with primary cancer of the body of the uterus.” Problems of Oncology, 2.47 (2001): 13–19.

Downloads

Published

2021-09-24

How to Cite

Tatarchuk, T., Kvasha, T., Zakharenko, N., Kosei, N., Solskyy, V., & Shmulian, I. (2021). Therapeutic options of endometrial hyperplasia management. Current recommendations and prospective directions of treatment: Literature review. REPRODUCTIVE ENDOCRINOLOGY, (60), 86–90. https://doi.org/10.18370/2309-4117.2021.60.86-90

Issue

No. 60 (2021)

Section

Tumors and pretumoral pathology

License

Copyright (c) 2021 Т.Ф. Татарчук, Т.І. Кваша, Н.Ф. Захаренко, Н.В. Косей, В.С. Сольський, І.В. Шмулян

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish with this journal agree to the following terms:

    1. 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.

    1. 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.