Abnormal uterine bleeding in women of reproductive age and premenopause

Solovyeva A.V., Chegus L.A.

1) Department of Obstetrics and Gynecology with Course of Perinatology, Medical Institute, Peoples’ Friendship University of Russia, Ministry of Education and Science of the Russian Federation, Moscow, Russia; 2) Department of Obstetrics and Gynecology, Khanty Mansiysk State Medical Academy, Khanty-Mansiysk, Khanty-Mansiysk Autonomous Okrug–Yugra, Russia
Abnormal uterine bleeding (AUB) occurs in 3–30% of women and its prevalence depends on the living standards of a patient and the state of health care in different countries. This is most common in women with obesity, polycystic ovary syndrome, in premature ovarian failure and during premenopause. The review describes the efficacy of medicines, the frequency of complications (for example, the risk of venous thromboembolism when taking combined oral contraceptives, depending on the type of progestogen), and contraindications. Progestogens are widely used for the treatment of AUB since they neutralize progesterone deficiency and anovulation and have anti-inflammatory effects. In Russia, dydrogesterone is a progestogen with registered indications, such as irregular menstruation, dysfunctional uterine bleeding, endometriosis, secondary amenorrhea, premenstrual syndrome, and hormone replacement therapy.
Conclusion. Dydrogesterone therapy has been shown to be significantly effective in normalizing irregular menstrual cycles, including this in randomized controlled trials. Considering that dydrogesterone is a metabolically neutral drug; it lacks androgenic, glucocorticoid, mineralocorticoid, and antigonadotropic effects; it does not aggravate insulin resistance and dyslipidemic disorders or affect the hemostatic system; it can be recommended for a wide population of women with AUB.

Keywords

abnormal uterine bleeding
diagnosis
treatment
dydrogesterone

References

  1. Munro M.G., Critchley H.O.D., Fraser I.S. 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. Gynaecol. Obstet. 2018; 143(3): 393-408. https://dx.doi.org/10.1002/ijgo.12666.
  2. Quinn S., Higham J. Outcome measure for heavy menstrual bleeding. Women’s Health. 2016; 12(1): 21-6. https://dx.doi.org/10.2217/whe.15.85.
  3. Karlsson T.S., Marions L.B., Edlund M.G. Heavy menstrual bleeding significantly affects quality of life. Acta Obstet. Gynecol. Scand. 2014; 93(1): 52-7. https://dx.doi.org/10.1111/aogs.12292.
  4. Jabbour H.N., Kelly R.W., Fraser H.M., Critchley H.O. Endocrine regulation of menstruation. Endocr. Rev. 2006; 27(1): 17-46. https://dx.doi.org/10.1210/er.2004-0021.
  5. Hapangama D.K., Bulmer J.N. Pathophysiology of heavy menstrual bleeding. Women’s Health. 2016; 12(1): 3-13. https://dx.doi.org/10.2217/whe.15.81.
  6. Соловьева А.В., Ермоленко К.С. Дифференцированный подход к выбору терапии у женщин с аномальными маточными кровотечениями. Акушерство и гинекология. 2018; 3: 157-60. [Solovyeva A.V., Ermolenko K.S. Differentiated approach to choosing therapy for women with abnormal uterine bleeding. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; (3): 157-60. (in Russian)]. https://dx.doi.org/10.18565/aig.2018.3.157-160.
  7. Munro M.G., Critchley H.O., Fraser I.S.; FIGO Menstrual Disorders Working Group. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertil. Steril. 2011; 95(7): 2204-08. e22083. https://dx.doi.org/10.1016/j.fertnstert.2011.03.079.
  8. Радзинский В.Е. Акушерская агрессия v 2.0. М.: Журнал StatusPraesens; 2017. 872 с. [Radzinsky V.E. Obstetric aggression v 2.0. Moscow: Publ. Status Praesens; 2017. 872 p. (in Russian)].
  9. Indraccolo U., Di Iorio R., Matteo M., Corona G., Greco P., Indraccolo S.R. The pathogenesis of endometrial polyps: a systematic semi-quantitative review. Eur. J. Gynaecol. Oncol. 2013; 34(1): 5-22.
  10. Lee S.C., Kaunitz A.M., Sanchez-Ramos L., Rhatigan R.M. The oncogenic potential of endometrial polyps: a systematic review and meta-analysis. Obstet. Gynecol. 2010; 116(5): 1197-205. https://dx.doi.org/10.1097/AOG.0b013e3181f74864.
  11. Amesse L.S., Pfaff-Amesse T., Gunning W.T., Duffy N., French J.A. Clinical and laboratory characteristics of adolescents with platelet function disorders and heavy menstrual bleeding. Exp. Hematol. Oncol. 2013; 2(1): 3. https://dx.doi.org/10.1186/2162-3619-2-3.
  12. García-Solares J., Donnez J., Donnez O., Dolmans M.M. Pathogenesis of uterine adenomyosis: invagination or metaplasia? Fertil. Steril. 2018; 109(3): 371-9. https://dx.doi.org/10.1016/j.fertnstert.2017.12.030.
  13. Gordts S., Grimbizis G., Campo R. Symptoms and classification of uterine adenomyosis. Fertil. Steril. 2018; 109(3): 380-8. https://dx.doi.org/10.1016/j. fertnstert.2018.01.006.
  14. Naftalin J., Hoo W., Pateman K., Mavrelos D., Holland T., Jurkovic D. How common is adenomyosis? A prospective study of prevalence using transvaginal ultrasound in a gynaecology clinic. Hum. Reprod. 2012; 27(12): 3432-9. https://dx.doi.org/10.1093/humrep/des332.
  15. Aguilar H.N., Mitchell B.F. Physiological pathways and molecular mechanisms regulating uterine contractility. Hum. Reprod. Update. 2010; 16(6): 725-44. https://dx.doi.org/10.1093/humupd/dmq016.
  16. Ordi J., Bergeron C., Hardisson D., McCluggage W.G., Hollema H., Felix A. et al. Reproducibility of current classifications of endometrial endometrioid glandular proliferations: further evidence supporting a simplified classification. Histopathology. 2013; 64(2): 284-92. https://dx.doi.org/10.1111/his.12249.
  17. Zaino R., Carinelli S.G., Ellenson L.H. Tumours of the uterine corpus: epithelial tumours and precursors. In: Kurman R.J., Carcangiu M.L., Herrington C.S., Young R.H., eds. WHO classification of tumours of female reproductive organs. Geneva: WHO Press; 125-6.
  18. Hapangama D.K., Kamal A.M., Bulmer J.N. Estrogen receptor beta: the guardian of the endometrium. Hum. Reprod. Update. 2015; 21(2): 174-93. https://dx.doi.org/10.1093/humupd/dmu053.
  19. Colombo N., Preti E., Landoni F., Carinelli S., Colombo A., Marini C., Sessa C.; ESMO Guidelines Working Group. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2013; 24(Suppl. 6): vi33-8. https://dx.doi.org/10.1093/annonc/mdt353.
  20. Park J.C., Lim S.Y., Jang T.K., Bae J.G., Kim J.I., Rhee J.H. Endometrial histology and predictable clinical factors for endometrial disease in women with polycystic ovary syndrome. Clin. Exp. Reprod. Med. 2011; 38(1): 42-6. https://dx.doi.org/10.5653/cerm.2011.38.1.42.
  21. Sivridis E., Giatromanolaki A. The pathogenesis of endometrial carcinomas at menopause: facts and figures. J. Clin. Pathol. 2011; 64(7): 553-60. https://dx.doi.org/10.1136/jcp.2010.085951.
  22. Setiawan V.W., Yang H.P., Pike M.C., McCann S.E., Yu H., Xiang Y.B. et al. Type I and II endometrial cancers: have they different risk factors? J. Clin. Oncol. 2013; 31(20): 2607-18. https://dx.doi.org/10.1200/JCO.2012.48.2596.
  23. Kouides P.A. Bleeding symptom assessment and hemostasis evaluation of menorrhagia. Curr. Opin. Hematol. 2008; 15(5): 465-7. https://dx.doi.org/10.1097/MOH.0b013e32830a4ed4.
  24. Archer D.F. Vascular dysfunction as a cause of endometrial bleeding. Gynecol. Endocrinol. 2012; 28(9): 688-93. https://dx.doi.org/10.3109/09513590.2011.588848.
  25. Pinkerton J.A.V. Pharmacological therapy for abnormal uterine bleeding Menopause. 2011; 18(4): 453-61. https://dx.doi.org/10.1097/gme.0b013e318212499c.
  26. Deligeoroglou E., Karountzos V., Creatsas G. Abnormal uterine bleeding and dysfunctional uterine bleeding in pediatric and adolescent gynecology. Gynecol. Endocrinol. 2013; 29(1): 74-8. https://dx.doi.org/10.3109/09513590.2012.705384.
  27. Bradley L.D., Gueye N.A. The medical management of abnormal uterine bleeding in reproductive-aged women. Am. J. Obstet. Gynecol. 2016; 214(1): 31-44. https://dx.doi.org/10.1016/j.ajog.2015.07.044.
  28. Подзолкова Н.М., Глазкова О.Л. Симптом, синдром, диагноз. Дифференциальная диагностика в гинекологии. М.: ГЭОТАР-Медиа; 2014. 736 с. [Podzolkova N.M., Glazkova O.L. Simptom, sindrom, diagnoz. Differentsial'naya diagnostika v ginekologii. 3rd Moscow: GEOTAR-Media; 2014. 736 p. (in Russian)].
  29. Nandi A., Chen Z., Patel R., Poretsky L. Polycystic ovary syndrome. Endocrinol. Metab. Clin. North Am. 2014; 43(1): 123-47. https://dx.doi.org/10.1016/j.ecl.2013.10.003.
  30. Nouri M., Tavakkolian A., Mousavi S.R. Association of dysfunctional uterine bleeding with high body mass index and obesity as a main predisposing factor. Diabetes Metab. Syndr. Jan-Mar 2014; 8(1): 1-2. https://dx.doi.org/10.1016/j.dsx.2013.10.013.
  31. Garry R., Hart R., Karthigasu K.A., Burke C. A re-appraisal of the morphological changes within the endometrium during menstruation: a hysteroscopic, histological and scanning electron microscopic study. Hum. Reprod. 2009; 24(6): 1393-401. https://dx.doi.org/10.1093/humrep/dep036.
  32. Royal College of Obstetricians and Gynaecologists. National menstrual heavy bleeding audit. Second Annual Report. London, UK: Royal College of Obstetricians and Gynaecologists; 2012. Available at: https://www.rcog.org.uk
  33. Valentijn A.J., Palial K., Al-Lamee H., Tempest N., Drury J., Von Zglinicki T. et al. SSEA-1 isolates human endometrial basal glandular epithelial cells: phenotypic and functional characterization and implications in the pathogenesis of endometriosis. Hum. Reprod. 2013; 28(10): 2695-708. https://dx.doi.org/10.1093/humrep/det285.
  34. Critchley H.O., Maybin J.A., Armstrong G.M., Wiliams A.R. Physiology of the endometrium and regulation of menstruation. Physiol. Rev. 2019; 100(3): 1149-79. https://dx.doi.org/10.1152/physrev.00031.2019.
  35. Maybin J.A., Critchley H.O. Menstrual physiology: implications for endometrial pathology and beyond. Hum. Reprod. Update. 2015; 21(6): 748e61. https://dx.doi.org/10.1093/humupd/dmv038.
  36. Lethaby A., Duckitt K., Farquhar C. Non‐steroidal anti‐inflammatory drugs for heavy menstrual bleeding. Cochrane Database Syst. Rev. 2013; (1): CD000400. https://dx.doi.org/10.1002/14651858.CD000400.pub3.
  37. Heavy menstrual bleeding: assessment and management. NICE guideline. NICE: National Institute for Health and Clinical Excellence; 14 March 2018.
  38. The American College of Obstetricians and Gynecologists. Abnormal uterine bleeding. FAQ: Gynecologic Problems. Available at: https://www.acog.org/patient-resources/faqs Accessed 22.07.2020.
  39. Kumar P., Sharma A. Gonadotropin-releasing hormone analogs: Understanding advantages and limitations. J. Hum. Reprod. Sci. 2014; 7(3): 170. https://dx.doi.org/10.4103/0974-1208.142476.
  40. Madden T., Secura G.M., Nease R.F., Politi M.C., Peipert J.F. The role of contraceptive attributes in women’s contraceptive decision making. Am. J. Obstet. Gynecol. 2015; 213(1): 46. e1-6. https://dx.doi.org/10.1016/j.ajog.2015.01.051.
  41. Lidegaard O., Milsom I., Geirsson R.T., Skjeldestad F.E. Hormonal contraception and venous thromboembolism. Acta Obstet. Gynecol. Scand. 2012; 91(7): 769-78. https://dx.doi.org/10.1111/j.1600-0412.2012.01444.x.
  42. Combined hormonal contraception and the risk of venous thromboembolism: a guideline/ Practice Committee of American Society for reproductive medicine. Fertil. Steril. 2017; 107(1): 43-51. https://dx.doi.org/10.1016/j.fertnstert.2016.09.027.
  43. Федеральная служба по надзору в сфере защиты прав потребителей и благополучия человека. [The Federal Service for Surveillance on Consumer Rights Protection and Human Well-being.] Available at: https://rospotrebnadzor.ru/about/info/news/news_details.php?ELEMENT_ID=12067&sphrase_id=2072508 Accessed 22.07.2020. (in Russian).
  44. Kobayashi T., Sugiura K., Ojima T. Risks of thromboembolism associated with hormone contraceptives in Japanese compared with Western women. Obstet. Gynecol. Res. 2017; 43(5): 789-97. https://dx.doi.org/10.1111/jog.13304.
  45. Maxwell D., Jacob M., Spiryda L.B., Bennet C.L. Selection of contraceptive therapy for patients with thrombophilia: a review of the evidence. J. Women’s Health. 2014; 23(4): 318-26. https://dx.doi.org/10.1089/jwh.2013.4479.
  46. Cheng Y.J., Liu Z.H., Yao F.J., Zeng W.T., Zheng D.D., Dong Y.G., Wu S.H. Current and former smoking and risk for venous thromboembolism: a systematic rewiew and meta-analysis PLoS Med. 2013; 10(9): e1001515. https://dx.doi.org/10.1371/journal.pmed.1001515.
  47. Medical eligibility criteria for contraceptive use. 5th ed. Geneva: World Health Organization; 2015. Available at: https://www: euro.who.int/_data/assets/pdf_file/0005/348116/VCE-merged.pdf Accessed 22.07.2020.
  48. Плавинский С.Л., Баринова А.Н., Озолиня Л.А. Нежелательные последствия использования гормональных средств. Анализ фармакоэпидемиологических исследований и баз спонтанных отчетов. Вопросы гинекологии, акушерства и перинатологии. 2019; 18(6): 92-9. [Plavinskiy S.L., Barinova A.N., Ozolinya L.А. Adverse outcomes of using hormonal drugs. An analysis of pharmacoepidemiological research works and spontaneous reporting databases. Voprosy ginekologii, akusherstva i perinatologii/Gynecology, Obstetrics and Perinatology. 2019; 18(6): 92-9. (in Russian)]. https://dx.doi.org/10.20953/1726-1678-2019-6-92-99.
  49. Jensen J., Mansour D., Lukkari-Lax E., Inki P., Burock K., Fraser I.S. Bleeding patterns with the levonorgestrel-releasing intrauterine system when used for heavy menstrual bleeding in women without structural pelvic pathology: a pooled analysis of randomized controlled studies. Contraception. 2013; 87(1): 107-12. https://dx.doi.org/10.1016/j.contraception.2012.08.022.
  50. Podzolkova N., Tatarchuk T., Doshchanova A., Eshimbetova G., Pexman-Fieth C. Dydrogesterone treatment for menstrual-cycle regularization in routine clinical practice: a multicenter observational study. Gynecol. Endocrinol. 2016; 32(3): 246-9. https://dx.doi.org/10.3109/09513590.2015.1115832.
  51. Behera M.A., Lucidi R.S. What is role of progestins in the treatment of abnormal uterine bleeding (AUB)? Medscape. July 16, 2020.
  52. Сибирская Е.В., Пивазян Л.Г. Гормональная терапия аномальных маточных кровотечений у женщин позднего репродуктивного возраста. Вопросы гинекологии, акушерства и перинатологии. 2020; 19(2): 129-35. [Sibirskaya Е.V., Pivazyan L.G. Hormonal therapy for management of abnormal uterine bleeding in women of late reproductive age. Vopr. ginekol. akus. perinatol. Voprosy ginekologii, akusherstva i perinatologii/Gynecology, Obstetrics and Perinatology. 2020; 19(2): 129-35. (In Russian)]. https://dx.doi.org/10.20953/1726-1678-2020-2-129-135.
  53. Подзолкова Н.М., Татарчук Т.Ф., Дощанова А.М., Ешимбетова Г.З., Сумятина Л.В. Нормализация менструального цикла дидрогестероном. Акушерство и гинекология. 2018; 6: 70-5. [Podzolkova N.M., Tatarchuk T.F.,Doshchanova A.M., Eshimbetova G.Z., Sumyatina L.V. Menstrual cycle normalization with dydrogesterone. Akusherstvo i ginekologiya/Obstetrics and Gynecology. 2018; (6): 70-5. (in Russian)]. https://dx.doi.org/10.18565/aig.2018.6.70-76.
  54. Trivedi N., Chauhan N., Vaidya V. Effectiveness and safety of dydrogesterone in regularization of menstrual cycle: a post-marketing study. Gynecol. Endocrinol. 2016; Mar. 7: 1-5. https://dx.doi.org/10.3109/09513590.2016.1152238.
  55. Griesinger G., Tournaye H., Macklon N., Petraglia F., Arck P., Blockeel C., van Amsterdam P. et al. Dydrogesterone: pharmacological profile and mechanism of action as luteal phase support in assisted reproduction. Reprod. Biomed. Online. 2019; 38(2): 249-59. https://dx.doi.org/10.1016/j.rbmo.2018.11.017.
  56. Капустин Р.В., Аржанова О.Н., Беспалова О.Н. Экзогенный прогестерон как фактор развития гестационного сахарного диабета. Российский вестник акушера-гинеколога. 2019; 19(1): 38-45. [Kapustin R.V., Arzhanova O.N., Bespalova O.N. Exogenous progesterone as a factor for the development of gestational diabetes mellitus. Rossiyskiy vestnik akushera-ginekologa. 2019; 19(1): 38-45. (in Russian)]. https://dx.doi.org/10.17116/rosakush20191901138.
  57. Карева Е.Н. Тромбозы и гестагены. Доктор.Ру. 2019; 7: 57-64. [Kareva E.N. Thrombosis and gestagens. Doctor.Ru. 2019; (7): 57-64. (in Russian)]. https://dx.doi.org/10.31550/1727-2378-2019-162-7-57-64.

Received 17.05.2020

Accepted 03.08.2020

About the Authors

Alina V. Solovyeva, MD, professor of the Department of Obstetrics Gynecology with a course of perinatology, Peoples’ Friendship University of Russia,
Ministry of Education and Science of Russia. E-mail: av_soloveva@mail.ru. ORCID: 0000-0001-6711-1563.
117198, Russia, Moscow, Miklukho-Maklaya str., 8.
Larisa A. Chegus, PhD, MD, Department of Obstetrics and Gynecology, BI «Khanty Mansiysk State Medical Academy». E-mail: lchegus@mail.ru.
ORCID: 0000-0002-9698-8038. 628011, Russia, Khanty Mansiysk city, Yamskaya str., 12/91.

For citation: Solovyeva A.V., Chegus L.A. Abnormal uterine bleeding in women of reproductive age and premenopause.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2020; 8: 29-38 (in Russian).
https://dx.doi.org/10.18565/aig.2020.8.29-38

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