Non-hormonal therapy of patients with fibrocystic mastopathy in combination with endometrial hyperplasia

Introduction. The article presents a comparative analysis of the treatment of patients with combined estrogen-dependent pathology of female reproductive system: fibrocystic mastopathy and endometrial hyperplasia without atypia. The experience of treatment with an indole-carbinol-containing drug as monotherapy while using a levonorgestrel-releasing intrauterine system is presented.

Aim. To evaluate the clinical efficacy of indolecarbinol in the treatment of patients with combined estrogen-dependent pathology of the female reproductive system.

Materials and methods. The authors studied the responses to the treatment of patients with fibrocystic mastopathy and simple endometrial hyperplasia (n = 65) with the indole-carbinol-containing drug at a dose of 400 mg once daily for 12 months. All patients were divided into two groups: Group I (n = 32) – women who refused hormone therapy (indole-carbinol monotherapy); Group II (n = 33) – the use of indole-carbinol while using the levonorgestrel-releasing intrauterine system. Diagnostic methods: clinical and laboratory examination, ultrasound examination of mammary glands and pelvic organs, mammography, nipple discharge cytology at baseline and 6 and 12 months after the start of therapy. Before study group assignment to treatment, all patients underwent hysteroscopy with endometrial biopsy and histological examination. Descriptive statistics were used to evaluate the data: p-values below 0.05 were considered statistically significant.

Results and discussion. The presented experience in treating women with combined pathology of the female reproductive system (fibrocystic mastopathy and endometrial hyperplasia without atypia) with the indole-carbinol-containing drug showed high clinical efficacy in mastopathy (relief of mastodynia (83.0 ± 1.6%), improvement of the ultrasound view of BI-RADS (66.1 ± 1.4%), reductions in mammographic density (66.1 ± 2.1%, p < 0.05)), high tolerability and satisfactory compliance. This drug combined with hormone therapy is recommended for the treatment of endometrial hyperplasia.

Сonclusion. The use of indole-carbinol in the treatment of benign hyperplastic processes in mammary glands and endometrial hyperplasia is pathogenetically substantiated and shows high clinical efficacy

1. Tazina T.V. Pathogenetically based therapy of cyclic mastalgia. Akusherstvo i ginekologiya = Obstetrics and Gynecology. 2020;(9):187–190. (In Russ.) https://doi.org/10.18565/aig.2020.9.187-190.

2. Serov V.N., Tagieva T.T. Benign breast diseases. Gynecological endocrinology. Мoscow: MEDpress-inform; 2015. 370 p. (In Russ.).

3. Adamyan L.V., Andreeva E.N., Artymuk N.V., Ashrafyan L.A., Belokrinitskaya T.E., Dolgushina N.V. et al. Benign breast dysplasia: clinical guidelines. Moscow; 2020. (In Russ.) Available at: https://legalacts.ru/doc/ klinicheskie-rekomendatsii-dobrokachestvennaja-displazija-molochnoizhelezy-utv-minzdravom-rossii/.

4. Khashukoeva A.Z., Khlynova S.A., Ilyina I.Y., Kerchelaeva S.A. Estrogendependent states of the female reproductive system: the possibility of non-hormonal therapy with the use of indole-3-carbinol. Akusherstvo i ginekologiya = Obstetrics and Gynecology. 2020;(5):65–69. (In Russ.) https://doi.org/10.18565/aig.2020.5.65-69.

5. Morimoto Y., Conroy S.M., Pagano I.S., Isaki M., Franke A.A., Nordt F.J., Maskarinec G. Urinary estrogen metabolites during a randomized soy trial. Nutr Cancer. 2012;64(2):307–314. https://doi.org/10.1080/01635581.2012.648819.

6. Radzinskiy V.E. Breast medicine and gynecological diseases. Moscow: Status Praesens; 2017. 335 p. (In Russ.).

7. Tang Z.R., Zhang R., Lian Z.X., Deng S.L., Yu K. Estrogen-Receptor Expression and Function in Female Reproductive Disease. Cells. 2019;8(10):1123. https://doi.org/10.3390/cells8101123.

8. Babaeva N.A., Ashrafyan L.A., Antonova I.B., Motskobili T.A., Lyustik A.V. The role of estrogen metabolites in the pathogenesis of breast, endometrial and ovarian cancer. Vestnik Rossiyskogo nauchnogo tsentra rentgenoradiologii = Bulletin of the Russian Scientific Center for Roentgenoradiology. 2013;13:12–16. (In Russ.). Available at: http://vestnik.rncrr.ru/vestnik/v13/ papers/babaeva_v13.htm.

9. Kiselev V.I., Lyashenko A.A. Molecular mechanisms of regulation of hyperplastic processes. M.: Dimitreyd Grafik Grupp; 2015. 346 p. (In Russ.).

10. Ovsyannikova T.V. Benign breast diseases – antiprophyliferative therapy. RMJ. Mother and Child. 2018;1(1):67–70. (In Russ.) http://doi.org/10.32364/2618- 8430-2018-1-1-67-70.

11. Smetnik A.A., Smetnik V.P., Kiselev V.I. Experience with indole-3-carbinol used to treat diseases of the breast and to prevent breast cancer. Akusherstvo i ginekologiya = Obstetrics and Gynecology. 2017;(2):106–112. (In Russ.) http://doi.org/10.18565/aig.2017.2.106-12.

12. Licznerska B., Baer-Dubowska W. Indole-3-carbinol and its role in chronic diseases. Adv Exp Med Biol. 2016;928:131–154. http://doi.org/10.1007/978- 3-319-41334-1_6.

13. Silvera S., Rohan T. Benign proliferative epithelial disorders of the breast: a review of the epidemiologic evidence. Breast Cancer Res Treat. 2008;110(3):397–409. https://doi.org/10.1007/s10549-007-9740-3.

14. Szaefer H., Licznerska B., Krajka-Kuźniak V., Bartoszek A., BaerDubowska W. Modulation of CYP1A1, CYP1A2 and CYP1B1 expression by cabbage juices and indoles in human breast cell lines. Nutr Cancer. 2012;64(6):879–888. https://doi.org/10.1080/01635581.2012.690928.

15. Idrisova E.A., Badgoeva O.Kh., Vlasov R.S., Makarova I.I., Guriev T.D. Combination of hyperproliferative diseases of the uterus and mammary glands: the possibility of targeted therapy. Problems of reproduction: Proceedings of the IV International Congress on Reproductive Medicine. Moscow; 2010, pp. 186–187. (In Russ.).

16. Dobrokhotova Y.E., Narimanova M.R., Saprykina L.V., Ilina I.Yu., Mazo M.L. Mammary gland condition in premenopausal women with endometrial hyperplasia. Meditsinskiy sovet = Medical Council. 2021;(3):120–127. (In Russ.) https://doi.org/10.21518/2079-701X-2021-3-120-127.

17. Ashrafyan L.A., Babaeva N.A., Antonova I.B., Aleshikova O.I., Gerfanova E.V. The Role of Hormonal Disbalance in the Carcinogenesis of Tumors of the Female Reproductive System. Meditsinskiy opponent = Medical Opponent. 2019;(3):34–39. (In Russ.) http://proffopponent.ru/wp-content/ uploads/2019/11/block_light-1.pdf.

18. Weng J., Omar H., Kulp S., Chen C. Pharmacological exploitation of indole3-carbinol to develop potent antitumor agents. Mini Rev Med Chem. 2010;10(5):398–404. https://doi.org/10.2174/138955710791330945.

19. Khiyaeva V.A. Experience with indolecarbinol used to treat mastopathy. Meditsinskiy sovet = Medical Council. 2019;(13):154–158. (In Russ.) https://doi.org/10.21518/2079-701X-2019-13-154-158.

20. Ahmad A., Sakr W.A., Rahman K.M. Anticancer properties of indole compounds: mechanism of apoptosis induction and role in chemotherapy. Curr Drug Targets. 2010;11(6):652–666. https://doi.org/10.2174/138945010791170923.

21. Kulagina N.V. Therapy for fibrocystic breast disease in patients with uterine myoma. Opukholi zhenskoy reproduktivnoy sistemy = Tumors of Female Reproductive System. 2010;(1):40–43. (In Russ.) Available at: https://ojrs. abvpress.ru/ojrs/article/view/213.

22. Zhang N., Ho S., Mo X., Lin F., Huang W., Luo H. Glucosinolate and Isothiocyanate Intakes Are Inversely Associated with Breast Cancer Risk: A Case-Control Study in China. Br J Nutr. 2018;119(8):957–964. https://doi. org/10.1017/S0007114518000600.

23. Kogan E.A., Hunanyan A.L., Namiot V.A., Baburin D.V., Udaltsov S.N. A precision approach to the diagnosis and choice of tactics in the treatment of endometrial hyperplasia in perimenopause. Biophysics. 2019;64(4):649–656. (In Russ.) https://doi.org/10.1134/S0006350919040055.

24. Kerchelaeva S.B., Smetnik A.A., Bespalov V.G. Mastopathy and breast cancer prevention as interdisciplinary problem. RMJ. Mother and Child. 2016;24(15):1018–1025. (In Russ.) Available at: https://www.rmj.ru/articles/ginekologiya/Mastopatiya_i_profilaktika_raka_molochnoy_ghelezy_ kak_meghdisciplinarnaya_problema/.

25. Ampofo E., Lachnitt N., Rudzitis-Auth J. Indole-3-carbinol is a potent inhibitor of ischemia-reperfusion-induced inflammation. J Surg Res. 2017;215:34–46. https://doi.org/10.1016/j.jss.2017.03.019.

26. Ziegler R.G. Epidemiologic studies of estrogen metabolism and breast cancer. Steroids. 2015;99(Pt A):67–75. https://doi.org/10.1016/j.steroids.2015.02.015.

27. Vysotskaya I.V. Modern possibilities of therapy of fibrocystic disease. Opukholi zhenskoy reproduktivnoy sistemy = Tumors of the Female Reproductive System. 2009;(1–2):44–46. (In Russ.) Available at: https://ojrs. abvpress.ru/ojrs/article/view/289.

28. Morisky D., Green L., Levine D. Concurrent and predictive validity of a selfreported measure of medication adherence. Med Care. 2006;24(1):67–74. https://doi.org/10.12691/ajap-2-5-1.