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Obstetrics and Gynegology2020№12
Estrogen therapy: from science to...

Estrogen therapy: from science to practical solutions

DOI
https://dx.doi.org/10.18565/aig.2020.12.67-75

Bondarenko K.R., Dobrokhotova Yu.E., Nasyrova N.I., Shadrova P.A.

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow, Russia
The review presents the latest data on the safety and efficiency of hormone therapy with estrogens. The authors separate the concepts of "hormone replacement therapy" and "menopausal hormone therapy", focusing on the fundamental differences in approaches to treating reproductive-aged and postmenopausal women with estrogen deficiency. The article discusses the features of therapy selection in women with gynecologic pathology and some chronic diseases. The article contains information about the basic principles of prescribing menopausal hormone therapy to minimize the risks of cancer and adverse cardiovascular events during estrogen treatment that includes the use of transdermal estrogens, 17β-estradiol gel 0.1% in particular, in minimum effective doses and natural progesterone, at the beginning of treatment within the therapeutic time window, a therapy duration of up to five years, by reviewing the benefits/risks of an intervention during treatment over time. The article describes some clinical situations, in which it is recommended to avoid prescribing oral estrogens due to the pharmacokinetic features: hypertriglyceridemia, high basic risks of venous thromboembolic events and strokes, gallbladder diseases, intake of anticonvulsants and thyroxine, female alcoholism, and also probably coronavirus infection. In addition, the review analyzes updated recommendations for hormone replacement therapy in women with premature ovarian failure, by relying on data from international clinical protocols.
Conclusion. Hormone therapy is generally a safe pharmacological intervention, since it is prescribed either to reproductive-aged women with ovarian failure/loss of ovarian function or to healthy women with menopausal symptoms aged 40 to 50 years.

Keywords

menopause
menopausal hormone therapy
hormone replacement therapy
estrogen deficiency
premature ovarian failure
17β-estradiol gel 0.1%
breast cancer
vulvovaginal atrophy
COVID-19
venous thrombosis
Full text (in Russian)

References

  1. Pinkerton J.V., Aguirre F.S., Blake J., Cosman F., Hodis H.N., Hoffstetterhe S. et al.; The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of the North American Menopause Society. Menopause. 2017; 24(7): 728-53. https://dx.doi.org/10.1097/GME.0000000000000921.
  2. Менопаузальная гормонотерапия и сохранение здоровья женщин в зрелом возрасте. Клинические рекомендации (протокол лечения). Письмо Министерства здравоохранения Российской Федерации от 2 октября 2015 г. № 15-4/10/2-5804. [Menopausal hormone therapy and preservation of women's health in adulthood. Clinical recommendations (treatment Protocol). Letter of the Ministry of Health of the Russian Federation dated October 2, 2015 No. 15-4/10/2-5804. (in Russian)].
  3. Stuenkel C.A., Davis S.R., Gompel A., Lumsden M.A., Murad M.H., Pinkerton J.V. et al. Treatment of symptoms of the menopause: an Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 2015; 100(11): 3975-4011. https://dx.doi.org/10.1210/jc.2015-2236.
  4. Panay N., Anderson R.A., Nappi R.E., Vincent A.J., Vujovic S., Webber L. et al. Premature ovarian insufficiency: an International Menopause Society White Paper. Climacteric. 2020; 23(5): 426-46. https://dx.doi.org/ 10.1080/13697137.2020.1804547.
  5. 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.
  6. Beral V., Gaitskell K., Hermon C., Moser K., Reeves G., Peto R.; Collaborative Group On Epidemiological Studies Of Ovarian Cancer. Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. Lancet. 2015; 385(9980): 1835-42. https://dx.doi.org/10.1016/S0140-6736(14)61687-1.
  7. Grady D., Sawaya G.F. Discontinuation of postmenopausal hormone therapy. Am. J. Med. 2005; 118(Suppl. 12B): 163-5. https://dx.doi.org/10.1016/j.amjmed.2005.09.051.
  8. Mosca L., Benjamin E.J., Berra K., Bezanson J.L., Dolor R.J., Lloyd-Jones D.M. et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women - 2011 update: a guideline from the american heart association. Circulation. 2011; 123(11): 1243-62. https://dx.doi.org/10.1161/CIR.0b013e31820faaf8.
  9. Furness S., Roberts H., Marjoribanks J., Lethaby A. Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. Cochrane Database Syst. Rev. 2012; 2012(8): CD000402. https://dx.doi.org/10.1002/14651858.CD000402.pub4.
  10. Thurston R.C., Joffe H. Vasomotor symptoms and menopause: findings from the Study of Women's Health across the Nation. Obstet. Gynecol. Clin. North Am. 2011; 38(3): 489-501. https://dx.doi.org/10.1016/j.ogc.2011.05.006.
  11. Maclennan A.H., Broadbent J.L., Lester S., Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst. Rev. 2004; 2004(4): CD002978.https://dx.doi.org/10.1002/14651858.CD002978.pub2.
  12. Freedman R.R., Roehrs T.A. Sleep disturbance in menopause. Menopause. 2007; 14(5): 826-9. https://dx.doi.org/10.1097/GME.0b013e3180321a22.
  13. Freeman E.W., Sammel M.D., Liu L., Gracia C.R., Nelson D.B., Hollander L. Hormones and menopausal status as predictors of depression in women in transition to menopause. Arch. Gen. Psychiatry. 2004; 61(1): 62-70. https://dx.doi.org/10.1001/archpsyc.61.1.62.
  14. Barnabei V.M., Cochrane B.B., Aragaki A.K., Nygaard I., Williams R.S., McGovern P.G. et al. Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women's Health Initiative. Obstet. Gynecol. 2005; 105(5): 1063-73. https://dx.doi.org/10.1097/01.AOG.0000158120.47542.18.
  15. Woods N.F., Mitchell E.S. Symptoms during the perimenopause: prevalence, severity, trajectory, and significance in women's lives. Am. J. Med. 2005; 118(Suppl. 12B): 14-24. https://dx.doi.org/10.1016/j.amjmed.2005.09.031.
  16. National Institutes of Health. National Institutes of Health State-of-the-Science Conference statement: management of menopause-related symptoms. Ann. Intern. Med. 2005; 142(12 Pt. 1): 1003-13.
  17. Rossouw J.E., Anderson G.L., Prentice R.L., LaCroix A.Z., Kooperberg C., Stefanick M.L. et al.; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002; 288(3): 321-33. https://dx.doi.org/10.1001/jama.288.3.321.
  18. Santen R.J., Allred D.C., Ardoin S.P., Archer D.F., Boyd N., Braunstein G.D. et al. Endocrine Society. Postmenopausal hormone therapy: an Endocrine Society scientific statement. J. Clin. Endocrinol. Metab. 2010; 95(7 Suppl. 1): s1-66. https://dx.doi.org/10.1210/jc.2009-2509.
  19. ACOG Practice Bulletin No. 141: management of menopausal symptoms. Obstet. Gynecol. 2014; 123(1): 202-16. https://dx.doi.org/10.1097/01.AOG.0000441353.20693.78.
  20. Nanda K., Bastian L.A., Schulz K. Hormone replacement therapy and the risk of death from breast cancer: a systematic review. Am. J. Obstet. Gynecol. 2002; 186(2): 325-34. https://dx.doi.org/10.1067/mob.2002.121077.
  21. Derzko C., Sergerie M., Siliman G., Alberton M., Thorlund K. Comparative efficacy and safety of estradiol transdermal preparations for the treatment of vasomotor symptoms in postmenopausal women: an indirect comparison meta-analysis. Menopause. 2016; 23(3): 294-303. https://dx.doi.org/10.1097/GME.0000000000000552.rovi.
  22. Stute P., Neulen J., Wildt L. The impact of micronized progesterone on the endometrium: a systematic review. Climacteric. 2016; 19(4): 316-28.https://dx.doi.org/10.1080/13697137.2016.1187123.
  23. 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. https://dx.doi.org/10.3109/13697137.2015.1129166.
  24. Chlebowski R.T., Hendrix S.L., Langer R.D., Stefanick M.L., Gass M., Lane D.et al. WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA. 2003; 289(24): 3243-53. https://dx.doi.org/10.1001/jama.289.24.3243.
  25. Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. 2019; 394(10204): 1159-68. https://dx.doi.org/10.1016/S0140-6736(19)31709-X.
  26. Fournier A., Berrino F., Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res. Treat. 2008; 107(1): 103-11.https://dx.doi.org/10.1007/s10549-007-9523-x.
  27. Christante D., Pommier S., Garreau J., Muller P., LaFleur B., Pommier R. Improved breast cancer survival among hormone replacement therapy users is durable after 5 years of additional follow-up. Am. J. Surg. 2008; 196(4): 505-11. https://dx.doi.org/10.1016/j.amjsurg.2008.06.023.
  28. Beral V., Bull D., Reeves G.; Million Women Study Collaborators. Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2005; 365(9470): 1543-51. https://dx.doi.org/10.1016/S0140-6736(05)66455-0.
  29. Moro E., Degli Esposti E., Borghese G., Manzara F., Zanello M., Raimondo D. et al. The impact of hormonal replacement treatment in postmenopausal women with uterine fibroids: a state-of-the-art review of the literature. Medicina (Kaunas). 2019; 55(9): 549. https://dx.doi.org/10.3390/medicina55090549.
  30. Zanello M., Borghese G., Manzara F., Rodabough R.J., Psaty B.M., Stafford R.S. et al. Hormonal replacement therapy in menopausal women with history of endometriosis: a review of literature. Medicina (Kaunas). 2019; 55(8): 477. https://dx.doi.org/10.3390/medicina55080477.
  31. Rossouw J.E., Prentice R.L., Manson J.E., Wu L., Barad D., Barnabei V.M. et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007; 297(13): 1465-77. https://dx.doi.org/10.1001/jama.297.13.1465.
  32. Renoux C., Dell'aniello S., Garbe E., Suissa S. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. BMJ. 2010; 340: c2519. https://dx.doi.org/10.1136/bmj.c2519.
  33. Cushman M., Kuller L.H., Prentice R., Rodabough R.J., Psaty B.M., Stafford R.S. et al. Women's Health Initiative Investigators. Estrogen plus progestin and risk of venous thrombosis. JAMA. 2004; 292(13): 1573-80. https://dx.doi.org/10.1001/jama.292.13.1573.
  34. Curb J.D., Prentice R.L., Bray P.F., Langer R.D., Van Horn L., Barnabei V.M. et al. Venous thrombosis and conjugated equine estrogen in women without a uterus. Arch. Intern. Med. 2006; 166(7): 772-80. https://dx.doi.org/ 10.1001/archinte.166.7.772.
  35. Smith N.L., Heckbert S.R., Lemaitre R.N., Reiner A.P., Lumley T., Weiss N.S. et al. Esterified estrogens and conjugated equine estrogens and the risk of venous thrombosis. JAMA. 2004; 292(13): 1581-7. https://dx.doi.org/ 10.1001/jama.292.13.1581.
  36. Canonico M., Plu-Bureau G., Lowe G.D., Scarabin P.Y. Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis. BMJ. 2008; 336(7655): 1227-31. https://dx.doi.org/10.1136/bmj.39555.441944.BE.
  37. Renoux C., Dell'Aniello S., Suissa S. Hormone replacement therapy and the risk of venous thromboembolism: a population-based study. J. Thromb. Haemost. 2010; 8(5): 979-86. https://dx.doi.org/ 10.1111/j.1538-7836.2010.03839.x.
  38. Rovinski D., Ramos R.B., Fighera T.M., Casanova G.K., Spritzer P.M. Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: a systematic review and meta-analysis. Thromb. Res. 2018; 168: 83-95. https://dx.doi.org/ 10.1016/j.thromres.2018.06.014.
  39. Ramírez I., De la Viuda E., Baquedano L., Coronado P., Llaneza P., Mendoza N. et al. Managing thromboembolic risk with menopausal hormone therapy and hormonal contraception in the COVID-19 pandemic: recommendations from the Spanish Menopause Society, Sociedad Española de Ginecología y Obstetricia and Sociedad Española de Trombosis y Hemostasia. Maturitas. 2020; 137: 57-62. https://dx.doi.org/10.1016/j.maturitas.2020.04.019.
  40. Van Erpecum K.J., Van Berge Henegouwen G.P., Verschoor L., Stoelwinder B., Willekens F.L. Different hepatobiliary effects of oral and transdermal estradiol in postmenopausal women. Gastroenterology. 1991; 100(2): 482-8. https://dx.doi.org/10.1016/0016-5085(91)90220-f.
  41. Ших Е.В. Сравнительные клинико-фармакологические аспекты применения пероральных и трансдермальных форм эстрогенов. Акушерство и гинекология: новости, мнения, обучение. 2016; 1: 41-6. [Shih E.V. Comparative clinical and pharmacological aspects of oral and transdermal dosage forms of estrogens. Obstetrics and gynecology: news, opinions, training. 2016; 1: 41-6. (in Russian)].
  42. Mattson R.H., Cramer J.A., Darney P.D., Naftolin F. Use of oral contraceptives by women with epilepsy. JAMA. 1986; 256(2): 238-40.
  43. Ginsburg E.S., Mello N.K., Mendelson J.H., Barbieri R.L., Teoh S.K., Rothman M. et al. Effects of alcohol ingestion on estrogens in postmenopausal women. JAMA. 1996; 276(21): 1747-51. https://dx.doi.org/10.1001/jama.1996.03540210055034.
  44. Ginsburg E.S., Owen W.F. Jr., Greenberg L.M., Shea B.F., Lazarus J.M., Walsh B.W. Estrogen absorption and metabolism in postmenopausal women with end-stage renal disease. J. Clin. Endocrinol. Metab. 1996; 81(12): 4414-7. https://dx.doi.org/10.1210/jcem.81.12.8954051.
  45. Cirillo D.J., Wallace R.B., Rodabough R.J., Greenland P., LaCroix A.Z., Limacher M.C. et al. Effect of estrogen therapy on gallbladder disease. JAMA. 2005; 293(3): 330-9. https://dx.doi.org/10.1001/jama.293.3.330.
  46. Nelson L.M. Clinical practice. Primary ovarian insufficiency. N. Engl. J. Med. 2009; 360(6): 606-14. https://dx.doi.org/10.1056/NEJMcp0808697.
  47. Kalantaridou S.N., Naka K.K., Papanikolaou E., Kazakos N., Kravariti M., Calis K.A. et al. Impaired endothelial function in young women with premature ovarian failure: normalization with hormone therapy. J. Clin. Endocrinol. Metab. 2004; 89(8): 3907-13. https://dx.doi.org/10.1210/jc.2004-0015.
  48. Ostberg J.E., Storry C., Donald A.E., Attar M.J., Halcox J.P., Conway G.S. A dose-response study of hormone replacement in young hypogonadal women: effects on intima media thickness and metabolism. Clin. Endocrinol. (Oxf). 2007; 66(4): 557-64. https://dx.doi.org/10.1111/j.1365-2265.2007.02772.x.
  49. 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.

Received 08.12.2020

Accepted 14.12.2020

About the Authors

Karina R. Bondarenko, MD, PhD, assistant professor of the Department of Obstetrics and Gynecology, Therapeutic faculty, N.I. Pirogov Russian National Research Medical University. E-mail: karinabond@mail.ru. ORCID: 0000-0003-4147-1151; SPIN: 9976-0735; AuthorID: 798660. 1, Ostrovityanova str., Moscow, 117437, Russia.
Yulia E. Dobrokhotova, MD, PhD, professor of the Department of Obstetrics and Gynecology, Therapeutic faculty, N.I. Pirogov Russian National Research Medical University. E-mail: pr.dobrohotova@mail.ru. ORCID: 0000-0002-7830-2290; SPIN: 2925-9948; AuthorID: 312767. 1, Ostrovityanova str., Moscow, 117437, Russia.
Nailya I. Nasyrova, MD, PhD, assistant professor of the Department of Obstetrics and Gynecology, Therapeutic faculty, N.I. Pirogov Russian National Research Medical University; Head of the Department of Gynecology, Central Clinical Hospital of Civil Aviation. E-mail: ni_nasyrova@mail.ru. ORCID: 0000-0003-0657-7655.
1, Ostrovityanova str., Moscow, 117437, Russia; 7, Ivan’kovskoe h., Moscow, 125367, Russia.
Polina A. Shadrova, postgraduate student of the Department of Obstetrics and Gynecology, Therapeutic faculty, N.I. Pirogov Russian National Research Medical University. E-mail: shadrovapolina@hotmail.com. ORCID: 0000-0002-3721-1421; SPIN: 9935-8003. 1, Ostrovityanova str., Moscow, 117437, Russia.

For citation: Bondarenko K.R., Dobrokhotova Yu.E., Nasyrova N.I., Shadrova P.A. Estrogen therapy: from science to practical solutions.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2020; 12: 67-75 (in Russian)
https://dx.doi.org/10.18565/aig.2020.12.67-75

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