Расширение возможностей органосохраняющего лечения миомы матки с использованием улипристала ацетата

1. Fernandez H. Uterine fibroids. Rev Prat 2014; 64: 540–4.
2. Ciavattini A, Di Giuseppe J, Stortoni P et al. Uterine fibroids: pathogenesis and interactions with endometrium and endomyometrial junction. Obstet Gynecol Int 2013; 2013: 173–84.
3. Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for a debate? Hum Reprod 2002; 17: 1424–30.
4. Practice Committee of American Society for Reproductive Medicine in collaboration with Society of Reproductive Surgeons. Myomas and reproductive function. Fertil Steril 2008; 90 (Suppl. 5): S125–S130.
5. Тихомиров А.Л. Миома, патогенетическое обоснование органосохраняющего лечения. М., 2013. / Tikhomirov A.L. Mioma, patogeneticheskoe obosnovanie organosokhraniaiushchego lecheniia. M., 2013. [in Russian]
6. Тихомиров А.Л., Манухина Е.И., Вученович Ю.Д. и др. Миома матки. Дифференцированный лечебный подход. Учебное пособие для врачей акушеров-гинекологов. М., 2015. / Tikhomirov A.L., Manukhina E.I., Vuchenovich Iu.D. i dr. Mioma matki. Differentsirovannyi lechebnyi podkhod. Uchebnoe posobie dlia vrachei akusherov-ginekologov. M., 2015. [in Russian]
7. Lethaby A, Vollenhoven B, Sowter M. Preoperative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev 2001; CD000547.
8. Tan YH, Lethaby A. Preoperative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding. Cochrane Database Syst Rev 2013; 11: CD010241.
9. Nisolle M, Gillerot S, Casanas-Roux F et al. Immunohistochemical study of the proliferation index, oestrogen receptors and progesterone receptors A and B in leiomyomata and normal myometrium during the menstrual cycle and under gonadotrophin-releasing hormone agonist therapy. Hum Reprod 1999; 14: 2844–50.
10. Kim JJ, Sefton EC. The role of progesterone signaling in the pathogenesis of uterine leiomyoma. Mol Cell Endocrinol 2012; 358: 223–31.
11. Donnez J, Tatarchuk TF, Bouchard P et al; PEARL I Study Group. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med 2012; 366: 409–20.
12. Donnez J, Tomaszewski J, Vazquez F et al; PEARL II Study Group. Ulipristalacetate versus leuprolide acetate for uterine fibroids. N Engl J Med 2012; 366: 421–32.
13. Donnez J, Vazquez F, Tomaszewski J et al; PEARL III and PEARL III Extension Study Group. Long-term treatment of uterine fibroids with ulipristal acetate. Fertil Steril 2014; 101: 1565–73. First study on long-term efficacy, which is maximized by long-term intermittent therapy.
14. Donnez J, Hudecek R, Donnez O et al. Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids.Fertil Steril 2015; 103: 519–27.
15. 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: 170–5. Study suggesting that progesterone receptor signaling may favor leiomyoma growth while alleviating clinical symptoms.
16. 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 5 0-diphosphateribose) polymerase expression in cultured human uterine leiomyoma cells. J Clin Endocrinol Metab 2005; 90: 953–61.
17. Horne FM, Blithe DL. Progesterone receptor modulators and the endometrium: changes and consequences. Hum Reprod Update 2007; 13: 567–80.
18. Bouchard P, Chabbert-Buffet N, Fauser BC. Selective progesterone receptor modulators in reproductive medicine: pharmacology, clinical efficacy and safety. Fertil Steril 2011; 96: 1175–89.
19. Bestel E, Donnez J. The potential of selective progesterone receptor modulators for the treatment of uterine fibroids. Expert Rev Endocrinol Metab 2014; 9: 79–92.
20. Chen W, Ohara N, Wang J et al. A novel selective progesterone receptor modulator asoprisnil (J867) inhibits proliferation and induces apoptosis in cultured human uterine leiomyoma cells in the absence of comparable effects on Myometrial Cells Chen W, Ohara N, Wang J et al (Kobe Univ, Japan; TAP Pharmaceutical Products, Inc, Lake Forest, III). J Clin Endocrinol Metab 2006; 91: 1296–304.
21. Morikawa A, Ohara N, Xu Q et al. Selective progesterone receptor modulator asoprisnil down-regulates collagen synthesis in cultured human uterineleiomyoma cells through up-regulating extracellular matrix metalloproteinase inducer. Hum Reprod 2008; 23: 944–51.
22. Koji T, Chedid M, Rubin JS et al. Progesterone-dependent expression of keratinocyte growth factor mRNA in stromal cells of the primate endometrium: keratinocyte growth factor as a progestomedin. J Cell Biol 1994; 125: 393–401.
23. 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: 2408–16.
24. Reinsch RC, Murphy AA, Morales AJ, Yen SS. The effects of RU 486 and leuprolide acetate on uterine artery blood flow in the fibroid uterus: a prospective, randomized study. Am J Obstet Gynecol 1994; 170: 1623–7.
25. Wilkens J, Chwalisz K, Han C et al. Effects of the selective progesterone receptor modulator asoprisnil on uterine artery blood flow, ovarian activity, and clinical symptoms in patients with uterine leiomyomata scheduled for hysterectomy. J Clin Endocrinol Metab 2008; 93: 4664–71.
26. Courtoy G, Donnez J, Marbaix E, Dolmans MM. In vivo mechanisms of uterinemyoma volume reduction with ulipristal acetate treatment. Fertil Steril 2015; 104: 426–34.
27. Chwalisz K, Larsen L, Mattia-Goldberg C et al. A randomized, controlled trial of asoprisnil, a novel selective progesterone receptor modulator, in women with uterine leiomyomata. Fertil Steril 2007; 87:1399–412.
28. Chabbert-Buffet N, Pintiaux-Kairis A, Bouchard P. Effects of the progesterone receptor modulator VA2914 in a continuous low-dose on the hypothalamicpituitary-ovarian axis and endometrium in normal women: a prospective, randomized, placebo-controlled trial. J Clin Endocrinol Metab 2007; 92: 3582–9.
29. Brache V, Cochon L, Jesam C et al. Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture. Hum Reprod 2010; 25: 2256–63.
30. Stratton P, Hartog B, Hajizadeh N et al. A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women. Hum Reprod 2000; 15: 1092–9.
31. Mutter GL, Bergeron C, Deligdisch L et al. The spectrum of endometrial pathology induced by progesterone receptormodulators. Mod Pathol 2008; 21: 591–8.
32. Eisinger SH, Bonfiglio T, Fiscella K et al. Twelve-month safety and efficacy of low-dose mifepristone for uterine myomas. J Minim Invasive Gynecol 2005; 12: 227–33.
33. 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: 556–69.
34. Eisinger SH, Meldrum S, Fiscella K et al. Low-dose mifepristone for uterine leiomyomata. Obstet Gynecol 2003; 101: 243–50.
35. Engman M, Granberg S, Williams AR et al. Mifepristone for treatment of uterine leiomyoma. A prospective randomized placebo controlled trial. Hum Reprod 2009; 24: 1870–9.
36. Chwalisz K, Elger W, Stickler T et al. The effects of 1-month administration of asoprisnil (J867), a selective progesterone receptor modulator, in healthy premenopausal women. Hum Reprod 2005; 20: 1090–9.
37. Maruo T, Ohara N, Yoshida S et al. Lessons learned from the preclinical drug discovery of asoprisnil and ulipristal for non-surgical treatment of uterine leiomyomas. Expert Opin Drug Dis 2011; 6: 897–911.
38. Musallam KM, Tamim HM, Richards T et al. Preoperative anaemia and postoperative outcomes in noncardiac surgery: a retrospective cohort study. Lancet 2011; 378: 1396–407.
39. Donnez J, Donnez O, Dolmans MM. With the advent of selective progesterone receptor modulators, what is the place of myoma surgery in current practice? Fertil Steril 2014; 102: 640–8. Review of current techniques of myoma surgery. New algorithms are proposed depending on age, symptoms and wish to preserve the uterus.
40. Islam MS, Protic O, Giannubilo SR et al. Uterine leiomyoma: available medical treatments and new possible therapeutic options. J Clin Endocrinol Metab 2013; 98: 921–34.
41. Luyckx M, Squifflet JL, Jadoul P et al. First series of 18 pregnancies after ulipristal acetate treatment for uterine fibroids. Fertil Steril 2014; 102: 1404–9.

________________________________________________

1. Fernandez H. Uterine fibroids. Rev Prat 2014; 64: 540–4.
2. Ciavattini A, Di Giuseppe J, Stortoni P et al. Uterine fibroids: pathogenesis and interactions with endometrium and endomyometrial junction. Obstet Gynecol Int 2013; 2013: 173–84.
3. Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for a debate? Hum Reprod 2002; 17: 1424–30.
4. Practice Committee of American Society for Reproductive Medicine in collaboration with Society of Reproductive Surgeons. Myomas and reproductive function. Fertil Steril 2008; 90 (Suppl. 5): S125–S130.
5. Tikhomirov A.L. Mioma, patogeneticheskoe obosnovanie organosokhraniaiushchego lecheniia. M., 2013. [in Russian]
6. Tikhomirov A.L., Manukhina E.I., Vuchenovich Iu.D. i dr. Mioma matki. Differentsirovannyi lechebnyi podkhod. Uchebnoe posobie dlia vrachei akusherov-ginekologov. M., 2015. [in Russian]
7. Lethaby A, Vollenhoven B, Sowter M. Preoperative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev 2001; CD000547.
8. Tan YH, Lethaby A. Preoperative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding. Cochrane Database Syst Rev 2013; 11: CD010241.
9. Nisolle M, Gillerot S, Casanas-Roux F et al. Immunohistochemical study of the proliferation index, oestrogen receptors and progesterone receptors A and B in leiomyomata and normal myometrium during the menstrual cycle and under gonadotrophin-releasing hormone agonist therapy. Hum Reprod 1999; 14: 2844–50.
10. Kim JJ, Sefton EC. The role of progesterone signaling in the pathogenesis of uterine leiomyoma. Mol Cell Endocrinol 2012; 358: 223–31.
11. Donnez J, Tatarchuk TF, Bouchard P et al; PEARL I Study Group. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med 2012; 366: 409–20.
12. Donnez J, Tomaszewski J, Vazquez F et al; PEARL II Study Group. Ulipristalacetate versus leuprolide acetate for uterine fibroids. N Engl J Med 2012; 366: 421–32.
13. Donnez J, Vazquez F, Tomaszewski J et al; PEARL III and PEARL III Extension Study Group. Long-term treatment of uterine fibroids with ulipristal acetate. Fertil Steril 2014; 101: 1565–73. First study on long-term efficacy, which is maximized by long-term intermittent therapy.
14. Donnez J, Hudecek R, Donnez O et al. Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids.Fertil Steril 2015; 103: 519–27.
15. 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: 170–5. Study suggesting that progesterone receptor signaling may favor leiomyoma growth while alleviating clinical symptoms.
16. 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 5 0-diphosphateribose) polymerase expression in cultured human uterine leiomyoma cells. J Clin Endocrinol Metab 2005; 90: 953–61.
17. Horne FM, Blithe DL. Progesterone receptor modulators and the endometrium: changes and consequences. Hum Reprod Update 2007; 13: 567–80.
18. Bouchard P, Chabbert-Buffet N, Fauser BC. Selective progesterone receptor modulators in reproductive medicine: pharmacology, clinical efficacy and safety. Fertil Steril 2011; 96: 1175–89.
19. Bestel E, Donnez J. The potential of selective progesterone receptor modulators for the treatment of uterine fibroids. Expert Rev Endocrinol Metab 2014; 9: 79–92.
20. Chen W, Ohara N, Wang J et al. A novel selective progesterone receptor modulator asoprisnil (J867) inhibits proliferation and induces apoptosis in cultured human uterine leiomyoma cells in the absence of comparable effects on Myometrial Cells Chen W, Ohara N, Wang J et al (Kobe Univ, Japan; TAP Pharmaceutical Products, Inc, Lake Forest, III). J Clin Endocrinol Metab 2006; 91: 1296–304.
21. Morikawa A, Ohara N, Xu Q et al. Selective progesterone receptor modulator asoprisnil down-regulates collagen synthesis in cultured human uterineleiomyoma cells through up-regulating extracellular matrix metalloproteinase inducer. Hum Reprod 2008; 23: 944–51.
22. Koji T, Chedid M, Rubin JS et al. Progesterone-dependent expression of keratinocyte growth factor mRNA in stromal cells of the primate endometrium: keratinocyte growth factor as a progestomedin. J Cell Biol 1994; 125: 393–401.
23. 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: 2408–16.
24. Reinsch RC, Murphy AA, Morales AJ, Yen SS. The effects of RU 486 and leuprolide acetate on uterine artery blood flow in the fibroid uterus: a prospective, randomized study. Am J Obstet Gynecol 1994; 170: 1623–7.
25. Wilkens J, Chwalisz K, Han C et al. Effects of the selective progesterone receptor modulator asoprisnil on uterine artery blood flow, ovarian activity, and clinical symptoms in patients with uterine leiomyomata scheduled for hysterectomy. J Clin Endocrinol Metab 2008; 93: 4664–71.
26. Courtoy G, Donnez J, Marbaix E, Dolmans MM. In vivo mechanisms of uterinemyoma volume reduction with ulipristal acetate treatment. Fertil Steril 2015; 104: 426–34.
27. Chwalisz K, Larsen L, Mattia-Goldberg C et al. A randomized, controlled trial of asoprisnil, a novel selective progesterone receptor modulator, in women with uterine leiomyomata. Fertil Steril 2007; 87:1399–412.
28. Chabbert-Buffet N, Pintiaux-Kairis A, Bouchard P. Effects of the progesterone receptor modulator VA2914 in a continuous low-dose on the hypothalamicpituitary-ovarian axis and endometrium in normal women: a prospective, randomized, placebo-controlled trial. J Clin Endocrinol Metab 2007; 92: 3582–9.
29. Brache V, Cochon L, Jesam C et al. Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture. Hum Reprod 2010; 25: 2256–63.
30. Stratton P, Hartog B, Hajizadeh N et al. A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women. Hum Reprod 2000; 15: 1092–9.
31. Mutter GL, Bergeron C, Deligdisch L et al. The spectrum of endometrial pathology induced by progesterone receptormodulators. Mod Pathol 2008; 21: 591–8.
32. Eisinger SH, Bonfiglio T, Fiscella K et al. Twelve-month safety and efficacy of low-dose mifepristone for uterine myomas. J Minim Invasive Gynecol 2005; 12: 227–33.
33. 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: 556–69.
34. Eisinger SH, Meldrum S, Fiscella K et al. Low-dose mifepristone for uterine leiomyomata. Obstet Gynecol 2003; 101: 243–50.
35. Engman M, Granberg S, Williams AR et al. Mifepristone for treatment of uterine leiomyoma. A prospective randomized placebo controlled trial. Hum Reprod 2009; 24: 1870–9.
36. Chwalisz K, Elger W, Stickler T et al. The effects of 1-month administration of asoprisnil (J867), a selective progesterone receptor modulator, in healthy premenopausal women. Hum Reprod 2005; 20: 1090–9.
37. Maruo T, Ohara N, Yoshida S et al. Lessons learned from the preclinical drug discovery of asoprisnil and ulipristal for non-surgical treatment of uterine leiomyomas. Expert Opin Drug Dis 2011; 6: 897–911.
38. Musallam KM, Tamim HM, Richards T et al. Preoperative anaemia and postoperative outcomes in noncardiac surgery: a retrospective cohort study. Lancet 2011; 378: 1396–407.
39. Donnez J, Donnez O, Dolmans MM. With the advent of selective progesterone receptor modulators, what is the place of myoma surgery in current practice? Fertil Steril 2014; 102: 640–8. Review of current techniques of myoma surgery. New algorithms are proposed depending on age, symptoms and wish to preserve the uterus.
40. Islam MS, Protic O, Giannubilo SR et al. Uterine leiomyoma: available medical treatments and new possible therapeutic options. J Clin Endocrinol Metab 2013; 98: 921–34.
41. Luyckx M, Squifflet JL, Jadoul P et al. First series of 18 pregnancies after ulipristal acetate treatment for uterine fibroids. Fertil Steril 2014; 102: 1404–9.

А.Л.Тихомиров*

ГБОУ ВПО Московский государственный медико-стоматологический университет им. А.И.Евдокимова Минздрава России. 127473, Россия, Москва, ул. Делегатская, д. 20, стр. 1
*pacificoff@mail.ru

________________________________________________

A.L.Tikhomirov*

A.I.Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health of the Russian Federation. 127473, Russian Federation, Moscow, ul. Delegatskaia, d. 20, str. 1
*pacificoff@mail.ru