Beyond Traditional HRT: The Effect of the Phytoestrogen Equol on Vasomotor Symptoms and Anxiety-Depression Comorbidity in Perimenopausal Women: A Psychobiological Mechanism Study
TL;DR
Path analysis indicated that Equol's effect on mood was partially mediated by its modulation of inflammatory markers, whereas HRT's effect was more directly linked to estrogen levels, with Equol showing a stronger correlation with inflammatory pathway downregulation.
Abstract
This study investigates the intervention effect of the phytoestrogen Equol on vasomotor symptoms (VMS) and anxiety-depression comorbidity in perimenopausal women, compared to traditional hormone replacement therapy (HRT). It aims to explore the associated psychobiological mechanisms, focusing on mental health outcomes alongside physiological relief. A randomized, double-blind, controlled trial was conducted with 150 eligible perimenopausal women, assigned to an Equol supplement group, a standard HRT group, and a placebo group for 12 weeks. Primary outcomes included the frequency/severity of hot flashes (diary) and scores on the Menopause Rating Scale (MRS), Hospital Anxiety and Depression Scale (HADS), and Perceived Stress Scale (PSS). Serum levels of sex hormones, inflammatory markers (e.g., IL-6, TNF-α), and salivary cortisol were analyzed as potential biological mediators. The Equol group showed a significant reduction in VMS frequency (comparable to HRT, p<0.01) and a greater improvement in HADS anxiety and depression sub-scores (35% reduction vs. placebo, p<0.001) than the HRT group. Path analysis indicated that Equol's effect on mood was partially mediated by its modulation of inflammatory markers, whereas HRT's effect was more directly linked to estrogen levels. Both active treatments reduced perceived stress, with Equol showing a stronger correlation with inflammatory pathway downregulation. Equol is an effective non-traditional intervention for alleviating both vasomotor symptoms and anxiety-depression comorbidity in perimenopause, potentially via distinct anti-inflammatory psychobiological pathways. It offers a promising alternative for women seeking mental health benefits alongside symptom management, highlighting the importance of integrative approaches to menopausal care. Yanhong Liu, Eclinutri (Shandong) Health Industry Co., Ltd., Jinan, China.