Hoeger 2008b.

Study characteristics
Methods	Randomised controlled trial Location of the trial: quote: New York, USA Method of randomisation: quote: "Subjects were assigned by a random number table." 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: Postmenarchal adolescent women between the ages of 12 and 18 yr with BMI above the 95th percentile and evidence of menstrual irregularity (fewer than eight menses in the preceding year) and clinical or biochemical evidence of hyperandrogenism, currently healthy, studied off any hormonal therapy or insulin sensitisers for at least 2 months, non‐smokers, must be able to swallow capsules, at least 6 months since onset of first menstrual cycle. PCOS diagnosis consistent with NIH. Exclusion criteria: exclusion of other causes of hyperandrogenism and menstrual irregularity; diabetes; kidney or lLiver disease; tobacco use; depression or bipolar disease; contraindication to exercise; weight > 300 lbs Number of women randomised: 36 MET + OCP: 18 OCP: 18 Number of women analysed: 32 MET + OCP: 16 OCP: 16 Number of withdrawal and reasons: MET + OCP: 2, GI symptoms: 1/ 5.6% not stated: 1/ 5.6% OCP: 2, GI symptoms: 1/ 5.6% not stated: 1/ 5.6% Summary characteristics: PCOS, young (12 to 18years), obese Age (years): MET + OCP mean(± SD): 14.7 (1.6) OCP mean(± SD): 15.8 (1.6) BMI (kg/m2): MET + OCP OCP mean (± SD): 34.1 (4.3) OCP mean (± SD): 35.7 (4.9)
Interventions	Treatment: MET 2000 mg/day (divided into four doses with a gradual build up at study start) + OCP (Ethinyl estradiol 30 mcg drosporenone 3 mg) Control: OCP (Ethinyl estradiol 30 mcg drospirenone 3 mg) + PBO Duration: 6 months Co‐intervention(s): co‐intervention with lifestyle (24‐week program with adult family member in classes for training for diet, exercise and behaviour modification skills in open group format with rolling admission). Frequent contact with participants and a combination of structured lectures and flexible personal strategies emphasised self‐esteem and social support. The format included a core curriculum taught in separate adolescent and parent groups repeated over the 24 weeks, interspersed with individual appointments. Exercise was monitored in a group setting on a weekly basis. Contact between participants was encouraged outside the weekly setting with electronic communications such as Internet chat groups to support continued lifestyle changes. Structured group exercise was included weekly. Goals of therapy were based on initial caloric intake by diet record aiming for a 500 kcal/day deficit. Exercise was recommended to include 30 minutes/day of moderate to intense activity.
Outcomes	Primary outcomes: Hirsutism score Adverse events: severe (requiring stopping of medication) and minor Secondary outcomes: Menstrual cyclicity, initiation of menses or significant shortening of cycles Body weight (kg) BMI (kg/m2) Blood pressure (systolic) (mm Hg) Blood pressure (diastolic) (mm Hg) Serum total testosterone (nmol/L) 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. Adverse events: severe (requiring stopping of medication) and minor 2. Menstrual cyclicity, initiation of menses or significant shortening of cycles 3. Body weight (kg) and/or BMI (kg/m2) 4. Blood pressure (systolic, diastolic) (mm Hg) (b) Hormonal parameters 1. Serum total testosterone (nmol/L) 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
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Subjects were assigned by a random number table to metformin or placebo."
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	Unclear risk	Quote: "Double Blind (Subject, Investigator)". Unclear if investigator blinding refers to blinding for clinician reported outcomes. Potential for lack of clinician blinding to impact on results reporting and result in bias for clinician reported outcomes.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "Double Blind (Subject, Investigator)". Unclear if investigator blinding refers to blinding for clinician reported outcomes. Potential for lack of clinician blinding to impact on results reporting and result in bias for clinician reported outcomes.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Reason for missing outcome data "not stated" in 2 cases could be related to intervention. Insufficient reporting of attrition/exclusion 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, menstrual rate. 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.