Folic Acid Supplementation in Postmenopausal Women with Hot Flushes:
Phase III Randomised Double-Blind Placebo-Controlled Trial
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) with p=0.098. There was 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: Folic
acid had a greater benefit in reducing Hot Flush Score over 12 weeks in
postmenopausal women when compared with placebo; however, the difference
did not reach statistical significance. Definitive evidence of benefit
requires a larger study.