Watson 1989.

Methods	Randomized double blind placebo‐controlled cross‐over trial, cross‐over at 3 months
Participants	Women with severe PMS characterised by a significant positive and negative trend on at least 3 of the symptoms on a prospectively kept daily rating scale (PDQ).
Interventions	Oestradiol patches versus placebo, 20 women given 100 µg Oestradiol patch with 5 mg oral norethisterone day 19 to 26. 20 women given placebo patch with 5 mg oral norethisterone day 19 to 26. Cross‐over of groups at 3 months Duration: 6 months divided into 3 months' active treatment and 3 months' placebo for each participant
Outcomes	Moos Menstrual Distress Questionnaire Withdrawal due to adverse effects Adverse events (e.g. skin reactions, skin pigmentation)
Notes	Trial conducted in the UK, funding source unknown
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details on randomization method provided
Allocation concealment (selection bias)	Unclear risk	No details on concealment method provided
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo and active treatment looked identical
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Patient‐reported outcomes
Incomplete outcome data (attrition bias) All outcomes	Low risk	12.5% of patients withdrew
Selective reporting (reporting bias)	Low risk	All expected outcomes were reported
Other bias	Unclear risk	Risk of carry‐over effects

MDQ = Menstrual distress questionnaire

PDQ = Premenstrual distress questionnaire

PMS = Premenstrual syndrome