Cibula 2005.

Study characteristics
Methods	Randomised controlled trial Location of the trial: quote: Prague, Czech Republic Method of randomisation: quote: "All patients were randomly assigned to two groups using a computer generator of random values with a uniform distribution within the interval 0 to 1. The values obtained were transformed into rank values, ranks 1‐15 were assigned to the OCP group and remaining 15 were assigned to identical OCP in combination with metformin" Method of allocation concealment: not stated Source of funding: not stated
Participants	Inclusion criteria: PCOS: (i) oligomenorrhoea from menarche (menstrual cycle > 35 days); (ii) an increased concentration of at least one androgen above the upper reference limit (testosterone 0.5 to 2.63 n mol/L, androstenedione 1.57 to 5.4 n mol/L, dehydroepiandrosterone (DHEA) 0.8 to 10.5 n mol/L); and (iii) clinical manifestation of hyperandrogenism (acne, hirsutism or both). Exclusion criteria: secondary endocrine disorder, such as hyperprolactinaemia, thyroid dysfunction or a non‐classical form of congenital adrenal hyperplasia, those wishing to conceive within the next 6 months, or contraindications to oral contraceptive use. Number of women randomised: 30: OCP + MET arm: 15 OCP arm: 15 Number of women analysed: 28: OCP + MET: 13 OCP 15 Number of withdrawal and reasons: OCP + MET: 2: GIT problem: 1/ 6.7% Non compliance: 1/ 6.7% OCP: 0 Summary characteristics: PCOS Age (years): MET + OCP Mean (± SD): 23.8 (5.4) OCP Mean (+ SD) 23.2 (4.6) BMI (kg/m2): MET + OCP Mean (± SD): 24.7(4.9) OCP Mean (+ SD): 22.1(3.1)
Interventions	Treatment(s): MET 500 mg three times a day + OCP (Ethinyl estradiol 35 mcg norgestimate 250 mcg) once daily (21 days per month followed by 7 days pill‐free period) Control: OCP (Ethinyl estradiol 35 mcg norgestimate 250 mcg) once daily (21 days per month followed by 7 days pill‐free period) Duration: 6 months Co‐intervention(s): none
Outcomes	Primary outcomes: Adverse events: severe (requiring stopping of medication) and minor Secondary outcomes: Body weight (kg) BMI (kg/m2)) Serum total testosterone (nmol/L) Free androgen index (FAI) (%) Fasting insulin (pmol/L) Fasting glucose (mmol/L) Total Cholesterol (mmol/L) HDL Cholesterol (mmol/L) LDL Cholesterol (mmol/L) Triglycerides (mmol/L)
Subjective outcomes	None
Objective outcomes	(a) Clinical parameters 1. Adverse events: severe (requiring stopping of medication) and minor 2. Body weight (kg) 3. (BMI (kg/m2) (b) Hormonal parameters 1.Serum total testosterone (nmol/L) 3.Free androgen index (FAI) (%) (c) Metabolic parameters 1. Fasting insulin (pmol/L) 2. Fasting glucose (mmol/L) 3. Total Cholesterol (mmol/L) 4. HDL Cholesterol (mmol/L) 5. LDL Cholesterol (mmol/L) 6. Triglycerides (mmol/L)
Notes	Authors contacted about power calculation, method of randomisation and co‐intervention: Calculated statistical power of study not sufficient as due to wide physiological range for insulin sensitivity the sufficient number is extremely high (personal communication with author). Method of randomisation and co intervention kindly provided by the authors that was not in the original paper Power calculation: unclear
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "All patients were randomly assigned to two groups using a generator of random values with a uniform distribution within the interval 0 to 1 (statistical software NCSS 2002). The values obtained were transformed into rank values. The subjects with ranks 1–15 were assigned to the COC group and received a monophasic COC (EE 35 mg/NGM 250mg) in a cyclic regimen (21 days of active pills followed by 7 days of pill‐free interval) for 6 months. The remaining 15 subjects received an identical COC in combination with metformin (1500 mg/day) for 6 months (METOC group)."
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment not stated. Insufficient information to permit judgement of ‘Yes’ or ‘No’.
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	High risk	Withdrawal OCP 0% versus metformin + OCP 13% due to n = 1 GIT problem and n = 1 study protocol non‐compliance. Reason for missing outcome data is likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention.
Selective reporting (reporting bias)	Low risk	From results section of paper, 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.
Other bias	Low risk	The study appears to be free of other sources of bias.