The role of steroid receptors in the pathogenesis of adenomyosis in the presence of concomitant endometrial pathology in postmenopause

  • G.Yu. Honcharenko Odessa National Medical University, Odessa, Ukraine
Keywords: adenomyosis, postmenopause, estrogen receptors, progesterone receptors, androgen receptors.


Determining the pathogenesis of adenomyosis in postmenopausal women is promising, as it will allow a more thorough study of the mechanisms of hormonal changes and resolve issues related to adenomyosis in women of reproductive age. The purpose of the study is to establish the role of steroid receptors in the pathogenesis of adenomyosis in the presence of concomitant endometrial pathology in postmenopausal women. Study material is removed uteri with parovaria from 117 patients of 49-76 years old. The cases were divided into 4 groups depending on the presence of adenomyosis (AM) and background pathology (endometrioid carcinoma of the endometrium (ECE) and endometrial hyperplasia (EHP)): 1) 27 women with adenomyosis and EHP; 2) 30 women with adenomyosis and ECE; 3) 30 women with adenomyosis and age-related changes in the endometrium; 4) 30 women with age-related changes without AM (comparison group). The immunohistochemical reaction was carried out using primary antibodies to estrogen (ER), progesterone (PR) and androgen (AR) receptors. Statistical processing was carried out using parametric methods of variation statistics (calculated the arithmetic mean, standard deviation, confidence interval, Student criterion). The predominance of the ER expression in the glandular and stromal components of the eutopic endometrium in the presence of AM and hyperplastic processes was compared with the comparison group (p<0.01). A high level of ER expression is characteristic of the epithelium of the endometrium with EHP (7.333±0.314) and ECE (6.200±0.712) rather than for the endometrium with atrophic changes in the presence of AM (4.433±0.773). In the stroma, a high ER activity was detected with EHP (7.148±0.276) rather than with atrophic changes (4.567±0.738) and ECE (4.167±0.602). It was established that in the epithelium of adenomyosis foci, ER expression indices were lower in atrophy (3.433±1.074) than with AM foci in ECE (4.667±0.526) and EHP (5.148±0.745). In the stroma of adenomyosis foci, ER expression is higher in EHP than in ECE and atrophy. The activity of PR in the eutopic endometrium decreases from simple non-typical to complex atypical EHP and in patients with adenomyosis and ECE, as the degree of differentiation of cells of ECA decreases (from G1 to G3 ECE). A minimal expression of PR was found in the comparison group. In the cells of internal endometriosis there were positive indices of immunohistochemical reaction with PR. There were obtained minimum scores for receptor expression of AR in eu- and ectopic endometria. Conclusion: adenomyosis foci have a regulatory effect on the uterine endometrium, stimulating the expression of ER and, to a lesser extent, PR, and do not affect the level of AR in the eutopic endometrium.


[1] Adamyan, L. V., Andreeva, E. N., Apolikhina, I. A., Balan, V. E., Bezhenar, V. F., Gevorkyan, M. A., & Torubanov, S. F. (2015). Combined benign tumors and hyperplastic processes of the uterus (myoma, adenomyosis, hyperplasia, endometritis). Retrieved from:>contect>pdf.
[2] Agarwal, S., Alzahrani, F.A., & Ahmed, A. (2018). Hormone Replacement Therapy: Would it be Possible to Replicate a Functional Ovary? Int. J. Mol. Sci., 19(10), 3160. doi: 10.3390/ijms19103160.
[3] Agostinho, L., Cruz, R., Osório, F., Alves, J., Setúbal, A., & Guerra, A. (2017). MRI for adenomyosis: a pictorial review. Insights Imaging, 8(6), 549-556. doi: 10.1007/s13244-017-0576-z.
[4] Akopian, A. R., & Pechenikova, V. A. (2014). Clinical and morphological features of adenomyosis in women of various age groups. Bulletin of the Russian Military Medical Academy, 45(1), 65-70.
[5] Afinogenova, E. A., & Cherstvyy, Ye. D. (2016). Active and inactive adenomyosis: a comparative analysis in the eyes of the ectopic endometrium (expression of aromatase P-450, estrogen receptors A and B, progesterone receptors). Bulletin of education and development of science of the Russian Academy of Natural Sciences, 20(2), 74-82.
[6] Aznaurova, Y. B., Zhumataev, M. B., Roberts, T. K., Aliper, A. M., & Zhavoronkov, A. A. (2014). Molecular aspects of development and regulation of endometriosis. Reprod. Biol. Endocrinol., 12, 50. doi: 10.1186/1477-7827-12-50.
[7] Beniuk, V. A., Vinyarski, Y. M., Goncharenko, V. M., Kalenska, O. V., & Ponomarchuk, R. M. (2013). Diagnostic significance of determining the expression of hormone receptors and apoptosis markers in endometrial hyperplastic processes. Health of the nation, 3(27), 14-20.
[8] Beniuk, V. O., & Goncharenko, V. M. (2014). Individualization of treatment of women of reproductive and premenopausal age with endometrial hyperplastic processes. Woman’s health, 10(96), 125-129. Retrieved from:
[9] Bodur, S., Dundar, O., Pektas, M. K., Babayigit, M. A., Ozden, O., & Kucukodacı, Z. (2015). The clinical significance of classical and new emerging determinants of adenomyosis. Int. J. Clin. Exp. Med., 8(5), 7958-7964.
[10] Caixia, J., Chao, L., Jing, G., Li, C., Ning, L., Xiaoyan, Q., & Zhongping, C. (2017). The Expression of Toll-like receptors in eutopic and ectopic endometrium and its implication in the inflammatory pathogenesis of adenomyosis. Sci. Rep., 7, 7365. doi: 10.1038/s41598-017-07859-5.
[11] Chumak, Z. V., Zelinsky, A. A., Shapoval, N. V., Shapoval, N. V., & Isterin, N. S. (2014). Assessment of hormonal-receptor status and proliferative activity of hyperplastic endometrium. Odessa Medical Journal, 142(2), 66-70. Retrieved from:
[12] Divakova, T. S., & Medvedskaya, S. E. (2006). Management of patients with recurrent endometrial hyperplasia in peri- and postmenopausal women. Bulletin of Vitebsk State Medical University, 5(3), 75-79. Retrieved from:
[13] Eun, L. C., Seong, B. C., Sa, R. L., Young, M. L., Kyungah, J., Hye-Sung, M., & Hyewon, C. (2017). Comorbidity of gynecological and non-gynecological diseases with adenomyosis and endometriosis. Obstetr. Gynecol. Sci., 60(6), 579-586. doi: 10.5468/ogs.2017.60.6.579.
[14] Garavaglia, E., Serafini A., Inversetti, A., Ferrari, S., Tandoi, I., Corti, L., & Candiani, M. (2015). Adenomyosis and its impact on women fertility. Iran J. Reprod. Med., 13(6), 327-336. Retrieved from:
[15] Gemmell, L. C., Webster, K. E., Kirtley, S., Vincent, K., Zondervan, K. T., & Becker, C. M. (2017). The management of menopause in women with a history of endometriosis: a systematic review. Hum Reprod Update, 23(4), 481-500. doi: 10.1093/humupd/dmx011.
[16] Gizzo, S., Patrelli, T. S., Dall'asta, A., Di Gangi, S., Giordano, G., Migliavacca, C., & Berretta, R. (2016). Coexistence of adenomyosis and endometrioid endometrial cancer: Role in surgical guidance and prognosis estimation. Oncol. Lett., 11(2), 1213-1219. doi:10.3892/ol.2015.4032
[17] Kudrina, E. A., Zholobova, M. N., & Masyakina, A. V. (2016). Modern aspects of the pathogenesis and treatment of endometrial hyperplasia, uterine fibroids and adenomyosis. Archive of Obstetrics and Gynecology named after V.F. Snegireva, 3(3), 131-135. doi: 10.18821/2313-8726-2016-3-3-130-135
[18] Kurik, O. G. & Kalenska, O. V. (2014). Immunologic hormonal activity of ectopic and eutopic endometria with adenomyosis. Scientific journal of the Ministry of Health of Ukraine, 1(5), 100-105. Retrieved from:
[19] Meliksetian, A. V., Kuryk, O. G., Kalenskaya O. V. & Lysenko B. M. (2014). Immunohistochemical study of estrogen and progesterone receptors in foci of genital endometriosis. Ukrainian scientific-medical youth journal, 3(82), 71-73.
[20] Pozharisski, K. M., Vinokurov, V. L., Zharinov, G. M., Boldaryan, N. A., Kuznetsova, M. Ye., Gasparyan, N. A., & Samsonova, Ye. A. (2008). Immunohistochemical markers as prognosticators in oncogynecology. Problems in Oncology, 54(4), 463-470. ISSN: 0507-3758.
[21] Tumansky, V. A., & Baudarbekova, M. M. (2009). Study of estrogen and progesterone receptors in glandular hyperplasia, atypical hyperplasia and endometrial adenocarcinoma. Pathology, 6(2), 111-113. Retrieved from:
[22] Tumansky, V. A. & Chepets, A. V. (2016). Comparative immunohistochemical characterization of the expression of estrogen-α and progesterone receptors, p16 and p53, Ki-67 and caspase 3 in invasive endometrioid adenocarcinoma of the uterus and in proliferative endometrium. Pathology, 1(36), 22-28. DOI: 10.14739/2310-1237.2016.1.72165
[23] Rizner, T. L. (2009). Estrogen metabolism and action in endometriosis. Mol. Cell. Endocrinol., 307(1-2), 8-18. doi: 10.1016/j.mce.2009.03.022.
[24] Rižner, T. L. (2016). The Important Roles of Steroid Sulfatase and Sulfotransferases in Gynecological Diseases. Front. Pharmacol., 7, 30. doi: 10.3389/fphar.2016.00030.
[25] Taran, F. A., Stewart, E. A., & Brucker, S. (2013). Adenomyosis: Epidemiology, Risk Factors, Clinical Phenotype and Surgical and Interventional Alternatives to Hysterectomy. Geburtshilfe Frauenheilkd, 73(9), 924-931. doi: 10.1055/s-0033-1350840.
[26] Tetikkurt, S., Çelik, E., Taş, H., Cay, T., Işik, S., & Usta, A. T. (2018). Coexistence of adenomyosis, adenocarcinoma, endometrial and myometrial lesions in resected uterine specimens. Mol. Clin. Oncol., 9(2), 231-237. doi: 10.3892/mco.2018.1660
[27] Tingthanatikul, Y., Lertvikool, S., Rodratn, N., Waiyaput, W., Dittharot, K., Sroyraya, M., & Sophonsritsuk, A. (2018). The Effects of Dienogest on Macrophage and Natural Killer Cells in Adenomyosis: A Randomized Controlled Study. Int. J. Fertil. Steril., 11(4), 279-286. doi: 10.22074/ijfs.2018.5137.
[28] Tze-Sing, H., Yi-Jen, C., Teh-Ying, C., Chih-Yao, C., Hsin-Yang L., Ben-Shian, H., & Muh-Hwa, Y. (2014). Oestrogen-induced angiogenesis promotes adenomyosis by activating the Slug-VEGF axis in endometrial epithelial cells. J. Cell. Mol. Med., 18(7), 1358-1371. doi: 10.1111/jcmm.12300.
[29] Vlahos, N. F., Theodoridis, T. D., & Partsinevelos, G. A. (2017). Myomas and Adenomyosis: Impact on Reproductive Outcome. Biomed. Res. Int., 5926470. doi: 10.1155/2017/5926470.
[30] Zakharenko, N. F., Kovalenko, N. V., & Manolyak, I. P. (2015). On the subject of complex therapy of endometriosis. Reproductive endocrinology, 23(3), 28-33.
How to Cite
Honcharenko, G. (2019). The role of steroid receptors in the pathogenesis of adenomyosis in the presence of concomitant endometrial pathology in postmenopause. Reports of Morphology, 25(1), 45-54.