Кровотечение из половых путей на фоне менопаузальной гормональной терапии. Всегда ли это рак эндометрия? Как выбрать правильную тактику обследования и ведения пациентов?
Кровотечение из половых путей на фоне менопаузальной гормональной терапии. Всегда ли это рак эндометрия? Как выбрать правильную тактику обследования и ведения пациентов?
Протасова А.Э., Солнцева И.А., Вандеева Е.Н. Кровотечение из половых путей на фоне менопаузальной гормональной терапии. Всегда ли это рак эндометрия? Как выбрать правильную тактику обследования и ведения пациентов? Гинекология. 2020; 22 (5): 37–43. DOI: 10.26442/20795696.2020.5.200419
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Protasova A.E., Solntseva I.A., Vandeeva E.N. Vaginal bleeding during menopause hormone therapy. Is it always endometrial cancer? How to choose the appropriate tactics for examination and management of patients? Gynecology. 2020; 22 (5): 37–43. DOI: 10.2
Кровотечение из половых путей на фоне менопаузальной гормональной терапии. Всегда ли это рак эндометрия? Как выбрать правильную тактику обследования и ведения пациентов?
Протасова А.Э., Солнцева И.А., Вандеева Е.Н. Кровотечение из половых путей на фоне менопаузальной гормональной терапии. Всегда ли это рак эндометрия? Как выбрать правильную тактику обследования и ведения пациентов? Гинекология. 2020; 22 (5): 37–43. DOI: 10.26442/20795696.2020.5.200419
________________________________________________
Protasova A.E., Solntseva I.A., Vandeeva E.N. Vaginal bleeding during menopause hormone therapy. Is it always endometrial cancer? How to choose the appropriate tactics for examination and management of patients? Gynecology. 2020; 22 (5): 37–43. DOI: 10.2
В статье представлен обзор возможных причин кровотечения из половых путей в постменопаузе. Описан правильный подход к пациенткам с аномальными маточными кровотечениями на фоне менопаузальной гормональной терапии. Произведен современный анализ данных о диагностике и лечении постменопаузального вагинального кровотечения на фоне менопаузальной гормональной терапии. Показаны современные возможности диагностики и лечения патологии эндометрия.
The article provides an overview of the possible causes of bleeding from the genital tract in peri- and postmenopausal women. The correct approach to patients with abnormal uterine bleeding during menopausal hormone therapy is described. A modern analysis of data on the diagnosis and treatment of postmenopausal vaginal bleeding against the background of menopausal hormone therapy was carried out. The modern possibilities of endometrial diagnostics and treatment are shown.
1. Gerontology research group mission: Slow and ultimately reverse age related decline Founded 1990–2015 Twenty Five Year Anniversary. http://www.grg.org/SC/SCindex.html
2. Sydora BC, Yuksel N, Veltri NL et al. Patient characteristics, menopause symptoms, and care provided at an interdisciplinary menopause clinic: retrospective chart review. Menopause 2018; 25: 102–5.
3. Torgerson DJ, Thomas RE, Campbell MK, Reid DM. Alcohol consumption and age of maternal menopause are associated with menopause onset. Maturitas 1997; 26: 21–5.
4. Yang HJ, Suh PS, Kim SJ, Lee SY. Effects of smoking on menopausal age: results from the Korea National Health and Nutrition Examination Survey, 2007 to 2012. J Prev Med Public Health 2015; 48: 216–24.
5. Ertunc D, Tok EC, Aytan H, Gozukara YM. Passive smoking is associated with lower age at menopause. Climacteric 2015; 18: 47–52.
6. Akkina JE, Reif JS, Keefe TJ, Bachand AM. Age at natural menopause and exposure to organochlorine pesticides in Hispanic women. J Toxicol Environ Health Part A 2004; 67: 1407–22.
7. Stock D, Knight JA, Raboud J et al. Rotating night shift work and menopausal age. Hum Reprod 2019; 34: 539–48.
8. Gupta A, Desai A, Bhatt S. Imaging of the endometrium: physiologic changes and diseases: women’s imaging. Radiographics 2017; 37: 2206–7.
9. Grady D. Clinical practice. Management of menopausal symptoms. N Engl J Med 2006; 355: 2338–47.
10. Менопаузальная гормональная терапия и сохранение здоровья женщин зрелого возраста. Клинические рекомендации. М., 2014.
[Menopausal hormone therapy and maintaining the health of Mature women. Clinical recommendations. Moscow, 2014 (in Russian).]
11. Allen NE, Tsilidis KK, Key TJ et al. Menopausal hormone therapy and risk of endometrial carcinoma among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition. Am J Epidemiol 2010; 172: 1394–403.
12. Barboss N, Musonda P, Duncan TJ et al. Postmenopausal vaginal bleeding in women using hormone replacement therapy. Menopause Int 2012; 18 (1): 5–9.
13. Winter TC 3rd. Endometrial thickness in symptomatic postmenopausal patients receiving hormone replacement therapy or tamoxifen. Radiographics 2018; 38: 658–9.
14. Colombo N, Creutzberg C, Amant F et al. ESMO-ESGO-ESTRO Consensus conference on endometrial cancer. Diagnosis, treatment and follow-up. Int J Gynecol Cancer 2016; 26 (1): 2–30.
15. Astrup K, Olivarius N de F. Frequency of spontaneously occurring postmenopausal bleeding in the general population. Acta Obstet Gynecol Scand 2004; 83: 203–7.
16. Raouf SA, Gupta P, Papaioannou S, Pradhan P. Endometrial thickness for invasive investigations in women with postmenopausal bleeding. Climacteric 2011; 14: 117–20.
17. Wolman I. Berek and Novak’s Gynecology. 15th Ed. Philadelphia, PA: Lippincott Williams and Wilkins, 2012.
18. Bradshaw KD, Tait D. Postmenopausal bleeding. In: Marshburn PB, Hurst BS (Eds.) Disorders of Menstruation. Chicester, West Sussex, UK: Wiley-Blackwell, 2011; p. 166–83.
19. Riggs BL, Hartmann LC. Selective estrogen-receptor modulators – mechanisms of action and application to clinical practice. N Engl J Med 2003; 348: 618–29.
20. Amant F, Moerman P, Neven P et al. Endometrial cancer. Lancet 2005; 366: 491–505.
21. Kwon JS, Scott JL, Gilks CB et al. Testing women with endometrial cancer to detect Lynch syndrome. JCO 2011; 29: 2247–52.
22. Burbos N, Musonda P, Giarenis I et al. Age-related differential diagnosis of vaginal bleeding in postmenopausal women: a series of 3047 symptomatic postmenopausal women. Menopause Int 2010; 16: 5–8.
23. Ronghe R, Gaudoin M. Women with recurrent postmenopausal bleeding should be re-investigated but are not more likely to have endometrial cancer. Menopause Int 2010; 16: 9–11.
24. SOGC Practice Guideline Asymptomatic Endometrial Thickening. JOGC 2010; 249: 990–9.
25. Guidelines For Professional Ultrasound Practice Society and College of Radiographers and British Medical Ultrasound Society 2015.
26. Smith-Bindman R, Kerlikowske K, Feldstein VA et al. Evaluation of the woman with postmenopausal bleeding: Society of Radiologists in Ultrasound-Sponsored Consensus Conference statement. J Ultrasound Med 2001; 20: 1025–36.
27. ACOG Committee Opinion No. 734: The role of transvaginal ultrasonography in evaluating the endometrium of women with postmenopausal bleeding. Obstet Gynecol 2018; 131: e124–9.
28. Smith-Bindman R, Weiss E, Feldstein V. How thick is too thick? When endometrial thickness should prompt biopsy in postmenopausal women without vaginal bleeding. Ultrasound Obstet Gynecol 2004; 24: 558–65.
29. Timmermans A, Opmeer BC, Khan KS et al. Endometrial thickness measurement for detecting endometrial cancer in women with postmenopausal bleeding: a systematic review and meta-analysis. Obstet Gynecol 2010; 116: 160–7.
30. Wong AS, Lao TT, Cheung CW et al. Reappraisal of endometrial thickness for the detection of endometrial cancer in postmenopausal bleeding: a retrospective cohort study. BJOG 2016; 123: 439–46.
31. Ragupathy K, Cawley N, Ridout A et al. Non-assessable endometrium in women with post-menopausal bleeding: to investigate or ignore. Arch Gynecol Obstet 2013; 288: 375–8.
32. Kamel HS, Darwish AM, Mohamed SA. Comparison of transvaginal ultrasonography and vaginal sonohysterography in the detection of endometrial polyps. Acta Obstet Gynecol Scand 2000; 79: 60–4.
33. Ghoubara A, Sundar S, Ewies AA. Predictors of malignancy in endometrial polyps: study of 421 women with postmenopausal bleeding. Climacteric 2018; 21: 82–7.
34. Lee SC, Kaunitz AM, Sanchez-Ramos L, Rhatigan RM. The oncogenic potential of endometrial polyps: a systematic review and meta-analysis. Obstet Gynecol 2010; 116: 1197–205.
35. Uglietti A, Buggio L, Farella M et al. The risk of malignancy in uterine polyps: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2019; 237: 48–56.
36. Opolskiene G, Sladkevicius P, Jokubkiene L, Valentin L. Threedimensional ultrasound imaging for discrimination between benign and malignant endometrium in women with postmenopausal bleeding and sonographic endometrial thickness of at least 4.5 mm. Ultrasound Obstet Gynecol 2010; 35: 94–102.
37. Ragupathy K, Cawley N, Ridout A et al. Non-assessable endometrium in women with post-menopausal bleeding: to investigate or ignore. Arch Gynecol Obstet 2013; 288: 375–8.
38. Practice Bulletin No. 149: endometrial cancer. Obstet Gynecol 2015; 125: 1006–26.
39. Stock RJ, Kanbour A. Prehysterectomy curettage. Obstet Gynecol 1975; 45: 537–41.
40. Dijkhuizen FP, Mol BW, Brolmann HA, Heintz AP. The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer 2000; 89: 1765–72.
41. Rodriguez MH, Platt LD, Medearis AL et al. The use of transvaginal sonography for evaluation of postmenopausal ovarian size and morphology. Am J Obstet Gynecol 1988; 159: 810–4.
42. Munro MM, Crithley HO, Fraser IS et al. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynecol Obstet 2018; 143: 393–408.
43. Loffer FD. The time has come to quit relying on a blind endometrial biopsy or dilation and curettage to rule out malignant endometrial changes. J Minim Invasive Gynecol 2019; 26: 1207–8.
44. Angioni S, Loddo A, Milano F et al. Detection of benign intracavitary lesions in postmenopausal women with abnormal uterine bleeding: a prospective comparative study on outpatient hysteroscopy and blind biopsy. J Minim Invasive Gynecol 2008; 15: 87–91.
45. Gebauer G, Hafner A, Siebzehnrubl E, Lang N. Role of hysteroscopy in detection and extraction of endometrial polyps: results of a prospective study. Am J Obstet Gynecol 2001; 184: 59–63.
46. Bingol B, Gunenc Z, Gedikbasi A et al. Comparison of diagnostic accuracy of saline infusion sonohysterography, transvaginal sonography and hysteroscopy. J Obstet Gynaecol 2011; 31: 54–8.
47. Timmermans A, Opmeer BC, Veersema S, Mol BW. Patients’ preferences in the evaluation of postmenopausal bleeding. BJOG 2007; 114: 1146–9.
48. Sardo ADS, Calagna G, Di Carlo C. Tips and tricks in office hysteroscopy. Gynecol Minim Invasive Ther 2015; 4: 3–7.
49. Clark TJ, Barton PM, Coomarasamy A et al. Investigating postmenopausal bleeding for endometrial cancer: cost-effectiveness of initial diagnostic strategies. BJOG 2006; 113: 502–10.
50. Burbos N, Musonda P, Duncan TJ et al. Postmenopausal vaginal bleeding in women using hormone replacement therapy. Menopause Int 2012; 18: 5–9.
51. Uglietti A, Buggio L, Farella M et al. The risk of malignancy in uterine polyps: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2019; 237: 48–56.
52. Curcic A, Djurdjevic S, Mihaldzic-Tubic S et al. Ultrasound detection of endometrial fluid in postmenopausal women. Med Pregl 2009; 62: 337–41.
53. Seckin B, Ozgu-Erdinc AS, Dogan M et al. The utility of endometrial thickness measurement in asymptomatic postmenopausal women with endometrial fluid. J Obstet Gynaecol 2016; 36: 230–3.
54. Topcu HO, Tasdemir U, Islimye M et al. The clinical significance of endometrial fluid collection in asymptomatic postmenopausal women. Climacteric 2015; 18: 733–6.
55. Chopra V, Sangha R, Gadde R, Alkhoory W. Endometrial biopsies with insufficient tissue: descriptive analysis and cancer outcomes in women aged 50 and above [26G]. Obstet Gynecol 2018; 131: 82S.
56. Gonzalez Rios AR, Chu Lam MT, Shollenberger C et al. Tissue insufficient for diagnosis on endometrial biopsy: what’s the next step? Obstet Gynecol 2016; 127: 73S.
57. Dave FG et al. Unscheduled bleeding with hormone replacement therapy. Obstet Gynaecol 2019; 21 (2): 95–101.
58. Tsiligiannis S, Wick-Urban BC, van der Stam J, Stevenson JC. Efficacy and safety of a low-dose continuous combined hormone replacement therapy with 0.5 mg 17b-estradiol and 2.5 mg dydrogesterone in subgroups of postmenopausal women with vasomotor symptoms. Maturitas 2020; 9 (139): 20–6. DOI: 10.1016/j.maturitas.2020.05.002
________________________________________________
1. Gerontology research group mission: Slow and ultimately reverse age related decline Founded 1990–2015 Twenty Five Year Anniversary. http://www.grg.org/SC/SCindex.html
2. Sydora BC, Yuksel N, Veltri NL et al. Patient characteristics, menopause symptoms, and care provided at an interdisciplinary menopause clinic: retrospective chart review. Menopause 2018; 25: 102–5.
3. Torgerson DJ, Thomas RE, Campbell MK, Reid DM. Alcohol consumption and age of maternal menopause are associated with menopause onset. Maturitas 1997; 26: 21–5.
4. Yang HJ, Suh PS, Kim SJ, Lee SY. Effects of smoking on menopausal age: results from the Korea National Health and Nutrition Examination Survey, 2007 to 2012. J Prev Med Public Health 2015; 48: 216–24.
5. Ertunc D, Tok EC, Aytan H, Gozukara YM. Passive smoking is associated with lower age at menopause. Climacteric 2015; 18: 47–52.
6. Akkina JE, Reif JS, Keefe TJ, Bachand AM. Age at natural menopause and exposure to organochlorine pesticides in Hispanic women. J Toxicol Environ Health Part A 2004; 67: 1407–22.
7. Stock D, Knight JA, Raboud J et al. Rotating night shift work and menopausal age. Hum Reprod 2019; 34: 539–48.
8. Gupta A, Desai A, Bhatt S. Imaging of the endometrium: physiologic changes and diseases: women’s imaging. Radiographics 2017; 37: 2206–7.
9. Grady D. Clinical practice. Management of menopausal symptoms. N Engl J Med 2006; 355: 2338–47.
10. Menopausal hormone therapy and maintaining the health of Mature women. Clinical recommendations. Moscow, 2014 (in Russian).
11. Allen NE, Tsilidis KK, Key TJ et al. Menopausal hormone therapy and risk of endometrial carcinoma among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition. Am J Epidemiol 2010; 172: 1394–403.
12. Barboss N, Musonda P, Duncan TJ et al. Postmenopausal vaginal bleeding in women using hormone replacement therapy. Menopause Int 2012; 18 (1): 5–9.
13. Winter TC 3rd. Endometrial thickness in symptomatic postmenopausal patients receiving hormone replacement therapy or tamoxifen. Radiographics 2018; 38: 658–9.
14. Colombo N, Creutzberg C, Amant F et al. ESMO-ESGO-ESTRO Consensus conference on endometrial cancer. Diagnosis, treatment and follow-up. Int J Gynecol Cancer 2016; 26 (1): 2–30.
15. Astrup K, Olivarius N de F. Frequency of spontaneously occurring postmenopausal bleeding in the general population. Acta Obstet Gynecol Scand 2004; 83: 203–7.
16. Raouf SA, Gupta P, Papaioannou S, Pradhan P. Endometrial thickness for invasive investigations in women with postmenopausal bleeding. Climacteric 2011; 14: 117–20.
17. Wolman I. Berek and Novak’s Gynecology. 15th Ed. Philadelphia, PA: Lippincott Williams and Wilkins, 2012.
18. Bradshaw KD, Tait D. Postmenopausal bleeding. In: Marshburn PB, Hurst BS (Eds.) Disorders of Menstruation. Chicester, West Sussex, UK: Wiley-Blackwell, 2011; p. 166–83.
19. Riggs BL, Hartmann LC. Selective estrogen-receptor modulators – mechanisms of action and application to clinical practice. N Engl J Med 2003; 348: 618–29.
20. Amant F, Moerman P, Neven P et al. Endometrial cancer. Lancet 2005; 366: 491–505.
21. Kwon JS, Scott JL, Gilks CB et al. Testing women with endometrial cancer to detect Lynch syndrome. JCO 2011; 29: 2247–52.
22. Burbos N, Musonda P, Giarenis I et al. Age-related differential diagnosis of vaginal bleeding in postmenopausal women: a series of 3047 symptomatic postmenopausal women. Menopause Int 2010; 16: 5–8.
23. Ronghe R, Gaudoin M. Women with recurrent postmenopausal bleeding should be re-investigated but are not more likely to have endometrial cancer. Menopause Int 2010; 16: 9–11.
24. SOGC Practice Guideline Asymptomatic Endometrial Thickening. JOGC 2010; 249: 990–9.
25. Guidelines For Professional Ultrasound Practice Society and College of Radiographers and British Medical Ultrasound Society 2015.
26. Smith-Bindman R, Kerlikowske K, Feldstein VA et al. Evaluation of the woman with postmenopausal bleeding: Society of Radiologists in Ultrasound-Sponsored Consensus Conference statement. J Ultrasound Med 2001; 20: 1025–36.
27. ACOG Committee Opinion No. 734: The role of transvaginal ultrasonography in evaluating the endometrium of women with postmenopausal bleeding. Obstet Gynecol 2018; 131: e124–9.
28. Smith-Bindman R, Weiss E, Feldstein V. How thick is too thick? When endometrial thickness should prompt biopsy in postmenopausal women without vaginal bleeding. Ultrasound Obstet Gynecol 2004; 24: 558–65.
29. Timmermans A, Opmeer BC, Khan KS et al. Endometrial thickness measurement for detecting endometrial cancer in women with postmenopausal bleeding: a systematic review and meta-analysis. Obstet Gynecol 2010; 116: 160–7.
30. Wong AS, Lao TT, Cheung CW et al. Reappraisal of endometrial thickness for the detection of endometrial cancer in postmenopausal bleeding: a retrospective cohort study. BJOG 2016; 123: 439–46.
31. Ragupathy K, Cawley N, Ridout A et al. Non-assessable endometrium in women with post-menopausal bleeding: to investigate or ignore. Arch Gynecol Obstet 2013; 288: 375–8.
32. Kamel HS, Darwish AM, Mohamed SA. Comparison of transvaginal ultrasonography and vaginal sonohysterography in the detection of endometrial polyps. Acta Obstet Gynecol Scand 2000; 79: 60–4.
33. Ghoubara A, Sundar S, Ewies AA. Predictors of malignancy in endometrial polyps: study of 421 women with postmenopausal bleeding. Climacteric 2018; 21: 82–7.
34. Lee SC, Kaunitz AM, Sanchez-Ramos L, Rhatigan RM. The oncogenic potential of endometrial polyps: a systematic review and meta-analysis. Obstet Gynecol 2010; 116: 1197–205.
35. Uglietti A, Buggio L, Farella M et al. The risk of malignancy in uterine polyps: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2019; 237: 48–56.
36. Opolskiene G, Sladkevicius P, Jokubkiene L, Valentin L. Threedimensional ultrasound imaging for discrimination between benign and malignant endometrium in women with postmenopausal bleeding and sonographic endometrial thickness of at least 4.5 mm. Ultrasound Obstet Gynecol 2010; 35: 94–102.
37. Ragupathy K, Cawley N, Ridout A et al. Non-assessable endometrium in women with post-menopausal bleeding: to investigate or ignore. Arch Gynecol Obstet 2013; 288: 375–8.
38. Practice Bulletin No. 149: endometrial cancer. Obstet Gynecol 2015; 125: 1006–26.
39. Stock RJ, Kanbour A. Prehysterectomy curettage. Obstet Gynecol 1975; 45: 537–41.
40. Dijkhuizen FP, Mol BW, Brolmann HA, Heintz AP. The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer 2000; 89: 1765–72.
41. Rodriguez MH, Platt LD, Medearis AL et al. The use of transvaginal sonography for evaluation of postmenopausal ovarian size and morphology. Am J Obstet Gynecol 1988; 159: 810–4.
42. Munro MM, Crithley HO, Fraser IS et al. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynecol Obstet 2018; 143: 393–408.
43. Loffer FD. The time has come to quit relying on a blind endometrial biopsy or dilation and curettage to rule out malignant endometrial changes. J Minim Invasive Gynecol 2019; 26: 1207–8.
44. Angioni S, Loddo A, Milano F et al. Detection of benign intracavitary lesions in postmenopausal women with abnormal uterine bleeding: a prospective comparative study on outpatient hysteroscopy and blind biopsy. J Minim Invasive Gynecol 2008; 15: 87–91.
45. Gebauer G, Hafner A, Siebzehnrubl E, Lang N. Role of hysteroscopy in detection and extraction of endometrial polyps: results of a prospective study. Am J Obstet Gynecol 2001; 184: 59–63.
46. Bingol B, Gunenc Z, Gedikbasi A et al. Comparison of diagnostic accuracy of saline infusion sonohysterography, transvaginal sonography and hysteroscopy. J Obstet Gynaecol 2011; 31: 54–8.
47. Timmermans A, Opmeer BC, Veersema S, Mol BW. Patients’ preferences in the evaluation of postmenopausal bleeding. BJOG 2007; 114: 1146–9.
48. Sardo ADS, Calagna G, Di Carlo C. Tips and tricks in office hysteroscopy. Gynecol Minim Invasive Ther 2015; 4: 3–7.
49. Clark TJ, Barton PM, Coomarasamy A et al. Investigating postmenopausal bleeding for endometrial cancer: cost-effectiveness of initial diagnostic strategies. BJOG 2006; 113: 502–10.
50. Burbos N, Musonda P, Duncan TJ et al. Postmenopausal vaginal bleeding in women using hormone replacement therapy. Menopause Int 2012; 18: 5–9.
51. Uglietti A, Buggio L, Farella M et al. The risk of malignancy in uterine polyps: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2019; 237: 48–56.
52. Curcic A, Djurdjevic S, Mihaldzic-Tubic S et al. Ultrasound detection of endometrial fluid in postmenopausal women. Med Pregl 2009; 62: 337–41.
53. Seckin B, Ozgu-Erdinc AS, Dogan M et al. The utility of endometrial thickness measurement in asymptomatic postmenopausal women with endometrial fluid. J Obstet Gynaecol 2016; 36: 230–3.
54. Topcu HO, Tasdemir U, Islimye M et al. The clinical significance of endometrial fluid collection in asymptomatic postmenopausal women. Climacteric 2015; 18: 733–6.
55. Chopra V, Sangha R, Gadde R, Alkhoory W. Endometrial biopsies with insufficient tissue: descriptive analysis and cancer outcomes in women aged 50 and above [26G]. Obstet Gynecol 2018; 131: 82S.
56. Gonzalez Rios AR, Chu Lam MT, Shollenberger C et al. Tissue insufficient for diagnosis on endometrial biopsy: what’s the next step? Obstet Gynecol 2016; 127: 73S.
57. Dave FG et al. Unscheduled bleeding with hormone replacement therapy. Obstet Gynaecol 2019; 21 (2): 95–101.
58. Tsiligiannis S, Wick-Urban BC, van der Stam J, Stevenson JC. Efficacy and safety of a low-dose continuous combined hormone replacement therapy with 0.5 mg 17b-estradiol and 2.5 mg dydrogesterone in subgroups of postmenopausal women with vasomotor symptoms. Maturitas 2020; 9 (139): 20–6. DOI: 10.1016/j.maturitas.2020.05.002
1 ФГБУ «Национальный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, Санкт-Петербург, Россия;
2 ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава России, Санкт-Петербург, Россия;
3 ФГБОУ ВО «Санкт-Петербургский государственный университет», Санкт-Петербург, Россия
*protasova1966@yandex.ru
________________________________________________
Anna E. Protasova*1–3, Irina A. Solntseva2, Ekaterina N. Vandeeva1
1 Almazov National Medical Research Centre, Saint Petersburg, Russia;
2 Mechnikov North-Western State Medical University, Saint Petersburg, Russia;
3 Saint Petersburg State University, Saint Petersburg, Russia
*protasova1966@yandex.ru