Effects of a standardised extract of Trifolium pratense (Promensil) at a dosage of 80 mg in the treatment of menopausal hot flushes : a systematic review and meta-analysis

Objective To critically assess the evidence for a specific standardised extract of Trifolium pratense isoflavones (Promensil) at a dosage of 80 mg/day in the treatment of menopausal hot flushes. Data sources Systematic literature searches were performed in Medline, Scopus, CINAHL Plus, Cochrane, AMED and InforRMIT and citations obtained from 1996 to March 2016. Reference lists were checked; corresponding authors contacted and the grey literature searched for additional publications. Review methods Studies were selected according to predefined inclusion and exclusion criteria. All randomised clinical trials of a specific standardised extract of Trifolium pratense isoflavones (Promensil) used as a mono-component at 80 mg/day and measuring vasomotor symptoms were included. The data extraction and quality assessment were performed independently by one reviewer and validated by a second with any disagreements being settled by discussion. Weighted mean differences and 95% confidence intervals were calculated for continuous data using the fixed-effects model. Results Twenty potentially relevant papers were identified, with only five studies meeting the inclusion criteria. The meta-analysis demonstrated a statistical and clinically relevant reduction in hot flush frequency in the active treatment group compared to placebo. Weighted mean difference 3.63 hot flushes per day: [95% CI 2.70–4.56]; p ˂ 0.00001). Due to a lack of homogeneity a priori defined sub-group analyses were performed demonstrating a substantive difference between cross-over and parallel-arm clinical trial designs. Conclusion There is evidence for a statistical and clinically significant benefit for using a specific standardised extract of red clover isoflavones (Promensil) at 80 mg/day for treating hot flushes in menopausal women across the 3 studies included in the meta-analysis. The preparation was safe over the short-term duration of the studies (3 months).