The Use of Tranexamic Acid to Treat Melasma: A Systematic Review and Meta‐Analysis

Introduction Tranexamic acid (TXA) is a synthetic derivative of the amino acid lysine that inhibits bleeding due to its effects on plasminogen conversion, approved by the FDA to treat menorrhagia and prevent bleeding in hemophilia patients undergoing dental extraction. Several studies have shown TXA benefits in treating melasma, but there is uncertainty about its potential association with an increased risk of thromboembolism. Objectives To evaluate the efficacy and safety of TXA for the treatment of melasma, alone or in combination therapy. Methods Randomized clinical trials (RCTs) were included that assessed the effect of TA (alone or in combination) compared to placebo or other active interventions in adults diagnosed with melasma. All studies reporting the use of TA were included in this review, as we aimed to find out if TA would have benefits in treating melasma, alone or in combination therapy. Records were searched in the CENTRAL, MEDLINE/PubMed, Embase, Lilacs, and IBECS databases, as well as RCT registration platforms up to September 2020 and updated in January 2024. The studies were evaluated for methodological quality using the Cochrane risk‐of‐bias tool Version 2 and synthesized in meta‐analyses with a random‐effects model. Results Thirty‐two studies were included, totaling 2376 participants with melasma and comprising 14 different comparisons. For the three main comparisons, TA showed little to no difference in skin lightening compared to placebo (standardized mean difference (SMD) = −0.36, 95% confidence interval (CI) −0.77 to 0.06; I 2 = 65%) and when compared to hydroquinone (SMD = 0.40, 95% CI −0.04 to 0.8; I 2 = 87%), and TA combined with hydroquinone showed the small clinically important difference compared to hydroquinone (SMD = −1.59, 95% CI ‐2.51 to −0.66; I 2 = 97%). Conclusions The current meta‐analysis has demonstrated a proven benefit in the association between hydroquinone and TXA when compared to each agent individually. In the present meta‐analysis, the combination of hydroquinone and tranexamic acid demonstrated superior efficacy compared to the use of either agent alone. Further studies are warranted to determine whether this combination could enable shorter treatment durations with both hydroquinone and TXA, thereby substantially reducing their associated adverse effects.