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Current trends in the pharmacotherapy of uterine myoma, associated with heavy menstrual bleeding and anemia: a literature review

https://doi.org/10.17749/2313-7347/ob.gyn.rep.2020.195

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Abstract

Aim: to summarize up-to-date world data on current opportunities of drug therapy in treatment of symptomatic myoma accompanied with heavy menstrual bleeding and anemia.
Materials and Methods. A search of publications was carried out in the main international databases published in Russian and English: PubMed/MEDLINE, The Cochrane Library, Embase, and eLibrary. The analysis included studies published over the last 10 years examining the clinical efficacy and safety of various groups of pharmacological agents used for treatment of uterine myoma combined with heavy menstrual bleeding in women of reproductive age.
Results. Currently, treatment of uterine fibroids consists of the three major approaches: surgical, minimally invasive organpreserving methods, and pharmacotherapy. Until now, surgical intervention remains the main method of treatment, unfortunately being often performed in a foem of hysterectomy. However, today it is important to apply a personalized approach to the management of a female patient with symptomatic uterine myoma, taking into account her wish to preserve reproductive function. Advances in drug therapy greatly contributed to optimizing management of such patients.
Conclusion. Treatment of symptomatic uterine fibroids globally tends to lowering the number of radical interventions, as well as develop and improve new therapeutic approaches for. Currently, pharmacotherapy of leiomyoma can substantially improve the quality of patients' life, lower number of radical surgical interventions, optimize surgical treatment, and even fully negate, in some cases, a need for surgery.

About the Authors

Z. V. Revazova
Evdokimov Moscow State University of Medicine and Dentistry, Health Ministry of Russian Federation
Russian Federation

Zarina V. Revazova - MD, PhD, Obstetrician-Gynecologist, Research Technician, Department of Reproductive Medicine and Surgery, Faculty of Additional Professional Education, Evdokimov Moscow State University of Medicine and Dentistry.
20/1 Delegatskaya Str., Moscow 127473.



L. V. Adamyan
Evdokimov Moscow State University of Medicine and Dentistry, Health Ministry of Russian Federation; Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Health Ministry of Russian Federation
Russian Federation

Leyla V. Adamyan - MD, Dr Sci Med, Professor, Academician of RAS, Head of the Department of Reproductive Medicine and Surgery, Faculty of Additional Professional Education, Evdokimov Moscow State University of Medicine and Dentistry; Director for Science, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology; Honored Scientist of the Russian Federation, Chief Specialist in Obstetrics and Gynecology of Health Ministry of Russian Federation.
20/1 Delegatskaya Str., Moscow 127473; 4, Academika Oparina Str., Moscow 117997.



O. N. Loginova
Evdokimov Moscow State University of Medicine and Dentistry, Health Ministry of Russian Federation
Russian Federation

Olga N. Loginova - MD, PhD, Associate Professor, Department of Reproductive Medicine and Surgery, Faculty of Additional Professional Education, Evdokimov Moscow State University of Medicine and Dentistry.
20/1 Delegatskaya Str., Moscow 127473.



L. M. Manukyan
Evdokimov Moscow State University of Medicine and Dentistry, Health Ministry of Russian Federation
Russian Federation

Liana M. Manukyan - MD, PhD, Obstetrician-Gynecologist, Research Technician, Department of Reproductive Medicine and Surgery, Faculty of Additional Professional Education, Evdokimov Moscow State University of Medicine and Dentistry.
20/1 Delegatskaya Str., Moscow 127473.



K. N. Arslanyan
Evdokimov Moscow State University of Medicine and Dentistry, Health Ministry of Russian Federation
Russian Federation

Karine N. Arslanyan - MD, PhD, Associate Professor, Department of Reproductive Medicine and Surgery, Faculty of Additional Professional Education, Evdokimov Moscow State University of Medicine and Dentistry.
20/1 Delegatskaya Str., Moscow 127473.



References

1. Vilos J.A., Allaire C., Laberge P.Y., Leyland N. The management of uterine leiomyomas. J Obstet Gynecol Canada. 2015;37(2):157-78. https://doi.org/10.1016/S1701-2163(15)30338-8.

2. Uterine fibroids: diagnosis, treatment and rehabilitation. Clinical guidelines. Eds. L.V. Adamyan et al. [Mioma matki: diagnostika, lechenie i reabilitaciya. Klinicheskie rekomendacii. Pod red. L.V. Adamyan i dr.]. Moscow: Nauchnyj centr akusherstva, ginekologii i perinatologii imeni akademika V.I. Kulakova, 2015. 100 p. (In Russ.).

3. Islam M.S., Protic O., Giannubilo S.R. et al. Uterine leiomyoma: available medical treatments and new possible therapeutic options. J Clin Endocrinol Metab. 2013;98(3):921-34. https://doi.org/10.1210/jc.2012-3237.

4. Wallach E.E., Vlahos N.F. Uterine myomas: an overview of development, clinical features, and management. Obstet Gynecol. 2004;104(2):393-406. https://doi.org/10.1097/01.AOG.0000136079.62513.39.

5. Flake G.P., Anderson J., Dixon D. Etiology and pathophysiology of uterine leiomyomas; a review. Environ Health Perspect. 2003;111(8):1037-54. https://doi.org/10.1289/ehp.5787.

6. Lui Z., Doan Q.V., Blumenthal P., Dubois R.W. Systematic review evaluating health-related quality of life, work impairement, and healthcare costs and utilization in abnormal uterine bleeding. Value Health. 2007;10(3):183-94. https://doi.org/10.1111/j.1524-4733.2007.00168.x.

7. Buianova S.N., Mgeliashvili M.V., Petrakova S.A. Current views of the etiology, pathogenesis and morphogenesis of uterine myoma. [Sovremennye predstavleniya ob etiologii, patogeneze i morfogeneze miomy matki]. Rossijskij vestnik akushera-ginekologa. 2008;8(6):45-51. (In Russ.).

8. Dobrokhotova Yu.E., Khachatryan A.S., Ibragimova D.M. Uretrineleiomyoma: current insights into pathogenesis and use of medication tumor-reduction therapy. [Mioma matki. Sovremennye voprosy patogeneza i medikamentoznoj redukcionnoj terapii]. Doktor.Ru. 2013;7-1(85):29-32. (In Russ.).

9. Munro M.G., Critchley H.O.D., Fraser I.S.; FIGO Menstrual Disorders Committee. 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://doi.org/10.1002/ijgo.12666.

10. Andreeva E.N. Heavy menstrual bleeding: modern approach to problem solution. [Obil'nye menstrual'nye krovotecheniya: sovremennyj podhod k probleme i puti ee resheniya]. Problemy reprodukcii. 2015;21(6):47-55. (In Russ.).

11. Dorsey K.A. Menorrhagia, active component service women, U.S. Armed Forces, 1998-2012. MSMR. 2013;20(9):20-4.

12. Stewart E.A., Nowak R.A. Leiomyoma-related bleeding: a classic hypothesis updated for the molecular era. Hum Reprod Update. 1996;2(4):295-306. https://doi.org/10.1093/humupd/2.4.295.

13. Vilos G.A., Vilos A., Ferrazzi S. Symptomatic uterine fibroids (UFs) are common in premenopausal Canadian women and lead to reduced quality of life (QoL) across multiple domains. J Obstet Gynecol Can. 2014;36:1-26.

14. Fonseca-Moutinho J.A., Barbosa L.S., Nunes S.M. et al. Abnormal uterine bleeding as a presenting symptom is related to multiple uterine leiomyoma: an ultrasound-based study. Int J Womens Health. 2013;5:689-94. https://doi.org/10.2147/IJWH.S50786.

15. Gokyildiz S., Aslan E., Beji N.K., Mecdi M. The effects of menorrhagia on women's quality of life: a case-control study. ISRN Obstet Gynecol. 2013;2013:918179. https://doi.org/10.1155/2013/918179.

16. Burlev V.A., Konovodova E.N., Fedorova T.A., Danilov A.Yu. Diagnostics and treatment of iron deficiency in gynecological patients: clinical protocol. [Diagnostika i lechenie zhelezodeficitnyh sostoyanij u ginekologicheskih bol'nyh: klinicheskij protocol]. Akusherstvo i ginekologiya. 2014;(3):3-10. (In Russ.).

17. Stuklov N.I. Anemia in female reproductive system diseases. [Anemii pri zabolevaniyah zhenskoj reproduktivnoj sistemy]. Poliklinika. 2014;(3-2):87-9. (In Russ.).

18. Pundir J., Walawalkar R., Seshadri S. et al. Perioperative morbidity associated with abdominal myomectomy compared with total abdominal hysterectomy for uterine fibroids. J Obstet Gynaecol. 2013;33(7):655-62. https://doi.org/10.3109/01443615.2013.816661.

19. Donnez J., Dolmans M.M. Uterine fibroids management: from the present to the future. Hum Reprod Update. 2016;22(6):665-86. https://doi.org/10.1093/humupd/dmw023.

20. Farris M., Bastianelli C., Rosato E. et al. Uterine fibroids: an update on current and emerging medical treatment options. Ther Clin Risk Manag. 2019;15:157-78. https://doi.org/10.2147/TCRM.S147318.

21. Puchkov K.V., Andreeva Yu.E., Dobychina A.V. Laparoscopic hysterectomy. [Laparoskopicheskaya gisterektomiya]. Zhurnal akusherstva i zhenskih boleznej. 2011;60(S):70-1. (In Russ.).

22. Lefebvre G. Allaire C., Jeffrey J., Vilos G.A. Hysterectomy; Society of Obstetricians Clinical Practice Committee. SOGC Clinical Practice Guidelines. 2002;24(109):37-48. PMID: 12196887.

23. Flynn M., Jamison M., Datta S., Myers E. Health care resource use for uterine fibroid tumors in the United States. Am J Obstet Gynecol. 2006;195(4):955-64. https://doi.org/10.1016/j.ajog.2006.02.020

24. Kulakov V.I., Adamyan L.V., Askolskaya S.I. Hysterectomy and woman's health. [Gisterektomiya i zdorov'e zhenshchiny]. Moscow: Medicina, 1999. 312 p. (In Russ.).

25. Sohn G.S., Cho S., Kim Y.M. et al. Current medical treatment of uterine fibroids. Obstet Gynecol Sci. 2018;61(2):192-201. https://doi.org/10.5468/ogs.2018.61.2.192.

26. El-Balat A., DeWilde R.L., Schmeil I. et al. Modern myoma treatment in the last 20 years: a review of the literature. BioMed Research International. 2018;4:1-6. https://doi.org/10.1155/2018/4593875.

27. Ghonim M., Magby R., Sabbour M. et al. A systematic review and metaanalysis of ulipristal acetate for symptomatic uterine fibroids. Int J Gynecol Obstet. 2019;146(2):141-8. https://doi.org/10.1002/ijga.12868.

28. Eder S., Baker J., Gersten J. et al. Efficacy and safety of oral tranexamic acid in women with heavy menstrual bleeding and fibroids. Women's Health (Lond). 2013;9(4):397-403. https://doi.org/10.2217/whe.13.28.

29. Puchar A., Feyeux C., Luton D., Koskas M. Therapeutic management of uterine fibroid tumors. Minerva Ginecol. 2016;68(4):466-76.

30. Lethaby A., Duckitt K., Farquhar C. Non-steroidal antiinflammatory drugs for heavy menstrual bleeding. Cochrane Database Syst Rev. 2013;(1):CD0004000. https://doi.org/10.1002/14651858.CD000400.pub3.

31. Farquhar C., Ekeroma A., Fentiman G. et al. An evidence-based guideline for the management of uterine fibroids. Aust N Z J Obstet Gynecol. 2001;41(2):125-40. https://doi.org/10.1111/j.1479-828x.2001.tb01198.x.

32. Duhan N., Madaan Sh., Sen J. Role of the aromatase inhibitor letrozole in the management of uterine leiomyomas in premenopausal women. Eur J Obstet Gynecol Reprod Biol. 2013;171(2):329-32. https://doi.org/10.1016/j.ejogrb.2013.09.010.

33. Liu J.P., Yang H., Xia Y., Cardini F. Herbal preparations for uterine fibroids. Cochrane Database Syst Rev. 2013;(4):CD005292. https://doi.org/10.1002/14651858.CD005292.pub3.

34. Song H., Lu D., Navaratnam K., Shi G. Aromatase inhibitors for uterine fibroids. Cochrane Database Syst Rev. 2013;(10):CD009505. https://doi.org/10.1002/14651858.CD009505.pub2.

35. Fedorova T.A., Borzykina O.M., Bakuridze E.M. et al. Correction of iron deficiency anemia in patients with gynecological diseases using liposomal iron. [Korrekciya zhelezodeficitnoj anemii u pacientok s ginekologicheskimi zabolevaniyami s ispol'zovaniem liposomal'nogo zheleza]. Ginekologiya. 2017;19(1):68-73. (In Russ.).

36. Whitaker L., Critchley H.O.D. Abnormal uterine bleeding. Best Pract Res Clin Obstet Gynaecol. 2016;34:54-65. https://doi.org/10.1016/j.bpobgyn.2015.11.012.

37. Donnez J. Uterine fibroids and progestogen treatment: lack of evidence of its efficacy: a review. J Clin Med. 2020;9(12):E3948. https://doi.org/10.3390/jcm9123948.

38. Bulun S.E., Moravek M.B., Yin P. et al. Uterine leiomyoma stem cells: linking progesterone to growth. Semin Reprod Med. 2015;33(5):357-65. https://doi.org/10.1055/s-0035-1558451.

39. Xu Q., Ohara N., Liu J. et al. Progesterone receptor modulator CDB-2914 induces extracellular matrix metalloproteinase inducer in cultured human uterine leiomyoma cells. Mol Hum Reprod. 2008;14(3):181-91. https://doi.org/10.1093/molehr/gan004.

40. Maruo T., Ohara N., Wang J., Matduo H. Sex steroidal regulation of uterine leiomyoma growth and apoptosis. Hum Reprod Update. 2004;10(3):207-20. https://doi.org/10.1093/humupd/dmh019.

41. Socolov D., Blidaru I., Tamba B. et al. Levonorgestrel releasing-intrauterine system for the treatment of menorrhagia and/or frequent irregular uterine bleeding associated with uterine leiomyoma. Eur J Contracept Reprod Health Care. 2011;16(6):480-7. https://doi.org/10.3109/13625187.2011.614028.

42. Senol T., Kahramanoglu I., Dogan Y. et al. Levonorgestrel-releasing intrauterine device use as an alternative to surgical therapy for uterine leiomyoma. Clin Exp Obstet Gynecol. 2015;42(2):224-7.

43. Islam S., Protic O., Giannubilo S.R. et al. Uterine leiomyoma: available medical treatments and new possible therapeutic options. J Clin Endocrinol Metab. 2013;98(3):921-34. https://doi.org/10.1210/jc.2012-3237.

44. Tosun A.K., Tosun I., Suer N. Comparison of levonorgestrel-releasing intrauterine device with oral progestins in heavy menstrual bleeding (HMB) cases with uterine leiomyoma (LNG-IUD and oral progestin usage in myoma uteri). Pak J Med Sci. 2014;30(4):834-9.

45. Mittermeier Th., Farrant Ch., Wise M.R. Levonorgestrel-releasing intrauterine system for endometrial hyperplasia. Cochrane Database Syst Rev. 2020;9:CD012658. https://doi.org/10.1002/14651858.CD012658.pub2.

46. Sayed G.H., Zakherah M.S., El-Nashar S.A., Shaaban M.M. A randomizad clinical trial of a levonorgestrel-releasing intrauterine system and a low-dose combined oral contraceptive for fibroid-related menorrhagia. Int J Gynaecol Obstet. 2011;112(2):126-30. https://doi.org/10.1016/j.ijgo.2010.08.009.

47. Tikhomirov A.L., Ledenkova A.A., Abysheva V.G., Sharkova S.M. Hormonal contraception and prevention of uterine myoma. [Gormonal'naya kontracepciya i profilaktika miomy matki]. Voprosy ginekologii, akusherstva i perinatologii. 2009;8(6):71-5. (In Russ.).

48. Lethaby A., Puscasiu L., Vollenhoven B. Preoperative medical therapy before surgery for uterine fibroids. Cochrane Database Syst Rev. 2017;11(11):CD000547. https://doi.org/10.1002/14651858.CD000547.pub2.

49. Doherty L., Mutlu L., Sinclair D., Taylor H. Uterine fibroids: clinical manifestations and contemporary management. Reprod Sci. 2014;21(9):1067-92. https://doi.org/10.1177/1933719114533728.

50. Camanni M., Bonino E.M., Delpiano A. et al. Hysteroscopic management of large symptomatic submucous uterine myomas. J Minim Invasive Gynecol. 2010;17(1):59-65. https://doi.org/10.1016/j.jmig.2009.10.013.

51. Guo X.C., Segars J.H. The impact and management of fibroids for fertility: an evidence-based approach. Obstet Gynecol Clin North Am. 2012;39(4):521-33. https://doi.org/10.1016/j.ogc.2012.09.005.

52. Moroni R.M., Martins W.P., Ferriani R.A. et al. Add-back therapy with GnRH analogues for uterine fibroids. Cochrane Database Syst Rev. 2015(3):CD010854. https://doi.org/10.1002/14651858.CD010854.pub2.

53. Griffiths A.N., D'Angelo A., Amso N.N. Surgical treatment of fibroids for subfertility. Cochrane Database Syst Rev. 2006;(3):CD003857. https://doi.org/10.1002/14651858.CD003857.pub2.

54. Bouchard P., Chabbert-Buffet N., Fauser B.C. Selective progesterone receptor modulators in reproductive medicine: pharmacology, clinical efficacy and safety. Fertil Steril. 2011;96(5):1175-89. https://doi.org/10.1016/j.fertnstert.2011.08.021.

55. Chabbert-Buffet N., Pintiaux A., Bouchard P. The imminent dawn of SPRMs in obstetrics and gynecology. Mol Cell Endocrinol. 2012;358(2):232-43. https://doi.org/10.1016/j.mce.2012.02.021.

56. Fleisher R., Blanck A., Gustavsson I. et al. Pathophysiology of fibroid disease: angiogenesis and regulation of smooth muscle proliferation. Best Pract Res Clin Obstet Gynaecol. 2008;22(4):603-14. https://doi.org/10.1016/j.bpobgyn.2008.01.005.

57. Bestel E., Donnez J. The potential of selective progesterone receptor modulators for the treatment of uterine fibroids. Expert Rev Endocrinol Metab. 2014;9(1):79-92. https://doi.org/10.1586/17446651.2014.862495.

58. Movarek M.B., Yin P., Ono M. et al. Ovarian steroids, stem cells and uterine leiomyoma: therapeutic implications. Hum Reprod Update. 2015;21(1):1-12. https://doi.org/10.1093/humupd/dmu048.

59. Spitz I.M. Mifepristone: where do we come from and where are we going? Clinical development over a quarter of a century. Contraception. 2010;82(5):442-52. https://doi.org/10.1016/j.contraception.2009.12.012.

60. Uchikawa J., Shiozawa T., Shih H.C. et al. Expression of steroid receptor coactovators and corepressors in human endometrial hyperplasia and carcinoma with relevance ro steroid receptors and Ki-67 expression. Cancer. 2003;98(10):2207-13. https://doi.org/10.1002/cncr.11760.

61. Tristan M., Orozco L.J., Steed A. et al. Mifepristone for uterine fibroids. Cochrane Database Syst Rev. 2012;(8):CD007687. https://doi.org/10.1002/14651858.CD007687.pub2.

62. Esteve J.L., Acosta R., Perez Y. et al. Mifepristone versus placebo to trial uterine myoma: a double-blind, randomized clinical trial. Int J Womens Health. 2013;5:361-9. https://doi.org/10.2147/IJWH.S42770.

63. FDA approves ellaTM tablets for prescription emergency contraception. FDA News Room, 2010. Available at: https://www.prnewswire.com/news-releases/fda-approves-ella-tablets-for-prescription-emergency-contraception-100652599.html.

64. Williams A., Bergeron C., Barlow D.H, Ferenczy A. Endometrial morphology after treatment of uterine fibroids with the selective progesterone receptor modulator, ulipristal acetate. Int J Gynecol Pathology. 2012;31(6):556-69. https://doi.org/10.1097/PGP.0b013e318251035b.

65. Allergan Receives Complete Response Letter from the U.S. Food and Drug Administration for Ulipristal Acetate New Drug Application. Dublin: Aug. 21, 2018. Available at: https://www.drugs.com/nda/ulipristal_acetate_180821.html.

66. EMA/PRAC/459031/2020 Human Medicines Division. Pharmacovigilance Risk Assessment Committee (PRAC). European Medicine Agency: 31.08.2020. Available at: https://www.ema.europa.eu/en/documents/agenda/agenda-prac-draft-agenda-meeting-31-august-3-september_en.pdf.

67. FIBRISTAL (ulipristal acetate tablets, 5 mg) - Voluntary withdrawal in Canada due to risk of drug-induced liver injury. Health Canada: 30 September, 2020. Available at: https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2020/74063a-eng.php.

68. National Pharmaceutical Regulatory Agency Esmya (ulipristal acetate 5 mg): Withdrawal of product registration. Ministry of Health Malaysia: 14.12.2020. Available at: https://npra.gov.my/index.php/en/health-professionals/recent-updates/419-english/safety-alerts-main/safety-alerts-2020/1527169-esmya-ulipristal-acetate-5-mg-withdrawal-of-product-registration.html.

69. Temporary suspension of sales of Esmya™ (ulipristal acetate) tablet 5 mg. Health Sciences Authority (HSA). A Singapor Government Agency: Sep 2020. Available at: https://www.hsa.gov.sg/announcements/safety-alert/temporary-suspension-of-sales-of-esmya-(ulipristal-acetate)-tablet-5-mg-(sep-2020).

70. EMA/PRAC/ 593162/2020. Ulipristal acetate for uterine fibroids: EMA recommends restricting use. European Medicine Agency: 13.11.2020. Available at: https://www.ema.europa.eu/en/documents/referral/ulipristal-acetate-5mg-medicinal-products-article-31-referral-ulipristal-acetate-uterine-fibroids_en.pdf.

71. Gemzell-Danielsson K., Heikinheimo O., Zatik J. et al. Efficacy and safety of vilaprisan in women with uterine fibroids: Data from the phase 2b randomized controlled trial ASTEROID 2. Eur J Obstet Gynecol Reprod Biol. 2020;252:7-14. https://doi.org/10.1016/j.ejogrb.2020.05.043.


For citation:


Revazova Z.V., Adamyan L.V., Loginova O.N., Manukyan L.M., Arslanyan K.N. Current trends in the pharmacotherapy of uterine myoma, associated with heavy menstrual bleeding and anemia: a literature review. Obstetrics, Gynecology and Reproduction. 2021;15(1):80-92. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2020.195

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