Hammar 2007.

Methods	Randomised controlled trial
Participants	572 postmenopausal healthy women with an intact uterus, with or without vasomotor symptoms. Mean age 55 years. Time since menopause 5 years. Mean number of hot flashes at baseline 5.8
Interventions	Tibolone 2.5 mg/d 17‐beta‐oestradiol 1 mg + norethisterone acetate 0.5 mg/d Administered for 48 weeks
Outcomes	Unscheduled vaginal bleeding or spotting, hot flashes, thromboembolic events, breast cancer
Notes	Hot flashes measured as median number per treatment period and reported as graph Timing: from November 2002 to March 2005 Location: 7 Northern European countries Multi‐centre: 32 centres
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Restricted block‐wise randomisation (1:1 ratio within each specific site). No details on random generation of the allocation sequence, but use of an interactive voice response system should keep risk of selection bias very low
Allocation concealment (selection bias)	Low risk	Automatic interactive voice response system
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind, double‐dummy method
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Investigators, study site personnel and participants remained blinded until after database was locked
Incomplete outcome data (attrition bias) All outcomes	High risk	87% of randomised participants analysed but reasons for withdrawals/dropouts not given
Selective reporting (reporting bias)	Low risk	Outcomes assessed in the study and of specific interest for the review had been indicated in the protocol
Conflict of interest	High risk	Financed by the drug producer. One study author was an employee of the drug producer