Harborne 2003.
| Study characteristics | ||
| Methods | Randomised controlled trial
Location of the trial: quote: Glasgow, Scotland, UK Method of randomisation: quote "Block‐randomized (n = 10/block) in a 1:1 ratio to receive either OCP or metformin. Randomization was by random number tables, the patient number treatment codes were held by a third party." Method of allocation concealment:quote "The patient number treatment codes were held by a third party and were allocated individually after obtaining written consent" Source of fundings: not stated |
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| Participants |
Inclusion criteria: women with PCOS, whose primary complaint was hirsutism (Ferriman‐Gallwey score > 8). PCOS: at least two of the three following features: oligomenorrhoea/ amenorrhoea, polycystic ovaries on ultrasound, or an elevated FAI.
Exclusion criteria: Contraindications to either metformin or Dianette (including BMI > 38), use of oral contraception or metformin within the previous 3 months, and those taking medication known to affect gonadal or adrenal function, or carbohydrate or lipid metabolism. Thyroid dysfunction, hyperprolactinaemia, diabetes mellitus, or late‐on‐set congenital adrenal hyperplasia
Number of women randomised: 52: MET arm: 26 OCP arm: 26 Number of women analysed: 34: MET: 18 OCP: 16 Number of withdrawal and reasons: 18 MET: 8: Pregnant 3/ 11.5% GI 3/ 11.5% Lost of F/U 2/ 7.7% OCP: 10: Weight gain 5/ 19% BP 1/ 3.8% Depression 1/ 3.8% Chest pain 1/ 3.8% Loss of F/U 2/ 7.7% Summary characteristics: PCOS, hirsute women Age (years): MET mean (95% CL): 31.3 (27.9‐34.7) OCP mean (95% CL): 31.7 (26.8‐36.5) BMI (kg/m2): MET mean (95% CL): 31.7 (29.5‐35.5) OCP mean (95% CL) 31.8 (28.4‐34.4) |
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| Interventions |
Treatment(s): MET 500 mg three times a day Control: OCP (Ethinyl estradiol 35 mcg Cyproterone acetate 2mg) once daily (21 days per month followed by 7 days pill‐free period) Duration: 12 months Co‐intervention: none |
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| Outcomes |
Primary outcomes: Hirsutism score (Ferriman‐Gallwey) Hirsutism ‐ subjective (VAS) Adverse events: severe (requiring stopping of medication) and minor Secondary outcomes: Acne ‐ subjective (VAS) BMI (kg/m2) Blood pressure (systolic) (mm Hg) Blood pressure (diastolic) (mm Hg) 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) |
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| Subjective outcomes | (a) Clinical parameters
1. Hirsutism ‐ subjective (VAS) 2. Hirsutism score (Ferriman‐Gallwey) 3. Acne ‐ subjective (VAS) |
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| Objective outcomes | (a) Clinical parameters 1. Adverse events: severe (requiring stopping of medication) and minor 2. BMI (kg/m2) 3. Blood pressure (systolic) (mm Hg) 4. Blood pressure (diastolic) (mm Hg) (b) Hormonal parameters 1. Serum total testosterone (n mol/L) 2. 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) |
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| Notes |
Authors contacted about: BMI result and co intervention kindly provided by the authors that was not in the original paper. Power calculation: unclear |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Patients were block‐randomized (n=10/block) in a 1:1 ratio. Randomization was by random number tables" |
| Allocation concealment (selection bias) | Low risk | Quote: "The patient number treatment codes were held by a third party and were allocated individually after obtaining written consent." |
| 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 | "Loss to F/U" reason is 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) | 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. |