Efficacy and safety of phytoestrogens in the treatment of postmenopausal depressive disorders: a systematic review and meta-analysis

Background：Depression is one of the most common and specific symptoms among postmenopausal women, leading to significant personal, family, and economic burdens. Some studies have shown that phytoestrogens can help relieve symptoms of depression. Objectives: This systematic review and meta-analysis aims to assess the efficacy and safety of phytoestrogens in treating depression among postmenopausal women. Methods: A comprehensive search for relevant studies published until November 25, 2020, was conducted in PubMed, the Cochrane Library, Chinese Biomedical Literature Database, Web of Science, and EMBASE. Statistical analyses were performed with Stata12.0, Comprehensive Meta-Analysis 3.0, and Review Manager 5.4. Results: 2,183 studies were identified and 10 studies were included, involving 1,248 participants. The quality of the four studies was assessed as high risk, six studies were assessed as unclear. The analyses conducted according random effects model indicated a positive effect on depressive symptoms for postmenopausal women compared to the placebo (SMD=-0.45; 95% [CI]= -0.60 to -0.29; Q=40.42, df=18, P=0.002; I2=55.5%). The high dose phytoestrogens (dose>100mg/day) have better effectiveness (SMD =-0.48; 95%[CI]= -0.76 to -0.20; I2=52.8%, P<0.05) than low dose (25mg/day≤dose≤100mg/day) (SMD=-0.45; 95%[CI]=-0.68 to-0.23; I2=66.7%; P>0.05) and ultralow dose (00.05). Isoflavones had better effectiveness (SMD=-0.52; 95% [CI]= -0.75 to 0.30; I2=65.8%, P<0.05) than lignans of phytoestrogens (SMD= -0.23; 95% [CI]= -0.05 to 0.01; I2=0%, P>0.05). The effectiveness varies in regions. The adverse reactions frequently reported were gastrointestinal symptoms and cold or upper respiratory tract infection. Conclusions: Phytoestrogen can relieve depression symptoms among postmenopausal women. High-dose isoflavones is the most effective. Although mild adverse reactions have been reported, phytoestrogen could be considered as a complementary treatment for postmenopausal depression.