CYTOKINE PROFILE IN COMPLICATIONS OF HORMONE THERAPY ADMINISTERED FOR UTERINE FIBROIDS

Uterine fibroids take a second place in the structure of gynecological diseases, after inflammation of genital organs, with a share of 40%. The aim of the study was to investigate cytokine profile and factors of immune dysfunction in patients with uterine fibroids complicated by hemorrhagic syndrome during a course of hormone replacement therapy.
А detailed comparative analysis of a survey was performed in 95 women with uterine fibroids. Tumor size did not exceed 12 weeks of pregnancy, mainly with intramural and subserous localization of nodes, having indications for conservative treatment. The main group consisted of 43 patients with uterine fibroids and clinical signs of hemorrhagic syndrome observed in the course of hormone replacement therapy (Buserelindepot 3.75 mg). In a comparison group (n = 52), treatment of fibroids with hormonal therapy was not carried out.
A control group comprised healthy women (n = 27). The survey consisted of a comprehensive ultrasound scan with Doppler ultrasound apparatus HITACHI 5500. The immune parameters were evaluated as contents of cytokines (interleukins IL-1β, IL-4, IL-6, IL-2, IFNγ, TNFα) and levels of the Fas-ligand apoptosis marker in blood serum using solid-phase immunoassay technique. For identification of urogenital infection pathogens, methods of diagnostic PCR and ELISA were used.
The results of the study were as follows: it is established that emergence of hemorrhagic syndrome on the during hormone therapy for uterine fibroids is associated with activation of latent forms of urogenital infections, being a probable result of potentiating immunosuppressive action of hormonal drugs that promote alterations of immune status, reduction of Th1 and Th2 lymphocyte functions, as well as significant inhibition of apoptosis. In the main group, IL-1β, IL-2, IL-4, IL-6 and IFNγ concentrations were decreased by 1.3 to 1.5 – fold, whereas TNFα and FasL contents were 2 times lower than the levels in control group. In addition, qualitative analysis of uterine hemodynamics has shown that the complications associated with hormone therapy of uterine fibroids are accompanied by a significant increase of the systolic blood flow velocity in the uterine arteries (1.8%), against decrease in diastolic blood flow (2.5 times) and increased resistance index of the vascular wall (1.6 times), as compared with appropriate parameters in healthy women. In conclusion, the received data suggest a need for more detailed examination of women, in order to detect chronic forms of urogenital infections, by means of improving conservative treatment strategies of uterine fibroids, reducing frequency of complications and effectiveness of hormone therapy

1. Буянова С.Н., Мгелиашвили М.В., Петракова С.А. Современные представления об этиологии, патогенезе и морфогенезе миомы матки // Российский вестник акушера-гинеколога, 2008. Т. 8, № 6. С. 45-50. [Buianova S.N., Mgeliashvili M.V., Petrakova S.A. Current views of the etiology, pathogenesis, and morphogenesis of uterine myoma. Rossiyskiy vestnik akushera-ginekologa, 2008, Vol. 8, no. 6, pp. 45-50. (In Russ.)]

2. Джакупов Д.В., Локшин В.Н., Хамко В.А. Патогенетические особенности изменения морфологической структуры при миоме матки, осложненной кровотечением // Вестник Новгородского государственного университета им. Ярослава Мудрого, 2014. № 78. С. 122-124. [Dzhakupov D.V., Lokshin V.N., Khamko V.A. Pathogenetic characteristics of change in anatomical structure in hysteromyoma complicated by bleeding. Vestnik Novgorodskogo gosudarstvennogo universiteta im. Yaroslava Mudrogo = Vestnik of Yaroslav the Wise Novgorod State University, 2014, no. 78, pp. 122-124. (In Russ.)]

3. Дивакова Т.С., Бекиш В.Я. Роль апоптоза, индуцированного Луприд Депо, в лечении женщин с интерстициальной миомой матки в репродуктивном возрасте // Репродуктивное здоровье. Восточная Европа, 2014. № 1 (31). С. 123-128. [Divakova T.S, Bekish V.Ya. The role of apoptosis induced by Lupride depo in women with interstitial myoma treatment in reproductive age. Reproduktivnoe zdorovye. Vostochnaya Evropa = Reproductive Health. Eastern Europe, 2014, no. 1 (31), pp. 123-128. (In Russ.)]

4. Зацепин А.В., Новикова В.А., Васина И.Б. Сравнение эффективности фармакологических методов антирецидивного лечения миомы матки после консервативной миомэктомии // Кубанский научный медицинский вестник, 2012. № 2. С. 88-93. [Zatsepin A.V., Novikova V.A., Vasina I.B. Efficiency comparison of pharmaceutical antirecurrent methods of fibroids treatment after conservative myomectomy. Kubanskij nauchnyj medicinskij vestnik, 2012, no. 2, pp. 88-93. (In Russ.)]

5. Кичигин О.В., Арестова И.М., Занько Ю.В. Факторы риска развития миомы матки и качество жизни пациенток, оперированных по поводу миомы матки // Охрана материнства и детства, 2013. № 2 (22). С. 36-41. [Kichigin O.V., Arestova I.M., Zanko Yu.V. Risk factors of hysteromyoma development and quality of life of patients operated in connection with hysteromyoma. Okhrana materinstva i detstva = Maternal and Child Health, 2013, no. 2 (22), pp. 36-41. (In Russ.)]

6. Коренная В.В., Подзолкова Н.М., Пучков К.В. Органосохраняющие методы лечения миомы матки: есть ли повод для дискуссии? // Гинекология, 2015. Т. 17, № 1. С. 78-82. [Korennaya V.V., Podzolkova N.M., Puchkov K.V. Methods of organ-preservation of uterine fibroids. Is there a cause for debate? Ginekologiya = Gynecology, 2015, Vol. 17, no. 1, pp. 78-82. (In Russ.)]

7. Липатова Н.А., Лабзина М.В., Лабзина Л.Я. Исследование содержания женских половых гормонов у больных миомой матки // Medicus, 2015. № 2 (2). С. 18-19. [Lipatova N.A., Labzina M.V., Labzina L.Ya. The research of the content of female sex hormones in patients with hysteromyoma. Medicus = Medicus, 2015, no. 2 (2), pp. 18-19. (In Russ.)]

8. Макацария А.Д. Системные синдромы в акушерско-гинекологической клинике: руководство для врачей. М.: МИА, 2010. 888 с. [Makatsaria A.D. System syndromes in obstetric-gynecological clinic: Guide for physicians]. Moscow: MIA, 2010. 888 р.

9. Никитина Е.С., Рымашевский А.Н., Набока Ю.Л. Особенности микробиоценоза влагалища у женщин позднего репродуктивного возраста при миоме матки // Медицинский вестник Юга России, 2013. № 3. 63-65. [Nikitina E.S., Rymashevskiy A.N., Naboka Yu.L. Features microbiocenosis sheath in women reproductive age with hysteromyoma. Meditsinskiy vestnik Yuga Rossii = Medical Herald of the South of Russia, 2013, no. 3, pp. 63-65. (In Russ.)]

10. Озерская И.А., Девицкий А.А. Изменения гемодинамики матки, пораженной миомой, у женщин репродуктивного и пременопаузального возраста // Медицинская визуализация, 2014. № 1. С. 70-80. [Ozerskaya I.A., Devitsky A.A. Hemodynamic changes in the myomas uterus in women of reproductive and premenopausal period. Meditsinskaya vizualizatsiya = Medical Visualization, 2014, no. 1, pp. 70-80. (In Russ.)]

11. Радзинский В.Е., Архипова М.П. Миома матки: проблемы и перспективы начала века // Медицинский совет, 2014. № 9. С. 30-33. [Radzinsky V.E., Arkhipova M.P. Uterine fibroids: problems and prospects at the turn of the century. Meditsinskiy sovet = Medical Council, 2014, no. 9, pp. 30-33. (In Russ.)]

12. Рогожина И.Е., Хворостухина Н.Ф. Малоинвазивные технологии и система гемостаза при миоме матки // Саратовский научно-медицинский журнал, 2011. Т. 7, № 3. С. 587-592. [Rogozhina I.E., Khvorostukhina N.F. Lowinvasive technologies and hemostasis system at a hysteromyoma. Saratovskiy nauchnomeditsinskiy zhurnal = Saratov Journal of Medical Scientific Research, 2011, Vol. 7, no. 3, pp. 587-592. (In Russ.)]

13. Рогожина И.Е., Хворостухина Н.Ф., Столярова У.В., Нейфельд И.В. Влияние эмболизации маточных артерий на состояние иммунной системы у больных миомой матки // Фундаментальные исследования, 2011. № 9 (2). С. 290-294. [Rogozhina I.E., Khvorostukhina N.F., Stolyarova U.V., Neyfeld I.V. Influence of aa. uterinae embolization on the condition of immune system at patients of the hysteromyoma. Fundamental`nye issledovaniya = Fundamental Research, 2011, no. 9 (2), pp. 290-294. (In Russ.)]

14. Рогожина И.Е., Хворостухина Н.Ф., Нейфельд И.В., Проданова Е.В. Преимущества эмболизации маточных артерий в хирургическом лечении миомы матки // Лечение и профилактика, 2013. № 2 (6). С. 13-19. [Rogozhina I.Е., Khvorostukhina N.F., Neyfeld I.V., Prodanova Е.V. The embolization of uterine arteries in surgical treatment of hysteromyoma. Lechenie i profilaktika = Disease Treatment and Prevention, 2013, no. 2 (6), pp. 13-19. (In Russ.)]

15. Сидорова И.С., Унанян А.Л., Агеев М.Б., Ведерникова Н.В., Жолобова М.Н. Современное состояние вопроса о патогенезе, клинике, диагностике и лечении миомы матки у женщин репродуктивного возраста // Акушерство, гинекология и репродукция, 2012. Т. 6, № 4. С. 22-28. [Sidorova I.S., Unanyan A.L., Ageev M.B., Vedernikova N.V., Zholobova M.N. Current status of the pathogenesis, clinical features, diagnosis, and treatment. Akusherstvo, ginekologiya i reproduktsiya = Obstetrics, Gynecology, and Reproduction, 2012, Vol. 6, no. 4, pp. 22-28. (In Russ.)]

16. Тихомиров А.Л. Современные принципы терапевтического лечения миомы матки // Эффективная фармакотерапия, 2015. № 5. С. 56-60. [Tikhomirov A.L. Modern principles of therapeutic treatment of uterine fibroids. Effektivnaya farmakoterapiya = Effective Pharmacotherapy, 2015, no. 5, pp. 56-60. (In Russ.)]

17. Тихомиров А.Л. Расширение возможностей органосохраняющего лечения миомы матки с использованием улипристала ацетата // Гинекология, 2016. Т. 18, № 1. С. 56-60. [Tikhomirov A.L. Empowering organpreserving treatment of uterine fibroids using ulipristal acetate. Ginekologiya = Gynecology, 2016, Vol. 18, no. 1, pp. 56-60. (In Russ.)]

18. Хворостухина Н.Ф., Островская А.Е., Рогожина И.Е., Новичков Д.А., Степанова Н.Н. Особенности маточной гемодинамики и системы гемостаза при миоме, осложненной геморрагическим синдромом // Акушерство и гинекология, 2016. № 6. С. 87-93. [Khvorostukhina N.F., Ostrovskaya A.E., Rogozhina I.E., Novichkov D.A., Stepanova N.N. The specific features of uterine hemodynamics and hemostatic system in myoma complicated by hemorrhagic syndrome. Akusherstvo i ginekologiya = Obstetrics and Gynecology, 2016, no. 6, pp. 87-93. (In Russ.)]

19. Cain-Nielsen A.H., Moriarty J.P., Stewart E.A., Borah B.J. Cost-Effectiveness of Uterine-Preserving Procedures for the Treatment of Uterine Fibroid Symptoms in the United States. J. Comp. Eff. Res., 2014, Vol. 3, no. 5, pp. 503-514.

20. Donnez J., Vázquez F., Tomaszewski J., Nouri K., Bouchard P., Fauser B.C., Barlow D.H., Palacios S., Donnez O., Bestel E., Osterloh I., Loumaye E. Long-term treatment of uterine fibroids with ulipristal acetate. Fertil. Steril, 2014, Vol. 101, no. 6, pp. 1565-1573.

21. Engman M., Granberg S., Williams A.R., Meng C.X., Lalitkumar P.G., Gemzell-Danielsson K. Mifepristone for treatment of uterine leiomyoma. A prospective randomized placebo controlled trial. Human Reproduction, 2009, Vol. 1, no. 1, pp. 1-10.

22. Jiang X., Thapa A., Lu J., Bhujohory V.S., Liu Y., Qiao S. Ultrasound-guided transvaginal radiofrequency myolysis for symptomatic uterine myomas. Eur. J. Obstet. Gynecol. Reprod. Biol., 2014, no. 177, pp. 38-43.

23. Khan A.T., Shehmar M., Gupta J.K. Uterine fibroids: current perspectives. Int. J. Women’s Health, 2014, no. 6, pp. 95-114.

24. Yoo E.H., Lee P.I., Huh C.Y., Kim D.H., Lee B.S., Lee J.K., Kim D. Predictors of leiomyoma recurrence after laparoscopic myomectomy. J. Minim. Invasive Gynecol., 2007, Vol. 14, no. 6, pp. 690-697.