Folic Acid Supplementation in Postmenopausal Women with Hot Flushes: Phase III Randomised Double-Blind Placebo-Controlled Trial.

Ewies, Ayman A A; Ahmed, Ikhlaaq; Al-Azzawi, Farook; Pitkin, Joan; Gupta, Pratima; Persic, Mojca; Sahu, Banchhita; El-Ghobashy, Alaa; Barraclough, Lisa; Woodman, Jacqueline; Babrah, Jaspreet; Bowden, Sarah; Stocken, Deborah; Billingham, Lucinda; Sundar, Sudha; Rea, Daniel

OBJECTIVE To assess whether folic acid supplementation ameliorates hot flushes. DESIGN Double-blind, placebo-controlled randomised trial. SETTING Nine hospitals in England. POPULATION Postmenopausal women experiencing ≥50 hot flushes weekly. METHODS Women (n=164) were randomly assigned in a 1:1 ratio to receive folic acid 5mg tablet or placebo daily for 12 weeks. Participants recorded frequency and severity of hot flushes in Sloan Diary daily and completed Greene Climacteric and Utian Quality of Life (UQoL) Scales at 4-weekly intervals. MAIN OUTCOME MEASURES The change in daily Hot Flush Score at week-12 from randomisation based on Sloan Diary Composite Score B calculation. RESULTS Data of 143 (87%) women was available for the primary outcome. The mean change (SD) in Hot Flush Score at week-12 was -6.98 (10.30) and -4.57 (9.46) for folic acid and placebo group, respectively. The difference between groups in the mean change was -2.41 (95% CI: -5.68, 0.87), p=0.149 and in the adjusted mean change was -2.61 (95% CI: -5.72, 0.49), p=0.098. Analysis of secondary outcomes indicated an increased benefit in the folic acid group regarding changes in total and emotional UQoL scores at week-8 when compared with placebo. The difference in the mean change from baseline was 5.22 (95% CI: 1.16, 9.28) and 1.88 (95% CI: 0.23, 3.52) for total and emotional score, respectively. CONCLUSIONS The study was not able to demonstrate that folic acid had a statistically significant greater benefit in reducing Hot Flush Score over 12 weeks in postmenopausal women when compared with placebo.