Evaluation of Clinical Meaningfulness of Red Clover (Trifolium pratense L.) Extract to Relieve Hot Flushes and Menopausal Symptoms in Peri- and Post-Menopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

The meta-analysis presented in this article covered the efficacy of red clover isoflavones in relieving hot flushes and menopausal symptoms in perimenopausal and postmenopausal women. Studies were identified by MEDLINE (PubMed), Embase, and the Cochrane Library searches. The quality of the studies was evaluated according to Cochrane criteria. A meta-analysis of eight trials (ten comparisons) demonstrated a statistically significant reduction in the daily incidence of hot flushes in women receiving red clover compared to those receiving placebo: weighted mean difference (WMD-weighted mean difference) -1.73 hot flushes per day, 95% CI (confidence interval) -3.28 to -0.18; p = 0.0292. Due to 87.34% homogeneity, the performed analysis showed substantive difference in comparisons of postmenopausal women with ≥5 hot flushes per day, when the follow-up period was 12 weeks, with an isoflavone dose of ≥80 mg/day, and when the formulations contained a higher proportion of biochanin A. The meta-analysis of included studies assessing the effect of red clover isoflavone extract on menopausal symptoms showed a statistically moderate relationship with the reduction in the daily frequency of hot flushes. However, further well-designed studies are required to confirm the present findings and to finally determine the effects of red clover on the relief of flushing episodes.

Keywords: Trifolium pratense; hot flushes; isoflavones; menopausal symptoms; perimenopausal women; postmenopausal women; red clover.

Figure 1

Flowchart of the selection procedure for studies included in the current review regarding red clover in menopausal symptoms. Abbreviations: RCTs, randomized controlled trials.

Figure 2

Risk of bias summary for each study as assessed by the authors [33,34,35,36,37,38,39,40,41,42,43,44].

Figure 3

The assessment of risk of bias for each item; data are shown as a percentage for trials.

Figure 4

Effects of isoflavones with red clover (Trifolium pratense) vs. placebo on the daily frequency of hot flushes in peri- and post-menopausal women. Number in brackets following author’s name refers to dose of isoflavones in the study with more than one active group [33,34,35,36,37,38,41,44]. Abbreviations: RCIE, red clover isoflavone extract; WMD, weighted mean difference.

Figure 5

Effects of red clover (Trifolium pratense) isoflavones vs. placebo on rating menopausal symptoms using the following questionnaires, based on the respondents’ replies concerning the intensity of complaints. Number in brackets following author’s name refers to the dose of isoflavones in the study with more than one active group [33,34,36,38,39,40,41,42,43,44]. The letter A marks the first part of the figure containing the Kupperman Menopausal Index analysis. The letter B marks the second part of the figure containing the Greene Climacteric Scale analysis. The letter C marks the third part of the figure containing the Menopause Rating Scale analysis. Abbreviations: WMD, weighted mean difference.