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Early menopause and premature ovarian insufficiency: problems and perspectives

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In this review we summarize current data on prevalence, etiology and pathogenesis resulting in premature ovarian insufficiency (POI). In particular, genetic, autoimmune, metabolic, iatrogenic disorders as well as unfavorable impact of environmental factors represent key pathogenetic mechanisms underlying POI development. Clinical picture of this disease is mainly manifested by oligo- and amenorrhea as well as genitourinary menopausal syndrome (GUMS). Special attention is paid to a link between such clinical signs and psychosocial discomfort not being a life-threatening condition but still able to markedly lower quality of woman’s life and considered as a comorbidity with type 2 diabetes mellitus, osteoporosis and cardiovascular diseases. Hormone replacement therapy (HRT) serves as the first-line therapeutic approach for treating POI, which is performed according to the principles similar to those used to perform menopausal hormone therapy (MHT) in case of natural menopause that should be continued until reaching at least the average age for the onset of menopause. Topical estriol therapy eliminates GUMS symptoms, which in turn positively affects sexual function and woman’s psychosocial status and contributes to improved quality of life. The data from recent studies examining topical estriol therapy in POI demonstrated high efficacy and safety. Finally, we also discuss diverse strategies to support reproductive function in women with POI.

About the Authors

D. V. Blinov
Institute for Preventive and Social Medicine; Lapino Clinic Hospital, MD Medical Group; Moscow Haass Medical - Social Institute
Russian Federation

Dmitry V. Blinov - MD, PhD, MBA, Head of Medical and Scientific Affairs

4–10 Sadovaya-Triumfalnaya Str., Moscow 127006

1st Uspenskoye Highway, 111, Moscow Region, Odintsovo District, Lapino 143081

5, 1–1a 2nd Brestskaya Str., Moscow 123056

P. L. Hasan
Research Institute of Urology and Interventional Radiology named after N.А. Lopatkin - branch of National Medical Research Radiological Centre, Health Ministry of Russian Federation
Russian Federation

Peter L. Khazan - MD, PhD

51 bldg. 1, Str. 3rd Parkovaya, Moscow 105425

A. N. Mnatsakanyan
National Research University «Higher School of Economics»
Russian Federation

Anna N. Mnatsakanyan - MD, PhD

20 Myasnitskaya Str., Moscow 101000

D. I. Korabelnikov
Moscow Haass Medical - Social Institute
Russian Federation

Daniil I. Korabelnikov - MD, PhD, Professor

5, 1–1a 2nd Brestskaya Str., Moscow 123056

RSCI: 7380-7790

A. T. Safarov
Samarkand State Medical Institute

Aliaskar T. Safarov - MD, PhD, Associate Professor, Head of the Department of Obstetrics and Gynecology, Faculty of Advanced Training for Doctors

18 Amir Temur Str., Samarkand 140100

N. V. Pavlova
Moscow State University of Medicine and Dentistry named after А.I. Evdokimov, Health Ministry of Russian Federation
Russian Federation

Nadezhda V. Pavlova - MD, PhD

20/1 Delegatskaya Str., Moscow 127473

N. S. Zakharova
Samarkand State Medical Institute
Russian Federation

Natalya S. Zakharova - MD, Obstetrician-Gynecologist, Department of Pregnancy Pathology, City Clinical Hospital named after V.V. Vinogradov

18 Amir Temur Str., Samarkand 140100

D. A. Ponomarev
Maternity Hospital № 4 - Branch of City Clinical Hospital named after V.V. Vinogradov, Moscow Healthcare Department
Russian Federation

Dmitry A. Ponomarev - MD

3 Novatorov Str., Moscow 117421

D. A. Petrenko
Sechenov University
Russian Federation

Daria A. Petrenko - 5th year Student

8 bldg. 2, Trubetskaya Str., Moscow 119991


1. Conway G.S. Premature ovarian insufficiency, menopause, and hormone replacement therapy. In: Advanced Practice in Endocrinology Nursing. Cham: Springer International Publishing, 2019. 803–15.

2. Gunning M.N., Troìa L., Janse F.J. et al. Premature ovarian insufficiency. Female Reprod Dysfunct. 2020:287–307.

3. Novikova V.A., Fedorovich O.A., Atanesyan E.G. Complex therapy of urogenital tract atrophy in premenopausal women with premature ovarian insufficiency. [Kompleksnaya terapiya atrofii urogenital’nogo trakta u zhenshchin premenopauzal’nogo perioda s prezhdevremennoj nedostatochnost’yu funkcii yaichnikov]. Akusherstvo, Ginekologia i Reprodukcia. 2008;(7):14–6. (In Russ.).

4. Galtsev E.V., Kazenashev V.V. Psychosocial discomfort in women with urogenital disorders. [Psihosocial’nyj diskomfort u zhenshchin s urogenital’nymi rasstrojstvami. Akusherstvo, Ginekologia i Reprodukcia. 2007;(2):4–9. (In Russ.)

5. Golezar S., Ramezani Tehrani F., Khazaei S. et al. The global prevalence of primary ovarian insufficiency and early menopause: a meta-analysis. Climacteric. 2019;22(4):403–11.

6. Paschou S.A., Augoulea A., Syggelos N., Lambrinoudaki I. Premature ovarian insufficiency. Why male Mod contraception? 2019:5.

7. European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI; Webber L., Davies M., Anderson R. et al. ESHRE guideline. Management of women with premature ovarian insufficiency. Hum Reprod. 2016;31(5):926–37.

8. Reed D. Primary ovarian insufficiency: a primary care overview. Proc UCLA Heal, 2019. 23. Available at: [Accessed: 14.08.2020].

9. Gunning M.N., Meun C., van Rijn B.B. et al. Coronary artery calcification in middle-aged women with premature ovarian insufficiency. Clin Endocrinol (Oxf). 2019;91(2):314–22.

10. Hubayter Z.R., Popat V., Vanderhoof V. et al. A prospective evaluation of antral follicle function in women with spontaneous 46,xx primary ovarian insufficiency (hypergonadotropic hypogonadism). Fertil Steril. 2008;90:S98.

11. Hubayter Z.R., Popat V., Vanderhoof V.H. et al. A prospective evaluation of antral follicle function in women with 46,XX spontaneous primary ovarian insufficiency. Fertil Steril. 2010;94(5):1769–74.

12. Serna J., Varela E., García-Velasco J.A. Genetics of premature ovarian insufficiency. In: Human Reproductive Genetics. Elsevier Science, 2020. 173–99.

13. Wang Q., Li D., Cai B. et al. Whole-exome sequencing reveals SALL4 variants in premature ovarian insufficiency: an update on genotype–phenotype correlations. Hum Genet. 2019;138(1):83–92.

14. Barros F., Carvalho F., Barros A., Dória S. Premature ovarian insufficiency: clinical orientations for genetic testing and genetic counseling. Porto Biomed J. 2020;5(3):e62.

15. Jiao X., Ke H., Qin Y., Chen Z-J. Molecular genetics of premature ovarian insufficiency. Trends Endocrinol Metab. 2018;29(11):795–807.

16. Simpson J.L. Genetic and phenotypic heterogeneity in ovarian failure: overview of selected candidate genes. Ann N Y Acad Sci. 2008;1135(1):146–54.

17. Persani L., Rossetti R., Cacciatore C. Genes involved in human premature ovarian failure. J Mol Endocrinol. 2010;45(5):257–79.

18. De Vos M., Devroey P., Fauser B.C.J.M. Primary ovarian insufficiency. Lancet. 2010;376(9744):911–21.

19. Domniz N., Meirow D. Premature ovarian insufficiency and autoimmune diseases. Best Pract Res Clin Obstet Gynaecol. 2019;60:42–55.

20. Colafrancesco S., Perricone C., Tomljenovic L., Shoenfeld Y. Human papilloma virus vaccine and primary ovarian failure: another facet of the autoimmune/inflammatory syndrome induced by adjuvants. Am J Reprod Immunol. 2013;70(4):309–16.

21. Little D.T., Ward H.R.G. Premature ovarian failure 3 years after menarche in a 16-year-old girl following human papillomavirus vaccination. Case Reports. 2012;2012:bcr2012006879.

22. Pozdnyakova A.A., Volodina M.A., Rshtuni S.D. et al. Mitochondrial dysfunction as possible cause of impaired follicular development. [Mitohondrial’naya disfunkciya kak odna iz vozmozhnyh prichin narusheniya follikulo- i steroidogeneza pri prezhdevremennoj nedostatochnosti yaichnikov]. Akusherstvo, Ginekologia i Reprodukcia. 2015;9(4):55–65. (In Russ.).

23. Ohl J., Partisani M,. Demangeat C. et al. Alterations of ovarian reserve tests in Human Immunodeficiency Virus (HIV)-infected women. Gynecol Obstet Fertil. 2010;38(5):313–7. (In French).

24. Wallace W.H.B., Smith A.G., Kelsey T.W. et al. Fertility preservation for girls and young women with cancer: population-based validation of criteria for ovarian tissue cryopreservation. Lancet Oncol. 2014;15(10):1129–36.

25. Morgan S., Anderson R.A., Gourley C. et al. How do chemotherapeutic agents damage the ovary? Hum Reprod Update. 2012;18(5):525–35.

26. Zahorodnia O.S., Ventskivska I.B., Kazak A.V. Premature ovarian insufficiency – to treat or not to treat? Reprod Endocrinol. 2019;(50):12–6.

27. Ermakova E.I., Balan V.E., Tikhomirova E.V. et al. Genitourinary syndrome of menopause: diagnosis and principles of treatment (brief clinical recommendations). [Genitourinarnyj menopauzal’nyj sindrom: diagnostika i principy lecheniya (kratkie metodicheskie rekomendacii)]. Rossijskij vestnik akushera-ginekologa. 2017;17(6):89–95. (In Russ.).

28. Makatsariya A.D., Blinov D.V., Bitsadze V.O., Khizroeva J.Kh. Treatment of postmenopausal vulvovaginal atrophy with estriol: a scientific update for 2014–2018. [Lechenie estriolom vul’vovaginal’noj atrofii v postmenopauze: obnovlenie nauchnyh dannyh 2014–2018 gg]. Akusherstvo, Ginekologia i Reprodukcia. 2019;13(3):227–38. (In Russ.).

29. Perepanova T., Khazan P.L. Modern approaches to therapy of urogenital disorders in postmenopausal femails. [Sovremennye podhody k terapii urogenital’nyh rasstrojstv u zhenshchin v postmenopauze]. Akusherstvo, Ginekologia i Reprodukcia. 2011;5(1):10–3. (In Russ.).

30. Pozdnyakova A.A., Marchenko L.A., Runikhina N.K. Cardiovascular risk and the possibility of its correction in women with premature ovarian insufficiency. [Serdechno-sosudistyj risk i vozmozhnosti ego korrekcii u zhenshchin s prezhdevremennoj nedostatochnost’yu yaichnikov]. Akusherstvo, Ginekologia i Reprodukcia. 2019;12(4):37–46. (In Russ.).

31. Serov V.N. Treatment for urogenital disorders caused by estrogen deficiency. [Terapiya urogenital’nyh rasstrojstv, obuslovlennyh deficitom estrogenov]. Akusherstvo, Ginekologia i Reprodukcia. 2010;4(1):21–35. (In Russ.).

32. Podfigurna-Stopa A., Czyzyk A., Grymowicz M. et al. Premature ovarian insufficiency: the context of long-term effects. J Endocrinol Invest. 2016;39(9):983–90.

33. de Almeida D.M.B, Benetti-Pinto C.L., Makuch M.Y. et al. Sexual function of women with premature ovarian failure. Menopause. 2011;18(3):262–6.

34. Nappi R.E., Cucinella L., Martini E. et al. Sexuality in premature ovarian insufficiency. Climacteric. 2019;22(3):289–95.

35. Ovsyannikova T.V., Makarov I.O., Borovkova E.I., Kulikov I.A. Local treatment of peri- and postmenopausal urogenital disorders. [Mestnaya terapiya urogenital’nyh narushenij v peri- i postmenopauze]. Akusherstvo, Ginekologia i Reprodukcia. 2010;4(3):25–8. (In Russ.).

36. Bachelot A., Nicolas C., Bidet M. et al. Long-term outcome of ovarian function in women with intermittent premature ovarian insufficiency. Clin Endocrinol (Oxf). 2017;86(2):223–8.

37. Anagnostis P., Christou K., Artzouchaltzi A-M. et al. Early menopause and premature ovarian insufficiency are associated with increased risk of type 2 diabetes: a systematic review and meta-analysis. Eur J Endocrinol. 2019;180(1):41–50.

38. Goh M., Nguyen H.H., Khan N.N. et al. Identifying and addressing osteoporosis knowledge gaps in women with premature ovarian insufficiency and early menopause: A mixed-methods study. Clin Endocrinol (Oxf). 2019;91(4):498–507.

39. Muka T., Oliver-Williams C., Kunutsor S. et al. Association of age at onset of menopause and time since onset of menopause with cardiovascular outcomes, intermediate vascular traits, and all-cause mortality: a systematic review and meta-analysis. JAMA Cardiol. 2016;1(7):767–76.

40. Sullivan S.D., Sarrel P.M., Nelson L.M. Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertil Steril. 2016;106(7):1588–99.

41. Yeganeh L., Boyle J.A., Wood A. et al. Menopause guideline appraisal and algorithm development for premature ovarian insufficiency. Maturitas. 2019;130:21–31.

42. Baber R.J., Panay N., Fenton A., IMS Writing Group. 2016 IMS Recommendations on women’s midlife health and menopause hormone therapy. Climacteric. 2016;19(2):109–50.

43. Razzakberganova G.O., Matyakubova Z.Sh., Sapaev M.G. Ovestin – in the complex therapy of urogenital disorders in women with premature ovarian insufficiency. [Ovestin – v kompleksnoj terapii urogenital’nyh rasstrojstv u zhenshchin s prezhdevremennoj nedostatochnost’yu yaichnikov]. Int Sci Rev. 2016;1(11):121–3. (In Russ.). Available at: [Accessed: 14.08.2020].

44. van Kasteren Y.M., Schoemaker J. Premature ovarian failure: a systematic review on therapeutic interventions to restore ovarian function and achieve pregnancy. Hum Reprod Update. 1999;5(5):483–92.

45. Męczekalski B., Maciejewska-Jeske M., Podfigurna A. Reproduction in premature ovarian insufficiency patients – from latest studies to therapeutic approach. Menopausal Rev. 2018;17(3):117–9.

46. Lee H.N., Chang E.M. Primordial follicle activation as new treatment for primary ovarian insufficiency. Clin Exp Reprod Med. 2019;46(2):43–9.

47. Suzuki N., Yoshioka N., Takae S. et al. Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod. 2015;30(3):608–15.


For citations:

Blinov D.V., Hasan P.L., Mnatsakanyan A.N., Korabelnikov D.I., Safarov A.T., Pavlova N.V., Zakharova N.S., Ponomarev D.A., Petrenko D.A. Early menopause and premature ovarian insufficiency: problems and perspectives. Obstetrics, Gynecology and Reproduction. 2020;14(3):328-345. (In Russ.)

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