Ferenczy 2002.

Methods	Stated purpose: to assess endometrial safety and bleeding patterns of 17B‐oestradiol sequentially combined with dydrogesterone Stratification: not mentioned Blinding: double‐blinded No. of women screened for eligibility: 844 No. randomised: 595 (HT group 1: 117, HT group 2: 114, HT group 3: 117, HT group 4: 118, placebo group: 113 (see Interventions)) No. analysed: 442 (for endometrial cancer, which is the only outcome of interest for this review) Losses to follow‐up: Endometrial status was evaluated by a biopsy, which was available only for women who remained on active treatment for over a year, or who received placebo and completed the 2‐year study. This resulted in 153 losses to follow‐up for this outcome (87 from active treatment groups (24%) and 50 from the placebo group (44%), plus another 16 who received no study medication). Adherence to treatment: not reported Analysis by intention to treat: no No. of centres: multi‐centre (number not stated) Years of recruitment: not stated Design: parallel Funding: Solvay Pharmaceutical
Participants	Included Postmenopausal women with a uterus with amenorrhoea of at least 6 months or surgically postmenopausal (following bilateral oophorectomy without hysterectomy, more than 3 months before enrolment), FSH within normal postmenopausal range Excluded Abnormal (uninvestigated bleeding) vaginal bleeding, use of oestrogens and/or progestogens and/or androgens in the preceding 6 months or more, and any previous use of oestradiol pellet/implant therapy Age range: 45‐65 Baseline equality of treatment groups: yes Countries: Canada and Netherlands
Interventions	HT arm 1 mg/d 17B‐oestradiol/ 5 mg dydrogesterone for the last 14 days of each 28‐day cycle 1 mg/d 17B‐oestradiol/10 mg dydrogesterone for the last 14 days of each 28‐day cycle 2 mg/d 17B‐oestradiol/10 mg dydrogesterone for the last 14 days of each 28‐day cycle 2 mg/d 17B‐oestradiol/20 mg dydrogesterone for the last 14 days of each 28‐day cycle Control arm: placebo Duration: 26 cycles (104 weeks)
Outcomes	Endometrial cancer
Notes	Power calculation: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	High risk	Endometrial status was evaluated by a biopsy, which was available only for women who remained on active treatment for over a year, or who received placebo and completed the 2‐year study. This resulted in 153 losses to follow‐up (26%) for this outcome.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	States double‐blinded ‐ review authors believe risk of bias low owing to 'hard' nature of outcomes
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Review authors believe risk of bias low owing to 'hard' nature of outcomes
Selective reporting (reporting bias)	Low risk	All expected outcomes reported
Other bias	Low risk	No apparent source of other bias