<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Gynecology</journal-id><journal-title-group><journal-title xml:lang="en">Gynecology</journal-title><trans-title-group xml:lang="ru"><trans-title>Гинекология</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2079-5696</issn><issn publication-format="electronic">2079-5831</issn><publisher><publisher-name xml:lang="en">Consilium Medicum</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">50858</article-id><article-id pub-id-type="doi">10.26442/20795696.2020.5.200419</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>REVIEW</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОБЗОР</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Vaginal bleeding during menopause hormone therapy. Is it always endometrial cancer? How to choose the appropriate tactics for examination and management of patients?</article-title><trans-title-group xml:lang="ru"><trans-title>Кровотечение из половых путей на фоне менопаузальной гормональной терапии. Всегда ли это рак эндометрия? Как выбрать правильную тактику обследования и ведения пациентов?</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7930-8048</contrib-id><name-alternatives><name xml:lang="en"><surname>Protasova</surname><given-names>Anna E.</given-names></name><name xml:lang="ru"><surname>Протасова</surname><given-names>Анна Эдуардовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>D. Sci. (Med.), Prof., Saint Petersburg State University, Mechnikov North-Western State Medical University, Almazov National Medical Research Centre</p></bio><bio xml:lang="ru"><p>д-р мед. наук, проф. каф. онкологии ФГБОУ ВО СПбГУ, проф. каф. онкологии ФГБОУ ВО «СЗГМУ им. И.И. Мечникова», ФГБУ «НМИЦ им. В.А. Алмазова»</p></bio><email>protasova1966@yandex.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2692-2156</contrib-id><name-alternatives><name xml:lang="en"><surname>Solntseva</surname><given-names>Irina A.</given-names></name><name xml:lang="ru"><surname>Солнцева</surname><given-names>Ирина Александровна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Cand. Sci. (Med.), Mechnikov North-Western State Medical University</p></bio><bio xml:lang="ru"><p>канд. мед. наук, доц. каф. лучевой диагностики и лучевой терапии ФГБОУ ВО «СЗГМУ им. И.И. Мечникова»</p></bio><email>protasova1966@yandex.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9878-3338</contrib-id><name-alternatives><name xml:lang="en"><surname>Vandeeva</surname><given-names>Ekaterina N.</given-names></name><name xml:lang="ru"><surname>Вандеева</surname><given-names>Екатерина Николаевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Cand. Sci. (Med.), Almazov National Medical Research Centre</p></bio><bio xml:lang="ru"><p>канд. мед. наук, ассистент каф. акушерства и гинекологии ФГБУ «НМИЦ им. В.А. Алмазова»</p></bio><email>protasova1966@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Almazov National Medical Research Centre</institution></aff><aff><institution xml:lang="ru">ФГБУ «Национальный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Mechnikov North-Western State Medical University</institution></aff><aff><institution xml:lang="ru">ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">Saint Petersburg State University</institution></aff><aff><institution xml:lang="ru">ФГБОУ ВО «Санкт-Петербургский государственный университет»</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2020-11-23" publication-format="electronic"><day>23</day><month>11</month><year>2020</year></pub-date><volume>22</volume><issue>5</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>37</fpage><lpage>43</lpage><history><date date-type="received" iso-8601-date="2020-11-22"><day>22</day><month>11</month><year>2020</year></date><date date-type="accepted" iso-8601-date="2020-11-22"><day>22</day><month>11</month><year>2020</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2020, Consilium Medicum</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2020, ООО "Консилиум Медикум"</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="en">Consilium Medicum</copyright-holder><copyright-holder xml:lang="ru">ООО "Консилиум Медикум"</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-sa/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://gynecology.orscience.ru/2079-5831/article/view/50858">https://gynecology.orscience.ru/2079-5831/article/view/50858</self-uri><abstract xml:lang="en"><p>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.</p></abstract><trans-abstract xml:lang="ru"><p>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.</p></trans-abstract><kwd-group xml:lang="en"><kwd>menopause</kwd><kwd>menopausal hormone therapy</kwd><kwd>genital tract bleeding</kwd><kwd>endometrial cancer</kwd><kwd>hysteroscopy</kwd><kwd>endometrial biopsy</kwd><kwd>sonography</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>менопауза</kwd><kwd>менопаузальная гормональная терапия</kwd><kwd>кровотечение из половых путей</kwd><kwd>рак эндометрия</kwd><kwd>гистероскопия</kwd><kwd>биопсия эндометрия</kwd><kwd>сонография</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>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</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>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.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>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.</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>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.</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Ertunc D, Tok EC, Aytan H, Gozukara YM. Passive smoking is associated with lower age at menopause. Climacteric 2015; 18: 47–52.</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>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.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Stock D, Knight JA, Raboud J et al. Rotating night shift work and menopausal age. Hum Reprod 2019; 34: 539–48.</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Gupta A, Desai A, Bhatt S. Imaging of the endometrium: physiologic changes and diseases: women’s imaging. Radiographics 2017; 37: 2206–7.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Grady D. Clinical practice. Management of menopausal symptoms. N Engl J Med 2006; 355: 2338–47.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>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).]</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>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.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Barboss N, Musonda P, Duncan TJ et al. Postmenopausal vaginal bleeding in women using hormone replacement therapy. Menopause Int 2012; 18 (1): 5–9.</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Winter TC 3rd. Endometrial thickness in symptomatic postmenopausal patients receiving hormone replacement therapy or tamoxifen. Radiographics 2018; 38: 658–9.</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>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.</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Astrup K, Olivarius N de F. Frequency of spontaneously occurring postmenopausal bleeding in the general population. Acta Obstet Gynecol Scand 2004; 83: 203–7.</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Raouf SA, Gupta P, Papaioannou S, Pradhan P. Endometrial thickness for invasive investigations in women with postmenopausal bleeding. Climacteric 2011; 14: 117–20.</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Wolman I. Berek and Novak’s Gynecology. 15th Ed. Philadelphia, PA: Lippincott Williams and Wilkins, 2012.</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>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.</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Riggs BL, Hartmann LC. Selective estrogen-receptor modulators – mechanisms of action and application to clinical practice. N Engl J Med 2003; 348: 618–29.</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Amant F, Moerman P, Neven P et al. Endometrial cancer. Lancet 2005; 366: 491–505.</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Kwon JS, Scott JL, Gilks CB et al. Testing women with endometrial cancer to detect Lynch syndrome. JCO 2011; 29: 2247–52.</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>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.</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>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.</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>SOGC Practice Guideline Asymptomatic Endometrial Thickening. JOGC 2010; 249: 990–9.</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Guidelines For Professional Ultrasound Practice Society and College of Radiographers and British Medical Ultrasound Society 2015.</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>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.</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>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.</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>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.</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>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.</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>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.</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>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.</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>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.</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Ghoubara A, Sundar S, Ewies AA. Predictors of malignancy in endometrial polyps: study of 421 women with postmenopausal bleeding. Climacteric 2018; 21: 82–7.</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>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.</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>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.</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>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.</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>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.</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Practice Bulletin No. 149: endometrial cancer. Obstet Gynecol 2015; 125: 1006–26.</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Stock RJ, Kanbour A. Prehysterectomy curettage. Obstet Gynecol 1975; 45: 537–41.</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>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.</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>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.</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>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.</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>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.</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>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.</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>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.</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>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.</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Timmermans A, Opmeer BC, Veersema S, Mol BW. Patients’ preferences in the evaluation of postmenopausal bleeding. BJOG 2007; 114: 1146–9.</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Sardo ADS, Calagna G, Di Carlo C. Tips and tricks in office hysteroscopy. Gynecol Minim Invasive Ther 2015; 4: 3–7.</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>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.</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>Burbos N, Musonda P, Duncan TJ et al. Postmenopausal vaginal bleeding in women using hormone replacement therapy. Menopause Int 2012; 18: 5–9.</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>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.</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Curcic A, Djurdjevic S, Mihaldzic-Tubic S et al. Ultrasound detection of endometrial fluid in postmenopausal women. Med Pregl 2009; 62: 337–41.</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>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.</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Topcu HO, Tasdemir U, Islimye M et al. The clinical significance of endometrial fluid collection in asymptomatic postmenopausal women. Climacteric 2015; 18: 733–6.</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>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.</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>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.</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Dave FG et al. Unscheduled bleeding with hormone replacement therapy. Obstet Gynaecol 2019; 21 (2): 95–101.</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>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</mixed-citation></ref></ref-list></back></article>
