В представленном обзоре литературы рассмотрены вопросы эпидемиологии, патоморфологии, патогенеза, клиники, диагностики миомы матки. Представлены данные об использовании антагониста рецепторов прогестерона – мифепристона. Терапия миомы матки мифепристоном по эффективности и безопасности не уступает аналогам агонистов гонадотропин-рилизинг-гормона, при этом не обладает отрицательным воздействием на эстрогензависимые экстрагенитальные системы и органы (сердечно-сосудистую систему, костную ткань, молочные железы и т.д.), поскольку показатель сывороточного эстрадиола остается на уровне, соответствующем ранней фолликулярной фазе менструального цикла. Ключевые слова: миома матки, патогенез, диагностика, лечение, антагонист рецепторов прогестерона, мифепристон.
________________________________________________
In the presented review of the literature questions of epidemiology, pathomorphology, pathogenesis, clinic, diagnostics of uterine myomas are considered. Presented are data accentuating the use of the progesterone receptor antagonist drug mifepristone. The therapy of myoma of the uterus by mifepristone is not inferior in effectiveness or safety to analogs of gonadotropin-releasing hormone agonists, and does not have a negative effect on estrogen-dependent extragenital systems and organs (cardiovascular system, bone tissue, mammary glands, etc.), since the serum Estradiol remains at a level corresponding to the early follicular phase of the menstrual cycle. Key words: uterine myoma, pathogenesis, diagnosis, treatment, progesterone receptor antagonist, mifepristone.
1. Миома матки: диагностика, лечение и реабилитация. Клинические рекомендации (протокол лечения). М., 2015. / Mioma matki: diagnostika, lechenie i reabilitatsiia. Klinicheskie rekomendatsii (protokol lecheniia). M., 2015. [in Russian]
2. Руководство по репродуктивной медицине. Под ред. Б.Карра, Р.Блэкуэлла и Р.Азиза. Пер. с англ. М.: Практика, 2015. / Rukovodstvo po reproduktivnoi meditsine. Pod red. B.Karra, R.Blekuella i R.Aziza. Per. s angl. M.: Praktika, 2015. [in Russian]
3. Вихляева Е.М. Руководство по диагностике и лечению миомы матки. М.: МЕДпресс-информ. 2004. / Vikhlyaeva E.M. Rukovodstvo po diagnostike i lecheniiu miomy matki. M.: MEDpress-inform. 2004. [in Russian]
4. Ахмедова Н.М., Муфтайдинова Ш.К., Мамаджанова Ш.К. Оценка эффективности нового метода лечения миомы матки. Молодой ученый. 2017; 18: 113–5. / Akhmedova N.M., Muftaidinova Sh.K., Mamadzhanova Sh.K. Otsenka effektivnosti novogo metoda lecheniia miomy matki. Molodoi uchenyi. 2017; 18: 113–5. [in Russian]
5. Okolo S. Incidence, aetiology and epidemiology of uterine fibroids. Best Pract Res Clin Obst Gyn 2008; 22: 571–88.
6. Lee EJ, Kong G, Lee SH et al. Profiling of differentially expressed genes in human uterine leiomyomas. Inf J Gynecol. Cancer 2005; 15: 146–54.
7. Parker WH. Etiology, symptomatology and diagnosis of uterine myomas. Fertil Steril 2007; 87: 725–36.
8. Mäkinen N et al. МЕD12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science 2011; 334: 252–9.
9. Strauss III JK. Cell biology. In: Reproductive Medicine. Molecular, Cellular and Genetic Fundamentals. Ed. O.J.Bart, M.Fauser, 2003; p. 55–196.
10. Vegan K. МЕD12 mutation and uterine fibrinoids. Nature Genetics 2011; 43: 928–31.
11. Тихомиров А.Л. Миома. Патогенетическое обоснование органосохраняющего лечения. М.: Фарм-Синтез, 2013. / Tikhomirov A.L. Mioma. Patogeneticheskoe obosnovanie organosokhraniaiushchego lecheniia. M.: Farm-Sintez, 2013. [in Russian]
12. Rabinovici J. Pregnancies and Deliveries After MR-Guided Focused Ultrasound Surgery For the Conservative Treatment of Symptomatic Uterine Fibroids: MRgFUS 2008-Selected scientific abstracts. Washington, 2008.
13. Международная статистическая классификация болезней и проблем, связанных со здоровьем. Всемирная организация здравоохранения. Женева, 2005. / Mezhdunarodnaia statisticheskaia klassifikatsiia boleznei i problem, sviazannykh so zdorov'em. Vsemirnaia organizatsiia zdravookhraneniia. Zheneva, 2005. [in Russian]
14. Pritts EA, Parker WH, Olive DL. Fibroids and infertility: an update systematic review of the evidence. Fertil Steril 2009; 91 (4): 1215–23.
15. Mutter GL, Bergeron C, Deligdisch L et al. The spectrum of endometrial pathology induced by progesterone receptor modulators. Mod Pathol 2008; 21: 591–8.
16. Spitz I.M. Progesterone antagonidts and progesterone receptor modulators: an overwiew. Steroids 2003; 68 (10–13): 981–93.
17. Murji A, Whitaker L, Chow TL, Sobel ML. Selective progesterone receptor modulators (SPRMs) for uterine fibroids. Cochrane Database Syst Rev 2017; 4: CD010770. DOI: 10.1002/14651858.CD010770.pub2
18. Тихомиров А.Л., Леденкова А.А., Батаева А.Е., Абышева В.Г. Антагонисты рецепторов прогестерона в структуре комплексного органосохраняющего лечения миомы матки. Акушерство и гинекология. 2012; 5: 115–9. / Tikhomirov A.L., Ledenkova A.A., Bataeva A.E., Abysheva V.G. Antagonisty retseptorov progesterona v strukture kompleksnogo organosokhraniaiushchego lecheniia miomy matki. Akusherstvo i ginekologiia. 2012; 5: 115–9. [in Russian]
19. Карева Е.Н. Мифепристон и миома матки. Фарматека. 2010; 14: 18–30. / Kareva E.N. Mifepriston i mioma matki. Farmateka. 2010; 14: 18–30. [in Russian]
20. Engman M, Granberg S, Williams ARW et al. Mifepristone for Treatment of Uterine Leiomyoma. A Prospective Randomized Placebo Controlled Trial. Human Reproduction 2009; 24 (8): 1870–79.
21. Ramachandran S, Kwon K-Y, Shin S-J et al. Cyclin-Dependent Kinase Inhibitor p27Kip1 Controls Growth and Cell Cycle Progression in Human Uterine Leiomyoma. J Korean Med Sci 2008; 23: 667–73.
22. Bagaria M, Suneja A, Vaid NB et al. Low-dose mifepristone in treatment of uterine leiomyoma: a randomised double-blind placebo-controlled clinical trial. Aust N Z J Obstet Gynaecol 2009; 49 (1): 77–83.
23. Фаткуллин И.Ф., Баканова А.Р. Применение антипрогестинов для профилактики рецидивов после консервативной миомэктомии. Акушерство и гинекология. 2011; 1: 101–4. / Fatkullin I.F., Bakanova A.R. Primenenie antiprogestinov dlia profilaktiki retsidivov posle konservativnoi miomektomii. Akusherstvo i ginekologiia. 2011; 1: 101–4. [in Russian]
24. Steinauer J, Pritts EA, Jackson R et al. Systematic review of mifepristone for the treatment of uterine leiomyomata. Obst Gynecol 2004; 103 (6): 1331–6.
25. Engman M, Skoog L, Söderqvist G, Gemzell-Danielsson K. The effect of mifepristone on breast cell proliferation in premenopausal women evaluated through fine needle aspiration cytology. Human Reproduction 2008; 23 (9): 2072–9.
26. Новикова В.А., Пенжоян Г.А., Хорольский В.А. и др. Влияние антирецидивной терапии миомы матки антигестагенами на состояние молочных желез у женщин репродуктивного возраста. Акушерство и гинекология. 2017; 4: 108–3. / Novikova V.A., Penzhoian G.A., Khorol'skii V.A. i dr. Vliianie antiretsidivnoi terapii miomy matki antigestagenami na sostoianie molochnykh zhelez u zhenshchin reproduktivnogo vozrasta. Akusherstvo i ginekologiia. 2017; 4: 108–3. [in Russian]
27. Пономаренко И.В., Алтухова О.Б., Прощаев К.И. и др. Клинические особенности у пациенток старших возрастных групп с миомой матки. Успехи геронтологии. 2016; 5: 760–3. / Ponomarenko I.V., Altukhova O.B., Proshchaev K.I. i dr. Klinicheskie osobennosti u patsientok starshikh vozrastnykh grupp s miomoi matki. Uspekhi gerontologii. 2016; 5: 760–3. [in Russian]
28. Липман А.Д., Левина И.С., Кочев Д.М. Использование мифепристона для медикаментозного прерывания беременности и других целей. Сибирский мед. журн. 2002; 4: 46–62. / Lipman A.D., Levina I.S., Kochev D.M. Ispol'zovanie mifepristona dlia medikamentoznogo preryvaniia beremennosti i drugikh tselei. Sibirskii med. zhurn. 2002; 4: 46–62. [in Russian]
29. Morgan FH. Mifepristone for management of Cushing's. Pharmacotherapy 2013; 33 (3): 319–29.
30. Карева Е.Н., Бехбудова Л.Х., Горенкова О.С., Самойлова Т.Е. Персонализированный подход к назначению мифепристона пациенткам с миомой матки. Акушерство и гинекология. 2015; 5: 61–5. / Kareva E.N., Bekhbudova L.Kh., Gorenkova O.S., Samoilova T.E. Personalizirovannyi podkhod k naznacheniiu mifepristona patsientkam s miomoi matki. Akusherstvo i ginekologiia. 2015; 5: 61–5. [in Russian]
31. Tieszen СR, Goyeneche AA, Brandhagen BN et al. Antiprogestin mifepristone inhibits the growth of cancer cells of reproductive and non-reproductive origin regardless of progesterone receptor expression. BMC Cancer 2011; 11 (1): 207.
________________________________________________
1. Mioma matki: diagnostika, lechenie i reabilitatsiia. Klinicheskie rekomendatsii (protokol lecheniia). M., 2015. [in Russian]
2. Rukovodstvo po reproduktivnoi meditsine. Pod red. B.Karra, R.Blekuella i R.Aziza. Per. s angl. M.: Praktika, 2015. [in Russian]
3. Vikhlyaeva E.M. Rukovodstvo po diagnostike i lecheniiu miomy matki. M.: MEDpress-inform. 2004. [in Russian]
4. Akhmedova N.M., Muftaidinova Sh.K., Mamadzhanova Sh.K. Otsenka effektivnosti novogo metoda lecheniia miomy matki. Molodoi uchenyi. 2017; 18: 113–5. [in Russian]
5. Okolo S. Incidence, aetiology and epidemiology of uterine fibroids. Best Pract Res Clin Obst Gyn 2008; 22: 571–88.
6. Lee EJ, Kong G, Lee SH et al. Profiling of differentially expressed genes in human uterine leiomyomas. Inf J Gynecol. Cancer 2005; 15: 146–54.
7. Parker WH. Etiology, symptomatology and diagnosis of uterine myomas. Fertil Steril 2007; 87: 725–36.
8. Mäkinen N et al. МЕD12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science 2011; 334: 252–9.
9. Strauss III JK. Cell biology. In: Reproductive Medicine. Molecular, Cellular and Genetic Fundamentals. Ed. O.J.Bart, M.Fauser, 2003; p. 55–196.
10. Vegan K. МЕD12 mutation and uterine fibrinoids. Nature Genetics 2011; 43: 928–31.
11. Tikhomirov A.L. Mioma. Patogeneticheskoe obosnovanie organosokhraniaiushchego lecheniia. M.: Farm-Sintez, 2013. [in Russian]
12. Rabinovici J. Pregnancies and Deliveries After MR-Guided Focused Ultrasound Surgery For the Conservative Treatment of Symptomatic Uterine Fibroids: MRgFUS 2008-Selected scientific abstracts. Washington, 2008.
13. Mezhdunarodnaia statisticheskaia klassifikatsiia boleznei i problem, sviazannykh so zdorov'em. Vsemirnaia organizatsiia zdravookhraneniia. Zheneva, 2005. [in Russian]
14. Pritts EA, Parker WH, Olive DL. Fibroids and infertility: an update systematic review of the evidence. Fertil Steril 2009; 91 (4): 1215–23.
15. Mutter GL, Bergeron C, Deligdisch L et al. The spectrum of endometrial pathology induced by progesterone receptor modulators. Mod Pathol 2008; 21: 591–8.
16. Spitz I.M. Progesterone antagonidts and progesterone receptor modulators: an overwiew. Steroids 2003; 68 (10–13): 981–93.
17. Murji A, Whitaker L, Chow TL, Sobel ML. Selective progesterone receptor modulators (SPRMs) for uterine fibroids. Cochrane Database Syst Rev 2017; 4: CD010770. DOI: 10.1002/14651858.CD010770.pub2
18. Tikhomirov A.L., Ledenkova A.A., Bataeva A.E., Abysheva V.G. Antagonisty retseptorov progesterona v strukture kompleksnogo organosokhraniaiushchego lecheniia miomy matki. Akusherstvo i ginekologiia. 2012; 5: 115–9. [in Russian]
19. Kareva E.N. Mifepriston i mioma matki. Farmateka. 2010; 14: 18–30. [in Russian]
20. Engman M, Granberg S, Williams ARW et al. Mifepristone for Treatment of Uterine Leiomyoma. A Prospective Randomized Placebo Controlled Trial. Human Reproduction 2009; 24 (8): 1870–79.
21. Ramachandran S, Kwon K-Y, Shin S-J et al. Cyclin-Dependent Kinase Inhibitor p27Kip1 Controls Growth and Cell Cycle Progression in Human Uterine Leiomyoma. J Korean Med Sci 2008; 23: 667–73.
22. Bagaria M, Suneja A, Vaid NB et al. Low-dose mifepristone in treatment of uterine leiomyoma: a randomised double-blind placebo-controlled clinical trial. Aust N Z J Obstet Gynaecol 2009; 49 (1): 77–83.
23. Fatkullin I.F., Bakanova A.R. Primenenie antiprogestinov dlia profilaktiki retsidivov posle konservativnoi miomektomii. Akusherstvo i ginekologiia. 2011; 1: 101–4. [in Russian]
24. Steinauer J, Pritts EA, Jackson R et al. Systematic review of mifepristone for the treatment of uterine leiomyomata. Obst Gynecol 2004; 103 (6): 1331–6.
25. Engman M, Skoog L, Söderqvist G, Gemzell-Danielsson K. The effect of mifepristone on breast cell proliferation in premenopausal women evaluated through fine needle aspiration cytology. Human Reproduction 2008; 23 (9): 2072–9.
26. Novikova V.A., Penzhoian G.A., Khorol'skii V.A. i dr. Vliianie antiretsidivnoi terapii miomy matki antigestagenami na sostoianie molochnykh zhelez u zhenshchin reproduktivnogo vozrasta. Akusherstvo i ginekologiia. 2017; 4: 108–3. [in Russian]
27. Ponomarenko I.V., Altukhova O.B., Proshchaev K.I. i dr. Klinicheskie osobennosti u patsientok starshikh vozrastnykh grupp s miomoi matki. Uspekhi gerontologii. 2016; 5: 760–3. [in Russian]
28. Lipman A.D., Levina I.S., Kochev D.M. Ispol'zovanie mifepristona dlia medikamentoznogo preryvaniia beremennosti i drugikh tselei. Sibirskii med. zhurn. 2002; 4: 46–62. [in Russian]
29. Morgan FH. Mifepristone for management of Cushing's. Pharmacotherapy 2013; 33 (3): 319–29.
30. Kareva E.N., Bekhbudova L.Kh., Gorenkova O.S., Samoilova T.E. Personalizirovannyi podkhod k naznacheniiu mifepristona patsientkam s miomoi matki. Akusherstvo i ginekologiia. 2015; 5: 61–5. [in Russian]
31. Tieszen СR, Goyeneche AA, Brandhagen BN et al. Antiprogestin mifepristone inhibits the growth of cancer cells of reproductive and non-reproductive origin regardless of progesterone receptor expression. BMC Cancer 2011; 11 (1): 207.
ФГБОУ ВО «Дальневосточный государственный медицинский университет» Минздрава России.
680000, Россия, Хабаровск, ул. Муравьева-Амурского, д. 35
*typ50@rambler.ru
Far Eastern State Medical University of the Ministry of Health of the Russian Federation. 680000, Russian Federation, Khabarovsk, ul. Murav'eva-Amurskogo, d. 35
*typ50@rambler.ru