Upmalis 2000.

Methods	Design: parallel‐group Number screened for inclusion: not stated Number randomly assigned: 177 Number dropped out: 40 (21 in active arm: one did not take supplement, nine ineligible, 11 violated protocol, one had urinary tract infection; 18 in placebo arm: one did not take supplement, four ineligible, 13 violated protocol) Number lost to follow‐up: 15 (nine in active group, six in placebo group) discontinued before week 12 Number analysed: 122 (for efficacy) Intention‐to‐treat analysis: no Power calculation: not stated Duration: 12 weeks Timing: not stated Location: 15 outpatient sites in USA Funding: industry funded (Advanced Care Products)
Participants	Inclusion criteria: postmenopausal women experiencing average of at least five hot flushes per day, over 50 years of age, in good health, weight within ± 35% range for BMI, FSH at least 40 mIU/mL, oestradiol level 25 pg/mL or less, no menses for at least six months, discontinued HT at least 60 days before study entry Exclusion criteria: history of breast cancer, hyperplasia, endometrial carcinoma or cervical neoplasia, positive pregnancy test, undiagnosed abnormal vaginal bleeding, bilateral oophorectomy or hysterectomy, thromboembolic disorders, cardiovascular disease, liver disease, chronic alcoholism, medication hypersensitivity, allergy to dietary supplement ingredients, uncontrolled addiction, severe depression, acute systemic infection or abnormal laboratory values Age, years: mean 55 Recruitment method: not stated
Interventions	Phytoestrogen: isoflavone Formulation: soy isoflavone extract tablet (50 mg genistein and daidzein daily, approximately 25 g of each) Placebo Dose, duration and timing of administration: two tablets at bedtime for 12 weeks Intake of other soy products and dietary supplements restricted during the study
Outcomes	Menopausal symptoms: daily diary card for number and severity of hot flushes and night sweats; 3‐point scale for severity Compliance: check of unused medication at week six and week 12 Endometrial thickness Adverse events
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not stated
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Stated as double‐blind
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Stated as double‐blind
Incomplete outcome data (attrition bias) All outcomes	High risk	Very high rate of dropout
Selective reporting (reporting bias)	High risk	Quality of life prespecified as an outcome in the methods section but not reported on in the results section