Efficacy and safety of phytoestrogens in the treatment of perimenopausal and postmenopausal depressive disorders: A systematic review and meta‐analysis

Abstract

Background: Depression is one of the most common and specific symptoms among menopausal 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 aim to assess the efficacy and safety of phytoestrogens in treating depression among menopausal 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 R 4.0.3.and Review Manager 5.4.Results:2183 studies were identified and 10 studies with 15 independent reports were included, involving 1248 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 the significant positive effect on depressive symptoms for postmenopausal women compared with the placebo (SMD = −0.62; 95% CI = −1.13 to −0.12; Q = 45.62, df = 14, P < .01; I 2 = 79%). The low dose phytoestrogens (25 mg/d ≤ dose ≤ 100 mg/d) have better effectiveness (SMD = −0.52; 95% CI = −0.85 to −0.20; I 2 = 79%, P< .01) than high dose (dose > 100 mg/d) and ultralow dose (0 < dose < 25 mg/d), but showed no statistical significance (Q = 0.81 df = 2, P = .67). Isoflavones had better effectiveness (SMD = −0.48; 95% CI = −0.75 to 0.21; I 2 = 75%, P < .01) than lignans of phytoestrogens (SMD = −0.22; 95% CI = −0.37 to 0.08; I 2 = 0%, P = .96). The duration of intervention affects the efficacy of phytoestrogens (β = −0.03; 95% CI: [−0.05, 0.00]; P = .045). 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 menopausal, especially for postmenopausal women who take low doses(25 mg/d ≤ dose ≤ 100 mg/d) of phytoestrogens for a long-term duration. Although mild adverse reactions have been reported, phytoestrogen could be considered as a complementary treatment for postmenopausal depression.

Effects of Isoflavone Supplementation on the Response to Medroxyprogesterone in Premenopausal Women with Nonatypical Endometrial Hyperplasia: A Randomized, Double-Blind, Placebo-Controlled Trial

“…Based on a recent meta-analysis study, low-dose isofavone (dose <100 mg/day) has a safety profle without any serious side efects. Only minimal adverse effects such as abdominal pain, diarrhea, myalgia, and headache have been reported [33]. Te limitations of this trial include the short period of intervention, relatively small sample size, and single-center design.…”

The role of diet in managing menopausal symptoms: A narrative review

“…A meta‐analysis including 10 RCTs ( n = 1248) found that phytoestrogens significantly reduced depressive symptoms in postmenopausal women relative to control (Li, Li, et al, 2021), with isoflavones reported as more effective (Standardised Mean Difference [SMD] = −0.48; 95% CI: −0.75, 0.21) than lignans (SMD = −0.22; 95% CI: −0.37, 0.08). However, no significant difference in symptoms was reported among perimenopausal women (Li, Guo, et al, 2021).…”

“…Although low levels of vitamin B12 have been associated with lower cognitive performance (Lambrinoudaki et al, 2013), studies exploring the relationship between vitamin B12 supplementation and cognitive decline have tended to focus on the ageing process rather than the menopausal transition (Ford & Almeida, 2019; Li, Li, et al, 2021; Markun et al, 2021; Wang et al, 2021). Therefore, the potential benefits of B vitamin supplementation during the menopausal transition remain unclear.…”

Overview on postmenopausal osteoporosis and periodontitis: The therapeutic potential of phytoestrogens against alveolar bone loss

“…Phytoestrogens have been extensively studied for their potential role to prevent and treat diseases related to aging such as menopausal symptoms and skin aging, cardiovascular, neurodegenerative, immune and metabolic diseases and cancer. Recent systematic review and meta-analysis reported that consumption of low doses of phytoestrogen (25 mg/d ≤ dose ≤100 mg/d) for a long-term duration were effective in relieving depression symptoms in postmenopausal women (Li et al, 2021). Some reported adverse effect associated to phytoestrogens in menopausal women however are not yet clear and required more supportive evidence from high-quality randomized control trial (RCT) studies.…”