Premature ovarian failure: an arsenal of approaches
Premature ovarian failure (POF) is a term that has acquired particular significance in recent years. It occurs in 1% of women who are under 40 years old. The typical manifestation of this syndrome is episodic or stable hypergonadotropic amenorrhea. It is diagnosed in about 10—28% of women with primary amenorrhea and in 4—18% of women with secondary amenorrhea. Unlike postmenopausal women, many patients with POF ovulate intermittently; there is resumption of regular periods in some cases; and spontaneous pregnancy can occur in 5—10%. But in one way or another long-term menstrual irregularities lead to irreversible cessation of ovarian function at a relatively young age, despite the fact that modern treatment approaches, timely diagnosis, and menopausal hormone therapy (MHT) can improve a woman's quality of life at the present time. This paper discusses the theoretical and practical aspects of the diagnosis and etiological features of POF, highlights key issues and choice of approaches to managing patients with POF in order to correct the symptoms of estrogen deficiency, to possibly restore fertility and minimize cardiometabolic risks.Dubrovina S.O., Aleksandrina A.D.
Conclusion: Women with POF need a special approach and specific therapy depending on their future reproductive plans. Timely MHT remains the main way to relieve the symptoms of estrogen deficiency and leads to an improvement in the level of biochemical and functional markers of endothelial dysfunction. This suggests that MHT is first-line therapy in patients with POF contributing to the normalization of the lipid profile and the functional state of the endothelium, and also confirms the need for its mandatory implementation as the primary prevention of cardiovascular diseases in women with POF.
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References
1. Lambrinoudaki I., Paschou S.A., Lumsden M.A., Faubion S., Makrakis E., Kalantaridou S., Panay N. Premature ovarian insufficiency: a toolkit for the primary care physician. Climacteric. 2021; 24(5): 425-37. https://dx.doi.org/ 10.1080/13697137.2020.1859246.
2. Baber R.J., Panay N., Fenton A. 2016 IMS Recommendations on women’s midlife health and menopause hormone therapy. Climacteric. 2016; 19(2): 10950. https://dx.doi.org/10.3109/13697137.2015.1129166.
3. NICE Guideline [NG23]: Menopause diagnosis and management. Available at: https://www.nice.org.uk/guidance/ng23 Accessed 27.02.2022.
4. Webber L., Davies M., Anderson R., Bartlett J., Braat D., Cartwright B. et al.; European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI. ESHRE Guideline: management of women with premature ovarian insufficiency, Hum. Reprod. 2016; 31(5): 926-37. https://dx.doi.org/10.1093/humrep/dew027.
5. Anderson R.A., Mansi J., Coleman R.E., Adamson D.J.A., Leonard R.C.F. The utility of anti-Mullerian hormone in the diagnosis and prediction of loss of ovarian function following chemotherapy for early breast cancer, Eur. J. Cancer. 2017; 87: 58-64. https://dx.doi.org/10.1016/j.ejca.2017.10.001.
6. Panay N., Anderson R.A., Nappi R.E., Vincent A.J., Vujovic S., Webber L., Wolfman W. Premature ovarian insufciency: an International Menopause Society White Paper. Climacteric. 2020; 23(5): 426-46. https://dx.doi.org/ 10.1080/13697137.2020.1804547.
7. Huhtaniemi I., Alevizaki M. Gonadotrophin resistance. Best Pract. Res. Clin. Endocrinol. Metab. 2006; 20(4): 561-76. https://dx.doi.org/10.1016/j. beem.2006.09.003.
8. Kirshenbaum M., Orvieto R. Premature ovarian insufficiency (POI) and autoimmunity-an update appraisal. J. Assist. Reprod. Genet. 2019; 36(11): 2207-15. https://dx.doi.org/10.1007/s10815-019-01572-0.
9. Silva C.A., Yamakami L.Y.S., Aikawa N.E., Araujo D.B., Carvalho J.F., Bonfa E. Autoimmune primary ovarian insufciency. Autoimmun. Rev. 2014; 13(4-5): 427-30. https://dx.doi.org/10.1016/j.autrev.2014.01.003.
10. Vabre P., Gatimel N., Moreau J., Gayrard V., Picard-Hagen N., Parinaud J., Leandri R.D. Environmental pollutants, a possible etiology for premature ovarian insufficiency: a narrative review of animal and human data. Environ. Health. 2017; 16(1): 37. https://dx.doi.org/10.1186/ s12940-017-0242-4.
11. Rocca W.A., Mielkea M.M., Gazzuola Rocca L., Stewart E.A. Premature or early bilateral oophorectomy: a 2021 update. Climacteric. 2021; 24(5): 466-73. https://dx.doi.org/10.1080/13697137.2021.1893686.
12. ACOG Committee Opinion No. 774: Opportunistic salpingectomy as a strategy for epithelial ovarian cancer prevention. Obstet. Gynecol. 2019; 133(4): e279-84. https://dx.doi.org/10.1097/AOG.0000000000003164.
13. van Lieshout L.A.M., Steenbeek M.P., De Hullu J.A., Vos M.C., Houterman S., Wilkinson J., Piek J.M. Hysterectomy with opportunistic salpingectomy versus hysterectomy alone. Cochrane Database Syst. Rev. 2019; 8(8): CD012858. https://dx.doi.org/10.1002/14651858.CD012858.pub2.
14. Honigberg M.C., Zekavat S.M., Aragam K., Finneran P., Klarin D., Bhatt D.L. et al. Association of premature natural and surgical menopause with incident cardiovascular disease. JAMA. 2019; 322(24): 2411-21. https://dx.doi.org/10.1001/jama.2019.19191.
15. Rocca W.A., Gazzuola-Rocca L., Smith C.Y., Grossardt B.R., Faubion S.S, Shuster L.T. et al. Accelerated accumulation of multimorbidity after bilateral oophorectomy: a population-based cohort study. Mayo Clin. Proc. 2016; 91(11): 1577-89. https://dx.doi.org/10.1016/j.mayocp.2016.08.002.
16. Rocca W.A., Gazzuola Rocca L., Smith C.Y., Grossardt B.R., Faubion S.S., Shuster L.T. et al. Bilateral oophorectomy and accelerated aging: cause or effect? J. Gerontol. A Biol. Sci. Med. Sci. 2017; 72(9): 1213-7. https://dx.doi.org/10.1093/gerona/glx026.
17. Mytton J., Evison F., Chilton P.J., Lilford R.J. Removal of all ovarian tissue versus conserving ovarian tissue at time of hysterectomy in pre- menopausal patients with benign disease: study using routine data and data linkage. BMJ. 2017; 356: j372. https://dx.doi.org/10.1136/bmj.j372.
18. Parker W.H., Broder M.S., Chang E., Feskanich, Farquhar , Liu Z. et al. Ovarian conservation at the time of hysterectomy and long-term health outcomes in the Nurses’ Health Study. Obstet. Gynecol. 2009; 113(5): 1027-37. https://dx.doi.org/10.1097/AOG.0b013e3181a11c64.
19. Kaunitz A.M., Faubion S. Surgical menopause: health implications and hormonal management. Menopause. 2020; 28(1): 1-3. https://dx.doi.org/10.1097/ GME.0000000000001680.
20. Faubion S.S., Files J.A., Rocca W.A. When lowest dose for shortest amount of time does not apply. J. Womens Health (Larchmt). 2016; 25(4): 416-7. https://dx.doi.org/10.1089/jwh.2016.5781.
21. Roeters van Lennep J.E., Heida K.Y., Bots M.L., Hoek A.; Collaborators of the Dutch Multidisciplinary Guideline Development Group on Cardiovascular Risk Management after Reproductive Disorders. Cardiovascular disease risk in women with premature ovarian insufficiency: a systematic review and meta-analysis. Eur. J. Prev. Cardiol. 2016; 23(2): 178-86. https://dx.doi.org/10.1177/2047487314556004.
22. Muka T., Oliver-Williams C., Kunutsor S., Laven J.S., Fauser B.C., Chowdhury R. 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 metaanalysis. JAMA Cardiol. 2016; 1(7): 767-76. https://dx.doi.org/10.1001/ jamacardio.2016.2415.
23. Tao X.Y., Zuo A.Z., Wang J.Q., Tao F.B. Effect of primary ovarian insufficiency and early natural menopause on mortality: a meta-analysis. Climacteric. 2016; 19(1): 27-36. https://dx.doi.org/10.3109/13697137. 2015.1094784.
24. Zhu D., Chung H.F., Dobson A.J., Pandeya N., Giles G.G., Bruinsma F. et al. Age at natural menopause and risk of incident cardiovascular disease: a pooled analysis of individual patient data. Lancet Public Health. 2019; 4(11): e553-64. https://dx.doi.org/10.1016/S2468-2667(19)30155-0.
25. Faubion S.S., Kuhle C.L., Shuster L.T., Rocca W.A. Long-term health consequences of premature or early menopause and considerations for management. Climacteric. 2015; 18(4): 483-91. https://dx.doi.org/10.3109/ 13697137.2015.1020484.
26. Министерство здравоохранения Российской Федерации. Клинические рекомендации. Менопауза и климактерическое состояние у женщины. 2021. 45с. [Ministry of Health of the Russian Federation. Clinical guidelines. Menopause and the menopausal state in women. 2021. 45 p. (in Russian)].
27. Slopien R., Wender-Ozegowska E., Rogowicz-Frontczak A., Meczekalski B., Zozulinska-Ziolkiewicz D., Jaremek J.D. et al. Menopause and diabetes: EMAS clinical guide. Maturitas. 2018; 117: 6-10. https://dx.doi.org/10.1016/ j.maturitas.2018.08.009.
28. Ашрафян Л.А., Балан В.Е., Баранов И.И., Белая Ж.Е., Бобров С.А., Воронцова А.В., Дубровина С.О., Зазерская И.Е., Иловайская И.А., Карахалис Л.Ю., Лесняк О.М., Мазитова М.И., Подзолкова Н.М., Протасова А.Э., Серов В.Н., Сметник А.А., Сотникова Л.С., Ульрих Е.А., Чернуха Г.Е., Юренева С.В. Алгоритмы применения менопаузальной гормональной терапии у женщин в период пери- и постменопаузы. Совместная позиция экспертов РОАГ, РАМ, АГЭ, РАОП. Акушерство и гинекология. 2021; 3: 210-21. [Serov V.N., Yureneva S.V., ed. Algorithms for menopausal hormone therapy during the period of peri- and postmenopause. Joint position statement of RSOG RAM, AGE, RAOP experts. Obstetrics and Gynecology. 2021; 3: 210-21. (in Russian)]. https://dx.doi.org/10.18565/ aig.2021.3.210-221.
29. Hugon-Rodin J., Gompel A., Plu-Bureau G. Epidemiology of hormonal contraceptives-related venous thromboembolism. Eur. J. Endocrinol. 2014; 171(6): R221-30. https://dx.doi.org/10.1530/EJE-14-0527.
30. Davis S.R., Baber R., Panay N., Bitzer J., Perez S.C., Islam R.M. et al. Global consensus position statement on the use of testosterone therapy for women. Maturitas. 2019; 128: 89-93. https://dx.doi.org/10.1016/j.maturitas.2019.07.001.
31. Bidet M., Bachelot A., Bissauge E., Golmard J.L., Gricourt S., Dulon J. et al. Resumption of ovarian function and pregnancies in 358 patients with premature ovarian failure. J. Clin. Endocrinol. Metab. 2011; 96(12): 3864-72. https://dx.doi.org/10.1210/jc.2011-1038.
32. Rebar R.W. Premature ovarian failure. Obstet. Gynecol. 2009; 113(6): 1355-63. https://dx.doi.org/10.1097/AOG.0b013e3181a66843.
33. Wallace W.H., Thompson L., Anderson R.A., Guideline G. Development, Long term follow-up of survivors of childhood cancer: summary of updated SIGN guidance. BMJ. 2013; 346: f1190. https://dx.doi.org/10.1136/ bmj.f1190.
34. Wo J.Y., Viswanathan A.N. Impact of radiotherapy on fertility, pregnancy, and neonatal outcomes in female cancer patients. Int. J. Radiat. Oncol. Biol. Phys. 2009; 73(5): 1304-12. https://dx.doi.org/10.1016/j.ijrobp.2008.12.016.
35. Chen H., Xiao L., Li J., Cui L., Huang W. Adjuvant gonadotropin- releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in premenopausal women. Cochrane Database Syst. Rev. 2019; 3(3): CD008018. https://dx.doi.org/10.1002/14651858.CD008018.pub3.
36. Савельева Г.М., Сухих Г.Т., Серов В.Н., Радзинский В.Е., Манухин И.Б., ред. Гинекология. Национальное руководство. 2-е изд. М.: ГЭОТАР- Медиа; 2019. 1008с. [Savelyeva G.M., Sukhikh G.T., Serov V.N., Radzinsky V.E., Manukhin I.B., eds. Gynecology: National Guidance. 2nd ed., revised and extended. М.: GEOTAR-Media; 2019. 1008 p. (in Russian)].
37. Приказ Минздрава России от 20.10.2020 N 1130н «Об утверждении Порядка оказания медицинской помощи по профилю "акушерство и гинекология"». [Order of the Ministry of Health of Russia N 1130n dated October 20, 2020 "On Approval of the Procedure of Medical Care in the Profile of Obstetrics and Gynecology". (in Russian)].
38. Godsland I.F., Manassiev N.A., Felton C.V., Proudler A.J., Crook D., Whitehead M.I., Stevenson J.C. Effects of low and high dose oestradiol and dydrogesterone therapy on insulin and lipoprotein metabolism in healthy postmenopausal women. Clin. Endocrinol. (Oxford). 2004; 60(5): 541-9. https://dx.doi.org/10.1111/j.1365-2265.2004.02017.x.
39. Шестакова И.Г. Влияние заместительной гормональной терапии пре-паратом Фемостон на метаболизм. Проблемы репродукции. 2001; 2: 46-8. [Shestakova I.G. The effect of hormone replacement therapy with Femoston on metabolism. Problems of Reproduction. 2001; 2: 46-8. (in Russian)].
40. Van der Mooren M.J., Demacker P.N., Thomas C.M., Rolland R. Beneficial effects on serum lipoproteins by 17e-oestradiol—dydrogesterone therapy in postmenopausal women; a prospective study. Eur. J. Obstet. Gynecol. Reprod. Biol. 1992; 47(2): 153-60. https://dx.doi.org/10.1016/0028-2243(92)90046-2.
41. Yang Z., Hu Y., Zhang J., Xu L., Zeng R., Kang D. Estradiol therapy and breast cancer risk in perimenopausal and postmenopausal women: a systematic review and meta-analysis. Gynecol. Endocrinol. 2017; 33(2): 87-92. https://dx.doi.org/10.1080/09513590.2016.1248932.
42. Gompel A., Plu-Bureau G. Progesterone, progestins and the breast in menopause treatment. Climacteric. 2018; 21(4): 326-32. https://dx.doi.org/10.1080/13697137.2018.1476483.
43. Sjogren L.L., M0rch L.S., L0kkegaard E. Hormone replacement therapy and the risk of endometrial cancer: A systematic review. Maturitas. 2016; 91: 25-35. https://dx.doi.org/10.1016/j.maturitas.2016.05.013.
44. Vinogradova Y., Coupland C., Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019; 364: k4810. https://dx.doi.org/10.1136/bmj.k4810.
45. Pirog M., Jach R., Undas A. Effects of ultra-low-dose versus standard hormone therapy on fibrinolysis and thrombin generation in postmenopausal women. Eur J. Obstet. Gynecol. Reprod. Biol. 2017; 217: 77-82. https://dx.doi.org/10.1016/ j.ejogrb.2017.08.023.
46. Адамян Л.В., Дементьева В.О., Смольникова В.Ю., Асатурова А.В. Новые возможности хирургии в восстановлении утраченных функций яичников при преждевременной недостаточности яичников у женщин репродуктивного возраста. Доктор.Ру. 2019; 11: 44-9. [Adamyan L.V., Dementieva V.O., Smolnikova V.Yu., Asaturova A.V. New surgical ways to recover lost ovarian functions in premature ovarian insufficiency in women of reproductive age. Doctor.Ru. 2019; 11(166): 44-9. (in Russian)]. https://dx.doi.org/10.31550/1727-2378-2019-166-11-44-49.
47. Адамян Л.В., Дементьева В.О., Асатурова А.В., Степанян А.А., Смольникова В.Ю., Аракелян А.С., Гус А.И., Николаева А.В. Впервые в России: роды двойней у пациентки с преждевременной недостаточностью яичников после выполнения одноэтапного хирургического метода активации функции яичников. Акушерство и гинекология. 2020; 10: 42-7. [Adamyan L.V., Dementyeva V.O., Asaturova A.V., Stepanian A.A., Smolnikova V.Yu., Arakelyan A.S., Gus A.I., Nikolaeva A.V. For the first time in Russia: delivery of twins in patient with premature ovarian insufficiency after a onestage surgical procedure for activation of ovarian function. Obstetrics and Gynecology. 2020; 10: 42-7. (in Russian)]. https://dx.doi.org/10.18565/ aig.2020.10.42-47.
Received 05.03.2022
Accepted 10.03.2022
About the Authors
Svetlana O. Dubrovina, Dr. Med. Sci., Professor, Chief Researcher, Rostov State Medical University, Ministry of Health of Russia; Chief Researcher, Rostov-on-Don Scientific Research Institute of Obstetrics and Pediatrics, +7(863)250-42-00, s.dubrovina@gmail.com, 344012, Russia, Rostov-on-Don, Mechnikova str., 43.Anna D. Aleksandrina, obstetrician-gynecologist, Rostov-on-Don City Emergency Hospital, +7(863)233-67-42, anna221215@inbox.ru,
344068, Russia, Rostov-on-Don, Bodraya str., 88/35.
Authors’ contributions: Dubrovina S.O., Aleksandrina A.D. - an equal contribution to the writing and editing the manuscript. Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The article has been prepared without sponsorship.
For cuitation: Dubrovina S.O., Aleksandrina A.D. Premature ovarian failure: an arsenal of approaches. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2022; 3: 13-20 (in Russian)
https://dx.doi.org/10.18565/aig.2022.3.13-20