Twelve randomised controlled trials (RCTs) met the inclusion criteria (n=582 patients). Trials investigated the effects of Diane-35 versus metformin (nine RCTs), Diane-35 versus Diane-35 plus metformin (two RCTs) and metformin versus metformin plus Diane-35 (one RCT). Four trials reported adequate randomisation and two trials reported adequate allocation concealment. Three trials reported adequate levels of blinding. Only one trial reported using intention-to-treat analysis. Drop-out rates ranged from 0 to 43.75%, and were not found to be statistically different between control and intervention groups. Publication bias was not reported.
Diane-35 versus metformin (three months): Diane-35 did not improve hirsutism in comparison to the use of metformin (odds ratio -2.12, 95% confidence interval (CI): -4.78 to 0.53; two RCTs, n= 42 patients) or other clinical outcomes. Trials with no heterogeneity showed that Diane-35 was superior to metformin in reducing serum levels of androgens (odds ratio -0.41, 95% CI: -0.58 to -0.24; four RCTs, n=99 patients), luteinizing hormone (odds ratio -1.97, 95% CI: -3.16 to -0.77; four RCTs, n=99 patients), dehydroepiandrosterone sulphate (odds ratio -3.23, 95% CI: -5.10 to -1.37; two RCTs, n=42 patients) and increasing sex hormone binding globulin (odds ratio 127.39, 95% CI: 105.04 to 149.74; two RCTs, n=42 patients). Diane-35 showed no improvement for lipid or insulin metabolism in trials with no heterogeneity. Diane-35 did not significantly affect the reporting of severe side effects in one trial.
Diane-35 versus metformin (six months): The effects of Diane-35 were identical to those for three months for clinical, hormonal and metabolic outcomes. However, glucose metabolic abnormalities increased (odds ratio 3.5, 95% CI: 1.18 to10.35; three RCTs, n=83 patients) and fasting insulin increased (odds ratio 3.51, 95% CI: 1.53 to 5.49; three RCTs, n=69 patients). More studies could not be combined due to heterogeneity; the authors discussed possible sources for this. Side effects were reported as being identical to those at three months.
Diane-35 versus Diane-35 plus metformin: Trials demonstrating no heterogeneity found that Diane-35 did not significantly affect clinical, or lipid metabolic outcomes in comparison to Diane-35 plus metformin. Diane-35 significantly reduced sex hormone binding globulin levels in comparison to Diane 35 plus metformin (odds ratio -31.05, 95% CI: -42.58 to -19.58; two RCTs, n=90 patients) and increased fasting blood glucose (odds ratio 0.34, 95% CI: 0.12 to 0.56; two RCTs, n=90 patients) and fasting insulin levels (odds ratio 6.62, 95% CI: 3.87 to 9.38; two RCTs, n=90 patients). No severe side effects were found
Metformin versus Diane-35 plus metformin: One trial was included, hirsutism outcomes were not reported. Secondary outcomes were presented. No severe side effects were found.
Subgroup analyses were also presented.