Heger 2006.

Methods	Design: parallel‐group, multi‐centre Number of women randomly assigned: 110 Number of dropouts: n = 16 in ERr 731 group (one lack of efficacy, three violations of smoking ban, three adverse events, two organisational reasons, seven other reasons); n = 48 in placebo group (31 lack of efficacy, one violation of smoking ban, one adverse events, 16 other reasons) Number analysed: n = 109 (one woman refused to take the intervention) Intention‐to‐treat: yes, modified—only the women who took the interventions Power calculation: yes, using a group sequential design according to O'Brien and Fleming Duration: 12 weeks Timing: February 2003 to May 2004 Location: nine gynaecological outpatient departments in the Ukraine Funding: Health Research Services Ltd, Germany, and Chemisch‐Pharmazeutische Fabrik Goeppingen, Carl Muller, Apotheker, GmbH u Co KG, Goeppingen, Germany (manufacturer of the supplement)
Participants	Inclusion criteria: climacteric complaints with MRS II total score > 22 points; perimenopause, defined as 45 to 55 years of age with cycle irregularity during the past 12 months or LMP at least three but no longer than 12 months ago Exclusion criteria: regular cycles during the past three months; mandatory indication for HT; treatment with drugs containing oestrogen/progestogen during past six months or any other Rx in past three months; PAP smear class III/IV and/or endometrial hyperplasia; known or suspected hypersensitivity to experimental intervention; concomitant medications that might influence trial results; BMI < 18 kg/m2 or > 30 kg/m2 and/or abnormal eating habits; wish to become pregnant or to be breast‐feeding; previous or existing major diseases; previous or existing psychiatric disorders including depression; smoking, moderate alcohol intake, coffee/chocolate intake of 500 mg or more of caffeine per day and/or suspected drug abuse; participation in another clinical trial during past six months; incompetence or incapability of understanding the trial Mean age, years: 49 Recruitment method: from outpatient departments (women seeking treatment for climacteric complaints)
Interventions	One tablet (250 mg) of ERr 731 per day—containing 4 mg of Rheum rhaponticum dry extract—identical to the product Phytoestrol N One tablet of placebo per day
Outcomes	Primary Change in total score of MRS II (this outcome not extracted in this review) Secondary Changes in individual symptoms of MRS II: number and severity of hot flushes; number of bleeding/spotting days; intensity of bleeding; time until onset of Rx effect; scores on the Integrative Medicine Outcomes Scale, Clinical Global Impressions, MENQOL; satisfaction with Rx; changes in climacteric complaints; health‐related quality of life; endometrial biopsy findings; investigations of vagina, breast, cervix; tolerability of medication; adverse effects
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Computer generated randomisation list with a balanced 1:1 randomisation using a block size of 4"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants, investigators and data monitoring committee—all blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Participants, investigators and data monitoring committee—all blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	One woman did not take the intervention and was not included. When discontinuations were reported, the LOCF method was used for missing data
Selective reporting (reporting bias)	Low risk	Most prespecified outcomes reported; authors stated that an additional paper will report on the remaining outcomes