Consilium MedicumConsilium MedicumConsilium MedicumConsilium Medicum2075-17532542-2170Consilium Medicum9526710.26442/20751753.2020.6.200249ArticlesСтатьиReview ArticleRed clover extract phytoestrogens: action mechanism and clinical efficiencyФитоэстрогены экстракта красного клевера: механизм действия и клиническая эффективностьDikkeGalina B.ДиккеГалина Борисовна

д-р мед. наук, проф. каф. акушерства и гинекологии с курсом репродуктивной медицины

galadikke@yandex.ruInozemtsev Academy of Medical EducationЧОУ ДПО «Академия медицинского образования им. Ф.И. Иноземцева»15062020226VOL 22, NO6 (2020)ТОМ 22, №6 (2020)192428122021Copyright ©; 2020, Consilium MedicumCopyright ©; 2020, ООО "Консилиум Медикум"2020Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://consilium.orscience.ru/2075-1753/article/view/95267

Key points. Menopausal symptoms are clearly associated with impaired production of neurotransmitters (serotonin and norepinephrine), which allows the efficient use of phytoestrogens to treat disorders associated with menopause. Isoflavones of red clover show sufficient efficacy in a dose of 40 mg for symptoms (reduction of hot flashes in 47-85% of patients, insomnia in 53%, anxiety and depression in 76-81%, and also has a positive effect on endocrine and metabolic disorders) with admission for 3 months. The safety of their use during long-term use (3 years) is shown. Conclusion. To date, information about the effectiveness and safety of drugs based on red clover extract allows us to recommend them as an alternative to menopausal hormone therapy for the treatment of disorders associated with involuntary changes in the female reproductive system during peri- and postmenopause. Key words: menopause, menopausal syndrome, serotonin, norepinephrine, phytoestrogens, isoflavones, genistein, Feminal. For citation: Dikke G.B. Red clover extract phytoestrogens: action mechanism and clinical efficiency. Consilium Medicum. 2020; 22 (6): 19-24. DOI: 10.26442/20751753.2020.6.200249

Основные положения. Менопаузальные симптомы имеют очевидную связь с нарушениями выработки нейротрансмиттеров (серотонина и норадреналина), что позволяет эффективно использовать фитоэстрогены для лечения расстройств, ассоциированных с менопаузой. Изофлавоны красного клевера проявляют достаточную эффективность в дозе 40 мг на симптомы (редукция приливов у 47-85% пациенток, бессонницы - у 53%, тревоги и депрессии - у 76-81%, а также оказывает положительное действие на эндокринно-метаболические нарушения) при приеме в течение 3 мес. Показана безопасность их использования при длительном применении (3 года). Заключение. Накопленные к настоящему времени сведения об эффективности и безопасности препаратов на основе экстракта красного клевера позволяют рекомендовать их в качестве альтернативы менопаузальной гормональной терапии для лечения расстройств, ассоциированных с инволютивными изменениями женской репродуктивной системы в период пери- и постменопаузы. Ключевые слова: менопауза, менопаузальный синдром, серотонин, норадреналин, фитоэстрогены, изофлавоны, генистеин, Феминал. Для цитирования: Дикке Г.Б. Фитоэстрогены экстракта красного клевера: механизм действия и клиническая эффективность. Consilium Medicum. 2020; 22 (6): 19-24. DOI: 10.26442/20751753.2020.6.200249

menopausemenopausal syndromeserotoninnorepinephrinephytoestrogensisoflavonesgenisteinFeminalменопаузаменопаузальный синдромсеротониннорадреналинфитоэстрогеныизофлавоныгенистеинФеминалSantoro N, Epperson CN, Mathews SB. Menopausal Symptoms and Their Management. Endocrinol Metab Clin North Am 2015; 44 (3): 497-515. DOI:10.1016/j.ecl.2015.05.001Harlow SD, Gass M, Hall JE et al. Executive summary of the Stages of Reproductive Aging Workshop +10: addressing the unfinished agenda of staging reproductive aging. Climacteric 2012; 15 (2): 105-14. DOI: 10.3109/13697137.2011.650656Менопауза и климактерическое состояние у женщины. Клинические рекомендации РОАГ и РАМ. М., 2016.Fait T Menopause hormone therapy: latest developments and clinical practice. Drugs Context 2019; 8: 212551. DOI: 10.7573/dic.212551British Menopause Society further update on HRT supply shortages (30 April 2020). https://thebms.org.uk/Nikolic IL, Savic-Gajic IM, Tacic AD, Savic IM. Classification and biological activity of phytoestrogens: a review. Advanced Technologies 2017; 6 (2): 96-106. UDC: 577.175.6:615.322.07Krizova L, Dadakova K, Kasparovska J, Kasparovsky T Isoflavones. Molecules 2019; 24 (6): 1076. DOI: 10.3390/molecules24061076Кузнецова И.В. Эффективность и безопасность генистеина в лечении вазомоторных симптомов у женщин в постменопаузе (обзор исследований). Гинекология. 2013; 15 (3): 4-9.Yoon G, Park S. Antioxidant action of soy isoflavones on oxidative stress and antioxidant enzyme activities in exercised rats. Nutr Res Practice 2014; 8 (6): 618-24. DOI: 10.4162/nrp.2014.8.6.618Rietjens IMCM, Louisse J, Beekmann K. The potential health effects of dietary phytoestrogens. Br J Pharmacol 2017; 174 (11): 1263-80. DOI: 10.1111/bph.13622Pabich М, Materska М. Biological Effect of Soy Isoflavones in the Prevention of Civilization Diseases. Nutrients 2019; 11: 1660. DOI: 10.3390/nu11071660Lethaby A, Marjoribanks J, Kronenberg F et al. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database Syst Rev 2013; 12: CD001395. DOI: 10.1002/14651858.CD001395.pub4Geller SE, Shulman LP, van Breemen RB et al. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause 2009; 16 (6): 1156-66. DOI: 10.1097/gme.0b013e3181ace49bChen Li-Ru, Ko Nai-Yu, Chen Kuo-Hu. Isoflavone Supplements for Menopausal Women: A Systematic Review. Nutrients 2019; 11: 2649. DOI: 10.3390/nu11112649Beck V et al. Phytoestrogens derived from red clover: An alternative to estrogen replacement therapy? J Steroid Biochem Mol Biol 2005; 94: 499-518.Col NF, Guthrie JR, Politi M, Dennerstein L. Duration of vasomotor symptoms in middle-aged women: a longitudinal study. Menopause 2009; 16: 453-7. DOI: 10.1097/gme.0b013e31818d414eMattawanon N, Khunamornpong S. Short-Term Isoflavone Intervention in the Treatment of Severe Vasomotor Symptoms after Surgical Menopause: A Case Report and Literature Review. Case Reports Obstet Gynecol 2015. DOI: 10.1155/2015/962740Балан В.Е., Рафаэлян И.В., Левкович Е.А. и др. Особенности длительного применения фитоэстрогенов для лечения пациенток с климактерическим синдромом. Рос. вестн. акушера-гинеколога. 2013; 13 (5): 58-62.Keshavarz Z, Golezar S, Hajifoghaha M, Alizadeh S. The effect of phytoestrogens on menopause symptoms: A systematic review. J Isfahan Med Sch 2018; 36 (477): 446-59. DOI: 10.22122/jims.v36i477.9503Politi MC, Schleinitz MD, Col NF. Revisiting the duration of vasomotor symptoms of menopause: a meta-analysis. J Gen Int Med 2008; 23: 1507-13.Evans M, Elliott JG, Sharma P et al. The effect of synthetic genistein on menopause symptom management in healthy postmenopausal women: a multi-center, randomized, placebo-controlled study. Maturitas 2011; 68 (2): 189-96. DOI: 10.1016/j.maturitas.2010.11.012Chen MN, Lin CC, Liu C. Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric 2015; 18 (2): 260-9. DOI: 10.3109/13697137.2014.966241Ghazanfarpour M, Sadeghi R, Latifnejad Roudsari R et al. Effects of red clover on hot flash and circulating hormone concentrations in menopausal women: a systematic review and meta-analysis. Avicenna J Phytomed 2015; 5 (6): 498-511.Буянова С.Н., Юдина Н.В. Эффективность применения феминала в послеоперационном периоде у женщин, находящихся в хирургической менопаузе и медикаментозной псевдоменопаузе. Рос. вестн. акушера-гинеколога. 2014; 4: 81-7.Kligman L, Younus J. Management of hot flashes in women with breast cancer. Curr Oncol 2010; 17: 81-6.Boggia J, Thijs L, Hansen TW et al. Ambulatory blood pressure monitoring in 9357 subjects from 11 populations highlights missed opportunities for cardiovascular prevention in women. Hypertension 2011; 57: 397-405. DOI: 10.1161/HYPERTENSIONAHA.110.156828Hachul H, Brandao LC, D'Almeida V et al. Isoflavones decrease insomnia in postmenopause. Menopause 2011; 18 (2): 178-84. DOI: 10.1097/gme.0b013e3181ecf9b9Earley CJ. Latest guidelines and advances for treatment of restless legs syndrome. J Clin Psychiatry 2014; 75: e08. DOI: 10.4088/JCP.12074nr3cLipovac M, Chedraui P, Gruenhut C et al. Improvement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extracts. Maturitas 2010; 65 (3): 258-61. DOI: 10.1016/j.maturitas.2009.10.014Ильина И.Ю., Доброхотова Ю.Э., Ибрагимова Д.М. Альтернативные методы лечения климактерического синдрома. РМЖ. Мать и дитя. 2018; 2 (I): 8-12.Sliwinski JR, Johnson AK, Elkins GR. Memory decline in peri- and post-menopausal women: the potential of mind-body medicine to improve cognitive performance. Integr Med Insights 2014; 9: 17-23. DOI: 10.4137/IMI.S15682Mitchell ES, Woods NF. Cognitive symptoms during the menopausal transition and early postmenopause. Climacteric 2011; 14: 252-61.Drogos LL, Rubin LH, Geller SE et al. Objective cognitive performance is related to subjective memory complaints in midlife women with moderate to severe vasomotor symptoms. Menopause 2013; 20: 1236-42. DOI: 10.1097/GME.0b013e318291f5a6Lamporta DJ, Dyeb L, Wightmanc JD, Lawtonb CL. The effects of flavonoid and other polyphenol consumption on cognitive performance: A systematic research review of human experimental and epidemiological studies. Nutr Aging 2012; 1: 5-25. DOI: 10.3233/NUA-2012-0002Nutrition and Diet in Menopause. Ed.: CJ Hollins Martin, RR Watson, VR Preedy. Springer Science & Business Media; 2013.Ehsanpour S, Salehi K, Zolfaghari B, Bakhtiari S. The effects of red clover on quality of life in postmenopausal women. Iran J Nurs Midwifery Res 2012; 17 (1): 34-40.Sturdee DW, Panay N; International Menopause Society Writing Group. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010; 13 (6): 509-22. DOI: 10.3109/13697137.2010.522875Ghazanfarpour M, Sadeghi R, Roudsari RL. The application of soy isoflavones for subjective symptoms and objective signs of vaginal atrophy in menopause: A systematic review of randomised controlled trials. J Obstet Gynaecol 2016; 36 (2): 160-71. DOI: 10.3109/01443615.2015.1036409Saghafi N, Ghazanfarpour M, Sadeghi R et al. Effects of Phytoestrogens in Alleviating the Menopausal Symptoms: A Systematic Review and Meta-Analysis. Iran J Pharm Res 2017; 16 (Suppl.): 99-111.Lipovac M, Chedraui P, Gruenhut C et al. Effect of Red Clover Isoflavones over Skin, Appendages, and Mucosal Status in Postmenopausal Women. Obstet Gynecol Int 2011; 2011: 949302.Alfeu A-N, Mauro H, Ricardo S et al. Effects of isoflavones on the skin of postmenopausal women: a pilot study. Clinics 2009; 64 (6): 505-10. DOI: 10.1590/S1807-59322009000600004Luis A, Domingues F, Pereira L. Effects of red clover on perimenopausal and postmenopausal women’s blood lipid profile: A meta-analysis. Climacteric 2018: 21 (5): 446-53. DOI: 10.1080/13697137.2018.1501673Lee CC, Bloem CJ, Kasa-Vubu JZ, Liang LJ. Effect of oral phytoestrogen on androgenicity and insulin sensitivity in postmenopausal women. Diabetes Obes Metab 2012; 14 (4): 315-9. DOI: 10.1111/j.1463-1326.2011.01532.xЖуравель А.С., Балан В.Е. Возможности фитотерапии в профилактике сердечно-сосудистых заболеваний в пери- и постменопаузе. РМЖ. Мать и дитя. 2017; 15.Salari SP, Nikfar S, Abdollahi M. Prevention of bone resorption by intake of phytoestrogens in postmenopausal women: a meta-analysis. Age (Dordr) 2010; 33 (3): 421-31. DOI: 10.1007/s11357-010-9180-6Tempfer CB, Froese, G, Heinze, G. Side effects of phytoestrogens: a meta-analysis of randomized trials. Am J Med 2009; 122: 939-46. e9.Marini H, Bitto A, Altavilla D et al. Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study. J Clin Endocrinol Metab 2008; 93 (12): 4787-96. DOI: 10.1210/jc.2008-1087Spagnuolo C, Russo GL, Orhan IE et al. Genistein and cancer: current status, challenges, and future directions. Adv Nutr 2015; 6 (4): 408-19. DOI: 10.3945/an.114.008052