The place of alternative therapy in the algorithms for managing patients with climacteric syndrome in the context of personalized medicine

Andreeva E.N., Absatarova Yu.S.

National Medical Research Center of Endocrinology, Ministry of Health of the Russian Federation, Moscow, Russian Federation
Many women experience various climacteric manifestations. Despite the fact that menopausal hormone therapy is the gold standard for relieving hot flushes, as many as 80% of patients have used at least one alternative method in an effort to alleviate their condition. It is today known that vasomotor symptoms are a serious risk factor for cardiovascular diseases, such as coronary heart disease, hypertension, and hyperlipidemia. It is the cardiovascular mortality that holds the lead in women; therefore, therapeutic measures aimed at relieving menopausal syndrome become not only the struggle for their quality of life, but also for a reduction in all-cause mortality.
This topic is especially relevant for patients with contraindications to estrogen therapy, which forces physicians to look at evidence-based medicine for a safe treatment that is adequate to the severity of manifestations. The paper provides an overview of the current drug and non-drug methods that can relieve climacteric syndrome, by evaluating their efficiency and safety: exercises, diet therapy, psychological procedures, herbal remedies, amino acids, antidepressants (selective serotonin reuptake inhibitors), gabapentin, and neurokinin-3 receptor antagonists.
Conclusion: Thus, the modern possibilities of alternative therapy allow a physician and a patient to sufficiently widely and adequately choose drugs on the requests of a woman so that she can go through the menopausal transition comfortably and safely, by maintain her quality of life.

Keywords

menopause
climacteric syndrome
hot flushes
alternative therapy
beta-alanine

References

  1. Кузнецова И.В., Бурчаков Д.И. Комплементарная и альтернативная терапия менопаузальных симптомов. Акушерство и гинекология. 2017; 11: 168-75. [Kuznetsova I.V., Burchakov D.I. Complementary and alternative therapy for menopausal symptoms. Obstetrics and Gynecology. 2017; 11:168-75. (in Russian)]. https://dx.doi.org/10.18565/aig.2017.11.168-175.
  2. Schneider H.P.G., Birkhäuser M. Quality of life in climacteric women. Climacteric. 2017; 20(3): 187-94. https://dx.doi.org/10.1080/13697137.2017.1279599.
  3. Sourouni M., Zangger M., Honermann L., Foth D., Stute P. Assessment of the climacteric syndrome: a narrative review. Arch. Gynecol. Obstet. 2021; 304(4): 855-62. https://dx.doi.org/10.1007/s00404-021-06139-y.
  4. Rossouw J.E., Anderson G.L., Prentice R.L., LaCroix A.Z., Kooperberg C., Stefanick M.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. 2002; 288(3): 321-33. https://dx.doi.org/10.1001/jama.288.3.321.
  5. Mintziori G., Lambrinoudaki I., Goulis D.G., Ceausu I., Depypere H., Erel C.T. et al. EMAS position statement: non-hormonal management of menopausal vasomotor symptoms. Maturitas. 2015; 81(3): 410-3. https://dx.doi.org/10.1016/j.maturitas.2015.04.009.
  6. 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.
  7. Avis N.E., Colvin A., Bromberger J.T., Hess R., Matthews K.A., Ory M. et al. Change in health-related quality of life over the menopausal transition in a multiethnic cohort of middle-aged women: Study of Women’s Health Across the Nation. Menopause. 2009; 16(5): 860-9. https://dx.doi.org/10.1097/gme.0b013e3181a3cdaf.
  8. US Preventive Services Task Force: Grossman D.C., Curry S.J., Owens D.K., Barry M.J., Davidson K.W., Doubeni. C.A. et al. Hormone therapy for the primary prevention of chronic conditions in postmenopausal women: US Preventive Services Task Force Recommendation Statement. JAMA. 2017; 318(22): 2224-33. https://dx.doi.org/10.1001/jama.2017.18261.
  9. Franco O.H., Muka T., Colpani V., Kunutsor S., Chowdhury S., Chowdhury R. et al. Vasomotor symptoms in women and cardiovascular risk markers: systematic review and meta-analysis. Maturitas. 2015; 81(3): 353-61. https://dx.doi.org/10.1016/j.maturitas.2015.04.016.
  10. Muka T., Oliver-Williams C., Colpani V., Kunutsor S., Chowdhury S., Chowdhury R. et al. Association of vasomotor and other menopausal symptoms with risk of cardiovascular disease: a systematic review and meta-analysis. PLoS One. 2016; 11(6): e0157417. https://dx.doi.org/10.1371/journal.pone.0157417.
  11. Chung H.F., Zhu D., Dobson A.J., Kuh D., Gold E.B., Crawford S.L. et al. Age at menarche and risk of vasomotor menopausal symptoms: a pooled analysis of six studies. BJOG. 2021; 128(3): 603-13. https://dx.doi.org/10.1111/1471-0528.16393.
  12. Yoeli H., Macnaughton J., McLusky S. Menopausal symptoms and work: a narrative review of women's experiences in casual, informal, or precarious jobs. Maturitas. 2021; 150: 14-21. https://dx.doi.org/10.1016/j.maturitas.2021.05.007.
  13. Delanoë D., Hajri S., Bachelot A., Mahfoudh Draoui D., Hassoun D., Marsicano E. et al. Class, gender and culture in the experience of menopause. A comparative survey in Tunisia and France. Soc. Sci. Med. 2012; 75(2): 401-9. https://dx.doi.org/ 10.1016/j.socscimed.2012.02.051.
  14. Audet M., Dumas A., Binette R., Dionne I.J. Women, weight, poverty and menopause: understanding health practices in a context of chronic disease prevention. Sociol. Health Illn. 2017; 39(8): 1412-26. https://dx.doi.org/10.1111/1467-9566.12593.
  15. Ding T., Zhang J., Wang T., Cui P., Chen Z., Jiang J. et al. Potential influence of menstrual status and sex hormones on female severe acute respiratory syndrome coronavirus 2 infection: a cross-sectional multicenter study in Wuhan, China. Clin. Infect. Dis. 2021; 72(9): e240-e248. https://dx.doi.org/10.1093/cid/ciaa1022.
  16. Bair Y.A., Gold E.B., Zhang G., Rasor N., Utts J., Upchurch D.M. et al. Use of complementary and alternative medicine during the menopause transition: longitudinal results from the Study of Women’s Health Across the Nation. Menopause. 2008; 15(1): 32-43. https://dx.doi.org/10.1097/gme.0b013e31813429d6.
  17. Sternfeld B., Dugan S. Physical activity and health during the menopausal transition. Obstet. Gynecol. Clin. North Am. 2011; 38(3): 537-66. https://dx.doi.org/10.1016/j.ogc.2011.05.008.
  18. Warburton D.E.R., Bredin S.S.D. Health benefits of physical activity: a systematic review of current systematic reviews. Curr. Opin. Cardiol. 2017; 32(5): 541-56. https://dx.doi.org/10.1097/HCO.0000000000000437.
  19. Asikainen T.M., Kukkonen-Harjula K., Miilunpalo S. Exercise for health for early postmenopausal women: a systematic review of randomised controlled trials. Sports Med. 2004; 34(11): 753-78. https://dx.doi.org/10.2165/00007256-200434110-00004.
  20. Nguyen T.M., Do T.T.T., Tran T.N., Kim J.H. Exercise and quality of life in women with menopausal symptoms: a systematic review and meta-analysis of randomized controlled trials. Int. J. Environ. Res. Public Health. 2020; 17(19): 7049. https://dx.doi.org/10.3390/ijerph17197049.
  21. Carcelen-Fraile M.D.C., Aibar-Almazan A., Martinez-Amat A., Cruz-Diaz D., Diaz-Mohedo E., Redecillas-Peiro M.T. et al. Effects of physical exercise on sexual function and quality of sexual life related to menopausal symptoms in peri- and postmenopausal women: a systematic review. Int. J. Environ. Res. Public Health. 2020; 17(8): 2680. https://dx.doi.org/10.3390/ijerph17082680.
  22. van Driel C.M., Stuursma A., Schroevers M.J., Mourits M.J., de Bock G.H. Mindfulness, cognitive behavioural and behaviour-based therapy for natural and treatment-induced menopausal symptoms: a systematic review and meta-analysis. BJOG. 2019; 126(3): 330-9. https://dx.doi.org/10.1111/1471-0528.15153.
  23. Shams T., Firwana B., Habib F., Alshahrani A., Alnouh B., Murad M.H. et al. SSRIs for hot flashes: a systematic review and meta-analysis of randomized trials. J. Gen. Intern. Med. 2014; 29(1): 204-13. https://dx.doi.org/10.1007/s11606-013-2535-9.
  24. Yoon S.H., Lee J.Y., Lee C., Lee H., Kim S.N. Gabapentin for the treatment of hot flushes in menopause: a meta-analysis. Menopause. 2020; 27(4): 485-93. https://dx.doi.org/10.1097/GME.0000000000001491.
  25. Shan D., Zou L., Liu X., Shen Y., Cai Y., Zhang J. Efficacy and safety of gabapentin and pregabalin in patients with vasomotor symptoms: a systematic review and meta-analysis. Am. J. Obstet. Gynecol. 2020; 222(6): 564-579.e12. https://dx.doi.org/10.1016/j.ajog.2019.12.011.
  26. Кузнецова И.В. Применение фитоэстрогенов для улучшения качества жизни и сохранения здоровья женщин в периодах менопаузального перехода и постменопаузы. Акушерство и гинекология. 2020; 10: 182-8. [Kuznetsova I.V. The use of phytoestrogens to improve quality of life and to preserve health in women during the menopausal transition and postmenopause. Obstetrics and Gynecology. 2020; 10: 182-8. (in Russian)]. https://dx.doi.org/10.18565/aig.2020.10.182-188.
  27. Franco O.H., Chowdhury R., Troup J., Voortman T., Kunutsor S., Kavousi M. et al. Use of plant-based therapies and menopausal symptoms: a systematic review and meta-analysis. JAMA. 2016; 315(23): 2554-63. https://dx.doi.org/10.1001/jama.2016.8012.
  28. Dizavandi F.R., Ghazanfarpour M., Roozbeh N., Kargarfard L., Khadivzadeh T., Dashti S. An overview of the phytoestrogen effect on vaginal health and dyspareunia in peri- and post-menopausal women. Post Reprod. Health. 2019; 25(1): 11-20. https://dx.doi.org/10.1177/2053369118823365.
  29. Tempfer C.B., Froese G., Heinze G., Bentz E.K., Hefler L.A., Huber J.C. Side effects of phytoestrogens: a meta-analysis of randomized trials. Am. J. Med. 2009; 122(10): 939-46.e9. https://dx.doi.org/10.1016/j.amjmed.2009.04.018.
  30. Unfer V., Casini M.L., Costabile L., Mignosa M., Gerli S., Di Renzo G.C. Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study. Fertil. Steril. 2004; 82(1): 145-8, quiz 265. https://dx.doi.org/10.1016/j.fertnstert.2003.11.041.
  31. Zhong X.S., Ge J., Chen S.W., Xiong Y.Q., Ma S.J., Chen Q. Association between dietary isoflavones in soy and legumes and endometrial cancer: a systematic review and meta-analysis. J. Acad. Nutr. Diet. 2018; 118(4): 637-51. https://dx.doi.org/10.1016/j.jand.2016.09.036.
  32. Торшин И.Ю., Громова О.А., Лиманова О.А. «Быстрый эффект» клималанина (β-аланина) при приливах: сравнительное исследование взаимодействий бета-аланина, таурина и глицина с глициновыми рецепторами. Гинекология. 2012; 14(2): 65-9. [Torshin I.Y., Gromova O.A., Limanova O.A. Rapid effect of beta-alanine in the therapy of hot flashes: a comparative biophysical modeling of interactions beta-alanine, taurine and glycine with the glycine receptors. Gynecology. 2012; 14(2): 65-9. (in Russian)].
  33. Громова О.А., Торшин И.Ю., Лиманова О.А., Никонов А.А. Патофизиология вегетативно-сосудистых пароксизмов (приливы) у женщин в период менопаузы и механизм действия β-аланина. Новая клинико-фармакологическая концепция. Гинекология. 2010; 12(2): 29-36. [Gromova O.A., Torshin I.Y., Limanova O.A., Nikonov A.A. Pathophysiology of vegetative-vascular paroxysms (hot flashes) in menopausal women and the mechanism of action of β-alanine. A new clinical and pharmacological concept. Gynecology. 2010; 12(2): 29-36. (in Russian)].
  34. Юренева С.В., Моисеев С.В. Негормональные методы лечения вазомоторных симптомов менопаузы с позиции медицины, основанной на доказательствах. Клиническая фармакология и терапия. 2010; 19(2): 69-74. [Yureneva S., Moisseyev S. Evidence-based nonhormonal treatment of menopausal vasomotor symptoms. Clinical pharmacology and therapy. 2010; 19(2): 69-74. (in Russian)].
  35. Зароченцева Н.В., Джиджихия Л.К. Возможности применения клималанина при вазомоторных пароксизмах у женщин в климактерическом периоде. Российский вестник акушера-гинеколога. 2012; 12(3): 92-7. [Zarochentseva N.V., Dzhidzhikhiia L.K. Possibilities of using klimalanin in menopausal women with vasomotor paroxysms. Russian Bulletin of Obstetrician-Gynecologist. 2012; 12(3): 92-7. (in Russian)].
  36. Евтушенко И.Д., Петров И.А., Петрова М.С., Ткачев В.Н., Кисляк С.В. Применение β-аланина для терапии дефицита эстрогенов при хирургической менопаузе. Акушерство и гинекология. 2014; 4: 93-5. [Evtushenko I.D., Petrov I.A., Petrova M.S., Tkachev V.N., Kislyak S.V. Use of β-alanine for therapy for estrogen deficiency in surgical menopause. Obstetrics and Gynecology. 2014; 4: 93-5. (in Russian)].
  37. Григорян О.Р., Андреева Е.Н. Альтернативные и дополнительные методы терапии в климактерии у женщин с сахарным диабетом 1-го и 2-го типов. Проблемы репродукции. 2013; 1: 87-90. [Grigorian O.R., Andreeva E.N. The alternative and additional methods of therapy in climacteric patients with menopause and diabetes mellitus type 1 and 2. Russian Journal of Human Reproduction. 2013; 1: 87-90. (in Russian)].
  38. Depypere H., Lademacher C., Siddiqui E., Fraser G.L. Fezolinetant in the treatment of vasomotor symptoms associated with menopause. Expert Opin. Investig. Drugs. 2021; 30(7): 681-94. https://dx.doi.org/10.1080/13543784.2021.1893305.
  39. Jayasena C.N., Comninos A.N., Stefanopoulou E., Buckley A., Narayanaswamy S., Izzi-Engbeaya C. et al. Neurokinin B administration induces hot flushes in women. Sci. Rep. 2015; 5: 8466. https://dx.doi.org/10.1038/srep08466.
  40. Rance N.E., Dacks P.A., Mittelman-Smith M.A., Romanovsky A.A., Krajewski-Hall S.J. Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: a novel hypothesis on the mechanism of hot flushes. Front. Neuroendocrinol. 2013; 34(3): 211-27. https://dx.doi.org/10.1016/j.yfrne.2013.07.003.
  41. Dawson L.A., Porter R.A. Progress in the development of neurokinin 3 modulators for the treatment of schizophrenia: molecule development and clinical progress. Future Med. Chem. 2013; 5(13): 1525-46. https://dx.doi.org/10.4155/fmc.13.122.
  42. Fraser G.L., Hoveyda H.R., Clarke I.J., Ramaswamy S., Plant T.M., Rose C. et al. The NK3 receptor antagonist ESN364 interrupts pulsatile LH secretion and moderates levels of ovarian hormones throughout the menstrual cycle. Endocrinology. 2015; 156(11): 4214-25. https://dx.doi.org/10.1210/en.2015-1409.

Received 04.10.2021

Accepted 19.11.2021

About the Authors

Elena N. Andreeva, Dr. Med. Sci., Professor, Director of the Institute of Reproductive Medicine, National Medical Research Center of Endocrinology,
Ministry of Health of the Russian Federation; Professor, A.I. Yevdokimov Moscow State Medical and Dental University, Ministry of Health of the Russian Federation,
https://orcid.org/0000-0001-8425-0020, 117036, Russia, Moscow, Dmitry Ulyanov str. 11.
Yulia S. Absatarova, PhD, Senior Researcher of the Department of Endocrine Gynecology, National Medical Research Center of Endocrinology, Ministry of Health
of the Russian Federation, +7(499)126-75-44, korsil2008@yandex.ru, https://orcid.org/0000-0003-0696-5367, 117036, Russia, Moscow, Dmitry Ulyanov str. 11.

Authors’ contributions: Andreeva E.N., Absatarova Yu.S. – concept and design of the investigation, writing the text; Absatarova Yu.S. – material collection and processing; Andreeva E.N. – editing.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The investigation has not been sponsored.
For citation: Andreeva E.N., Absatarova Yu.S. The place of alternative therapy in the algorithms for managing patients with climacteric syndrome in the context of personalized medicine.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2021; 11: 96-102 (in Russian)
https://dx.doi.org/10.18565/aig.2021.11.96-102

Similar Articles

By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.