Study Design and Drug Regimen
Participants were randomly
assigned in a 1:1 ratio to receive tablets containing either folic acid
5mg or matched placebo to be taken orally once daily from the time of
randomisation for 12 completed weeks. The appearance of the study
medications was identical so that participants and researchers were
unaware of the study-group assignments throughout the trial.
Randomisation was performed centrally in a double-blinded manner via
telephone to CRCTU, which allocated treatments using a computer
minimisation technique with a random element that was developed by
CRCTU. Randomisation was stratified by participant subgroup; healthy
women versus breast or endometrial cancer survivors and body mass
index (BMI) ≤30 versus >30.
Participants were required to
record frequency and severity of hot flushes on daily basis in a Sloan
Diary24 over 12 weeks while taking the study
medications. Participants were also requested to complete Greene
Climacteric Scale26-28 and Utian QoL
Scale29 (Supplementary Document 1, p50-51) at entry
and at weeks 4, 8 and 12. Blood samples were obtained for serum folate
at trial entry and week 12.