Non-hormonal therapy for climacteric syndrome: efficacy, safety and a clinical rationale

Background. Climacteric syndrome is characterised by a combination of neurovegetative, psycho-emotional, and metabolic disorders, secondary to estrogen deficiency during the perimenopausal transition and postmenopause. Epidemiological studies suggest that up to 80% of peri- and postmenopausal women experience climacteric symptoms, including hot flashes, night sweats, anxiety, depression, sleep disturbances, a decline in libido, and genitourinary syndrome of menopause. Despite the high efficacy of menopausal hormone therapy, its clinical use is limited by contraindications and patient concerns regarding safety. Consequently, there is growing interest in non-hormonal therapies, including phytoestrogens, amino acids, and micronutrients. The most extensively studied components of nonhormonal therapy include phytoestrogens, amino acids, antioxidants and vitamins, providing a more comprehensive intervention targeting the pathogenesis of climacteric disorders. Phytoestrogens (soy and red clover isoflavones) can selectively bind to estrogen receptors β, exerting mild estrogen-like activity and alleviating vasomotor symptoms. The amino acids β-alanine and tryptophan are involved in the modulation of neurotransmition, including the synthesis of serotonin and melatonin, which improves sleep quality, reduce anxiety and the frequency of hot flashes. Antioxidants, particularly resveratrol, possess anti-inflammatory and cardioprotective properties, thereby improving cognitive functions and mitigating the risk of metabolic dysfunction, common in postmenopausal women. Vitamins B, C and E are involved in neurotransmitter synthesis, provide antioxidant protection and maintain optimal functioning of the nervous and cardiovascular systems, which alleviates climacteric symptoms.

Objective. The present study aims to evaluate clinical data supporting the efficacy and safety of a dietary supplement, which contains red clover isoflavones, resveratrol, β-alanine, 5-hydroxytryptophan, and vitamins B, C and E for the treatment of menopausal symptoms.

Conclusion. The body of evidence indicates that non-hormonal complexes derived from phytoestrogens and micronutrients can alleviate vasomotor symptoms, enhance psycho-emotional well-being and improve the quality of life in female patients while maintaining a favorable safety profile.

1. Saprykina L. V., Narimanova M. R., Ibragimova D. M. Climacteric syndrome. A nutritional approach to treatment. Rossiiskii meditsinskii zhurnal. Mat i ditya. 2020; 3 (3): 189-193. (In Russ.)

2. Gambacciani M., Levancini M. Management of postmenopausal osteoporosis and cardiovascular risk. Climacteric. 2014; 17 (4): 1-7.

3. Reed S. D., Newton K. M., LaCroix A. Z. Management of menopausal symptoms. Obstet Gynecol. 2014; 124 (5): 859-876.

4. Castelo-Branco C., Soveral I. Phytoestrogens and menopause: from physiology to clinical practice. J Steroid Biochem Mol Biol. 2017; 174: 148-154.

5. Freedman R. R. Menopausal hot flashes: mechanisms, endocrinology and treatment. J Steroid Biochem Mol Biol. 2014; 142: 115-120.

6. Pasman N. M. Application of botanical formulations for the treatment of estrogen deficiency syndrome in perimenopausal and postmenopausal women. 2008. (In Russ.)

7. Baber R. J., Panay N., Fenton A. IMS Recommendations on women’s midlife health and menopause hormone therapy. Climacteric. 2016; 19 (2): 109-150.

8. North American Menopause Society (NAMS). Nonhormonal management of menopause-associated vasomotor symptoms: position statement. Menopause. 2023.

9. Madyanov I. V., Madyanova T. S. Alternative (non-hormonal) methods of menopausal disorder treatment. 2020. (In Russ.)

10. Levakov S. A., Kaviladze M. G., Sukhanova M. A., et al. The impact of combination therapy on psycho-emotional well-being in female patients with hormone-related disorders. 2025; 2: 39-44. (In Russ.)

11. Lethaby A., Marjoribanks J., Kronenberg F., et al. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database of Systematic Reviews. 2013; CD001395.

12. Chen M. N., Lin C. C., Liu C. F. Efficacy of phytoestrogens for menopausal symptoms: meta-analysis and systematic review. Climacteric. 2015; 18 (2): 260-269.

13. Caufriez A. β-alanine supplementation and vasomotor symptoms in menopausal women. Clin Interv Aging. 2018; 13: 1-8.

14. Loprinzi C. L., Barton D. L., Qin R. Nonhormonal management of hot flashes in women. Lancet Oncology. 2012; 13 (11): e495-e503.

15. Evans H. M., Howe P. R. C., Wong R. H. X. Clinical effects of resveratrol supplementation in postmenopausal women: systematic review and metaanalysis. Nutrients. 2025.

16. Wong R. H. X., Thaung Zaw J. J., Xian C. J., Howe P. R. C. Resveratrol improves vascular function in postmenopausal women: randomized controlled trial. Nutrients. 2017; 9 (7).

17. Shikh E. V., Grebenschikova L. Yu. Rational grant of micronutrients as a way to improve quality of life in climacteric syndrome patients. Meditsinskii Sovet. 2017; 13. (In Russ.)

18. Teppeeva T. Kh., Karymshakova K. K., Musuraliev M. S. Efficiency of using phytohormones in mild menopausal disorders. (In Russ.)

19. Khamadyanov U. R., Saubanova T. V., Khamadyanova S. U. Experience of application of vegetative preparations in treatment of a climacteric syndrome in perimenopausal women. (In Russ.)

20. Instructions for use of EstroZhinel®.

21. Taku K., Melby M. K., Kurzer M. S., et al. Effects of soy isoflavones on bone mineral density in postmenopausal women: meta-analysis. Am J Clin Nutr. 2010; 92 (1): 146-156.

22. Lipovac M., Chedraui P., Gruenhut C., et al. The effect of red clover isoflavones on menopausal symptoms in postmenopausal women: randomized, double-blind, placebo-controlled study. Gynecological Endocrinology. 2010.

23. Franco O. H., Chowdhury R., Troup J., et al. Use of plant-based therapies and menopausal symptoms: systematic review and meta-analysis. Maturitas. 2016; 87: 7-15.

24. Messina M. Soy isoflavones and menopausal health: clinical evidence. Menopause. 2014; 21 (6): 1-12.

25. Thaung Zaw J. J., Howe P. R. C., Wong R. H. X. Long-term resveratrol supplementation improves arterial stiffness in postmenopausal women. J Transl Med. 2020; 18: 13.