Фитоэстрогены экстракта красного клевера: механизм действия и клиническая эффективность
Фитоэстрогены экстракта красного клевера: механизм действия и клиническая эффективность
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
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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
Фитоэстрогены экстракта красного клевера: механизм действия и клиническая эффективность
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
________________________________________________
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.
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.
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19. 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.v36i477.9503
20. Politi MC, Schleinitz MD, Col NF. Revisiting the duration of vasomotor symptoms of menopause: a meta-analysis. J Gen Int Med 2008; 23: 1507–13.
21. 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.2010.11.012
22. Chen MN, Lin CC, Liu C. Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric 2015; 18 (2): 260–9. DOI: 10.3109/13697137.2014.966241
23. Ghazanfarpour 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.
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27. Hachul H, Brandão LC, D'Almeida V et al. Isoflavones decrease insomnia in postmenopause. Menopause 2011; 18 (2): 178–84. DOI: 10.1097/gme.0b013e3181ecf9b9
28. Earley CJ. Latest guidelines and advances for treatment of restless legs syndrome. J Clin Psychiatry 2014; 75: e08. DOI: 10.4088/JCP.12074nr3c
29. Lipovac 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.2009.10.014
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31. 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.S15682
32. Mitchell ES, Woods NF. Cognitive symptoms during the menopausal transition and early postmenopause. Climacteric 2011; 14: 252–61.
33. 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.0b013e318291f5a6
34. Lamporta 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-2012-0002
35. Nutrition and Diet in Menopause. Ed.: CJ Hollins Martin, RR Watson, VR Preedy. Springer Science & Business Media; 2013.
36. Ehsanpour S, Salehi K, Zolfaghari B, Bakhtiari S. The effects of red clover on quality of life in post-menopausal women. Iran J Nurs Midwifery Res 2012; 17 (1): 34–40.
37. Sturdee DW, Panay N; International Menopause Society Writing Group. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010; 13 (6): 509–22. DOI: 10.3109/13697137.2010.522875
38. Ghazanfarpour 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: 10.3109/01443615.2015.1036409
39. Saghafi 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.
40. 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.
41. 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/S1807-59322009000600004
42. Luís Â, 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: 10.1080/13697137.2018.1501673
43. Lee 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.x
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46. Tempfer CB, Froese, G, Heinze, G. Side effects of phytoestrogens: a meta-analysis of randomized trials. Am J Med 2009; 122: 939–46. e9.
47. 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.2008-1087
48. Spagnuolo 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
________________________________________________
1. Santoro 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.2015.05.001
2. Harlow 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: 10.3109/13697137.2011.650656
3. Menopause and menopause in women. Clinical recommendations ROAG and RAM. Moscow, 2016 (in Russian).
4. Fait T. Menopause hormone therapy: latest developments and clinical practice. Drugs Context 2019; 8: 212551. DOI: 10.7573/dic.212551
5. British Menopause Society further update on HRT supply shortages (30 April 2020). https://thebms.org.uk/
6. Nikolić IL, Savić-Gajić IM, Tačić AD, Savić IM. Classification and biological activity of phytoestrogens: a review. Advanced Technologies 2017; 6 (2): 96–106. UDC: 577.175.6:615.322.07
7. Křížová L, Dadáková K, Kašparovská J, Kašparovský T. Isoflavones. Molecules 2019; 24 (6): 1076. DOI: 10.3390/molecules24061076
8. Kuznetsova I.V. Efficacy and safety of genistein in the treatment of vasomotor symptoms in postmenopausal women (research review). Gynecology. 2013; 15 (3): 4–9 (in Russian).
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.2014.8.6.618
10. Rietjens IMCM, Louisse J, Beekmann K. The potential health effects of dietary phytoestrogens. Br J Pharmacol 2017; 174 (11): 1263–80. DOI: 10.1111/bph.13622
11. Pabich М, Materska М. Biological Effect of Soy Isoflavones in the Prevention of Civilization Diseases. Nutrients 2019; 11: 1660. DOI: 10.3390/nu11071660
12. Lethaby A, Marjoribanks J, Kronenberg F et al. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database Syst Rev 2013; 12: CD001395. DOI: 10.1002/14651858.CD001395.pub4
13. Geller 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.0b013e3181ace49b
14. Chen Li-Ru, Ko Nai-Yu, Chen Kuo-Hu. Isoflavone Supplements for Menopausal Women: A Systematic Review. Nutrients 2019; 11: 2649. DOI: 10.3390/nu11112649
15. Beck V et al. Phytoestrogens derived from red clover: An alternative to estrogen replacement therapy? J Steroid Biochem Mol Biol 2005; 94: 499–518.
16. 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.0b013e31818d414e
17. Mattawanon 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: 10.1155/2015/962740
18. Balan V.E., Rafaelian I.V., Levkovich E.A. et al. Osobennosti dlitel'nogo primeneniia fitoestrogenov dlia lecheniia patsientok s klimaktericheskim sindromom. Ros. vestn. akushera-ginekologa. 2013; 13 (5): 58–62 (in Russian).
19. 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.v36i477.9503
20. Politi MC, Schleinitz MD, Col NF. Revisiting the duration of vasomotor symptoms of menopause: a meta-analysis. J Gen Int Med 2008; 23: 1507–13.
21. 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.2010.11.012
22. Chen MN, Lin CC, Liu C. Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric 2015; 18 (2): 260–9. DOI: 10.3109/13697137.2014.966241
23. Ghazanfarpour 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.
24. Buyanova S.N., Yudina N.V. The effectiveness of feminine use in the postoperative period in women who are in surgical menopause and drug pseudomenopause. Russian Bulletin of the Obstetrician-Gynecologist. 2014; 4: 81–7 (in Russian).
25. Kligman L, Younus J. Management of hot flashes in women with breast cancer. Curr Oncol 2010; 17: 81–6.
26. 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.110.156828
27. Hachul H, Brandão LC, D'Almeida V et al. Isoflavones decrease insomnia in postmenopause. Menopause 2011; 18 (2): 178–84. DOI: 10.1097/gme.0b013e3181ecf9b9
28. Earley CJ. Latest guidelines and advances for treatment of restless legs syndrome. J Clin Psychiatry 2014; 75: e08. DOI: 10.4088/JCP.12074nr3c
29. Lipovac 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.2009.10.014
30. Ilina I.Yu., Dobrokhotova Yu.E., Ibragimova D.M. Alternative treatments for menopausal syndrome. Russian Medical Journal. Mother and Child. 2018; 2 (I): 8–12 (in Russian).
31. 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.S15682
32. Mitchell ES, Woods NF. Cognitive symptoms during the menopausal transition and early postmenopause. Climacteric 2011; 14: 252–61.
33. 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.0b013e318291f5a6
34. Lamporta 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-2012-0002
35. Nutrition and Diet in Menopause. Ed.: CJ Hollins Martin, RR Watson, VR Preedy. Springer Science & Business Media; 2013.
36. Ehsanpour S, Salehi K, Zolfaghari B, Bakhtiari S. The effects of red clover on quality of life in post-menopausal women. Iran J Nurs Midwifery Res 2012; 17 (1): 34–40.
37. Sturdee DW, Panay N; International Menopause Society Writing Group. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010; 13 (6): 509–22. DOI: 10.3109/13697137.2010.522875
38. Ghazanfarpour 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: 10.3109/01443615.2015.1036409
39. Saghafi 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.
40. 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.
41. 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/S1807-59322009000600004
42. Luís Â, 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: 10.1080/13697137.2018.1501673
43. Lee 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.x
44. Zhuravel A.S., Balan V.E. The possibilities of herbal medicine in the prevention of cardiovascular diseases in peri- and postmenopausal women. Russian Medical Journal. Mother and child. 2017; 15 (in Russian).
45. 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/s11357-010-9180-6
46. Tempfer CB, Froese, G, Heinze, G. Side effects of phytoestrogens: a meta-analysis of randomized trials. Am J Med 2009; 122: 939–46. e9.
47. 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.2008-1087
48. Spagnuolo 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
Авторы
Г.Б. Дикке*
ЧОУ ДПО «Академия медицинского образования им. Ф.И. Иноземцева», Санкт-Петербург, Россия
*galadikke@yandex.ru
________________________________________________
Galina B. Dikke*
Inozemtsev Academy of Medical Education, Saint Petersburg, Russia
*galadikke@yandex.ru