Sturrock 2002.

Methods	Cross‐over RCT Setting: UK Method of randomisation: performed by pharmacy* Blinding: double‐blind Number randomised: 19
Participants	Summary: metformin vs placebo in obese PCOS with CC resistance Inclusion criteria: oligomenorrhoea cycle > 40 d for 6 months, anovulation demonstrated by day 20‐22 progesterone ≤ 10 nmol/L, lack of response to CC 100 mg for 5 d with US showing endometrial thickness ≤ 5 mm and no ovarian follicle ≥ 14 mm. Age 18‐40 years Exclusion criteria: raised prolactin, adrenal hyperplasia, thyroid dysfunction, medication known to affect insulin action* Baseline characteristics of each group*: mean age (± SD) 29.1 (4.3), 31.1 (3.7) mean BMI (± SD) 34.2 (4.0), 35.0 (3.6) mean fasting insulin mIU/L (± SD) 14.6 (9.9), 17.2 (8.0) mean total testosterone mmol/L (± SD) 2.4 (0.8), 2.2 (0.4) Dropouts: 4 (40%) from metformin arm and 4 (44%) from placebo arm*. Not included in analysis
Interventions	Main intervention: 1 of metformin 500 mg 3/d, placebo Duration: 6 months Co‐interventions: 1st week of treatment at 500 mg 1/d, 2nd at 500 mg 2/d and 3rd at 500 mg 3/d Those that did not ovulate after 3 months had CC 50 mg days 2‐6, increased to 100 mg for a total of 3 cycles
Outcomes	Primay: none Secondary: clinical pregnancy, menstrual frequency, ovulation: by monthly serum progesterone (> 10 nmol/L) and presence of follicle ≥ 14 mm on ovarian US*, BMI, testosterone, fasting glucose, fasting insulin
Notes	This was designed as a cross‐over trial, with 6 months in the treatment/placebo arm followed by a 1‐month washout and then a 3‐month cross‐over. In this review, we only considered the first phase. The inclusion criteria were simply for CC‐resistant anovulation and not specifically PCOS. However only 2 women did not have US criteria of PCOS, and 75% had a raised FAI* In this review, only those participants who had a raised FAI were included in the analysis* *Information not in the original paper kindly provided by the study author
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Performed by pharmacy
Allocation concealment (selection bias)	Unclear risk	Performed by pharmacy
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Inadequate information
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Inadequate information
Incomplete outcome data (attrition bias) All outcomes	High risk	Dropouts: 4 (40%) from metformin arm and 4 (44%) from placebo arm.* Not included in analysis
Selective reporting (reporting bias)	Unclear risk	Insufficient information in the study
Other bias	Low risk	No evidence of other bias. See notes above