Hoeger 2008a.

Study characteristics
Methods	Randomised controlled trial Location of the trial: quote: New York, USA Method of randomisation: quote:"‘Subjects were randomized to one of four arms by random number assignment: placebo, metformin, OC, or lifestyle management" Method of allocation concealment: not stated Source of funding: this work was supported by Grants K23 HD043881‐01A1 and 5R03 HD41989‐02 from the National Institutes of Health (NIH), and Grant UL1RR024160 from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research. Desogen was supplied by Organon Pharmaceuticals, Inc.
Participants	Inclusion criteria: from methods section of paper and Clinical Trial Registry Postmenarchal adolescent women between the ages of 12 and 18 years withBMI above the 95th percentile (or BMI > 25 kg/m2) and evidence of menstrual irregularity (fewer than eight menses in the preceding year or cycle length > 45 days) and clinical or biochemical evidence of hyperandrogenism (testosterone > 50 ng/dL), currently healthy, studied off any hormonal therapy or insulin sensitisers for at least 2 months, non‐smokers. PCOS: Consistent with NIH. Exclusion criteria: from methods section of paper and Clinical Trial Registry Exclusion of other causes of hyperandrogenism and menstrual irregularity Exclusion of diabetes mellitus, Cushing’s disease, hyperprolactinaemia, untreated hypo or hyperthyroidism, history of adrenal hyperplasia, significant renal impairment, received oral contraceptives, oestrogen or progestin or other drugs known to effect lipoprotein metabolism within 2 months of starting study, exercise > 10 hours/week. Number of women randomised: 21 MET: 10 OCP: 11 Number of women analysed: 16 MET: 6 OCP: 10 Number of withdrawal and reasons: MET: 4 lost to follow‐up: 2/ 20% personal reasons: 2/ 20% OCP: 1 lost to follow‐up: 1/ 9% Summary characteristics: PCOS, young (12 to 18years), obese Age (years): MET mean (±SD): 16 (1.7) OCP mean (±SD): 15.4 (1.4) BMI (kg/m2): MET mean (± SD): 34.3 (6.5) OCP mean (± SD): 37.8 (6.1)
Interventions	Treatment: MET 850 mg twice a day, starting as single doses of 425 mg and building gradually to two capsules twice a day. Control: OCP (Ethinyl estradiol 30 mcg desogestrel 0.15 mg ) taken in a cyclic fashion. Duration: 6 months Co‐intervention(s): "Subjects who were not assigned to lifestyle treatment received standard office advice on nutrition and exercise for healthy living and were seen monthly."
Outcomes	Primary outcomes: Hirsutism score Secondary outcomes: Menstrual cyclicity, initiation of menses or significant shortening of cycles BMI (kg/m2) Blood pressure (systolic, diastolic) (mm Hg) Serum total testosterone (ng/dL) Free androgen index (FAI) (%) Fasting insulin (IU/mL) Fasting glucose (mmol/L) Fasting total cholesterol (mmol/L) Fasting HDL cholesterol (mmol/L) Fasting LDL cholesterol (mmol/L) Fasting triglycerides (mmol/L)
Subjective outcomes	(a) Clinical parameters 1. Hirsutism score
Objective outcomes	(a) Clinical parameters 1. Menstrual cyclicity, initiation of menses or significant shortening of cycles 2. BMI (kg/m2) 3. Blood pressure (systolic, diastolic) (mm Hg) (b) Hormonal parameters 1. Serum total testosterone (ng/dL) 2. Free androgen index (FAI) (%) (c) Metabolic parameters 1. Fasting insulin (IU/mL) 2. Fasting glucose (mmol/L) 3. Fasting total cholesterol (mmol/L) 4. Fasting HDL cholesterol (mmol/L) 5. Fasting LDL cholesterol (mmol/L) 6. Fasting triglycerides (mmol/L)
Notes	Authors contacted about: fasting insulin because expressed in wrong unit. Power calculation: unclear 4 arms treatment: PBO V MET versus OCP versus LS
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Subjects were randomized to one of four arms by random number assignment: placebo, metformin, OC, or lifestyle management"
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment not stated. Insufficient information to permit judgement of ‘low risk’ or ‘high risk’
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Assignment to metformin or placebo was blinded to subject and investigator." "outcome assessors and data analysts were unaware of study assignment"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Assignment to metformin or placebo was blinded to subject and investigator." "outcome assessors and data analysts were unaware of study assignment"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote: "Lost F/U, personal reason" are both unclear reason of withdrawal and could be related to intervention. Insufficient reporting attrition/exclusions to permit a judgement of 'low risk' or 'high risk'.
Selective reporting (reporting bias)	Unclear risk	From results section of paper and clinical trial registry, all of the studies pre‐specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre‐specified way with the exception of weight which was only reported as part of BMI and menstrual rate which was not reported for OCP. But not a primary or key outcomes. Insufficient information available to permit a judgment of 'low risk' or 'high risk'.
Other bias	Low risk	The study appears to be free of other sources of bias.