Аномальные маточные кровотечения (АМК) являются одной из наиболее частых причин обращения к гинекологу и проведения внутриматочных вмешательств. АМК вызывают железодефицитную анемию и снижение качества жизни женщин, что обусловливает социальную и клиническую значимость этих проблем. На основе анализа данных литературы и международных рекомендаций в обзоре изложены основные принципы диагностики, негормональной и гормональной терапии АМК. Представлены преимущества непрерывного режима применения прогестагенов, в частности левоноргестрелвыделяющей внутриматочной системы (ЛНГ-ВМС), а также комбинированных оральных контрацептивов, содержащих эстрадиола валерат, для снижения менструальной кровопотери. Показана необходимость дифференцированного подхода к выбору терапии с учетом возраста, причины кровотечения, а также баланса пользы и риска лекарственных средств.
Abnormal uterine bleeding (AUB) is one of the most common frequent reasons for contacting a gynecologist and conducting intrauterine interventions. AUB causes iron deficiency anemia and a decrease quality of life of women, which in turn is the reason of their social and clinical significance. Based on the analysis of literature and international data recommendations, the review outlines the basic principles of AUB diagnosis, non-hormonal and hormone therapy Advantages of continuous regimen for the administration of progestogens, in particular the LNG-IUS, and COCs containing estradiol valerate, to reduce menstrual flow blood loss are presented in the article. The need for a differentiated approach of choosing the therapy based on age, causes of bleeding, and balance benefits and risks of medicines.
1. American College of Obstetricians and Gynecologists. Management of acute abnormal uterine bleeding in non-pregnant women. Committee Opinion №557. Obstet Gynecol 2013; 121: 891–6.
2. SOGC Practice Bulletin No. 292-Abnormal Uterine Bleeding in Pre-Menopausal Women. Singh S, Best C, Dunn S, Leyland N, Wolfman WL; Clinical practice – Gynaecology Committee. J Obstet Gynaecol Can 2013; 35 (5): 473–5.
3. National Collaborating Centre for Women’s and Children’s Health; National Institute for Health and Clinical Excellence. NICE guideline [NG88]. Heavy menstrual bleeding: assessment and management. March 2018.
4. Jensen JT, Lefebvre P, Laliberté F et al. Cost burden and treatment patterns associated with management of heavy menstrual bleeding. J Womens Health (Larchmt) 2012; 21 (5): 539–47.
5. Woolcock JG, Critchley HO, Munro MG et al. Review of the confusion in current and historical terminology and defnitions for disturbances of menstrual bleeding. Fertil Steril 2008; 90 (6): 2269–80.
6. Munro MG, Critchley HOD, Brode MS, Fraser IS; for the FIGO Working Group on Menstrual Disorders. Intern. Special Communication. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. J Gynecol Obstet 2011; 113: 3–13.
7. Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO recommendations on terminologies and denitions for normal and abnormal uterine bleeding. Semin Reprod Med 2011; 29 (5): 383–90.
8. Calhoun AH, Gill N. Presenting a New, Non-Hormonally Mediated Cyclic Headache in Women: End-Menstrual Migraine. Headache 2017; 57: 17–20.
9. Sweet MG, Schmidt-Dalton TA, Weiss PM, Madsen KP. Evaluation and management of abnormal uterine bleeding in premenopausal women. Am Fam Physician 2012; 85 (1): 35–4.
10. Goodman NF, Cobin RH, Futterweit W et al. American Association of Clinical Endocrinologists, American College of Endocrinology, Androgen Excess and PCOS Society Disease State Clinical Review: Guide to the Best Practices in the Evaluation and Treatment of Polycystic Ovary Syndrome. PCOS Best Practices, Endocr Pract 2015; 21 (11): 1291–300.
11. Синдром поликистозных яичников в репродуктивном возрасте (современные подходы к диагностике и лечению). Клинические рекомендации (протокол лечения). Письмо Министерства здравоохранения РФ от 10.06.2015 г. №15–4/10/2–2814. / Sindrom polikistoznyh yaichnikov v reproduktivnom vozraste (sovremennye podhody k diagnostike i lecheniyu). Klinicheskie rekomendacii (protokol lecheniya). Pis'mo Ministerstva zdravoohraneniya RF ot 10.06.2015 g. №15–4/10/2–2814. [in Russian]
12. Matteson KA, Rahn DD, Wheeler TL et al. Nonsurgical management of heavy menstrual bleeding: a systematic review. Obstet Gynecol 2013; 121 (3): 632–43.
13. Trelle S, Reichenbach S, Wandel S et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ 2011; 342: 7086–9.
14. Sundstrom A, Seaman H, Kieler H, Alfredsson L. The risk of venous thromboembolism associated with the use of tranexamic acid and other drugs used to treat menorrhagia; a case-control study using the General Practice Research Database. BJOG 2009; 116: 91–7.
15. Wellington K, Wagstaff AJ. Tranexamic acid: a review of its use in management of menorrhagia. Drugs 2003; 63: 1417–33.
16. Lethaby A, Irvine GA, Cameron IT. Cyclical progestogens for heavy menstrual bleeding. Cochrane Database Syst Rev 2008; 1: CD001016.
17. Hickey M, Higham JM, Fraser I. Progestogens with or without oestrogen for irregular uterine bleeding associated with anovulation. Cochrane Database Syst Rev 2012; 9: CD001895.
18. Lethaby AE, Cooke I, Rees M. Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev 2005; 4: CD002126.
19. Farquhar C, Brown J. Oral contraceptive pill for heavy menstrual bleeding. Cochrane Database Syst Rev 2009; 4: CD000154.
20. Cooper K, Lee A, Chien P et al. Outcomes following hysterectomy or endometrial ablation for heavy menstrual bleeding: Retrospective analysis of hospital episode statistics in scotland. BJOG 2011; 118 (10): 1171–9.
21. Farquhar C, Brown J. Oral contraceptive pill for heavy menstrual bleeding. Cochrane Database Syst Rev 2009; 4: CD000154.
22. ACOG practice bulletin no. 110: noncontraceptive uses of hormonal contraceptives. Obstet Gynecol 2010; 115: 206–18.
23. Department of Reproductive Health, World Health Organization. Medical eligibility criteria for contraceptive use. Fifth edition – Executive Summary. Publication date: 2015. WHO reference number: WHO/RHR/15.07.
24. Collaborative Group on Epidemiological Studies on Endometrial Cancer. Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies. Lancet Oncol 2015; 16 (9): 1061–70.
25. Fraser IS, Parke S, Mellinger U et al. Effective treatment of heavy and/or prolonged menstrual bleeding without organic cause: pooled analysis of two multinational, randomised, double-blind, placebo-controlled trials of oestradiol valerate and dienogest. Eur J Contracept Reprod Health Care 2011; 16: 258–26.
26. Di Carlo C, Gargano V, De Rosa N et al. Effects of estradiol valerate and dienogest on quality of life and sexual function according to age. Gynecol Endocrinol 2014; 30 (12): 925–8.
27. Ahrendt HJ, Makalova D, Parke S et al. Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel. Contraception 2009; 80 (5): 436–44.
28. Briggs P, Serrani M, Vogtländer K, Рarke S. Continuation rates, bleeding profile acceptability, and satisfaction of women using an oral contraceptive pill containing estradiol valerate and dienogest versus a progestogen-only pill after switching from an ethinylestradiol-containing pill in a real-life setting: results of the CONTENT study. Int J Womens Health 2016; 8: 477–87.
29. Nappi RE, Terreno E, Sances G et al. Effect of a contraceptive pill containing estradiol valerate and dienogest (E2V/DNG) in women with menstrually-related migraine (MRM). Contraception 2013; 88 (3): 369–75.
30. Petraglia F, Parke S, Serrani M et al. Estradiol valerate plus dienogest versus ethinylestradiol plus levonorgestrel for the treatment of primary dysmenorrhea. Int J Gynaecol Obstet 2014; 125 (3): 270–4.
31. Macias G, Merki-Feld GS, Parke S et al. Effects of a combined oral contraceptive containing oestradiol valerate/dienogest on hormone withdrawal-associated symptoms: results from the multicentre, randomised, double-blind, active-controlled HARMONY II study. J Obstet Gynaecol 2013; 33: 591–6.
32. Чернуха Г.Е., Ильина Л.М. Воспаление – биологическая основа обильного менструального кровотечения, дисменореи и нарушений ЦНС. Комплексное решение проблемы. Мед. совет. Гинекологическая эндокринология. 2015; с. 20–7. / Chernuha G.E., Ilina L.M. Vospalenie – biologicheskaya osnova obil'nogo menstrual'nogo krovotecheniya, dismenorei i narushenij CNS. Kompleksnoe reshenie problemy. Med. sovet. Ginekologicheskaya endokrinologiya. 2015; s. 20–7. [in Russian]
33. Buhling KJ, Klovekorn L, Daniels B et al. Contraceptive counselling and self-prescription of contraceptives of German gynaecologists: Results of a nationwide survey. Eur J Contracept Reprod Health Care 2014; 19 (6): 448–56.
34. Junge W, Mellinger U, Parke S, Serrani M. Metabolic and haemostatic effects of estradiol valerate/dienogest, a novel oral contraceptive. Clin Drug Investig 2011; 31 (8): 573–84.
35. Dinger J, Minh TD, Heinemann K. Impact of Estrogen Type on Cardiovascular Safety of Combined Oral Contraceptives. Contraception 2016; 94: 328–39.
36. Graziottin A, Zanello PP. Menstruation, inflammation and comorbidities: implications for woman health. Minerva Gynecol 2015; 67: 21–34.
37. Agren UM, Anttila M, Mäenpää-Liukko K et al. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17b-estradiol compared with one containing levonorgestrel and ethinylestradiol on haemostasis, lipids and carbohydrate metabolism. Eur J Contracept Reprod Health Care 2011; 16: 444–57.
________________________________________________
1. American College of Obstetricians and Gynecologists. Management of acute abnormal uterine bleeding in non-pregnant women. Committee Opinion №557. Obstet Gynecol 2013; 121: 891–6.
2. SOGC Practice Bulletin No. 292-Abnormal Uterine Bleeding in Pre-Menopausal Women. Singh S, Best C, Dunn S, Leyland N, Wolfman WL; Clinical practice – Gynaecology Committee. J Obstet Gynaecol Can 2013; 35 (5): 473–5.
3. National Collaborating Centre for Women’s and Children’s Health; National Institute for Health and Clinical Excellence. NICE guideline [NG88]. Heavy menstrual bleeding: assessment and management. March 2018.
4. Jensen JT, Lefebvre P, Laliberté F et al. Cost burden and treatment patterns associated with management of heavy menstrual bleeding. J Womens Health (Larchmt) 2012; 21 (5): 539–47.
5. Woolcock JG, Critchley HO, Munro MG et al. Review of the confusion in current and historical terminology and defnitions for disturbances of menstrual bleeding. Fertil Steril 2008; 90 (6): 2269–80.
6. Munro MG, Critchley HOD, Brode MS, Fraser IS; for the FIGO Working Group on Menstrual Disorders. Intern. Special Communication. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. J Gynecol Obstet 2011; 113: 3–13.
7. Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO recommendations on terminologies and denitions for normal and abnormal uterine bleeding. Semin Reprod Med 2011; 29 (5): 383–90.
8. Calhoun AH, Gill N. Presenting a New, Non-Hormonally Mediated Cyclic Headache in Women: End-Menstrual Migraine. Headache 2017; 57: 17–20.
9. Sweet MG, Schmidt-Dalton TA, Weiss PM, Madsen KP. Evaluation and management of abnormal uterine bleeding in premenopausal women. Am Fam Physician 2012; 85 (1): 35–4.
10. Goodman NF, Cobin RH, Futterweit W et al. American Association of Clinical Endocrinologists, American College of Endocrinology, Androgen Excess and PCOS Society Disease State Clinical Review: Guide to the Best Practices in the Evaluation and Treatment of Polycystic Ovary Syndrome. PCOS Best Practices, Endocr Pract 2015; 21 (11): 1291–300.
11. Sindrom polikistoznyh yaichnikov v reproduktivnom vozraste (sovremennye podhody k diagnostike i lecheniyu). Klinicheskie rekomendacii (protokol lecheniya). Pis'mo Ministerstva zdravoohraneniya RF ot 10.06.2015 g. №15–4/10/2–2814. [in Russian]
12. Matteson KA, Rahn DD, Wheeler TL et al. Nonsurgical management of heavy menstrual bleeding: a systematic review. Obstet Gynecol 2013; 121 (3): 632–43.
13. Trelle S, Reichenbach S, Wandel S et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ 2011; 342: 7086–9.
14. Sundstrom A, Seaman H, Kieler H, Alfredsson L. The risk of venous thromboembolism associated with the use of tranexamic acid and other drugs used to treat menorrhagia; a case-control study using the General Practice Research Database. BJOG 2009; 116: 91–7.
15. Wellington K, Wagstaff AJ. Tranexamic acid: a review of its use in management of menorrhagia. Drugs 2003; 63: 1417–33.
16. Lethaby A, Irvine GA, Cameron IT. Cyclical progestogens for heavy menstrual bleeding. Cochrane Database Syst Rev 2008; 1: CD001016.
17. Hickey M, Higham JM, Fraser I. Progestogens with or without oestrogen for irregular uterine bleeding associated with anovulation. Cochrane Database Syst Rev 2012; 9: CD001895.
18. Lethaby AE, Cooke I, Rees M. Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev 2005; 4: CD002126.
19. Farquhar C, Brown J. Oral contraceptive pill for heavy menstrual bleeding. Cochrane Database Syst Rev 2009; 4: CD000154.
20. Cooper K, Lee A, Chien P et al. Outcomes following hysterectomy or endometrial ablation for heavy menstrual bleeding: Retrospective analysis of hospital episode statistics in scotland. BJOG 2011; 118 (10): 1171–9.
21. Farquhar C, Brown J. Oral contraceptive pill for heavy menstrual bleeding. Cochrane Database Syst Rev 2009; 4: CD000154.
22. ACOG practice bulletin no. 110: noncontraceptive uses of hormonal contraceptives. Obstet Gynecol 2010; 115: 206–18.
23. Department of Reproductive Health, World Health Organization. Medical eligibility criteria for contraceptive use. Fifth edition – Executive Summary. Publication date: 2015. WHO reference number: WHO/RHR/15.07.
24. Collaborative Group on Epidemiological Studies on Endometrial Cancer. Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies. Lancet Oncol 2015; 16 (9): 1061–70.
25. Fraser IS, Parke S, Mellinger U et al. Effective treatment of heavy and/or prolonged menstrual bleeding without organic cause: pooled analysis of two multinational, randomised, double-blind, placebo-controlled trials of oestradiol valerate and dienogest. Eur J Contracept Reprod Health Care 2011; 16: 258–26.
26. Di Carlo C, Gargano V, De Rosa N et al. Effects of estradiol valerate and dienogest on quality of life and sexual function according to age. Gynecol Endocrinol 2014; 30 (12): 925–8.
27. Ahrendt HJ, Makalova D, Parke S et al. Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel. Contraception 2009; 80 (5): 436–44.
28. Briggs P, Serrani M, Vogtländer K, Рarke S. Continuation rates, bleeding profile acceptability, and satisfaction of women using an oral contraceptive pill containing estradiol valerate and dienogest versus a progestogen-only pill after switching from an ethinylestradiol-containing pill in a real-life setting: results of the CONTENT study. Int J Womens Health 2016; 8: 477–87.
29. Nappi RE, Terreno E, Sances G et al. Effect of a contraceptive pill containing estradiol valerate and dienogest (E2V/DNG) in women with menstrually-related migraine (MRM). Contraception 2013; 88 (3): 369–75.
30. Petraglia F, Parke S, Serrani M et al. Estradiol valerate plus dienogest versus ethinylestradiol plus levonorgestrel for the treatment of primary dysmenorrhea. Int J Gynaecol Obstet 2014; 125 (3): 270–4.
31. Macias G, Merki-Feld GS, Parke S et al. Effects of a combined oral contraceptive containing oestradiol valerate/dienogest on hormone withdrawal-associated symptoms: results from the multicentre, randomised, double-blind, active-controlled HARMONY II study. J Obstet Gynaecol 2013; 33: 591–6.
32. Chernuha G.E., Ilina L.M. Vospalenie – biologicheskaya osnova obil'nogo menstrual'nogo krovotecheniya, dismenorei i narushenij CNS. Kompleksnoe reshenie problemy. Med. sovet. Ginekologicheskaya endokrinologiya. 2015; s. 20–7. [in Russian]
33. Buhling KJ, Klovekorn L, Daniels B et al. Contraceptive counselling and self-prescription of contraceptives of German gynaecologists: Results of a nationwide survey. Eur J Contracept Reprod Health Care 2014; 19 (6): 448–56.
34. Junge W, Mellinger U, Parke S, Serrani M. Metabolic and haemostatic effects of estradiol valerate/dienogest, a novel oral contraceptive. Clin Drug Investig 2011; 31 (8): 573–84.
35. Dinger J, Minh TD, Heinemann K. Impact of Estrogen Type on Cardiovascular Safety of Combined Oral Contraceptives. Contraception 2016; 94: 328–39.
36. Graziottin A, Zanello PP. Menstruation, inflammation and comorbidities: implications for woman health. Minerva Gynecol 2015; 67: 21–34.
37. Agren UM, Anttila M, Mäenpää-Liukko K et al. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17b-estradiol compared with one containing levonorgestrel and ethinylestradiol on haemostasis, lipids and carbohydrate metabolism. Eur J Contracept Reprod Health Care 2011; 16: 444–57.
Авторы
Г.Е.Чернуха, Л.М.Ильина, И.А.Иванов
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. В.И.Кулакова» Минздрава России. 117997, Россия, Москва, ул. Академика Опарина, д. 4
*g_chernukha@oparina4.ru
________________________________________________
G.E.Chernuha, L.M.Ilina, I.A.Ivanov
V.I.Kulakov Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Akademika Oparina, d. 4
*g_chernukha@oparina4.ru