Methodological limitations compromise the validity of results found in the first RCT comparing azelaic acid, tretinoin and sunscreen with azelaic acid and sunscreen.18

With the second RCT comparing azelaic acid cream, glycolic acid and sunscreen with hydroquinone and sunscreen, it was not possible to determine if the response varied between people with melasma and people with other hyperpigmentation conditions.29 It is therefore difficult to draw valid conclusions.

The third RCT comparing a gel containing kojic acid, hydroquinone, 10% glycolic acid followed by titanium dioxide sunblock, with a gel containing hydroquinone and glycolic acid followed by titanium dioxide sunblock had methodological limitations, which may compromise its validity, and the sample size may be insufficient to rule out an effect.30

The fourth RCT31 did not provide detail on the melasma type. Melasma type has been associated with treatment response. The study does not give details of the kind of alpha hydroxyacid used and lacks detail of demographic data.

The fifth RCT does not allow one to look at variables but gives percentage improvements and P values. It concludes that the addition of 2% kojic acid gel to glycolic acid is as efficacious as 2% hydroquinone.32 Addition of 2% kojic acid to a gel containing 10% glycolic acid and 2% hydroquinone further improves melasma. No additional side-effects were reported on the kojic acid side.32

We found one abstract33 which did not provide sufficient detail to make a critical appraisal of the study methodology.

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