Meuwissen 2001.

Methods	Randomisation: method not stated, into 2 parallel groups Double blind, multicentre Number of women randomised: 634 Number of premature withdrawals: 153 (74 in group 1 and 79 in group 2, owing to AEs (48 and 37, respectively, 7 from group 1 because of lack of efficacy, and 47 (group not specified) because of protocol violation
Participants	Country: 56 centres in Europe, countries not specified Inclusion criteria: postmenopausal women with at least 6 months' amenorrhoea, or who had received HT for < 12 months after 6 months' amenorrhoea (washout period 2 months). At least 4 hot flushes per day and FSH and estradiol levels in postmenopausal range Exclusion criteria: hysterectomy, serious specified intercurrent illness, endometrial hyperplasia/carcinoma at baseline biopsy
Interventions	Sequential (A) 2 mg 17 E2 daily + 0.5 mg TMG daily on days 15 to 28 (B) Placebo days 1 to 7, 2 mg EV daily days 8 to 28 + 0.5 NG daily on days 19 to 28 Duration: 1 year (13 cycles)
Outcomes	Endometrial histology, bleeding patterns
Power calculation described	No
Analysis by Intention to Treat	Yes
Notes	Mean daily number hot flushes = primary efficacy variable. Numbers randomised to each group calculated from percentages reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of sequence generation not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	153 of the 634 women randomised (24%) withdrew during the study. End of treatment biopsies on 396 women (62%) of those randomised
Other bias	Low risk	2 parallel groups well balanced at baseline