Abstract
BACKGROUND: Melasma is a chronic, relapsing hyperpigmentation disorder driven by complex interactions among genetic predisposition, hormonal fluctuations, UV exposure, oxidative stress, inflammation, and photoaging. Its psychosocial impact is substantial, especially among women with darker skin types, and treatment remains challenging due to its multifactorial pathogenesis and high recurrence rates. AIMS: This review aims to synthesize current knowledge on melasma pathophysiology, highlight recent innovations in topical and procedural therapies, identify limitations of existing treatments, and outline future directions toward personalized and regenerative approaches. PATIENTS/METHODS: A narrative literature review was performed, summarizing findings from epidemiologic studies, molecular investigations, and clinical trials. Key topics included pigment biology, hormonal and environmental triggers, oxidative stress pathways, emerging depigmenting agents, laser and microneedling technologies, combination therapies, and advances in precision medicine. RESULTS: Melasma arises from dysregulated melanogenesis involving hyperactive melanocytes, hormonal stimulation, UV-induced oxidative stress, dermal inflammation, fibroblast senescence, and pigmentary incontinence. Innovations include non-hydroquinone brighteners (e.g., thiamidol, melasyl), antioxidants, tranexamic acid, and improved topical delivery systems. Procedural advances-such as low-fluence picosecond lasers, fractional CO(2) laser-assisted drug delivery, chemical peel hybrids, and exosome-augmented microneedling-offer enhanced pigment clearance with improved safety profiles. Nevertheless, treatment durability remains limited by relapse, heterogeneous disease subtypes, PIH risk, and inconsistent adherence. CONCLUSIONS: Melasma management is evolving toward multi-target, combination-based strategies addressing pigmentation, inflammation, and photoaging simultaneously. Emerging regenerative technologies, biomarker-driven personalization, and AI-assisted assessment hold promise for improving long-term outcomes, though standardized protocols and long-term safety data are still needed.