medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2016-12-126-130medsovet-1445Research ArticleОнкологияOncologyВОЗМОЖНОСТИ ПРИМЕНЕНИЯ СЕЛЕКТИВНЫХ МОДУЛЯТОРОВ ПРОГЕСТЕРОНОВЫХ РЕЦЕПТОРОВ У ЖЕНЩИН РЕПРОДУКТИВНОГО ВОЗРАСТА С МИОМОЙ МАТКИPOSSIBILITIES TO APPLY PROGESTERONE RECEPTOR SELECTIVE MODULATORS IN WOMEN OF REPRODUCTIVE AGE WITH UTERINE MYOMAЧернухаГ. Е.ChernukhaG. E.

Доктор медицинских наук, профессор

MD, Prof.

ДумановскаяМ. Р.DumanovskayaM. R.

Кандидат медицинских наук

PhD in medicine

ТабееваГ. И.TabeevaG. I.

Кандидат медицинских наук

PhD  in medicine

Научный центр акушерства, гинекологии и перинатологии имени В.И. Кулакова, МоскваРоссияAcademician Kulakov Scientific Obstetrics, Gynecology and Perinatology Center, MoscowRussian Federation201630122016012126130Copyright © Чернуха Г.Е., Думановская М.Р., Табеева Г.И., 20162016Чернуха Г.Е., Думановская М.Р., Табеева Г.И.Chernukha G.E., Dumanovskaya M.R., Tabeeva G.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/1445

Миома матки считается наиболее  распространенной доброкачественной моноклональной опухолью. Частота миомы матки составляет  20–35%  у женщин репродуктивного возраста и достигает 70% после 50  лет. Современная  стратегия лечения миомы матки в значительной степени индивидуализирована, зависит от возраста пациентки, ее желания сохранить репродуктивную функцию, а также от размеров, локализации, темпов роста узлов, возможности проведения гормонотерапии. В последние годы в литературе стало появляться все больше публикаций об успешном использовании селективного модулятора прогестероновых рецепторов – улипристала  ацетата  (УПА) для лечения миомы матки. Важно заметить, что интерес к проблеме лечения миомы матки селективными  модуляторами прогестероновых рецепторов связан не только с их ингибирующим влиянием на рост и размеры миомы матки, но и с воздействием на эндометрий, механизмами возникновения аменореи и ановуляции без снижения эндогенной секреции эстрогенов. Проведение медикаментозной терапии дает возможность отсрочить или избежать хирургического лечения. С этих позиций длительная терапия прерывистыми курсами УПА в настоящее время рассматривается  как наиболее перспективная. Она позволяет расширить возможности консервативного лечения миомы матки, обеспечивая регресс симптомов заболевания и сохранение эффекта после завершения терапии.

миомаулипристала ацетатселективный модулятор прогестероновых рецепторовmyomauliprastal acetateprogesterone receptor selective modulatorReferencesDay Baird D, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol, 2003, 188: 100-7.Day Baird D, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol, 2003, 188: 100-7.Fernandez H. Uterine fibroids. Rev Prat, 2014, 64: 540-544.Fernandez H. Uterine fibroids. Rev Prat, 2014, 64: 540-544.Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for a debate? Hum Reprod, 2002, 17: 1424-1430.Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for a debate? Hum Reprod, 2002, 17: 1424-1430.Zimmermann A, Bernuit D, Gerlinger C, Schaefers M, Geppert K. Prevalence, symptoms and management of uterine fibroids: an international internet-based survey of 21,746 women. BMC Womens Health, 2012 March 26, 12: 6. Available at: http://www.biomedcentral.com/1472-6874/12/6. Accessed on November 10, 2014.Zimmermann A, Bernuit D, Gerlinger C, Schaefers M, Geppert K. Prevalence, symptoms and management of uterine fibroids: an international internet-based survey of 21,746 women. BMC Womens Health, 2012 March 26, 12: 6. Available at: http://www.biomedcentral.com/1472-6874/12/6. Accessed on November 10, 2014.Radosa MP, Owsianowski Z, Mothes A, Weisheit A, Vorwergk J, Asskaryar FA, Camara O, Bernardi TS, Runnebaum IB. Long-term risk of fibroid recurrence after laparoscopic myomectomy. Eur J Obstet Gynecol Reprod Biol, 2014 Sep, 180: 35-9. doi: 10.1016/j.ejogrb.2014.05.029. Epub 2014 Jun 2.Radosa MP, Owsianowski Z, Mothes A, Weisheit A, Vorwergk J, Asskaryar FA, Camara O, Bernardi TS, Runnebaum IB. Long-term risk of fibroid recurrence after laparoscopic myomectomy. Eur J Obstet Gynecol Reprod Biol, 2014 Sep, 180: 35-9. doi: 10.1016/j.ejogrb.2014.05.029. Epub 2014 Jun 2.Practice Committee of American Society for Reproductive Medicine in collaboration with Society of Reproductive Surgeons. Myomas and reproductive function. Fertil Steril, 2008, 90(5 Suppl): S125-S130.Practice Committee of American Society for Reproductive Medicine in collaboration with Society of Reproductive Surgeons. Myomas and reproductive function. Fertil Steril, 2008, 90(5 Suppl): S125-S130.Clark NA, Mumford SL, Segars JH. Reproductive impact of MRI-guided focused ultrasound surgery for fibroids: a systematic review of the evidence. Curr Opin Obstet Gynecol, 2014, 26: 151-161.Clark NA, Mumford SL, Segars JH. Reproductive impact of MRI-guided focused ultrasound surgery for fibroids: a systematic review of the evidence. Curr Opin Obstet Gynecol, 2014, 26: 151-161.Tan YH, Lethaby A. Preoperative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding. Cochrane Database Syst Rev, 2013, 11: CD010241.Tan YH, Lethaby A. Preoperative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding. Cochrane Database Syst Rev, 2013, 11: CD010241.Клинические рекомендации «Миома матки: диагностика, лечение и реабилитация», под редакцией Л.В. Адамян, 2015. / Clinical Guidance “Uterine Myoma: Diagnostics, Therapy and Rehabilitation”, ed. by L.V. Adamyan, 2015.Клинические рекомендации «Миома матки: диагностика, лечение и реабилитация», под редакцией Л.В. Адамян, 2015. / Clinical Guidance “Uterine Myoma: Diagnostics, Therapy and Rehabilitation”, ed. by L.V. Adamyan, 2015.Vilos GA, Allaire C, Laberge PY, Leyland N; Special Contributors, Vilos AG, Murji A, Chen I. The management of uterine leiomyomas. J Obstet Gynaecol Can, 2015 Feb, 37(2): 157-81.Vilos GA, Allaire C, Laberge PY, Leyland N; Special Contributors, Vilos AG, Murji A, Chen I. The management of uterine leiomyomas. J Obstet Gynaecol Can, 2015 Feb, 37(2): 157-81.Lethaby A, Vollenhoven B, Sowter M. Preoperative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev, 2001, CD000547.Lethaby A, Vollenhoven B, Sowter M. Preoperative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev, 2001, CD000547.Carr BR, Marshburn PB, Weatherall PT, Bradshaw KD, Breslau NA, Byrd W, et al. An evaluation of the effect of gonadotropinreleasing hormone analogs and medroxyprogesterone acetate on uterine leiomyomata volume by magnetic resonance imaging: a prospective, randomized, double blind, placebocontrolled, crossover trial. J Clin Endocrinol Metab, 1993, 76: 1217-23.Carr BR, Marshburn PB, Weatherall PT, Bradshaw KD, Breslau NA, Byrd W, et al. An evaluation of the effect of gonadotropinreleasing hormone analogs and medroxyprogesterone acetate on uterine leiomyomata volume by magnetic resonance imaging: a prospective, randomized, double blind, placebocontrolled, crossover trial. J Clin Endocrinol Metab, 1993, 76: 1217-23.Friedman AJ, Daly M, Juneau-Norcross M, Rein MS, Fine C, Gleason R, et al. A prospective, randomized trial of gonadotropin-releasing hormone agonist plus estrogen-progestin or progestin “add-back” regimens for women with leiomyomata uteri. J Clin Endocrinol Metab, 1993, 76: 1439-45.Friedman AJ, Daly M, Juneau-Norcross M, Rein MS, Fine C, Gleason R, et al. A prospective, randomized trial of gonadotropin-releasing hormone agonist plus estrogen-progestin or progestin “add-back” regimens for women with leiomyomata uteri. J Clin Endocrinol Metab, 1993, 76: 1439-45.Friedman AJ, Daly M, Juneau-Norcross M, Gleason R, Rein MS, LeBoff M. Long-term medical therapy for leiomyomata uteri: a prospective, randomized study of leuprolide acetate depot plus either oestrogen-progestin or progestin ‘add-back’ for 2 years. Hum Reprod, 1994, 9: 1618-25.Friedman AJ, Daly M, Juneau-Norcross M, Gleason R, Rein MS, LeBoff M. Long-term medical therapy for leiomyomata uteri: a prospective, randomized study of leuprolide acetate depot plus either oestrogen-progestin or progestin ‘add-back’ for 2 years. Hum Reprod, 1994, 9: 1618-25.Donnez J1, Arriagada P, Donnez O, Dolmans MM. Current management of myomas: the place of medical therapy with the advent of selective progesterone receptor modulators. Curr Opin Obstet Gynecol, 2015 Dec, 27(6): 422-31. doi: 10.1097/GCO.0000000000000229.Donnez J1, Arriagada P, Donnez O, Dolmans MM. Current management of myomas: the place of medical therapy with the advent of selective progesterone receptor modulators. Curr Opin Obstet Gynecol, 2015 Dec, 27(6): 422-31. doi: 10.1097/GCO.0000000000000229.Morikawa A, Ohara N, Xu Q et al. Selective progesterone receptor modulator asoprisnil downregulates collagen synthesis in cultured human uterine leiomyoma cells through up-regulating extracellular matrix metalloproteinase inducer. Hum Reprod, 2008, 23: 944-951.Morikawa A, Ohara N, Xu Q et al. Selective progesterone receptor modulator asoprisnil downregulates collagen synthesis in cultured human uterine leiomyoma cells through up-regulating extracellular matrix metalloproteinase inducer. Hum Reprod, 2008, 23: 944-951.Tsigkou A, Reis FM, Lee MH et al. Increased progesterone receptor expression in uterine leiomyoma: correlation with age, number of leiomyomas, and clinical symptoms. Fertil Steril, 2015, 104: 170-175.Tsigkou A, Reis FM, Lee MH et al. Increased progesterone receptor expression in uterine leiomyoma: correlation with age, number of leiomyomas, and clinical symptoms. Fertil Steril, 2015, 104: 170-175.Kim JJ, Sefton EC. The role of progesterone signaling in the pathogenesis of uterine leiomyoma. Mol Cell Endocrinol, 2012, 358: 223-231.Kim JJ, Sefton EC. The role of progesterone signaling in the pathogenesis of uterine leiomyoma. Mol Cell Endocrinol, 2012, 358: 223-231.Bouchard P, Chabbert-Buffet N, Fauser BC. Selective progesterone receptor modulators in reproductive medicine: pharmacology, clinical efficacy and safety. Fertil Steril, 2011, 96: 1175-1189.Bouchard P, Chabbert-Buffet N, Fauser BC. Selective progesterone receptor modulators in reproductive medicine: pharmacology, clinical efficacy and safety. Fertil Steril, 2011, 96: 1175-1189.Xu Q, Takekida S, Ohara N et al. Progesterone receptor modulator CDB-2914 down-regulates proliferative cell nuclear antigen and Bcl-2 protein expression and up-regulates caspase-3 and poly(adenosine 50-diphosphateribose) polymerase expression in cultured human uterine leiomyoma cells. J Clin Endocrinol Metab, 2005, 90: 953-961.Xu Q, Takekida S, Ohara N et al. Progesterone receptor modulator CDB-2914 down-regulates proliferative cell nuclear antigen and Bcl-2 protein expression and up-regulates caspase-3 and poly(adenosine 50-diphosphateribose) polymerase expression in cultured human uterine leiomyoma cells. J Clin Endocrinol Metab, 2005, 90: 953-961.Morikawa A, Ohara N, Xu Q et al. Selective progesterone receptor modulator asoprisnil downregulates collagen synthesis in cultured human uterine leiomyoma cells through up-regulating extracellular matrix metalloproteinase inducer. Hum Reprod, 2008, 23: 944-951.Morikawa A, Ohara N, Xu Q et al. Selective progesterone receptor modulator asoprisnil downregulates collagen synthesis in cultured human uterine leiomyoma cells through up-regulating extracellular matrix metalloproteinase inducer. Hum Reprod, 2008, 23: 944-951.Xu Q, Ohara N, Wei C et al. Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells. Hum Reprod, 2006, 21: 2408-2416.Xu Q, Ohara N, Wei C et al. Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells. Hum Reprod, 2006, 21: 2408-2416.Horne FM, Blithe DL. Progesterone receptor modulators and the endometrium: changes and consequences. Hum Reprod Update, 2007, 13: 567-580.Horne FM, Blithe DL. Progesterone receptor modulators and the endometrium: changes and consequences. Hum Reprod Update, 2007, 13: 567-580.Williams AR, Bergeron C, Barlow DH, Ferenczy A. Endometrial morphology after treatment of uterine fibroids with the selective progesterone receptor modulator, ulipristal acetate. Int J Gynecol Pathol, 2012, 31: 556-569.Williams AR, Bergeron C, Barlow DH, Ferenczy A. Endometrial morphology after treatment of uterine fibroids with the selective progesterone receptor modulator, ulipristal acetate. Int J Gynecol Pathol, 2012, 31: 556-569.Levens ED, Potlog-Nahari C, Armstrong AY, Wesley R, Premkumar A, Blithe DL, Blocker W, Nieman LK.CDB-2914 for uterine leiomyomata treatment: a randomized controlled trial. Obstet Gynecol, 2008 May, 111(5): 1129-36. doi: 10.1097/AOG.0b013e3181705d0e.Levens ED, Potlog-Nahari C, Armstrong AY, Wesley R, Premkumar A, Blithe DL, Blocker W, Nieman LK.CDB-2914 for uterine leiomyomata treatment: a randomized controlled trial. Obstet Gynecol, 2008 May, 111(5): 1129-36. doi: 10.1097/AOG.0b013e3181705d0e.Nieman LK, Blocker W, Nansel T, Mahoney S, Reynolds J, Blithe D, Wesley R, Armstrong A. Efficacy and tolerability of CDB-2914 treatment for symptomatic uterine fibroids: a randomized, double-blind, placebo-controlled, phase IIb study. Fertil Steril, 2011 Feb, 95(2): 767-72.e1-2. doi: 10.1016/j.fertnstert.2010.09.059.Nieman LK, Blocker W, Nansel T, Mahoney S, Reynolds J, Blithe D, Wesley R, Armstrong A. Efficacy and tolerability of CDB-2914 treatment for symptomatic uterine fibroids: a randomized, double-blind, placebo-controlled, phase IIb study. Fertil Steril, 2011 Feb, 95(2): 767-72.e1-2. doi: 10.1016/j.fertnstert.2010.09.059.Donnez J, Tatarchuk TF, Bouchard P et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. PEARL I Study Group. N Engl J Med, 2012, 366: 409-420.Donnez J, Tatarchuk TF, Bouchard P et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. PEARL I Study Group. N Engl J Med, 2012, 366: 409-420.Donnez J, Tomaszewski J, Vazquez F et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids. PEARL II Study Group. N Engl J Med, 2012, 366: 421-432.Donnez J, Tomaszewski J, Vazquez F et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids. PEARL II Study Group. N Engl J Med, 2012, 366: 421-432.Адамян Л.В., Зайратьянц О.В., Тихомиров А.Л., Манухин И.Б., Опаленов К.В., Казенашев В.В., Алиева Т.Д. Антипролиферативное и проапоптотическое действие селективного модулятора рецепторов прогестерона улипристала на лейомиому матки in vivo. Проблемы репродукции, 2014, 3: 41-44. / Adamyan L.V., Zayratyants O.V., Tikhomirov A.l., Manukhin I.B., Opalenov K.V., Kazenashev V.V., Alieva T.D. Antiproliferaive and proapoptotic action of ulipristal progesterone receptor selective modulator on uterine leiomyoma in vivo. Reproduction Problems, 2014, 3: 41-44.Адамян Л.В., Зайратьянц О.В., Тихомиров А.Л., Манухин И.Б., Опаленов К.В., Казенашев В.В., Алиева Т.Д. Антипролиферативное и проапоптотическое действие селективного модулятора рецепторов прогестерона улипристала на лейомиому матки in vivo. Проблемы репродукции, 2014, 3: 41-44. / Adamyan L.V., Zayratyants O.V., Tikhomirov A.l., Manukhin I.B., Opalenov K.V., Kazenashev V.V., Alieva T.D. Antiproliferaive and proapoptotic action of ulipristal progesterone receptor selective modulator on uterine leiomyoma in vivo. Reproduction Problems, 2014, 3: 41-44.Donnez J, Vazquez F, Tomaszewski J, et al. Longterm treatment of uterine fibroids with ulipristal acetate. PEARL III and PEARL III Extension Study Group. Fertil Steril, 2014, 101: 1565-1573.Donnez J, Vazquez F, Tomaszewski J, et al. Longterm treatment of uterine fibroids with ulipristal acetate. PEARL III and PEARL III Extension Study Group. Fertil Steril, 2014, 101: 1565-1573.Committee for Medicinal Products for Human Use (CHMP). Assessment report (license extension): Esmya, ulipristal acetate. Reference EMA/CHMP/84021/2015, April 2015 via www.ema.europa.eu.Committee for Medicinal Products for Human Use (CHMP). Assessment report (license extension): Esmya, ulipristal acetate. Reference EMA/CHMP/84021/2015, April 2015 via www.ema.europa.eu.Donnez J, Hudecek R, Donnez O et al. Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids. (PEARL IV) (Part 1). Fertility and Sterility, 2014, 103(2): 519-527.Donnez J, Hudecek R, Donnez O et al. Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids. (PEARL IV) (Part 1). Fertility and Sterility, 2014, 103(2): 519-527.

The authors declare that there are no conflicts of interest present.