Hydroquinone 3% cream

Melasma is a chronic, relapsing hypermelanosis characterized by symmetric facial pigmentation and high recurrence rates. Natural products have been investigated for their antioxidant, anti-inflammatory, and depigmenting properties. This systematic review evaluated the efficacy and safety of natural substances for melasma treatment in randomized controlled trials, using the Melasma Area and Severity Index (MASI) as the primary outcome measure. The review was conducted in accordance with PRISMA 2020 guidelines. Searches were performed across LILACS, SciELO, Scopus, PubMed, and ScienceDirect. Randomized controlled trials investigating natural compounds for melasma treatment and reporting MASI or modified MASI (mMASI) outcomes were included. Risk of bias was assessed using the Cochrane RoB 2.0 tool. Ten randomized controlled trials met the inclusion criteria. Lycopene, hydroxytyrosol, Dorema ammoniacum, parsley, Polypodium leucotomos, pycnogenol, and Aloe vera reduced MASI/mMASI scores by 20-70%, with effects often comparable to 4% hydroquinone. Reported adverse events were generally mild, comprising transient irritation and erythema. Heterogeneity in formulations, small sample sizes, and short follow-up durations limited the overall strength of evidence. Natural compounds act through tyrosinase inhibition, antioxidant activity, and modulation of melanogenesis, constituting well-tolerated alternatives for melasma management. Larger-scale, long-term randomized trials are required to confirm sustained efficacy and safety.

Abstract licence: CC BY-NC-ND

Melasma is a chronic hyperpigmentation disorder that significantly impacts quality of life. Given the persistent challenges in melasma management, there is a need to evaluate therapies that may offer long-term treatment. This review analyzes placebo- and hydroquinone (HQ)-controlled interventional studies of melasma published between January 1, 2014, and December 31, 2024. Screening, data extraction, and discussion synthesis were performed with artificial intelligence assistance under human oversight. Treatments were grouped into five categories: HQ-based Standard Treatments, Isolated Molecules as Depigmenting Therapies, Botanical and Antioxidant-Based Therapies, Regenerative and Microenvironment-Modulating Therapies, and Procedure-Assisted and Combination Treatments. HQ remained a key benchmark, although recurrence and tolerability limitations were frequently observed. Several non-HQ or adjunctive approaches demonstrated benefit when administered orally, topically, intradermally, or via iontophoresis. Botanical antioxidants, synbiotics, epidermal growth factor, and platelet-rich plasma also showed promising efficacy. Nevertheless, the evidence base was constrained by small sample sizes, heterogeneous comparators, inconsistent endpoints, mixed objective and subjective assessments, and variable follow-up durations, which prevented meta-analysis. Research on melasma treatment is growing worldwide, with several promising non-HQ and adjunctive strategies emerging. However, standardization of outcomes, comparator selection, and longer follow-up periods is needed to clarify efficacy, tolerability, and relapse prevention throughout diverse skin tones.

Abstract licence: CC BY