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Актуальное консервативное лечение миомы матки. Улипристала ацетат и повреждение печени: надуманная трагедия?
Тихомиров А.Л. Актуальное консервативное лечение миомы матки. Улипристала ацетат и повреждение печени: надуманная трагедия? Гинекология. 2018; 20 (6): 4–7. DOI: 10.26442/20795696.2018.6.000053
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Tikhomirov A.L. Current conservative treatment of uterine fibroids. Ulipristal acetate and liver damage: contrived tragedy? Gynecology. 2018; 20 (6): 4–7.
DOI: 10.26442/20795696.2018.6.000053
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Аннотация
Миома матки является наиболее часто встречающимся опухолевидным тазовым образованием у женщин и самым распространенным показанием к гистерэктомии. Ранее была доказана эффективность долгосрочного интермиттирующего применения улипристала ацетата (УА) у больных с миомой матки. В мае 2018 г. способность УА вызывать лекарственное поражение печени (drug-induced liver injury – DILI) была опровергнута, Европейская комиссия утвердила положительное решение. По заключению экспертизы Комитета по оценке рисков в сфере фармаконадзора (Pharmacovigilance Risk Assessment Committee – PRAC) соотношение польза/риск остается благоприятным. Выпущены рекомендации, направленные на уменьшение риска развития повреждения печени. УА остается 1-й линией лечения большинства миом.
Ключевые слова: лейомиома матки, гистерэктомия, регрессионные методы лечения, острая печеночная недостаточность, улипристала ацетат.
Ключевые слова: лейомиома матки, гистерэктомия, регрессионные методы лечения, острая печеночная недостаточность, улипристала ацетат.
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Uterine fibroids are the most common pelvic tumor formation in women and the most common indication for hysterectomy. The effectiveness of long-term intermittent use of ulipristal acetate (UA) in patients with uterine myoma has been proven earlier. In May 2018, the ability of UA to cause a drug-induced liver injury (drug-induced liver injury, DILI) was disproved, and the European Commission approved a positive decision. According to the conclusion Expertise of the Pharmacovigilance Risk Assessment Committee (Pharmacovigilance Risk Assessment Committee – PRAC) the benefit/risk ratio remains favorable. Published recommendations are aimed at reducing the risk of liver damage. UA remains the 1st line of treatment for most myomas.
Key words: uterine leiomyoma, hysterectomy, regression treatment methods, acute liver failure, ulipristal acetate.
Полный текст
Список литературы
1. Day Baird D, Dunson DB, Hill MC et al. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol 2003; 188 (1): 100–7.
2. Cramer SF, Patel A. The frequency of uterine leiomyomas. Am J Clin Pathol 1990; 94 (4): 435–8.
3. Stewart EA, Nicholson WK, Bradley L et al. The burden of uterine fibroids for African-American women: results of a national survey. J Womens Health (Larchmt) 2013; 22 (10): 807–16.
4. Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for a debate? Hum Reprod 2002; 17: 1424–30.
5. 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.
6. Тихомиров А.Л. Миома, патогенетическое обоснование органосохраняющего лечения. М., 2013. / Tikhomirov A.L. Mioma, patogeneticheskoe obosnovanie organosokhraniaiushchego lecheniia. M., 2013. [in Russian]
7. 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]
8. Borah BJ, Nicholson WK, Bradley L et al. The impact of uterine leiomyomas: a national survey of affected women. Am J Obstet Gynecol 2013; 209 (4): 319.e1–20.
9. Wright JD, Herzog TJ, Tsui J et al. Nationwide trends in the performance of inpatient hysterectomy in the United States. Obstet Gynecol 2013; 122 (2 Pt 1): 233–41.
10. Kim JJ, Sefton EC. The role of progesterone signaling in the pathogenesis of uterine leiomyoma. Mol Cell Endocrinol 2012; 358: 223–31.
11. PEARL I Study Group. Donnez J, Tatarchuk TF, Bouchard P et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med 2012; 366: 409–20.
12. PEARL II Study Group. Donnez J, Tomaszewski J, Vazquez F et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med 2012; 366: 421–32.
13. PEARL III and PEARL III Extension Study Group. Donnez J, Vazquez F, Tomaszewski J et al. Long-term treatment of uterine fibroids with ulipristal acetate. Fertil Steril 2014; 101: 1565–73.
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.
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′-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. 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.
19. 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.
20. 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: 1623–27.
21. Courtoy G, Donnez J, Marbaix E, Dolmans MM. In vivo mechanisms of uterine myoma volume reduction with ulipristal acetate treatment. Fertil Steril 2015; 104: 426–34.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. Chen M, Susuki A, Thakkar S et al. The largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016; 21: 648–53.
29. Lammert C, Einarsson S, Saha C et al. Relationship between daily dose of oral medications and idiosyncratic druginduced liver injury: search for signals. Hepatology 2008; 47: 2003–9.
2. Cramer SF, Patel A. The frequency of uterine leiomyomas. Am J Clin Pathol 1990; 94 (4): 435–8.
3. Stewart EA, Nicholson WK, Bradley L et al. The burden of uterine fibroids for African-American women: results of a national survey. J Womens Health (Larchmt) 2013; 22 (10): 807–16.
4. Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for a debate? Hum Reprod 2002; 17: 1424–30.
5. 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.
6. Тихомиров А.Л. Миома, патогенетическое обоснование органосохраняющего лечения. М., 2013. / Tikhomirov A.L. Mioma, patogeneticheskoe obosnovanie organosokhraniaiushchego lecheniia. M., 2013. [in Russian]
7. 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]
8. Borah BJ, Nicholson WK, Bradley L et al. The impact of uterine leiomyomas: a national survey of affected women. Am J Obstet Gynecol 2013; 209 (4): 319.e1–20.
9. Wright JD, Herzog TJ, Tsui J et al. Nationwide trends in the performance of inpatient hysterectomy in the United States. Obstet Gynecol 2013; 122 (2 Pt 1): 233–41.
10. Kim JJ, Sefton EC. The role of progesterone signaling in the pathogenesis of uterine leiomyoma. Mol Cell Endocrinol 2012; 358: 223–31.
11. PEARL I Study Group. Donnez J, Tatarchuk TF, Bouchard P et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med 2012; 366: 409–20.
12. PEARL II Study Group. Donnez J, Tomaszewski J, Vazquez F et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med 2012; 366: 421–32.
13. PEARL III and PEARL III Extension Study Group. Donnez J, Vazquez F, Tomaszewski J et al. Long-term treatment of uterine fibroids with ulipristal acetate. Fertil Steril 2014; 101: 1565–73.
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.
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′-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. 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.
19. 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.
20. 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: 1623–27.
21. Courtoy G, Donnez J, Marbaix E, Dolmans MM. In vivo mechanisms of uterine myoma volume reduction with ulipristal acetate treatment. Fertil Steril 2015; 104: 426–34.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. Chen M, Susuki A, Thakkar S et al. The largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016; 21: 648–53.
29. Lammert C, Einarsson S, Saha C et al. Relationship between daily dose of oral medications and idiosyncratic druginduced liver injury: search for signals. Hepatology 2008; 47: 2003–9.
________________________________________________
1. Day Baird D, Dunson DB, Hill MC et al. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol 2003; 188 (1): 100–7.
2. Cramer SF, Patel A. The frequency of uterine leiomyomas. Am J Clin Pathol 1990; 94 (4): 435–8.
3. Stewart EA, Nicholson WK, Bradley L et al. The burden of uterine fibroids for African-American women: results of a national survey. J Womens Health (Larchmt) 2013; 22 (10): 807–16.
4. Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for a debate? Hum Reprod 2002; 17: 1424–30.
5. 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.
6. Tikhomirov A.L. Mioma, patogeneticheskoe obosnovanie organosokhraniaiushchego lecheniia. M., 2013. [in Russian]
7. 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]
8. Borah BJ, Nicholson WK, Bradley L et al. The impact of uterine leiomyomas: a national survey of affected women. Am J Obstet Gynecol 2013; 209 (4): 319.e1–20.
9. Wright JD, Herzog TJ, Tsui J et al. Nationwide trends in the performance of inpatient hysterectomy in the United States. Obstet Gynecol 2013; 122 (2 Pt 1): 233–41.
10. Kim JJ, Sefton EC. The role of progesterone signaling in the pathogenesis of uterine leiomyoma. Mol Cell Endocrinol 2012; 358: 223–31.
11. PEARL I Study Group. Donnez J, Tatarchuk TF, Bouchard P et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med 2012; 366: 409–20.
12. PEARL II Study Group. Donnez J, Tomaszewski J, Vazquez F et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med 2012; 366: 421–32.
13. PEARL III and PEARL III Extension Study Group. Donnez J, Vazquez F, Tomaszewski J et al. Long-term treatment of uterine fibroids with ulipristal acetate. Fertil Steril 2014; 101: 1565–73.
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.
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′-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. 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.
19. 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.
20. 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: 1623–27.
21. Courtoy G, Donnez J, Marbaix E, Dolmans MM. In vivo mechanisms of uterine myoma volume reduction with ulipristal acetate treatment. Fertil Steril 2015; 104: 426–34.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. Chen M, Susuki A, Thakkar S et al. The largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016; 21: 648–53.
29. Lammert C, Einarsson S, Saha C et al. Relationship between daily dose of oral medications and idiosyncratic druginduced liver injury: search for signals. Hepatology 2008; 47: 2003–9.
Авторы
А.Л.Тихомиров
ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И.Евдокимова» Минздрава России. 127473, Россия, Москва, ул. Делегатская, д. 20, стр. 1
pacificoff@mail.ru
ФГБОУ ВО «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
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