TREATMENT OF ENDOMETRIAL HYPERPLASIA WITHOUT ATYPIA BY MICRONIZED PROGESTERONE. EXPECTED AND REAL RESULTS
DOI:
https://doi.org/10.11603/24116-4944.2021.2.12425Keywords:
endometrial hyperplasia without atypia, receptors, progesterone resistanceAbstract
The aim of the study – to determine the effect of progesterone receptor expression on the effectiveness of treatment of endometrial hyperplasia without atypia in women of reproductive age and to establish the effectiveness of treatment in groups with low and high endometrial receptivity.
Materials and Methods. A prospective cohort study was performed in 45 patients of reproductive age (25–38 years) with abnormal uterine bleeding (AUB). The control group consisted of 15 patients with changes in the endometrium of the secretory type. Material for morphological and immunohistochemical studies was obtained by scraping the uterine cavity. Studies of estrogen and progesterone receptors were performed immunohistochemically in the Laboratory of Immunohistochemistry of Dnipro State Medical University (DSMU). The study group was divided into two subgroups according to the degree of expression of progesterone receptors. The degree of expression of progesterone receptors was calculated by H-score: 0–100 – low, 101 and more – high. All patients received treatment with micronized progesterone at a dose of 100 mg per day sublingually in a continuous mode for 6 months. The criterion of a positive effect was considered: the absence of complaints in patients and the absence of endometrial hyperplasia (EH) according to the results of pipelle endometrial biopsy after 6 months of treatment.
Results and Discussion. In all women, there was a significant expression of estrogen receptors (ER) in endometrial cells, which led to its proliferative activity against the background of reduced expression of progesterone receptors. According to the results of a study of women with no effect from the therapy, in contrast to women with effective therapy, there was a decrease in receptor expression to progesterone by 65 %. As a result of treatment based on the results of morphological examination of endometrial scrapings in 12 women (48 %) there was a regression of hyperbolized endometrium and histological normalization of the ratio of stromal and epithelial component. Simple atypical endometrial hyperplasia was again diagnosed in 27 women (37.8 %). Complex atypical endometrial hyperplasia was diagnosed in 18 (13.3 %) women, ie disease progression was observed. Thus, the effectiveness of the prescribed progestins according to the results of therapy for 6 months was 75 %.
Conclusion. Significant expression of estrogen receptors in endometrial cells was observed in all women, which caused its proliferative activity against the background of reduced expression of progesterone receptors by 65 %, which led to no effect of therapy in 25 % of women.
References
Gromova, O.L., Potapov, V.O., Khaskhachykh, D.A., Finkova, O.P., Gaponova, O.V., Kukina, G.O., & Penner, K.V. (2021). Epigenetic profile of endometrial proliferation in the different morphotypes of endometrial hyperplasia. Reprod. Endocrinol., 57, 68-78. DOI: https://doi.org/10.18370/2309-4117.2021.57.68-78.
Gromova, O.L., Potapov, V.O., Khaskhachykh, D.A., Gaponova, O., & Kukina G.O. (2021). Retseptornyi status endometriiu pry hiperplastychnykh protsesakh u zhinok premenopauzalnoho viku [Receptors of endometrium in premenopausal women with different morphotypes of endometrial hyperplasia]. Neonatolohiia, khirurhiia ta perynatalna medytsyna – Neonatology, Surgery and Perinatal Medicine, 11, 1 (39), 33-38. DOI: 10.24061/2413-4260.XI.1.39.2021.5.
Laas, E., Ballester, M., Cortez, A., Gonin, J., Canlorbe, G., Daraï, E., & Graesslin, O. (2014). Supervised clustering of immunohistochemical markers to distinguish atypical and non-atypical endometrial hyperplasia. Gynecol. Endocrinol., 31 (4), 282-285. DOI: 10.3109/09513590.2014.989981.
Khaskhachykh, D.A., Potapov, V.O., & Kukina, H.O. (2019). Dyferentsiiovanyi pidkhid do likuvannia hiperplazii endometriiu bez atypii u zhinok reproduktyvnoho viku [Differentiated approach to treatment of endometrial hyperplasia without atypia in women of reproductive age]. Aktualni pytannia pediatrii, akusherstva ta hinekolohii – Actual Problems of Pediatrics, Obstetrics and Gynecology, 2, 149-155. DOI: https://doi.org/10.11603/24116-4944.2019.2.10935 [in Ukrainian].
Gromova, O.L., Potapov, V.O., Khaskhachykh, D.A., Haponova, O., & Kukina, G. (2020). Analiz prychyn neefektyvnosti hormonoterapii hiperplazii endometriia bez atypii u zhinok v premenopauzi [Analysis of the causes of unsuccessful hormonal treatment of non-atypical endometrial hyperplasia in premenopousal women]. Visnyk Vinnytskoho natsionalnoho medychnoho universytetu – Reports of Vinnytsia National Medical University, 24 (4), 604-610. DOI: 10.31393/reports-vnmedical-2020-24(4)-08.
Horban, N.Y., Vovk, I.B., Lysiana, T.O., Ponomariova, I.H., & Zhulkevych, I.V. (2019). Peculiarities of uterine cavity biocenosis in patients with different types of endometrial hyperproliferative pathology. J. Med. Life, 12 (3), 266-270. DOI: 10.25122/jml-2019-0074.
Saito, S., Ito, K., Nagase, S., Suzuki, T., Akahira, J., Okamura, K., ..., & Sasano, H. (2006). Progesterone receptor isoforms as a prognostic marker in human endometrial carcinoma. Cancer, Sci., 97 (12), 1308-1314. DOI: 10.1111/j.1349-7006.2006.00332.x.
Sanderson, P.A., Critchley, H.O., Williams, A.R., Arends, M.J., & Saunders, P.T. (2017). New concepts for an old problem: the diagnosis of endometrial hyperplasia. Hum. Reprod. Update, 23 (2), 232-254. DOI: 10.1093/humupd/dmw042.
Zaporozhan, V., Tatarchuk, T., Dubinina, V., & Kosey, N. (2012). Sovremennaya diagnostika i lecheniye giperplasticheskikh protsessov endometriya [Modern diagnosis and treatment of endometrial hyperplastic processes]. Reprod. Endocrinol., 1 (3), 5-12 [in Russian].
Fan, R., Wang, Y., Wang, Y., Wei, L., & Zheng, W. (2017). Mechanism of progestin resistance in endometrial precancer/cancer through Nrf2-survivin pathway. Am. J. Transl. Res., 9 (3), 1483-1491.
Steinbakk, A., Gudlaugsson, E., Aasprong, O.G., Skaland, I., Malpica, A., Feng, W., …, & Baak, J.P. (2011b). Molecular biomarkers in endometrial hyperplasias predict cancer progression. Am. J. Obstet. Gynecol., 204 (4), 357.e1-e12. DOI: 10.1016/j.ajog.2010.12.007.
Sletten, E.T., Arnes, M., Lyså, L.M., Larsen, M., & Ørbo, A. (2019). 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, 126 (7), 936-943. DOI: 10.1111/1471-0528.15579.
Travaglino, A., Raffone, A., Saccone, G., D'Alessandro, P., Arduino, B., de Placido, G., …, & Zullo, F. (2019). Significant risk of occult cancer in complex non-atypical endoemtrial hyperplasia. Arch. Gynecol. Obstet., 300 (5), 1147-1154. DOI: 10.1007/s00404-019-05299-2.
Ordi, J., Bergeron, C., Hardisson, D., McCluggage, W.G., Hollema, H., Felix, A., …, & Nogales, F.F. (2014). Reproducibility of current classifications of endometrial endometrioid glandular proliferations: further evidence supporting a simplified classification. Histopathology., 64 (2), 284-292. DOI: 10.1111/his.12249.
Ozdegirmenci, O., Kayikcioglu, F., Bozkurt, U., Akgul, M.A., & Haberal, A. (2011). Comparison of the efficacy of three progestins in the treatment of simple endometrial hyperplasia without atypia. Gynecol. Obstet. Invest., 72 (1), 10-14. DOI: 10.1159/000321390.
Raffone, A., Travaglino, A., Saccone, G., Insabato, L., Mollo, A., De Placido, G., & Zullo, F. (2019). Endometrial hyperplasia and progression to cancer: which classification system stratifies the risk better? A systematic review and meta-analysis. Arch. Gynecol. Obstet., 299 (5),1233-1242. DOI: 10.1007/s00404-019-05103-1.
Al-Sabbagh, M., Lam, E.W., & Brosens, J.J. (2012). Mechanisms of endometrial progesterone resistance. Mol. Cell. Endocrinol., 358 (2), 208-215. DOI: 10.1016/j.mce.2011.10.035.
Auclair, M.H., Yong, P.J., Salvador, S., Thurston, J., Colgan, T.T.J., & Sebastianelli, A. (2020). Guideline No. 390-Classification and management of endometrial hyperplasia. J. Obstet. Gynaecol. Can., 42 (10), 1289-1800. DOI: 10.1016/j.jogc.2019.03.025.
Tatarchuk, T., Kovalenko, E., & Filonenko, T. (2011). Ekspressiya retseptorov steroidnykh gormonov i urovni estrogena i progesterona v zhidkosti matki u zhenshchin s giperplaziyey endometriya [Expression of steroid hormone receptors and levels of estrogen and progesterone in the uterine fluid in women with endometrial hyperplasia]. Zhenskoye zdorovye – Women Health, 6 (62), 105-109 [in Russian].
Khaskhachikh, D.A., Potapov, V.O., Kukina, G.O., Gaponova, E.A., Penner, K.V., Reznichenko, V.V., & Nechaiev, V.V (2018). Znachennia ekspresii retseptoriv prohesterona (PR-A i PR-B) yak predyktoriv retsydyvu hiperplazii endometriiu pislia terapii z vykorystanniam prohestyniv [The value of the expression of progesterone receptors (PR-A and PR-B) as predictors of recurrence of endometrial hyperplasia after therapy with progestins]. Zbirnyk naukovykh prats Asotsiatsiii akusheriv-hinekolohiv Ukrainy – Scientific Digest of Association of Obstetricians and Gynaecologists of Ukraine, 2, 203-207 [in Ukrainian].
Khariyet, E.R., & Gatter, K.S. (1999). Immunotsitokhimiya: elektronnaya mikroskopiya. Molekulyarnaya klinicheskaya diagnostika. Metody [Immunocytochemistry: electron microscopy. Molecular clinical diagnostics. Methods]. Transl. from Engl. Kherrington, Dzh. Makgi, S. Ed. Moscow: Mir [in Russian].
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