Luque‐Ramirez 2007b.

Study characteristics
Methods	Randomised controlled trial Same population as Luque‐Ramirez 2007a Location of the trial: quote: Madrid, SpainMethod of randomisation: quote: “Simple randomization was conducted using blocks of 10 sealed opaque envelopes assigning five patients to receive Diane35 Diario and five patients to receive metformin”Method of allocation concealment: “One investigator generated the randomization envelopes, whereas another enrolled and assigned the participants to their arm of treatment”, “sealed opaque envelopes” Source of funding: "This study was supported by the Spanish Ministry of Health and Consumer Affairs, Instituto de Investigacion Carlos III Grants Fondo de Investigacion Sanitaria and Red de Diabetes Enfermedades Metabolicas Asociadas; Ministry of Education and Science Grant; and by economic aid from Hospital Ramon y Cajal."
Participants	Inclusion criteria: the diagnosis of PCOS was based on the presence of clinical and/or biochemical hyperandrogenism, oligo‐ovulation, and exclusion of secondary aetiologies. Hirsutism was defined by a modified Ferriman‐Gallwey score above 7 and oligomenorrhoea (more than six cycles longer than 36 days in the previous year) or amenorrhoea (absence of menstruation for three consecutive months), or luteal phase progesterone measurements less than 4 ng/ml (12.72 nmo/L) in women with regular menstrual cycles were considered indicative of oligo‐ovulation. Exclusion criteria:secondary aetiologies, including hyperprolactinaemia, thyroid dysfunction, Cushing’s syndrome, congenital adrenal hyperplasia, and virilising tumours, were actively ruled out in all the patients. None of the patients had a personal history of hypertension, diabetes mellitus, or cardiovascular events, or received treatment with oral contraceptives, antiandrogens, insulin sensitisers, or drugs that might interfere with blood pressure regulation, lipid profile, or carbohydrate metabolism for the previous 6 months. Number of women randomised: 34 MET: 19 OCP: 15 Number of women analysed: 27 MET: 12 OCP: 15 Number of withdrawal and reasons: MET: protocol violation: 3/ 15.8% GI adverse events: 2/ 10.5% Pregnancy: 1/ 5.3% Lost F/U: 1/ 5.3% OCP: 0 Summary characteristics: PCOS, hyperandrogenic (precised in an other study with same population) Age (years): MET mean (+SD): 25.1 (6.6) OCP mean (+ SD): 23.4 (5.6) BMI (kg/m2): MET mean (+ SD): 30.5 (6.9) OCP mean (+ SD): 29.2 (5.7)
Interventions	Treatment: MET 425 mg twice a day 1 week then 850 mg twice a day Control: OCP (Ethinyl estradiol 35 mcg Cyproterone acetate 2 mg) 21 days followed by 7 days placebo pills Duration: 6 months Co‐intervention(s): All the patients were instructed to maintain a diet containing 25 to 30 kcal per kg of body weight per day and moderate physical activity throughout the trial, although these measures were not stressed thereafter.
Outcomes	Primary outcomes: None Secondary outcomes: Menstrual cyclicity, initiation of menses or significant shortening of cycles
Subjective outcomes	None
Objective outcomes	(a) Clinical parameters: 1. Menstrual cyclicity, initiation of menses or significant shortening of cycles
Notes	Authors contacted about: the results because it was presented as a graph. Power calculation: yes, a priori, on secondary outcome
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “patients were randomized to receive an antiandrogenic low‐dose oral contraceptive pill or 850 mg of metformin twice daily for 24 wk”, “One investigator generated the randomization envelopes, whereas another enrolled and assigned the participants to their arm of treatment”, “Simple randomization was conducted using blocks of 10 sealed opaque envelopes assigning five patients to receive Diane 35 Diario and five patients to receive metformin” Insufficient information about the sequence generation process available to permit a judgement of ‘low risk’ or ‘high risk’
Allocation concealment (selection bias)	Low risk	Quote: “One investigator generated the randomization envelopes, whereas another enrolled and assigned the participants to their arm of treatment” and “sealed opaque envelopes”
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: “open label RCT”.
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	7 patients in MET group did not complete the entire study/ 0 in OCP group Quote: "protocol violation and lost to F/U" unclear if related to intervention. Insufficient reporting of attrition /exclusions to permit a judgement of 'low risk' or 'high risk.".
Selective reporting (reporting bias)	High risk	Menstrual cyclicity is the only outcome of interest in this study and was not described in the methods. One or more primary outcomes have been reported using measurements, analysis, methods or subset of the data THAT WERE NOT PRE‐SPECIFIED
Other bias	Low risk	The study appears to be free of other sources of bias.