Efficacy of Eflornithine Hydrochloride Cream in the Treatment of Melasma: A Randomized, Double‐Blinded, Split‐Face–Controlled Pilot Trial

Melasma treatment remains challenging with variable response to conventional lightening agents. Polyamine inhibition via ornithine decarboxylase 1 (ODC1) may offer an alternative approach, with eflornithine hydrochloride being an established ODC1 inhibitor. To compare the efficacy and safety of eflornithine hydrochloride 13% cream versus standard hydroquinone 2% cream for melasma treatment. A randomized, double‐blinded, split‐face–controlled pilot trial was conducted over 3 months with 20 patients (16 female, mean age 54). Efficacy was assessed via modified Melasma Area and Severity Index (mMASI), Mexameter measurements, physician assessments, and patient satisfaction scores. Both treatment groups showed improvements in mMASI scores and Mexameter measurements (erythema and melanin). No significant differences were found between treatment groups when comparing unit differences or fold changes. Only one patient reported mild irritation from eflornithine. Patient self‐assessments trended higher for eflornithine without reaching statistical significance. Eflornithine hydrochloride 13% cream demonstrates comparable efficacy to hydroquinone 2% cream with a favorable safety profile, presenting a promising alternative for melasma treatment. Trial Registration: ClinicalTrials.gov identifier: NCT06957834