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Сравнительная оценка эффективности перспективных препаратов для таргетной терапии эндометриоза на основании экспериментальной модели заболевания
Сравнительная оценка эффективности перспективных препаратов для таргетной терапии эндометриоза на основании экспериментальной модели заболевания
Ярмолинская М.И., Петросян М.А., Флорова М.С. и др. Сравнительная оценка эффективности перспективных препаратов для таргетной терапии эндометриоза на основании экспериментальной модели заболевания. Гинекология. 2018; 20 (5): 46–51. DOI: 10.26442/2079-5696_2018.5.46-51
DOI: 10.26442/2079-5696_2018.5.46-51
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DOI: 10.26442/2079-5696_2018.5.46-51
Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Аннотация
Актуальность. Хронический, прогрессирующий, рецидивирующий характер эндометриоза делает крайне актуальным поиск новых направлений таргетной терапии генитального эндометриоза, обладающих высокой терапевтической эффективностью и минимальными побочными действиями. В настоящий момент стандартом специфической терапии эндометриоза является применение диеногеста 2 мг – производного 19-нортестостерона, доказавшего свою эффективность in vitro, in vivo и в клинической практике.
Цель: оценить эффективность новых видов таргетной патогенетической терапии эндометриоза на модели эндометриоза у крыс по сравнению с диеногестом и отсутствием лечения.
Материалы и методы. Эндометриоз был индуцирован на 69 крысах линии Wistar путем аутотрансплантации маточных фрагментов на внутреннюю поверхность брюшной стенки. Через 14 дней была произведены оценка сформировавшихся гетеротопий путем лапароскопии и рандомизация крыс в одну из 6 основных групп (диеногест, летрозол, каберголин, метформин, витамин D, мелатонин) или группу контроля. Все препараты применялись ежедневно перорально в течение 3 нед, после чего были произведены вскрытие и повторная оценка размеров эндометриоидных имплантатов.
Результаты. Наиболее выраженное уменьшение размеров эндометриоидных имплантатов наблюдалось в группе животных, получавших диеногест (полная резорбция – 48%, регресс – 48%, без динамики – 4%) и летрозол (полная резорбция – 44%, регресс – 56%), без статистически значимой разницы между группами, в остальных группах, получавших терапию, было продемонстрировано достоверное уменьшение размеров эндометриоидных имплантатов по сравнению с контрольной группой, без статистически значимой разницы между группами.
Выводы. Представленное исследование подтверждает отсутствие в настоящий момент пероральных препаратов для лечения эндометриоза, сопоставимых по эффективности и безопасности с диеногестом. Необходимо дальнейшее изучение различных схем применения агонистов дофамина, бигуанидов, витамина D, мелатонина в качестве дополнения к классической гормономодулирующей терапии эндометриоза или в качестве монотерапии у пациенток с наличием противопоказаний к стандартной гормональной терапии.
Ключевые слова: эндометриоз, экспериментальная модель, диеногест, летрозол, каберголин, метформин, мелатонин, витамин D.
Purpose: to evaluate the effectiveness of new types of targeted pathogenetic therapy for endometriosis on the model of endometriosis in rats compared to dienogest and without treatment.
Materials and methods. Endometriosis was induced on 69 Wistar rats by autotransplantation of uterine fragments onto the inner surface of the abdominal wall. After 14 days, the heterotopies had been measured by laparoscopy and then rats were randomized of into one of 6 experimental groups (dienogest, letrozole, cabergoline, metformin, vitamin D, melatonin) or a control group. All drugs were administered daily orally for three weeks, after which an autopsy and re-measuring of the size of endometrial implants were performed.
Results. The most pronounced decrease in the size of endometrial implants was observed in the group of animals treated with dienogest (complete resorption – 48%, regression – 48%, without dynamics – 4%) and letrozole (complete resorption – 44%, regression – 56%) without the statistically significant difference between groups. In other groups, a significant decrease in the size of endometrial implants was demonstrated compared with the control, without a statistically significant difference between the groups.
Findings. The presented study confirms the absence at the present time of oral drugs for the treatment of endometriosis, comparable in efficacy and safety with dienogest. Further research are needed to evaluate the different combinations of dopamine agonists, biguanides, vitamin D, melatonin as the supplement to the classic hormone-modulating therapy for endometriosis or as monotherapy in patients with contraindications to standard hormone therapy.
Key words: endometriosis, experimental model, dienogest, letrozole, cabergoline, metformin, melatonin, vitamin D.
Цель: оценить эффективность новых видов таргетной патогенетической терапии эндометриоза на модели эндометриоза у крыс по сравнению с диеногестом и отсутствием лечения.
Материалы и методы. Эндометриоз был индуцирован на 69 крысах линии Wistar путем аутотрансплантации маточных фрагментов на внутреннюю поверхность брюшной стенки. Через 14 дней была произведены оценка сформировавшихся гетеротопий путем лапароскопии и рандомизация крыс в одну из 6 основных групп (диеногест, летрозол, каберголин, метформин, витамин D, мелатонин) или группу контроля. Все препараты применялись ежедневно перорально в течение 3 нед, после чего были произведены вскрытие и повторная оценка размеров эндометриоидных имплантатов.
Результаты. Наиболее выраженное уменьшение размеров эндометриоидных имплантатов наблюдалось в группе животных, получавших диеногест (полная резорбция – 48%, регресс – 48%, без динамики – 4%) и летрозол (полная резорбция – 44%, регресс – 56%), без статистически значимой разницы между группами, в остальных группах, получавших терапию, было продемонстрировано достоверное уменьшение размеров эндометриоидных имплантатов по сравнению с контрольной группой, без статистически значимой разницы между группами.
Выводы. Представленное исследование подтверждает отсутствие в настоящий момент пероральных препаратов для лечения эндометриоза, сопоставимых по эффективности и безопасности с диеногестом. Необходимо дальнейшее изучение различных схем применения агонистов дофамина, бигуанидов, витамина D, мелатонина в качестве дополнения к классической гормономодулирующей терапии эндометриоза или в качестве монотерапии у пациенток с наличием противопоказаний к стандартной гормональной терапии.
Ключевые слова: эндометриоз, экспериментальная модель, диеногест, летрозол, каберголин, метформин, мелатонин, витамин D.
________________________________________________
Purpose: to evaluate the effectiveness of new types of targeted pathogenetic therapy for endometriosis on the model of endometriosis in rats compared to dienogest and without treatment.
Materials and methods. Endometriosis was induced on 69 Wistar rats by autotransplantation of uterine fragments onto the inner surface of the abdominal wall. After 14 days, the heterotopies had been measured by laparoscopy and then rats were randomized of into one of 6 experimental groups (dienogest, letrozole, cabergoline, metformin, vitamin D, melatonin) or a control group. All drugs were administered daily orally for three weeks, after which an autopsy and re-measuring of the size of endometrial implants were performed.
Results. The most pronounced decrease in the size of endometrial implants was observed in the group of animals treated with dienogest (complete resorption – 48%, regression – 48%, without dynamics – 4%) and letrozole (complete resorption – 44%, regression – 56%) without the statistically significant difference between groups. In other groups, a significant decrease in the size of endometrial implants was demonstrated compared with the control, without a statistically significant difference between the groups.
Findings. The presented study confirms the absence at the present time of oral drugs for the treatment of endometriosis, comparable in efficacy and safety with dienogest. Further research are needed to evaluate the different combinations of dopamine agonists, biguanides, vitamin D, melatonin as the supplement to the classic hormone-modulating therapy for endometriosis or as monotherapy in patients with contraindications to standard hormone therapy.
Key words: endometriosis, experimental model, dienogest, letrozole, cabergoline, metformin, melatonin, vitamin D.
Полный текст
Список литературы
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2. Jones CJ, Inuwa IM, Nardo LG et al. Eutopic endometrium from women with endometriosis shows altered ultrastructure and glycosylation compared to that from healthy controls – a pilot observational study. Reprod Sci 2009; 16: 559–72.
3. Dinsdale NL, Crespi BJ. Revisiting the wandering womb: Oxytocin in endometriosis and bipolar disorder. Hormon Behav 2017; 69: 69–83.
4. Barbieri RL. Why are there delays in the diagnosis of endometriosis? OBG Manag 2017; 29 (3): 8, 10–11.
5. Angioni S, Peiretti M, Zirone M et al. Laparoscopic excision of posterior vaginal fornix in the treatment of patients with deep endometriosis without bowel involvement: surgical treatment and long-term follow-up. Hum Reprod 2006; 21: 1629–34.
6. Angioni S, Maricosu G, Mereu L et al. Single Port Access Laparoscopy (SPAL) for endometrioma excision. J Endometrios Pelvic Pain Dis 2010; 2: 95–8.
7. Busacca M, Candiani M, Chiàntera V et al. Guidelines for diagnosis and treatment of endometriosis. Ital J Gynaecol Obstet 2018; 30 (2): 7–15.
8. Pisanu A, Deplano D, Angioni S et al. Rectal perforation from endometriosis in pregnancy: case report and literature review. W J Gastroenterol 2010; 16: 648–51.
9. Angioni S, Pontis V, Tinelli A et al. New trends of progestins treatment of endometriosis. The official journal of the ISGE: Gynecol Endocrinol 2014; 30 (11): 1–5.
10. Rizzo A, Spedicato M, Mutinati M et al. Peritoneal adhesions in human and veterinary medicine: from pathogenesis to therapy: a review. Immunopharmacol Immunotoxicol 2010; 2: 481–94.
11. Litta P, D’Agostino G, Conte L et al. Mullerian hormone trend after laparoscopic surgery in women with ovarian endometrioma. Gynecol Endocrinol 2013; 29: 452–4.
12. Vercellini P, Fedele L, Aimi G et al. Reproductive performance, pain recurrenceand disease relapse after conservative surgical treatment for endometriosis: the predictive value of current system. Hum Reprod 2006; 21: 2679–85.
13. Katsuki Y, Takano Y, Futamura Y et al. Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats. Eur J Endocrinol 1998; 138 (2): 216–26.
14. Oettel M, Breitbarth H, Elger W et al. The pharmacological profile of dienogest. Eur J Contracept Reprod Health Care 1999; 4 (1): 2–13.
15. Oettel M, Breitbarth H, Elger W et al. The pharmacological profile of dienogest. Eur J Contracept Reprod Health Care 1999; 4 (1): 2–13.
16. Katsuki Y, Sasagawa S, Takano Y et al. Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid. Drugs Exp Clin Res 1997; 23: 45–62.
17. Sasagawa S, Shimizu Y, Kami H et al. Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile. Steroids 2008; 73: 222–31.
18. Strowitzki T, Faustmann T, Gerlinger C et al. Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study. Eur J Obstet Gynecol Reprod Biol 2010; 151 (2): 193–8.
19. Mita S, Shimizu Y, Sato A et al. Dienogest inhibits nerve growth factor expression induced by tumor necrosis factor-a or interleukin-1b. Fertility and sterility 2014; 101 (2): 595–601.
20. Katsuki Y, Takano Y, Futamura Y et al. Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats. Eur J Endocrinol 1998; 138 (2): 216–26.
21. Katayama H, Katayama T, Uematsu K et al. Effect of dienogest administration on angiogenesis and hemodynamics in a rat endometrial autograft model. Hum Reprod 2010; 25 (11): 2851–8.
22. Nakamura M, Katsuki Y, Shibutani Y et al. Dienogest, a synthetic steroid, suppresses both embryonic and tumor-cell-induced angiogenesis. Eur J Pharmacol 1999; 386 (1): 33–40.
23. Mönckedieck V, Sannecke C, Husen B et al. Progestins inhibit expression of MMPs and of angiogenic factors in human ectopic endometrial lesions in a mouse model. Mol Hum Reprod 2009; 15 (10): 633–43.
24. Okada H, Nakajima T, Yoshimura T et al. The inhibitory effect of dienogest, a synthetic steroid, on the growth of human endometrial stromal cells in vitro. MHR: Basic Sci Reprod Med 2001; 7 (4): 341–7.
25. Yarmolinskaya M, Makarova I, Veremiova R et al. A non-interventional study with dienogest 2 mg to assess the quality of life in patients with endometriosis (DIVA study) – 2016. SEUD, Barselona.
26. Lee SR, Yi KW, Song JY et al. Efficacy and Safety of Long-Term Use of Dienogest in Women With Ovarian Endometrioma. Reprod Sci 2018; 25 (3): 341–6.
27. Park SY, Kim SH, Chae HD et al. Efficacy and safety of dienogest in patients with endometriosis: A single-center observational study over 12 months. Clin Exp Reprod Med 2016; 43 (4): 215–20.
28. Sugimoto K, Nagata C, Hayashi H et al. Use of dienogest over 53 weeks for the treatment of endometriosis. J Obstet Gynaecol Res 2015; 41 (12): 1921–6.
29. Chandra A, Rho AM, Jeong K et al. Clinical experience of long-term use of dienogest after surgery for ovarian endometrioma. Obstet Gynecol Sci 2018; 61 (1): 111–7.
30. Romer T. Long-term treatment of endometriosis with dienogest: retrospective analysis of efficacy and safety in clinical practice. Arch Gynecol Obstet 2018; 298 (4): 747–53.
31. Yarmolinskaia M.I., Florova M.S. Vozmozhnosti terapii dienogestom 2 mg u bol'nykh naruzhnym genital'nym endometriozom. Problemy reproduktsii. 2017; 23 (1): 70–9. [in Russian]
32. Bulun SE, Zeitoun K, Takayama K et al. Estrogen production in endometriosis and use of aromatase inhibitors to treat endometriosis. Endo Rel Cancer 1999; 6: 293–301.
33. Molotkov A.S., Jarmolinskaia M.I., Poliakova V.O. i dr. Znachenie ekspressii aromatazy v patogeneze naruzhnogo genital'nogo endometrioza. Molekuliarnaia meditsina. 2012; 4: 41–4. [in Russian]
34. Meinhardt U, Mullis PE. The essential role of the aromatase/p450arom. Semin Reprod Med 2002; 20: 277–84.
35. Goss PE, Strasser K. Aromatase inhibitors in the treatment and prevention of breast cancer. J Clin Oncol 2001; 19: 881–94.
36. Takayama K, Zeitoun K, Gunby RT et al. Treatment of severe postmenopausal endometriosis with an aromatase inhibitor. Fertil Steril 1998; 69: 709–13.
37. Yarmolinskaia M.I., Molotkov A.S., Bezhenar' V.F. i dr. Effektivnost' ingibitorov aromatazy v kombinirovannom lechenii naruzhnogo genital'nogo endometrioza. Arkhiv akusherstva i ginekologii im. V.F.Snegireva. 2014; 1 (1): 36–40. [in Russian]
38. Novella-Maestre E, Carda C, Noguera I et al. Dopamine agonist administration causes a reduction in endometrial implants through modulation of angiogenesis in experimentally induced endometriosis. Hum Reprod 2009; 24: 1025–35.
39. Delgado RF, Gomez R, Herrero H et al. The effects of ergot and non-ergot derived dopamine agonists in an experimental mouse model of endometriosis. Reproduction 2011; 142: 745–55.
40. Gomez R, Abad A, Delgado F et al. Effects of hyperprolactinemia treatment with the dopamine agonist quinagolide on endometriotic lesions in patients with endometriosis-associated hyperprolactinemia. Fertil Steril 2011; 95: 882–8.
41. Takemura Y, Osuga Y, Yoshino O et al. Metformin suppresses interleukin (IL)-1b-induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells. J Clin Endocrinol Metab 2007; 92: 3213–8.
42. Oner G, Ozcelik B, Ozgun M et al. The effects of metformin and letrozole on endometriosis and comparison of the two treatment agents in a rat model. Hum Reprod 2010; 25 (4): 932–7.
43. Yilmaz B, Sucak A, Kilic S et al. Metformin regresses endometriotic implants in rats by improving implant levels of superoxide dismutase, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-2, and matrix metalloproteinase-9. Am J Obstet Gynecol 2010; 202 (4): 368.
44. An BS, Tavera-Mendoza LE, Dimitrov V et al. Stimulation of Sirt1-regulated FoxO protein function by the ligand-bound vitamin D receptor. Molecular Cell Biol 2010; 30 (20): 4890–900.
45. Yildirim B, Guler T, Akbulut M et al. 1-Alpha, 25-Dihydroxyvitamin D3 Regresses Endometriotic Implants in Rats by Inhibiting Neovascularization and Altering Regulation of Matrix Metalloproteinase. Postgrad Med 2014; 126 (1): 104–10.
46. Guney M, Oral B, Karahan N et al. Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil Steril 2008; 89: 934–42.
47. Yildirim G, Attar R, Ozkan F et al. The effects of letrozole and melatonin on surgically induced endometriosis in a rat model: a preliminary study. Fertil Steril 2010; 93: 1787–92.
48. Paul S, Sharma AV, Mahapatra PD et al. Role of melatonin in regulating matrix metalloproteinase-9 via tissue inhibitors of metalloproteinase-1 during protection against endometriosis. J Pineal Res 2008; 44: 439–49.
49. Guney M, Oral B, Karahan N et al. Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil Steril 2008; 89: 934–42.
50. Koc O, Gunduz B, Topcuoglu A et al. Effects of pinealectomy and melatonin supplementation on endometrial explants in a rat model. Eur J Obstet Gynecol Reprod Biol 2010; 153: 72–6.
2. Jones CJ, Inuwa IM, Nardo LG et al. Eutopic endometrium from women with endometriosis shows altered ultrastructure and glycosylation compared to that from healthy controls – a pilot observational study. Reprod Sci 2009; 16: 559–72.
3. Dinsdale NL, Crespi BJ. Revisiting the wandering womb: Oxytocin in endometriosis and bipolar disorder. Hormon Behav 2017; 69: 69–83.
4. Barbieri RL. Why are there delays in the diagnosis of endometriosis? OBG Manag 2017; 29 (3): 8, 10–11.
5. Angioni S, Peiretti M, Zirone M et al. Laparoscopic excision of posterior vaginal fornix in the treatment of patients with deep endometriosis without bowel involvement: surgical treatment and long-term follow-up. Hum Reprod 2006; 21: 1629–34.
6. Angioni S, Maricosu G, Mereu L et al. Single Port Access Laparoscopy (SPAL) for endometrioma excision. J Endometrios Pelvic Pain Dis 2010; 2: 95–8.
7. Busacca M, Candiani M, Chiàntera V et al. Guidelines for diagnosis and treatment of endometriosis. Ital J Gynaecol Obstet 2018; 30 (2): 7–15.
8. Pisanu A, Deplano D, Angioni S et al. Rectal perforation from endometriosis in pregnancy: case report and literature review. W J Gastroenterol 2010; 16: 648–51.
9. Angioni S, Pontis V, Tinelli A et al. New trends of progestins treatment of endometriosis. The official journal of the ISGE: Gynecol Endocrinol 2014; 30 (11): 1–5.
10. Rizzo A, Spedicato M, Mutinati M et al. Peritoneal adhesions in human and veterinary medicine: from pathogenesis to therapy: a review. Immunopharmacol Immunotoxicol 2010; 2: 481–94.
11. Litta P, D’Agostino G, Conte L et al. Mullerian hormone trend after laparoscopic surgery in women with ovarian endometrioma. Gynecol Endocrinol 2013; 29: 452–4.
12. Vercellini P, Fedele L, Aimi G et al. Reproductive performance, pain recurrenceand disease relapse after conservative surgical treatment for endometriosis: the predictive value of current system. Hum Reprod 2006; 21: 2679–85.
13. Katsuki Y, Takano Y, Futamura Y et al. Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats. Eur J Endocrinol 1998; 138 (2): 216–26.
14. Oettel M, Breitbarth H, Elger W et al. The pharmacological profile of dienogest. Eur J Contracept Reprod Health Care 1999; 4 (1): 2–13.
15. Oettel M, Breitbarth H, Elger W et al. The pharmacological profile of dienogest. Eur J Contracept Reprod Health Care 1999; 4 (1): 2–13.
16. Katsuki Y, Sasagawa S, Takano Y et al. Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid. Drugs Exp Clin Res 1997; 23: 45–62.
17. Sasagawa S, Shimizu Y, Kami H et al. Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile. Steroids 2008; 73: 222–31.
18. Strowitzki T, Faustmann T, Gerlinger C et al. Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study. Eur J Obstet Gynecol Reprod Biol 2010; 151 (2): 193–8.
19. Mita S, Shimizu Y, Sato A et al. Dienogest inhibits nerve growth factor expression induced by tumor necrosis factor-a or interleukin-1b. Fertility and sterility 2014; 101 (2): 595–601.
20. Katsuki Y, Takano Y, Futamura Y et al. Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats. Eur J Endocrinol 1998; 138 (2): 216–26.
21. Katayama H, Katayama T, Uematsu K et al. Effect of dienogest administration on angiogenesis and hemodynamics in a rat endometrial autograft model. Hum Reprod 2010; 25 (11): 2851–8.
22. Nakamura M, Katsuki Y, Shibutani Y et al. Dienogest, a synthetic steroid, suppresses both embryonic and tumor-cell-induced angiogenesis. Eur J Pharmacol 1999; 386 (1): 33–40.
23. Mönckedieck V, Sannecke C, Husen B et al. Progestins inhibit expression of MMPs and of angiogenic factors in human ectopic endometrial lesions in a mouse model. Mol Hum Reprod 2009; 15 (10): 633–43.
24. Okada H, Nakajima T, Yoshimura T et al. The inhibitory effect of dienogest, a synthetic steroid, on the growth of human endometrial stromal cells in vitro. MHR: Basic Sci Reprod Med 2001; 7 (4): 341–7.
25. Yarmolinskaya M, Makarova I, Veremiova R et al. A non-interventional study with dienogest 2 mg to assess the quality of life in patients with endometriosis (DIVA study) – 2016. SEUD, Barselona.
26. Lee SR, Yi KW, Song JY et al. Efficacy and Safety of Long-Term Use of Dienogest in Women With Ovarian Endometrioma. Reprod Sci 2018; 25 (3): 341–6.
27. Park SY, Kim SH, Chae HD et al. Efficacy and safety of dienogest in patients with endometriosis: A single-center observational study over 12 months. Clin Exp Reprod Med 2016; 43 (4): 215–20.
28. Sugimoto K, Nagata C, Hayashi H et al. Use of dienogest over 53 weeks for the treatment of endometriosis. J Obstet Gynaecol Res 2015; 41 (12): 1921–6.
29. Chandra A, Rho AM, Jeong K et al. Clinical experience of long-term use of dienogest after surgery for ovarian endometrioma. Obstet Gynecol Sci 2018; 61 (1): 111–7.
30. Romer T. Long-term treatment of endometriosis with dienogest: retrospective analysis of efficacy and safety in clinical practice. Arch Gynecol Obstet 2018; 298 (4): 747–53.
31. Ярмолинская М.И., Флорова М.С. Возможности терапии диеногестом 2 мг у больных наружным генитальным эндометриозом. Проблемы репродукции. 2017; 23 (1): 70–9. / Yarmolinskaia M.I., Florova M.S. Vozmozhnosti terapii dienogestom 2 mg u bol'nykh naruzhnym genital'nym endometriozom. Problemy reproduktsii. 2017; 23 (1): 70–9. [in Russian]
32. Bulun SE, Zeitoun K, Takayama K et al. Estrogen production in endometriosis and use of aromatase inhibitors to treat endometriosis. Endo Rel Cancer 1999; 6: 293–301.
33. Молотков А.С., Ярмолинская М.И., Полякова В.О. и др. Значение экспрессии ароматазы в патогенезе наружного генитального эндометриоза. Молекулярная медицина. 2012; 4: 41–4. / Molotkov A.S., Jarmolinskaia M.I., Poliakova V.O. i dr. Znachenie ekspressii aromatazy v patogeneze naruzhnogo genital'nogo endometrioza. Molekuliarnaia meditsina. 2012; 4: 41–4. [in Russian]
34. Meinhardt U, Mullis PE. The essential role of the aromatase/p450arom. Semin Reprod Med 2002; 20: 277–84.
35. Goss PE, Strasser K. Aromatase inhibitors in the treatment and prevention of breast cancer. J Clin Oncol 2001; 19: 881–94.
36. Takayama K, Zeitoun K, Gunby RT et al. Treatment of severe postmenopausal endometriosis with an aromatase inhibitor. Fertil Steril 1998; 69: 709–13.
37. Ярмолинская М.И., Молотков А.С., Беженарь В.Ф. и др. Эффективность ингибиторов ароматазы в комбинированном лечении наружного генитального эндометриоза. Архив акушерства и гинекологии им. В.Ф.Снегирева. 2014; 1 (1): 36–40. / Yarmolinskaia M.I., Molotkov A.S., Bezhenar' V.F. i dr. Effektivnost' ingibitorov aromatazy v kombinirovannom lechenii naruzhnogo genital'nogo endometrioza. Arkhiv akusherstva i ginekologii im. V.F.Snegireva. 2014; 1 (1): 36–40. [in Russian]
38. Novella-Maestre E, Carda C, Noguera I et al. Dopamine agonist administration causes a reduction in endometrial implants through modulation of angiogenesis in experimentally induced endometriosis. Hum Reprod 2009; 24: 1025–35.
39. Delgado RF, Gomez R, Herrero H et al. The effects of ergot and non-ergot derived dopamine agonists in an experimental mouse model of endometriosis. Reproduction 2011; 142: 745–55.
40. Gomez R, Abad A, Delgado F et al. Effects of hyperprolactinemia treatment with the dopamine agonist quinagolide on endometriotic lesions in patients with endometriosis-associated hyperprolactinemia. Fertil Steril 2011; 95: 882–8.
41. Takemura Y, Osuga Y, Yoshino O et al. Metformin suppresses interleukin (IL)-1b-induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells. J Clin Endocrinol Metab 2007; 92: 3213–8.
42. Oner G, Ozcelik B, Ozgun M et al. The effects of metformin and letrozole on endometriosis and comparison of the two treatment agents in a rat model. Hum Reprod 2010; 25 (4): 932–7.
43. Yilmaz B, Sucak A, Kilic S et al. Metformin regresses endometriotic implants in rats by improving implant levels of superoxide dismutase, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-2, and matrix metalloproteinase-9. Am J Obstet Gynecol 2010; 202 (4): 368.
44. An BS, Tavera-Mendoza LE, Dimitrov V et al. Stimulation of Sirt1-regulated FoxO protein function by the ligand-bound vitamin D receptor. Molecular Cell Biol 2010; 30 (20): 4890–900.
45. Yildirim B, Guler T, Akbulut M et al. 1-Alpha, 25-Dihydroxyvitamin D3 Regresses Endometriotic Implants in Rats by Inhibiting Neovascularization and Altering Regulation of Matrix Metalloproteinase. Postgrad Med 2014; 126 (1): 104–10.
46. Guney M, Oral B, Karahan N et al. Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil Steril 2008; 89: 934–42.
47. Yildirim G, Attar R, Ozkan F et al. The effects of letrozole and melatonin on surgically induced endometriosis in a rat model: a preliminary study. Fertil Steril 2010; 93: 1787–92.
48. Paul S, Sharma AV, Mahapatra PD et al. Role of melatonin in regulating matrix metalloproteinase-9 via tissue inhibitors of metalloproteinase-1 during protection against endometriosis. J Pineal Res 2008; 44: 439–49.
49. Guney M, Oral B, Karahan N et al. Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil Steril 2008; 89: 934–42.
50. Koc O, Gunduz B, Topcuoglu A et al. Effects of pinealectomy and melatonin supplementation on endometrial explants in a rat model. Eur J Obstet Gynecol Reprod Biol 2010; 153: 72–6.
________________________________________________
2. Jones CJ, Inuwa IM, Nardo LG et al. Eutopic endometrium from women with endometriosis shows altered ultrastructure and glycosylation compared to that from healthy controls – a pilot observational study. Reprod Sci 2009; 16: 559–72.
3. Dinsdale NL, Crespi BJ. Revisiting the wandering womb: Oxytocin in endometriosis and bipolar disorder. Hormon Behav 2017; 69: 69–83.
4. Barbieri RL. Why are there delays in the diagnosis of endometriosis? OBG Manag 2017; 29 (3): 8, 10–11.
5. Angioni S, Peiretti M, Zirone M et al. Laparoscopic excision of posterior vaginal fornix in the treatment of patients with deep endometriosis without bowel involvement: surgical treatment and long-term follow-up. Hum Reprod 2006; 21: 1629–34.
6. Angioni S, Maricosu G, Mereu L et al. Single Port Access Laparoscopy (SPAL) for endometrioma excision. J Endometrios Pelvic Pain Dis 2010; 2: 95–8.
7. Busacca M, Candiani M, Chiàntera V et al. Guidelines for diagnosis and treatment of endometriosis. Ital J Gynaecol Obstet 2018; 30 (2): 7–15.
8. Pisanu A, Deplano D, Angioni S et al. Rectal perforation from endometriosis in pregnancy: case report and literature review. W J Gastroenterol 2010; 16: 648–51.
9. Angioni S, Pontis V, Tinelli A et al. New trends of progestins treatment of endometriosis. The official journal of the ISGE: Gynecol Endocrinol 2014; 30 (11): 1–5.
10. Rizzo A, Spedicato M, Mutinati M et al. Peritoneal adhesions in human and veterinary medicine: from pathogenesis to therapy: a review. Immunopharmacol Immunotoxicol 2010; 2: 481–94.
11. Litta P, D’Agostino G, Conte L et al. Mullerian hormone trend after laparoscopic surgery in women with ovarian endometrioma. Gynecol Endocrinol 2013; 29: 452–4.
12. Vercellini P, Fedele L, Aimi G et al. Reproductive performance, pain recurrenceand disease relapse after conservative surgical treatment for endometriosis: the predictive value of current system. Hum Reprod 2006; 21: 2679–85.
13. Katsuki Y, Takano Y, Futamura Y et al. Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats. Eur J Endocrinol 1998; 138 (2): 216–26.
14. Oettel M, Breitbarth H, Elger W et al. The pharmacological profile of dienogest. Eur J Contracept Reprod Health Care 1999; 4 (1): 2–13.
15. Oettel M, Breitbarth H, Elger W et al. The pharmacological profile of dienogest. Eur J Contracept Reprod Health Care 1999; 4 (1): 2–13.
16. Katsuki Y, Sasagawa S, Takano Y et al. Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid. Drugs Exp Clin Res 1997; 23: 45–62.
17. Sasagawa S, Shimizu Y, Kami H et al. Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile. Steroids 2008; 73: 222–31.
18. Strowitzki T, Faustmann T, Gerlinger C et al. Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study. Eur J Obstet Gynecol Reprod Biol 2010; 151 (2): 193–8.
19. Mita S, Shimizu Y, Sato A et al. Dienogest inhibits nerve growth factor expression induced by tumor necrosis factor-a or interleukin-1b. Fertility and sterility 2014; 101 (2): 595–601.
20. Katsuki Y, Takano Y, Futamura Y et al. Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats. Eur J Endocrinol 1998; 138 (2): 216–26.
21. Katayama H, Katayama T, Uematsu K et al. Effect of dienogest administration on angiogenesis and hemodynamics in a rat endometrial autograft model. Hum Reprod 2010; 25 (11): 2851–8.
22. Nakamura M, Katsuki Y, Shibutani Y et al. Dienogest, a synthetic steroid, suppresses both embryonic and tumor-cell-induced angiogenesis. Eur J Pharmacol 1999; 386 (1): 33–40.
23. Mönckedieck V, Sannecke C, Husen B et al. Progestins inhibit expression of MMPs and of angiogenic factors in human ectopic endometrial lesions in a mouse model. Mol Hum Reprod 2009; 15 (10): 633–43.
24. Okada H, Nakajima T, Yoshimura T et al. The inhibitory effect of dienogest, a synthetic steroid, on the growth of human endometrial stromal cells in vitro. MHR: Basic Sci Reprod Med 2001; 7 (4): 341–7.
25. Yarmolinskaya M, Makarova I, Veremiova R et al. A non-interventional study with dienogest 2 mg to assess the quality of life in patients with endometriosis (DIVA study) – 2016. SEUD, Barselona.
26. Lee SR, Yi KW, Song JY et al. Efficacy and Safety of Long-Term Use of Dienogest in Women With Ovarian Endometrioma. Reprod Sci 2018; 25 (3): 341–6.
27. Park SY, Kim SH, Chae HD et al. Efficacy and safety of dienogest in patients with endometriosis: A single-center observational study over 12 months. Clin Exp Reprod Med 2016; 43 (4): 215–20.
28. Sugimoto K, Nagata C, Hayashi H et al. Use of dienogest over 53 weeks for the treatment of endometriosis. J Obstet Gynaecol Res 2015; 41 (12): 1921–6.
29. Chandra A, Rho AM, Jeong K et al. Clinical experience of long-term use of dienogest after surgery for ovarian endometrioma. Obstet Gynecol Sci 2018; 61 (1): 111–7.
30. Romer T. Long-term treatment of endometriosis with dienogest: retrospective analysis of efficacy and safety in clinical practice. Arch Gynecol Obstet 2018; 298 (4): 747–53.
31. Yarmolinskaia M.I., Florova M.S. Vozmozhnosti terapii dienogestom 2 mg u bol'nykh naruzhnym genital'nym endometriozom. Problemy reproduktsii. 2017; 23 (1): 70–9. [in Russian]
32. Bulun SE, Zeitoun K, Takayama K et al. Estrogen production in endometriosis and use of aromatase inhibitors to treat endometriosis. Endo Rel Cancer 1999; 6: 293–301.
33. Molotkov A.S., Jarmolinskaia M.I., Poliakova V.O. i dr. Znachenie ekspressii aromatazy v patogeneze naruzhnogo genital'nogo endometrioza. Molekuliarnaia meditsina. 2012; 4: 41–4. [in Russian]
34. Meinhardt U, Mullis PE. The essential role of the aromatase/p450arom. Semin Reprod Med 2002; 20: 277–84.
35. Goss PE, Strasser K. Aromatase inhibitors in the treatment and prevention of breast cancer. J Clin Oncol 2001; 19: 881–94.
36. Takayama K, Zeitoun K, Gunby RT et al. Treatment of severe postmenopausal endometriosis with an aromatase inhibitor. Fertil Steril 1998; 69: 709–13.
37. Yarmolinskaia M.I., Molotkov A.S., Bezhenar' V.F. i dr. Effektivnost' ingibitorov aromatazy v kombinirovannom lechenii naruzhnogo genital'nogo endometrioza. Arkhiv akusherstva i ginekologii im. V.F.Snegireva. 2014; 1 (1): 36–40. [in Russian]
38. Novella-Maestre E, Carda C, Noguera I et al. Dopamine agonist administration causes a reduction in endometrial implants through modulation of angiogenesis in experimentally induced endometriosis. Hum Reprod 2009; 24: 1025–35.
39. Delgado RF, Gomez R, Herrero H et al. The effects of ergot and non-ergot derived dopamine agonists in an experimental mouse model of endometriosis. Reproduction 2011; 142: 745–55.
40. Gomez R, Abad A, Delgado F et al. Effects of hyperprolactinemia treatment with the dopamine agonist quinagolide on endometriotic lesions in patients with endometriosis-associated hyperprolactinemia. Fertil Steril 2011; 95: 882–8.
41. Takemura Y, Osuga Y, Yoshino O et al. Metformin suppresses interleukin (IL)-1b-induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells. J Clin Endocrinol Metab 2007; 92: 3213–8.
42. Oner G, Ozcelik B, Ozgun M et al. The effects of metformin and letrozole on endometriosis and comparison of the two treatment agents in a rat model. Hum Reprod 2010; 25 (4): 932–7.
43. Yilmaz B, Sucak A, Kilic S et al. Metformin regresses endometriotic implants in rats by improving implant levels of superoxide dismutase, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-2, and matrix metalloproteinase-9. Am J Obstet Gynecol 2010; 202 (4): 368.
44. An BS, Tavera-Mendoza LE, Dimitrov V et al. Stimulation of Sirt1-regulated FoxO protein function by the ligand-bound vitamin D receptor. Molecular Cell Biol 2010; 30 (20): 4890–900.
45. Yildirim B, Guler T, Akbulut M et al. 1-Alpha, 25-Dihydroxyvitamin D3 Regresses Endometriotic Implants in Rats by Inhibiting Neovascularization and Altering Regulation of Matrix Metalloproteinase. Postgrad Med 2014; 126 (1): 104–10.
46. Guney M, Oral B, Karahan N et al. Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil Steril 2008; 89: 934–42.
47. Yildirim G, Attar R, Ozkan F et al. The effects of letrozole and melatonin on surgically induced endometriosis in a rat model: a preliminary study. Fertil Steril 2010; 93: 1787–92.
48. Paul S, Sharma AV, Mahapatra PD et al. Role of melatonin in regulating matrix metalloproteinase-9 via tissue inhibitors of metalloproteinase-1 during protection against endometriosis. J Pineal Res 2008; 44: 439–49.
49. Guney M, Oral B, Karahan N et al. Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil Steril 2008; 89: 934–42.
50. Koc O, Gunduz B, Topcuoglu A et al. Effects of pinealectomy and melatonin supplementation on endometrial explants in a rat model. Eur J Obstet Gynecol Reprod Biol 2010; 153: 72–6.
Авторы
М.И.Ярмолинская*1,2, М.А.Петросян1, М.С.Флорова1, А.С.Молотков1,3, А.С.Денисова1, Е.В.Суслова1, С.Ш.Тхазаплижева1
1. ФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д.О.Отта». 199034, Россия, Санкт-Петербург, Менделеевская линия, д. 3;
2. ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И.Мечникова» Минздрава России. 191015, Россия, Санкт-Петербург, ул. Кирочная, д. 41;
3. ФГБОУ ВО «Санкт-Петербургский государственный университет». 99034, Россия, Санкт-Петербург, Университетская наб., д. 7/9
*m.yarmolinskaya@gmail.com
1. D.O.Ott Research Institute of Obstetrics, Gynecology and Reproduction. 199034, Russian Federation, Saint Petersburg, Mendeleevskaia liniia, d. 3;
2. I.I.Mechnikov North-West State Medical University of the Ministry of Health of the Russian Federation. 191015, Russian Federation, Saint Petersburg, ul. Kirochnaia, d. 41;
3. Saint Petersburg State University. 199034, Russian Federation, Saint Petersburg, Universitetskaia nab., d. 7/9
*m.yarmolinskaya@gmail.com
1. ФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д.О.Отта». 199034, Россия, Санкт-Петербург, Менделеевская линия, д. 3;
2. ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И.Мечникова» Минздрава России. 191015, Россия, Санкт-Петербург, ул. Кирочная, д. 41;
3. ФГБОУ ВО «Санкт-Петербургский государственный университет». 99034, Россия, Санкт-Петербург, Университетская наб., д. 7/9
*m.yarmolinskaya@gmail.com
________________________________________________
1. D.O.Ott Research Institute of Obstetrics, Gynecology and Reproduction. 199034, Russian Federation, Saint Petersburg, Mendeleevskaia liniia, d. 3;
2. I.I.Mechnikov North-West State Medical University of the Ministry of Health of the Russian Federation. 191015, Russian Federation, Saint Petersburg, ul. Kirochnaia, d. 41;
3. Saint Petersburg State University. 199034, Russian Federation, Saint Petersburg, Universitetskaia nab., d. 7/9
*m.yarmolinskaya@gmail.com
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