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.