Hyaluronic acid-based skin booster with glutathione combined with 1064-nm Nd:YAG laser and oral tranexamic acid for melasma: A prospective comparative study

Melasma is a chronic, acquired facial hyperpigmentation disorder with multifactorial pathogenesis and frequent relapse. Low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) (LQSNY) laser with oral tranexamic acid (TA) is widely used, but responses are often incomplete and short-lived. glutathione (GSH), an antioxidant that inhibits melanogenesis, may improve outcomes when delivered intradermally with a hyaluronic acid (HA) carrier. We assessed whether adding an HA-based GSH skin booster (HA-GSH) to this regimen enhances efficacy and durability. Fifty Chinese women with epidermal melasma (Fitzpatrick III-IV) were randomized 1:1 to 6 monthly LQSNY sessions plus oral TA (250 mg daily), with (Group A) or without (Group B) intradermal HA-GSH. The primary outcome was change in modified melasma area and severity index (mMASI) at 6 months and at 2-month posttreatment follow-up. Secondary outcomes were patient satisfaction (short assessment of patient satisfaction) and safety. Sample size was determined a priori. mMASI was analyzed using a linear mixed-effects model with baseline mMASI as a covariate and Benjamini-Hochberg adjustment for visit-level comparisons. Thirty-six patients completed the study (18 per group); baseline mMASI was comparable (5.61 ± 1.29 vs 5.56 ± 1.20; P = .89). Fourteen participants withdrew (seven per group), none due to adverse events. Group A showed significantly greater mMASI reduction from the third session onward. Adjusted for baseline, the mean difference across all post-baseline visits was 0.72 points (95% confidence interval 0.46-0.98; P < .001) favoring Group A, evident at the first posttreatment assessment. At 6 months, mean mMASI was lower in Group A (2.50 ± 0.62 vs 3.39 ± 0.70; P < .001), an advantage maintained at follow-up (2.06 ± 0.54 vs 2.67 ± 0.59; P = .003). More Group A patients were "very satisfied" (28% vs 11%), though not significantly (P = .31). Both regimens were well tolerated; only transient erythema, mild swelling, and bruising occurred, with no serious or pigmentary adverse events. Adding intradermal HA-GSH to LQSNY laser and oral TA produced earlier, greater, and more durable melasma improvement with high satisfaction and a favorable safety profile, supporting HA-GSH as a promising adjuvant pending confirmation in larger, longer trials.