Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis

Phytomedicine. 2007 Feb;14(2-3):153-9. doi: 10.1016/j.phymed.2006.12.009. Epub 2007 Jan 18.


Objective: To critically assess the evidence of supplements containing Trifolium pratense (red clover) isoflavones in the reduction of hot flush frequency in menopausal women.

Data sources: Systematic literature searches were performed in (Medline (1951 - April 2006), Embase (1974 - April 2006), CINAHL (1982 - April 2006), Amed (1985 - April 2006) and The Cochrane Library (Issue 2, 2006). Reference lists located were checked for further relevant publications. Experts in the field and manufacturers of identified products were contacted for unpublished material. No language restrictions were imposed.

Review methods: Studies were selected according to predefined inclusion and exclusion criteria. All randomized clinical trials of monopreparations containing T. pratense isoflavones for treating hot flushes were included. Study selection, data extraction and validation were performed by at least two reviewers with disagreements being settled by discussion. Weighted means and 95% confidence intervals were calculated and sensitivity analyses were performed.

Results: Seventeen potentially relevant articles were retrieved for further evaluation. Five were suitable for inclusion in the meta-analysis. The meta-analysis indicates a reduction in hot flush frequency in the active treatment group (40-82 mg daily) compared with the placebo group (weighted mean difference -1.5 hot flushes daily; 95% CI -2.94 to 0.03; p=0.05).

Conclusion: There is evidence of a marginally significant effect of T. pratense isoflavones for treating hot flushes in menopausal women. Whether the size of this effect can be considered clinically relevant is unclear. Whereas there is no apparent evidence of adverse events during short-term use, there are no available data on the safety of long-term administration.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Female
  • Hot Flashes / drug therapy*
  • Hot Flashes / pathology
  • Humans
  • Isoflavones / administration & dosage
  • Isoflavones / therapeutic use*
  • Menopause*
  • Phytotherapy*
  • Randomized Controlled Trials as Topic
  • Trifolium*


  • Isoflavones