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Melasma is an acquired dysfunction of melanogenesis, that poses a major therapeutic challenge and tends to recur after therapy. Several combination therapies are being tested nowadays for the treatment of melasma, with promising results. Metformin, an anti-diabetic medication, seems to inhibit melanogenesis by different mechanisms. In addition, there has been a long-term improvement in melasma after microneedle therapy. To evaluate the potential therapeutic role of topical metformin combined with micro-needling for the treatment of melasma. Eighteen patients with melasma received treatment in split-face manner, right side with micro-needling and topical metformin, while the left side was treated with micro-needling and topical placebo for four sessions at 2-week intervals. Hemi-mMASI score was used for the final evaluation of results. The variability pattern in Hemi-mMASI score between both sides revealed significant reduction in the right side (micro-needling + metformin), as compared to the left side (micro-needling + placebo) (2.39 ± 1.42 vs 4.72 ± 1.27, p = 0.001). The effectiveness of topical metformin in the management of melasma could be significantly improved by pretreatment with micro-needling as a combined therapy, without any apparent side effects.

Introduction Melasma is a chronic refractory pigmentation disorder. Kligman triple (KT) formula is the gold standard. A dermocosmetic (DC) serum containing vitamin B3 and 2‐mercaptonicotinyl glycine has been developed for melasma. This study assessed the benefits of DC serum compared to KT in melasma. Material and Methods A randomized, single‐blind 6‐month study was conducted in women with melasma. Subjects were randomized to Group A (morning: serum; evening: cream, for 6 months) or to Group B (1st 3 months: morning: skin hydrating gel; evening: KT, followed by 3 months of DC routine regimen); all subjects applied a sunscreen with an SPF 50+ twice daily. Assessments included MASI, mMASI, IGA, skin hydration, radiance and fine wrinkles, tolerance, and quality of life (QoL) using MELASQOL. Results Ninety‐one women aged 44 ± 6 years of Phototypes III (30%) and IV (36%) were recruited. Both regimens significantly (p < 0.05) improved MASI after 3 months. A clinically relevant difference in favor of KT was observed. Three months after the switch, both Group A (38.1%) and Group B (41.2%) provided a similar significant (p < 0.05) percentage reduction of MASI score, with no between‐group difference. The mMASI and IGA showed similar results. QoL and skin hydration significantly (p < 0.05) improved in both groups after 6 months. Skin radiance and fine wrinkles also improved. Global tolerance was better with the DC routine. Conclusions Both DC routine and KT significantly improved melasma after 3 months of use. DC further improved melasma when replacing KT for 3 further months, with similar results when used alone for 6 months.

Background Melasma management remains challenging due to its multifactorial nature pathogenesis and recurrent nature. Previous studies showed positive effects of botulinum toxin A (BoNT‐A) for treating and preventing ultraviolet‐induced hyperpigmentation. Objective To evaluate the effectiveness of adjunctive incoBoNT‐A injection combined with triple combination cream (TCC, 4% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide) for treating and preventing melasma recurrence compared to topical therapy alone. Methods A split‐face study was conducted in 30 female patients with melasma. One side of the face was randomly applied TCC to the melasma‐affected areas for 12 weeks (monotherapy), while the contralateral side received TCC and intradermal incoBoNT‐A at baseline and week 12 (combination therapy side). Evaluations were performed at baseline and 2, 4, 8, 12, 16, 20, and 24 weeks. Clinical improvement and melanin index were assessed using the MASI score on the malar area (MASIm), and Colorimeter respectively. Patient satisfaction was also evaluated. Results Twenty‐eight subjects completed the study. The combination therapy side showed significant MASIm decrease at week 2 (p = 0.0032), while the monotherapy side showed no significant change. At 4 weeks, a greater reduction of MASIm was observed in the combination therapy side (MASIm 14.5 and 11.54, 20.41% reduction) when compared to the monotherapy side (MASIm 11.68 and 11.79, 0.93% worsening). At week 12, worsening of melasma was observed on both sides during the summer period. At week 24 (3 months after discontinuing TCC), MASIm was 14.79 on the monotherapy side (worsen 21.03% from baseline) and 9.14 on the combined technique (36.97% improvement, p = 0.0003). Patients' satisfaction was higher for the combination therapy when compared to the monotherapy at the end of the study (8.92 vs. 7.04, p < 0.0001). No serious adverse events occurred. Conclusion Intradermal incoBoNT‐A injection combined with TCC demonstrated superior efficacy in melasma treatment and recurrence prevention compared to TCC monotherapy.

Objective To investigate the efficacy and safety of broadband light (BBL) combined with intradermal injection of tranexamic acid for treating melasma. Methods 120 women with melasma admitted to our hospital from January 2021 to April 2022 were randomly categorized into the following groups: control group, treated with 250 mg tranexamic acid given orally twice daily, except during menstruation; group I, treated with BBL (Sciton, Inc., USA) monthly; group II, received intradermal injections of tranexamic acid monthly; and group III, treated with BBL with intradermal injection of tranexamic acid monthly. Treatment in each group lasted three months. The MASI (Melasma Area Severity Index) and VISIA (Canfield VISIA Complexion Analysis) were used for evaluation. Results After treatment course, MASI scores and VISIA brown spot and red zone ranking improved in all four groups (p < 0.05). The decrease in MASI scores and improvement rates of VISIA brown spot and red zone rankings were not significantly different among the control group, group I, and group II; however, the decreased MASI scores and improvement rates of VISIA brown spot and red zone rankings were significantly higher in group III than in the other three groups (p < 0.05). Conclusion The effect of BBL combined with the intradermal injection of TA in the treatment of melasma is remarkable. This combination therapy can be an alternative and effective treatment for managing melasma.

Background Melasma is a hyperpigmentary disorder causing cosmetic disfigurement. We aimed to compare the efficacy and safety of tranexamic acid (TXA) microinjections with TXA mesoneedling for facial melasma. Methods This randomized assessor‐blind split‐face controlled trial included patients with symmetric facial melasma. One side of the face received TXA (100 mg/ml) mesoneedling and the other side intradermal TXA microinjections. The interventions were repeated three times with 4‐week intervals (weeks 0, 4, and 8). The primary outcome was improvement in modified Melasma Area and Severity Index (mMASI) 4 weeks after the final treatment session. Secondary outcomes were complications and patient satisfaction with the treatments evaluated by a visual analog scale (VAS). Results All 27 patients included in the study were female (mean age: 44.22 ± 8.39 years). Both groups were comparable in terms of mMASI scores before and after treatment (standardized mean difference [SMD] = 0.32, 95% confidence interval [CI] −0.22; 0.85, p = 0.248 and SMD = −0.13, 95% CI −0.66; 0.40, p = 0.633, respectively). The mMASI score change from baseline was not different (SMD = −0.39, 95% CI −0.93; 0.15, p = 0.157). However, patient satisfaction was significantly higher with TXA mesoneedling (SMD = 0.77, 95% CI 0.21; 1.32, p = 0.007). Post‐inflammatory hyperpigmentation occurred in one patient in the TXA mesoneedling group. Erythema, scaling, and edema were significantly higher with TXA mesoneedling (p < 0.001). Conclusions TXA mesoneedling was comparable with TXA microinjection in the treatment of facial melasma, while patient satisfaction was significantly higher with TXA mesoneedling; however, the high frequency of complications occurring with this treatment should be taken into account.

Background While the gold standard treatment for melasma is triple combination cream (TCC), arbutin and kojic acid demonstrate their benefits and may be used as an alternative. Aims To investigate the efficacy of cream containing alpha‐arbutin 5% and kojic acid 2% (AAK) compared with TCC for melasma treatment. Patients/Methods A split‐faced, randomized study was conducted among 30 participants with melasma, and all were randomized to receive AAK or TCC on each side of their face for 12‐week along with 4‐week follow‐up period. The melanin index (MI), modified Melasma Area Severity Index (mMASI), and physician global assessment (PGA) scores were used to measure the effectiveness of interventions. Recurrence of melasma after treatment discontinuation was evaluated by MI and mMASI. Patient satisfactions and adverse effects were also evaluated. In the analysis, the mean difference (MD) was used for MI and mMASI, while Wilcoxon signed‐rank test was for the PGA scores, adverse effects, and patient satisfaction. Results The MD of MI and mMASI scores were not different between groups (mMASI [p = 0.344] and MI [p = 0.268]). The PGA scores only showed improvement on the TCC‐treated side (p = 0.032). Compared to the AKK group, the subjects with TCC showed higher severity of recurrence (MI [p = 0.004] and mMASI [p = 0.045]). No difference in patient satisfaction score between the groups, but erythema and stinging were higher in the TCC group. Conclusions The AAK cream appeared to be effective for melasma treatment, highlighting a lower recurrent rate and fewer adverse events than standard therapy. Trial Registration: thaiclinicaltrials.org: TCTR20230124004

Background Melasma is a prevalent skin condition that primarily affects females of reproductive age. Despite the various available treatments, managing melasma is challenging due to frequent relapses and partial responses. Tranexamic acid (TXA) has gained attention as a potential treatment because of its antifibrinolytic and anti‐melanogenic properties. However, there is still limited information on the efficacy of oral versus topical TXA formulations. Aim The present investigation explored the efficacy and safety of topical versus oral TXA in melasma patients to determine whether topical administration could provide a viable alternative with improved tolerability. Patients/Methods In this single‐center randomized trial, 50 melasma patients received oral TXA (250 mg twice daily) or topical TXA (a 5% cream applied twice daily) for 12 weeks. Melasma severity was measured using the Melasma Area and Severity Index (MASI) score at baseline and after 3 months. Data analysis was performed using SPSS version 24, with p < 0.05 considered statistically significant. Results Fifty female patients (mean age≈39.9 years) were equally randomized to the oral and topical TXA group. One patient in the topical group discontinued treatment due to sensitivity, while all in the oral group completed the study. At baseline, MASI scores were not significantly different between the two groups (p = 0.28). After 12 weeks, both groups demonstrated significant reductions in MASI scores (oral group: 58.86%; topical group: 50.88%; p = 0.001 for each), though the difference was insignificant. Discussion Fifty female patients (mean age≈39.9 years) were equally randomized to the oral and topical TXA groups. One patient in the topical group discontinued treatment due to sensitivity, while all in the oral group completed the study. Baseline MASI scores were similar (p = 0.28). After 12 weeks, both groups demonstrated significant reductions in MASI scores (oral group: 58.86%; topical group: 50.88%; p = 0.001 for each), though the difference was not statistically significant. Conclusion Both forms of TXA are effective with low side effects. The choice between oral and topical TXA can depend on patient preference and convenience.

Background The picosecond 755‐nm alexandrite laser and topical tranexamic acid (TA) have shown promise in treating melasma. Aim This aim of this study was to evaluate the efficacy and safety of combining to a picosecond 755‐nm alexandrite laser combined with topical TA for melasma treatment. Patients and Methods Forty‐eight patients’ facial halves with bilateral symmetrical melasma were randomized to receive either topical TA and picosecond laser treatment or laser monotherapy. All patients received three consecutive picosecond laser treatment sessions at 4‐week intervals, and additional one side facial received topical TA treatment twice daily until 4 weeks after the third treatments. Efficacy was assessed using the Modified Melasma Area and Severity Index (mMASI) score, VISIA (Canfield, USA) red area feature counts, and average pore volume as measured by Antera 3D®. Patient satisfaction was evaluated through questionnaires. Results Thirty‐five patients completed the study. Post‐treatment, mMASI scores and VISIA red area feature counts were lower in combination therapy halves and laser monotherapy halves, and average melanin level was lower in the combination therapy halves (p < 0.05). Comparisons between the combination therapy halves and laser monotherapy halves after the third treatment revealed significant differences in mMASI scores, melanin levels, and VISIA red area feature counts (p < 0.05). After treatment, patient satisfaction rates in the combination therapy halves and monotherapy halves was 71.4% and 54.3%, respectively (p < 0.05). No obvious adverse effects were observed in the combination therapy halves; whereas, 10.42% (5/48) of participants in the laser monotherapy halves experienced temporary pigmentation, which resolved within 3 months. Conclusion The picosecond 755‐nm alexandrite laser, when used independently and in combination with topical TA, has been proven to be effective in the improvement of melasma. However, the combined treatment approach showed a more pronounced improvement in melasma symptoms, with higher patient satisfaction, and was associated with a lower incidence of adverse effects. These findings strongly support that integrating topical TA with picosecond laser therapy as a superior therapeutic strategy for melasma management. Clinical Trial Registration Chinese Clinical Trial Registry: ChiCTR2200057771.

Background Cordyceps is a valuable Chinese herbal medicine known for its various components with antioxidant properties, which may theoretically improve melasma. This study aimed to evaluate the efficacy of a new skin‐lightening cosmetic containing Cordyceps extract (referred to as Cordyceps essence) in treating female patients with melasma. Methods Sixty‐two women with melasma were enrolled and randomly assigned to two groups for 12 weeks of treatment. Group A received oral tranexamic acid (TXA) combined with topical hydroquinone cream, while Group B received oral TXA combined with topical Cordyceps essence. Changes in the Melasma Area and Severity Index (MASI), melanin index (MI), and erythema index (EI) were monitored and assessed before and after treatment. Patient‐reported satisfaction and adverse events were also recorded. Additionally, a metabolomic analysis was conducted on 15 randomly selected patients from Group B. Results After 12 weeks of treatment, intra‐group comparisons revealed that MASI scores, MI, and EI significantly decreased in both Group A and B compared to baseline (p < 0.05). However, inter‐group comparisons showed no statistical differences in MASI scores, MI, or EI between the two groups after treatment (p > 0.05). Adverse reactions occurred in 4 people (13.8%) in Group A and 1 person (3.3%) in Group B. Patient satisfaction with treatment was similar in both groups. The metabolomic analysis identified significant differences in 29 metabolites and 15 metabolic pathways after treatment (p < 0.05). Conclusions Our study demonstrated that both oral TXA combined with hydroquinone cream and oral TXA combined with Cordyceps essence significantly improved melasma in women. However, the incidence of adverse reactions was lower with topical Cordyceps essence than that with hydroquinone cream. Cordyceps essence appeared to be a promising alternative for patients intolerant to hydroquinone cream. Metabolomic analysis revealed that modulation of melanogenesis‐related metabolites, enhanced antioxidant activity, and improved skin barrier function collectively contributed to the clinical improvement in melasma severity. The improvement of melasma with oral TXA and topical Cordyceps essence may be closely linked to changes in endogenous differential metabolites in the skin and the regulation of amino acid metabolic pathways.

Background Melasma is a common, relapsing hyperpigmentation disorder with limited long-term treatment success. Recent advances suggest that microneedling may enhance the transdermal delivery and efficacy of topical agents. This study compares the clinical outcomes of microneedling-assisted delivery of topical metformin and tranexamic acid (TXA) in the treatment of facial melasma, with modified Kligman’s formula as a control. Objectives To evaluate and compare the efficacy, safety, and patient satisfaction of microneedling with topical metformin versus TXA in melasma patients. Methods: Forty-five female patients with facial melasma were randomized into three equal groups. Group A received microneedling with topical metformin; Group B received microneedling with topical TXA; Group C applied modified Kligman’s formula nightly. Treatments were conducted over 8 weeks. Outcomes included changes in modified Melasma Area and Severity Index (mMASI), patient satisfaction scores, pain levels, and adverse events. Results: All groups showed significant mMASI reductions. Group B achieved the greatest reduction (mean 45.3%) followed by Group C (38.2%) and Group A (22.1%) ( p  < 0.001). Satisfaction scores were highest in Group B, with 33.3% reporting marked improvement. Minimal adverse events were reported across all groups, with no serious side effects. Pain scores were comparable between microneedling groups. Conclusion Microneedling with topical TXA demonstrated superior efficacy and patient satisfaction compared to metformin and Kligman’s formula. While topical metformin showed some potential, its formulation and clinical utility require further study. Microneedling offers a promising approach to improve treatment outcomes in melisma. Graphical Abstract