Glintborg 2014a.

Study characteristics
Methods	Randomised controlled trial Location of the trial: quote: Odense, DenmarkMethod of randomisation: not statedMethod of allocation concealment: not statedSource of funding: quote: "This work was supported by the Jacob Madsen’s and Olga Madsen’s Foundation, the Institute of Clinical Research, the Odense University Hospital, Kolding Hospital, the A. P. Møller’s Foundation, the Bernhard and Marie Kleins Foundation, The Novo Nordisk Foundation, and The Danish Medical Association. Oral contraceptive pills and metformin tablets were sponsored by Sandoz."
Participants	Inclusion criteria: aged 18 to 39 years fulfilling the Rotterdam criteria for PCOS were included in the study. The included patients fulfilled two of the criteria: 1) irregular periods during more than a year in combination with a cycle length longer than 35 days; 2) total‐ or free‐T levels above the reference interval (upper limits: total T >1.8 nmol/L, free T >0.035 nmol/L) and/or hirsutism; and 3) transvaginal ultrasound with polycystic ovaries. Exclusion criteria: Serious endocrine diseases were excluded. Patients with diabetes (fasting plasma glucose ≥ 7.0 mmol/L and/or HbA1c ≥ 44 mmol/mol), elevated liver enzymes, renal dysfunction, congestive heart disease, depression, and eating disorders were not included in the study. Obese patients (BMI) ≥ 35 kg/m2) and patients with other contraindications for OCP(previous or family history of thrombosis or breast cancer, coagulatory defects, and heavy smokers) were not included in the study. Patients were not included if they were pregnant or expressed a wish for conception during the study period. Patients paused OCP for at least 3 months and metformin for at least 1 month before evaluation, and no patients were treated with medicine known to affect hormonal or metabolic parameters. Number of women randomised: 90 MET + OCP: 30 MET: 30 OCP: 30 Number of women analysed: 65 MET + OCP: 23 MET: 19 OCP: 23 Number of withdrawal and reasons: MET + OCP: 7 Nausea: 3/ 10% Regrets: 2/ 6.7% Lost F/U: 2/ 6.7% MET:11 pregnant: 1/ 3.3% wants OCP: 2/ 6.7% depression: 1/ 3.3% nausea: 1/3.3% regrets: 4/ 13.3% lost F/U: 2/ 6.7% OCP: 7 wants pregnancy: 2/ 6.7% adverse events: 3/ 10% lost F/U: 2/ 6.7% Summary characteristics: PCOS, aged 18 to 39 years Age (years): MET + OCP mean (+SD): 28 (4.9) MET mean (+SD): 28 (4.8) OCP mean (+)SD: 28 (4.7) BMI (kg/m2): MET + OCP mean (+SD): 27.6 (3.9) MET mean (+SD): 25.9 (4.4) OCP mean (+SD): 27.2 (4.8)
Interventions	MET 1000 mg twice a day + OCP (Ethinyl estradiol 30 mcg desogestrel 150 mg) Metformin 1000 mg twice a day OCP (Ethinyl estradiol 30 mcg desogestrel 150 mg) Duration: 12 monthsCo‐intervention(s): general advice on lifestyle intervention, laser treatment was offered to patient with moderate or severe facial hirsutism and patients were allowed to shave/wax
Outcomes	Primary outcomes: Hirsutism score Adverse events: severe (requiring stopping of medication) and minor Secondary outcomes: Body weight (kg) BMI (kg/m2) Blood pressure (systolic) (mm Hg) Blood pressure (systolic) (mm Hg) Serum total testosterone (nmol/L) Fasting insulin (mIU/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. Body weight (kg) 3. BMI (kg/m2) 4. Blood pressure (systolic) (mm Hg) 5. Blood pressure (diastolic) (mm Hg) (b) Hormonal parameters 1. Serum total testosterone (nmol/L) 2. FAI (c) Metabolic parameters 1. Fasting insulin (mIU/L) 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: their results because they were expressed in median (25th and 75th quartiles) therefore not applicable, they kindly gave us theirs results presented in the study and a few more outcomes: blood pressure, FAI, fasting glucose, fasting total cholesterol (mmol/L), fasting HDL cholesterol (mmol/L), fasting LDL cholesterol (mmol/L), fasting triglycerides (mmol/L). We could finally calculate the mean + SD. Power calculation: no 3 arms study MET versus OCP versus OCP + MET
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “Included patients were randomized to 12 months of treatment with metformin (10001000 mg/d) or OCP (150 mg desogestrel/ 30 mcg ehinylestradiol) or combined treatment (metformin OCP)”. Method of randomisation not stated. Insufficient information available to permit a judgement of ‘low risk’ or ‘high risk’.
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment not stated. Insufficient information available to permit a judgement of ‘low risk’ or ‘high risk’.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information available to permit a judgement of ‘low risk’ or ‘high risk’. Blinding not stated.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information available to permit a judgement of ‘low risk’ or ‘high risk’. Blinding not stated.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Reason for missing outcome data "regrets, lost F/U, wants OCP" are unclear and could be related to intervention. insufficient reporting of attrition/exclusions to permit a judgement of 'low risk' or 'high risk'.
Selective reporting (reporting bias)	Unclear risk	Total cholesterol, HDL and triglycerides described in the method not stated in the results part. Improvment of menstrual cycles described for MET group not for OCP group. But not a primary or key outcomes. Insufficient information available to permit a judgment of 'low risk' or 'high risk'.
Other bias	High risk	The use of laser treatment, shaving or waxing to treat hirsutism is an important confounding factor to evaluate Ferriman‐Gallwey score.