Premature ovarian insufficiency – to treat or not to treat?

Authors

DOI:

https://doi.org/10.18370/2309-4117.2019.50.12-16

Keywords:

premature ovarian insufficiency, replace hormone therapy, estrogens

Abstract

Premature ovarian insufficiency (POI) is a rare but very damaging lifestyle condition that occurs at 1–1.5 of women and means termination of menstrual function up to 40 years old. POI impact on women’s wellbeing includes lipid metabolism dysregulation, haemostasis regulation changes, both leading to heart diseases risk increasing, psychological problems, based on early reproductive function termination and anxiety because possible sexual dysfunction, manifestation of pelvic floor disorders. Patients with POI have symptoms, similar to women in menopause, namely vegetative nerve system disorders (hot flashes, night sweats, and emotional lability), insomnia and sexual dysfunction due to vaginal dryness, dyspareunia, and libido loss. It is believed, that estrogen and progesterone deficiency is a leading reason of these complains, but in the same time the role of testosterone decreasing concentration is discussed. Speaking accurately, therapy with exogenous estrogens for women with POI is really replacement, while for patients with normal age menopause it is rather therapy of extension. Nevertheless, only 52% patients with POI have discussed it with their doctors.

The article deals with question hormone replacement therapy rationality from the point of view of most popular menopause disorders. Special trials for some of them are published, as for bone mineral density and sexual disorders, treatment for other is possible only by extrapolation from general cohort of menopausal women. For each position questions of effectiveness and safety is discussed. Different ways of estrogen administration are considered, as well as progestin variations. A special attention is paid to possibility of reproductive function restoration in patients with POI. Non-hormonal methods of menopause symptoms correction also discussed – from life style modification to drug administration.

Author Biographies

O. S. Zahorodnia, O.O. Bogomolets National Medical University, Kyiv

MD, associate professor of the Obstetrics and Gynecology Department №1

I. B. Ventskivska, O.O. Bogomolets National Medical University, Kyiv

MD, professor of the Obstetrics and Gynecology Department №1

A. V. Kazak, O.O. Bogomolets National Medical University, Kyiv

PhD, associate professor of the Obstetrics and Gynecology Department №1

References

  1. Okeke, Т.С., Anyaehie, U.B., Ezenyeaku, C.C. “Premature Menopause.” Ann Med Health Sci Res 3.1 (2013): 90–95. doi: 10.4103/2141-9248.109458
  2. Ventskivska, I.B., Zahorodnia, O.S., Narytnyk, T.T. “Early cessation of menstrual function: current views on pathogenesis and consequences.” Reproductive Endocrinology 4.48 (2019): 8–12.
  3. Keaney, J.J., Solomon, C.G. “Postmenopausal hormone therapy and atherosclerosis: time is of the essence.” N Eng J Med 374 (2016): 1279–80.
  4. Bhagavan, N.V. Medical Biochemistry. 4 edition. Harcourt. Academic Press (2002): 1060 p.
  5. Wilson, R.A., Wilson, T.A. “The fate of the nontreated postmenopausal woman: a plea for the maintenance of adequate estrogen from puberty to the grave.” J Am Geriatric Soc 11 (1963): 347–62.
  6. Writing Group for the Women's Health Initiative Investigators. “Risk and benefits of estrogen plus progestin in healthy menopausal women: principal results from the Women's Health Initiative randomized control trial.” JAMA 288 (2002): 321–33.
  7. Harman, S.K., Black, D.M., Naftolin, F., et al. “Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial.” Ann Intern Med 161 (2014): 249–60.
  8. Hodis, H.N., Mack, W.J., Henderson, V.W., et al. “Vascular effects of early versus late postmenopausal treatment with estradiol.” N Engl J Med 374 (2016): 1221–31.
  9. Avis, N.E., Crawford, S.L., Greendale, G., et al. “Duration of menopausal vasomotor symptoms over the menopause transition.” JAMA Intern Med 175 (2015): 531–9.
  10. Mikkola, T., Clarkson, T. “Estrogen replacement therapy, atherosclerosis, and vascular function.” Cardiovascular Research 53.3 (2002): 605–19. doi: 10.1016/S0008-6363(01)00466-7
  11. Rossouw, J.E., Anderson, G.L., Prentice, R.L., et al. “Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial.” JAMA 288 (2002): 321–33.
  12. Sullivan, S., Sarrel, P., Nelson, L. “Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause.” Fertil Steril 106.7 (2016): 1588–99.
  13. Hipp, H.S., Charen, K.H., Spencer, J.B., et al. “Reproductive and gynecologic care of women with fragile X primary ovarian insufficiency (FXPOI).” Menopause 23 (2016): 993–9.
  14. Turner, R., Kerber, I. “A theory of eu-estrogenemia: a unifying concept.” Menopause 24.9 (2017): 1086–97.
  15. Madalinska, J., van Beurden, M., Bleiker, E., et al. “The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingooophorectomy.” J Clin Oncol 24 (2006): 3576–82.
  16. Piccioni, P., Scirpa, P., D'Emilio, I., et al. “Hormonal replacement therapy after stem cell transplantation.” Maturitas 49 (2004): 327–33.
  17. Benetti-Pinto, C., Laguna, C., Giraldo, P., et al. “Vaginal epithelium and microflora characteristics in women with premature ovarian failure under hormone therapy compared to healthy women.” Archives of Gynecology and Obstetrics 292.1 (2015): 159–64.
  18. Karram, M.M., Yeko, T.R., Sauer, M.V., Bhatia, N.N. “Urodynamic changes following hormonal replacement therapy in women with premature ovarian failure.” Obstet Gynecol 74 (1989): 208–11.
  19. Pacello, P.C.C., Yela, D.A., Rabelo, S., et al. “Dyspareunia and lubrication in premature ovarian failure using hormonal therapy and vaginal health.” Climacteric 17 (2014): 342–7.
  20. Guerrieri, G.M., Martinez, P.E., Klug, S.P., et al. “Effects of physiologic testosterone therapy on quality of life, selfesteem, and mood in women with primary ovarian insufficiency.” Menopause 21 (2014): 952–61.
  21. Popat, V.B., Calis, K.A., Vanderhoof, V.H., et al. “Bone mineral density in estrogen-deficient young women.” J Clin Endocrinol Metab 94 (2009): 2277–83.
  22. Popat, V.B., Calis, K.A., Kalantaridou, S.N., et al. “Bone Mineral Density in Young Women with Primary Ovarian Insufficiency: Results of a Three-Year Randomized Controlled Trial of Physiological Transdermal Estradiol and Testosterone Replacement.” The Journal of Clinical Endocrinology & Metabolism 99 (214): 3418–26.
  23. Cartwright, B., Robinson, J., Seed, P.T., et al. “Hormone replacement therapy versus the combined oral contraceptive pill in premature ovarian failure: a randomized controlled trial of the effects on bone mineral density.” J Clin Endocrinol Metab 101 (2016): 3497–505.
  24. Leite-Silva, P., Bedone, A., Pinto-Neto, A.M., et al. “Factors associated with bone density in young women with karyotypically normal spontaneous premature ovarian failure.” Arch Gynecol Obstet 280 (2009): 177–81.
  25. Maki, P.M., Resnick, S.M. “Effects of estrogen on patterns of brain activity at rest and during cognitive activity: a review of neuroimaging studies.” Neuroimage 14 (2001): 789–801.
  26. Morrison, J.H., Brinton, R.D., Schmidt, P.J., Gore, A.C. “Estrogen, menopause, and the aging brain: how basic neuroscience can inform hormone therapy in women.” J Neurosci 26 (2006): 10332–48.
  27. LeBlanc, E.S., Janowsky, J., Chan, B.K., Nelson, H.D. “Hormone replacement therapy and cognition: systematic review and meta-analysis.” JAMA 285 (2001): 1489–99.
  28. 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 5 (1999): 483–92.
  29. Tartagni, M., Cicinelli, E., de Pergola, G., et al. “Effects of pretreatment with estrogens on ovarian stimulation with gonadotropins in women with premature ovarian failure: a randomized, placebo-controlled trial.” Fertil Steril 87 (2007): 858–61.
  30. Taylor, A.E., Adams, J.M., Mulder, J.E., et al. “A randomized, controlled trial of estradiol replacement therapy in women with hypergonadotropic amenorrhea.” J Clin Endocrinol Metab 81 (1996): 3615–21.
  31. Tartagni, M., Cicinelli, E., de Pergola, G., et al. “Effects of pretreatment with estrogens on ovarian stimulation with gonadotropins in women with premature ovarian failure: a randomized, placebo-controlled trial.” Fertil Steril 87 (2007): 858–86.
  32. Smith, J.A., Vitale, S., Reed, G.F., et al. “Dry eye signs and symptoms in women with premature ovarian failure.” Arch Ophthalmol 122 (2004): 151–6.
  33. Podfigurna-Stopa, A., Czyzyk, A., Grymowicz, M., et al. “Premature ovarian insufficiency: the context of long-term effects.” J Endocrinol Invest 39.9 (2016): 983–90. doi: 10.1007/s40618-016-0467
  34. Scarabin, P.Y., Oger, E., Plu-Bureau, G. “Differential association of oral and transdermal oestrogenreplacement therapy with venous thromboembolism risk.” Lancet 362 (2003): 428–32.
  35. Canonico, M., Oger, E., Plu-Bureau, G., et al. “Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study.” Circulation 115 (2007): 840–84.
  36. Sidney, S., Cheetham, T.C., Connell, F.A., et al. “Recent combined hormonal contraceptives (CHCs) and the risk of thromboembolism and other cardiovascular events in new users.” Contraception 87 (2013): 93–100.
  37. Langrish, J.P., Mills, N.L., Bath, L.E., et al. “Cardiovascular effects of physiological and standard sex steroid replacement regimens in premature ovarian failure.” Hypertension 53 (2009): 805–11.
  38. Bjarnason, K., Cerin, A., Lindgren, R., Weber, T., and Scandinavian Long Cycle Study Group. “Adverse endometrial effects during long cycle hormone replacement therapy.” Maturitas 32 (1999): 161–70.
  39. Maciejewska-Jeske, M., Szeliga, A., Męczekalski, B. “Consequences of premature ovarian insufficiency on women's sexual health.” Prz Menopauzalny 17.3 (2018): 127–30. doi: 10.5114/pm.2018.78557
  40. Gorbatiuk, O.G., Grigorenko, A.P., Shatkovska, A.S., Binkovska, V.Y. “Optimization of treatment of vegetative-vascular and psychoneurological disorders of climacteric syndrome.” Zaporizhzhya medical journal 19.4 (2017): 482–6.
  41. Palma, F., Xholli, A., Cagnacci, A., as the writing group of the AGATA study. “Management of vaginal atrophy: a real mess. Results from the AGATA study.” Gynecol Endocrinol 33 (2017): 702–7.
  42. Yela, D.A., Soares, P.M., Benetti-Pinto, C. “Influence of Sexual Function on the Social Relations and Quality of Life of Women with Premature Ovarian Insufficiency.” Rev Bras Ginecol Obstet 40 (2018): 66–71.
  43. British Menopause Society (BMS). Premature Menopause. BMS Council Consensus Statement (2007). Available from: [http: // www.thebms.org.uk].
  44. Tommaselli, G.A., Di Carlo, C., Di Spiezio Sardo, A., et al. “Serum leptin levels and body composition in postmenopausal women treated with tibolone and raloxifene.” Menopause 13.4 (2006): 660–8.
  45. Fagiolini, et al. “Rediscovering Trazodone for the treatment of major depressive disorder.” CNS Drugs 26 (2012): 1033–49.
  46. Jankowska, K. “Premature ovarian failure.” Menopause Rev 16.2 (2017): 51–6.
  47. Simon, A., Laufer, N. “Repeated implantation failure: clinical approach.” Fertil Steril 97 (2012): 1039–43.

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Published

2019-12-28

How to Cite

Zahorodnia, O. S., Ventskivska, I. B., & Kazak, A. V. (2019). Premature ovarian insufficiency – to treat or not to treat?. REPRODUCTIVE ENDOCRINOLOGY, (50), 12–16. https://doi.org/10.18370/2309-4117.2019.50.12-16

Issue

No. 50 (2019)

Section

Gynecology

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Copyright (c) 2019 O. S. Zahorodnia, I. B. Ventskivska, A. V. Kazak

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