3.4. Sensitivity and Publication Bias
According to the ”leave-one-out” strategy, 19 outcomes estimated values from -0.479 to -0.411 were got, indicated that there were no particularly prominent sensitivity issues in the included literature (Supplementary Material Fig 1).
The shape of the funnel plots appeared symmetrical in the comparison model showed that most effect sizes seem to locate symmetrically upwards the graph, and scatter around both sides of the line. Egger’s regression test did not show a publication bias (P =0.939). Besides, there was no obvious change in the results after the trim and -fill estimate. (Supplementary Material Fig.2)
3.5. Typeof phytoestrogens
A total of 10 studies with 19 independent reports with 1,248 participants were included in investigating the effects of different phytoestrogens on depressive symptoms in postmenopausal women. Among them, six studies employed isoflavones including red clover isoflavones18,37, daidzein isoflavone32, soy isoflavones20, isoflavones aglycone33 and phytoestrogen genistein16; two studies employed lignans including Schisandra chinensis34 and Kava-Kava38; two studies employed fenugreek extract35 and resveratrol36 which could not give a clear classification. The effectiveness of postmenopausal women based on two different categories of phytoestrogens indicated that isoflavone (SMD=-0.52; 95% [CI]= -0.75 to 0.30;I 2=65.8%, P <0.05) was better than treatment with lignans (SMD= -0.23; 95%[CI]= -0.05 to 0.01;I2 =0%; P >0.05) (Supplementary Material Fig.3).
3.6.Dose of phytoestrogens
To compare the effects of various doses of phytoestrogens more intuitively, phytoestrogens intake dose were classified33. After sorting by the daily dosage of phytoestrogens intake. Doses more than 0 and less than 25mg were classified as the ultra-low dose group (Ultra-low dose: 0<dose<25mg/day), doses more or equal to 25mg and less or equal to 100mg were in the low dose group (Low Dose: 25mg/day≤dose≤100mg/day), while doses more than 100mg were in the high dose group (High Dose: dose>100mg). According to the various dosages in Supplementary Material Figure 4, the results indicated that compared with the low dose (25mg/day≤dose≤100mg/day) (SMD=-0.45; 95%[CI]=-0.68 to-0.23;I 2=66.7%; P >0.05) and ultra-low-dose group (0<dose<25mg) (SMD=-0.31; 95%CI=-0.47 to 0.04; I 2=0%,P >0.05), the intake of phytoestrogens in the high dose group (dose>100mg/day) was the most effective in improving the symptoms of menopausal depression (SMD =-0.48; 95%[CI] = -0.76 to -0.20; I 2=52.8%,P <0.05).
3.7.Measurements of depression
Ten RCTs with 19 independent reports and 1,248 participants were included in investigating the effects of different measurements on depressive symptoms in postmenopausal women. All the included studies in this meta-analysis used the evaluation scales to evaluate depression in postmenopausal women. The result based on different assessment scales were detected in Supplementary Material Figure 5, indicated that using the HDS as an assessment scale was associated with the most varied data (SMD=-0.65; 95% [CI]=-1.38 to 0.08;I2=80.3% ; P <0.05). Meanwhile, the data in GCS (SMD=-0.37; 95%[CI]=-0.62 to -0.21;I2=54.1% ; P <0.05) and SDS (SMD=-0.59; 95% [CI]=-0.92 to 0.25,I2 =58.4%; P >0.05)
To explore whether different evaluation scales could reduce the moderate and high heterogeneity, assessment scales of specific postmenopausal evaluation (GCS42 and KMI43) with depression items were excluded for supplementary analysis. Results showed that heterogeneity of the isoflavone group slightly decreased from 65.8% to 60.6% (P= 0.01) (Supplementary Material Fig.6), as well as the heterogeneity of the low dose group obviously decreased from 66.7% to 10.5% (P= 0.34) (Supplementary Material Fig.7).