Okon 2001.

Methods	Randomisation: computer‐generated codes, with allocation concealed in sealed envelopes Single‐centre double‐blind parallel‐group design Number of women randomised: 33 Number of women analysed: 23 Number of early withdrawals: 10 (main reasons were hormone related side effects, e.g. fluid retention, weight gain, depression, breast tenderness) Funding: Schering
Participants	Countries: Denmark, Norway and Sweden. Inclusion criteria: women recruited aged 45 to 65 years (mean 52 ± 4 years) who had amenorrhoea for 12 to 72 months, serum FSH > 20 IU/L, plasma estradiol ≥ 30 pmol/L, intact uterus and requesting HT Exclusion criteria: women with a pathological biopsy at study entry, or abnormal liver or renal function test results
Interventions	Sequential (1) 2 mg E2 daily + 25 µg gestodene added days 17 to 28 (2) 2 mg E2 daily + 50 µg gestodene added days 17 to 28 Duration: 1 year
Outcomes	Endometrial hyperplasia, bleeding patterns
Power calculation described	No
Analysis by Intention to Treat	No per protocol only
Notes	PP14 and CA125 levels in endometrial flushing solutions
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation using computer‐generated codes
Allocation concealment (selection bias)	Low risk	Allocation concealed in sealed envelopes
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind
Incomplete outcome data (attrition bias) All outcomes	Low risk	23 of the 33 women randomised (70%) who completed the study had endometrial biopsies after 1 year of treatment
Other bias	Low risk	small trial 2 parallel groups, no differences at baseline