Received: 4 October 2016 | Revised: 21 December 2016 | Accepted: 3 January 2017

DOI 10.1111/dth.12465

REVIEW ARTICLE

Tranexamic acid in treatment of melasma: A comprehensive
review of clinical studies

Mohammad Taraz1 | Somayeh Niknam2 | Amir Houshang Ehsani3

1
Department of Clinical Pharmacy, Tehran
University of Medical Sciences, Tehran, Iran
Abstract
2
Department of Pharmaceutics, Tehran Melasma is a human melanogenesis dysfunction that results in localized, chronic acquired hyper-
University of Medical Sciences, Tehran, Iran pigmentation of the skin. It has a significant impact on appearance, causing psychosocial and
3
Department of Dermatology, Razi Hospital, emotional distress, and reducing the quality of life of the affected patients. Tranexamic acid (TA) is
School of Medicine, Tehran University of a plasmin inhibitor used to prevent abnormal fibrinolysis to reduce blood loss and exerts its effect
Medical Sciences, Tehran, Iran
by reversibly blocking lysine binding sites on plasminogen molecules, thus inhibiting plasminogen
Correspondence
activator (PA) from converting plasminogen to plasmin. As plasminogen also exists in human epi-
Mohammad Taraz, Department of Clinical
Pharmacy, Tehran University of Medical dermal basal cells and cultured human keratinocyte are known to produce PA, there is basic
Sciences, Tehran, Iran. rationale that TA will affect keratinocyte function and interaction. A thorough literature review
Email: taraz_mohammad@yahoo.com indicates that while TA is used through various route of administration including oral, topical, and
Funding information intradermal injection and as adjutant therapy with laser to treat melasma, its efficacy is not estab-
None
lished adequately. Further studies are needed to clarify the role of TA in treatment of melasma.

KEYWORDS
hyperpigmentation, melasma, tranexamic acid

1 | INTRODUCTION potentially promising options for patients who are refractory to other
modalities, but also carry a significant risk of worsening the disease
Melasma is a human melanogenesis dysfunction that results in chronic (Shankar et al., 2014). Tranexamic acid (TA) is a plasmin inhibitor used
acquired and localized hyperpigmentation of the skin. It occurs sym- to prevent fibrinolysis to reduce blood loss. It is a synthetic derivative
metrically on sun exposed areas of the body and affects especially of the amino acid lysine and exerts its effect by reversibly blocking
women of reproductive age (Miot, Miot, Silva, & Marques, 2009). Mel- lysine binding sites on plasminogen molecule, thus inhibiting plasmino-
asma is sometimes used interchangeably with the term “chloasma,” gen activator (PA) from converting plasminogen to plasmin. While plas-
which is a hyperpigmentation that often rise from pregnancy or minogen also exists in human epidermal basal cells and cultured human
changes in uterine and ovarian hormones. Melasma, however, can have keratinocyte are known to produce PA, there is basic rationale that TA
a variety of possible causes (Gupta, Gover, Nouri, & Taylor, 2006). The may be affect keratinocyte functions and interactions (Tse & Hui,
exact causes of melasma are unknown, although some triggering fac- 2013). Ultraviolet (UV) irradiation induces PA synthesis and increases
tors are described, such as sun exposure, pregnancy, use of oral contra- plasmin activity in keratinocytes, the intracellular release of arachidonic
ceptives and steroids, ovarian tumors, intestinal parasitoses, acid, a precursor of prostanoids, and the level of alpha-melanocyte-
hepatopathies, use of cosmetics and photosensitizing drugs, proce- stimulating hormone increase as the result of plasmin activity. These
dures and inflammatory processes of the skin and stressful events two substances can activate melanin synthesis. Therefore, the anti-
(Elling & Powell, 1997; Katsambas & Antoniou, 1995; Miot et al., 2009; plasmin activity of TA is thought as the main mechanism of hypopig-
Sheth & Pandya, 2011; Tamega Ade, Miot, Bonfietti, Gige, Marques, & mentory effect of this agent (Ando, Matsui, & Ichihashi, 2010; Chang
Miot, 2013). The objectives of melasma therapy should be protection et al., 1993; Maeda & Naganuma, 1998; Takashima, Yasuda, & Mizuno,
from sunlight and depigmentation. First-line treatment usually consists 1992; Wang, Zhang, Miles, & Hoover-Plow, 2004). Moreover, TA is
of topical compounds that interfere with the melanin synthesis, broad- found to be similar to tyrosine in the part of its structure, which can
spectrum photoprotection, and camouflage. Chemical peels are often competitively inhibit tyrosinase enzyme activity (Li, Shi, Li, Liu, & Feng,
added in second-line therapy. Laser and light therapies represent 2010). Several forms of TA, including oral, topical, and localized

Dermatologic Therapy 2017; e12465; wileyonlinelibrary.com/journal/dth V
C 2017 Wiley Periodicals, Inc. | 1 of 8
DOI: 10.1111/dth.12465

(2011) enrolled 32 women with senile lentigines with or (23% excellent. they found efficacy of oral TA along with routine topical therapies including hydro. from 25 to 561 patients.2 of 8 | TARAZ ET AL. and 8 weeks after treatment. Scopus.1 | Oral tranexamic acid and followed up for another 6 months. Altogether 25 patients were treated with TA follow-up. 8. Con- included. both scores for the perilesional skin increased. Twenty-five women were instructed to take two TA tablets (each con- tained 125 mg of TA. Patients randomized trial to assess the efficacy of oral TA in addition to the tri- were followed up for another 3 months after treatment period and effi.” “Hyperpigmentation. topical cream once daily for 8 weeks. 4 and 8 weeks. microinjection have been used to treat melasma. Among 32 patients who completed the study. and Yan (2014) enrolled 35 patients in a pro- (PIH) caused by Q-switched ruby laser (QSRL). faster reduction in pigmentation observed in combination therapy as Same year. and 16 weeks. recurrence was seen in 9. day along with topical therapy for 3 months in group A (n 5 130) while Padhi and Pradhan (2015) enrolled 40 patients in an open labeled group B (n 5 130) was treated only with topical preparations. the total improvement rate was found among 98. ple combination cream containing fluocinolone acetonide 0. After a 6 month independent physicians. (2012) enrolled 74 patients in their study and compared to topical treatment alone at 4 and 8 weeks. The patients chosen had if >90%. 4. Response was evaluated using Patients rating for good to excellent outcome accounted 82.3% and MASI at baseline.1% fair). the total improvement rate was found among 95. and Timalsina (2012) in a prospective manifestations revealed the color and size of skin lesions had signifi- randomized controlled trial of 260 patients with melasma. Objective assessment or 2 months (94.8% among group A and B. TA was prescribed at a dose of 250 mg twice a and 12 weeks. formed based on a post hoc analysis of photographic records by three jects (10. Amatya. Na et al. prophylactic effect of TA against postinflammatory hyperpigmentation Li. Results were measured by clini- Nine studies discussing oral TA for treatment of melasma were found cal and photographic assessment and were rated based on percentage (see Table 1). and 100% in 16 weeks. The initial refractory melasma treated with oral TA 250 mg twice daily in addition diminishment of melasma was detected after 1 month (82. Histological administration. The effects of treatment were evaluated by two physi. Razouria. All studies that evaluated the effect of TA. Fu. fair if >30% and poor if <30%). on melasema and hyperpigmentation were included. and 31. Chua. 12. period of 6 months and followed up all patients for another 6 months Tan. and 12% fair). After 6 months of treatment. The mean lesional melanin index (MI) scores and the Embase. 63% good. KC.117 patients.” No time limita. between participants in two groups. respectively.5% of the subjects Kato et al. for a mean period of 3.6% patients) of treatment. of oral TA in the treatment of melasma refractory to topical skin- cians independently based on improvement of pigmentation (excellent lightening agents in a retrospective study. noin 0. He.7 months (range 2–8 months). They used a 5-point scoring system in Skin Tone treatment. Subjects were given 250 mg oral TA twice a day for 6 months 3. Wu et al. The efficacy prescribed oral TA at a dosage of 250 mg twice daily for a therapeutic was maintained throughout the 6-month follow-up period.” each visit and skin biopsies were collected from eight subjects before “Pigmentation. that the improved patients accounted for 85% in 4 weeks. and hydroquinone 2% in melasma treatment.” “Chloasma. assessed the cantly improved. A 40. effects of oral TA in conjunction with topical TA on the melasma. Among 22 subjects that completed the tion was considered in this review. No significant difference in the incidence of PIH was shown Color Scale to evaluate the severity of melasma at baseline. Medline. in all route of siderably.5% of patients. Sun. This study seeks to Also. and Goh (2016) evaluated the therapeutic effects after treatment. vessel numbers and mast cell counts. treti- cacy was measured based on Melasma Area and Severity Index (MASI). 50 mg of ascorbic acid. 4 mg of calcium pantothenate and 1 mg of pyridoxine chloride) three times a 2 | METHODS day along with the use of topical TA (2% TA and 2% naicinamide) twice A literature search was performed using PubMed.3% of patients after follow-up period. Patients on treatment spective open label study and prescribed 500 mg oral TA three times arm (n 5 17) received 750 mg TA per day for first 4 weeks after laser daily for 4 months. parallel-group study to assess the 12. After 6 months of treat.01%. comprising a total of 1. clinical Karn. 40 mg of L-cysteine.” and “Lightening. 97% in 8 quinone and sunscreen. Group A While statistically significant decrease in the mean MASI from baseline patients (n 5 20) were asked to apply the cream only and group B to 8 and 12 weeks was observed in group A. a day for 8 weeks. From the objective evaluation of results.05%. among group B the patients (n 5 20) received oral TA 250 mg twice daily and applied the decrease in mean score was significant only at 8 weeks follow up. good if >60%. ment of melasma. (2013) carried out a clinical study to elucidate the review the available literature discussing the efficacy of TA in treat. analysis showed significant reduction of epidermal pigmentation.4% patients) to pre-existing combination topical therapy. Recurrence was seen in without melasma in a randomized. He. and the Cochrane database systematic reviews. All patients completed the study. Aamir and Naseem (2014) performed a cross sectional study of 65 3 | RESULTS patients to evaluate the efficacy of oral TA in the treatment of mel- asma. Key words erythema index (EI) scores was measured using a Mexameter® during used as search terms were “Tranexamic acid.” “Melasma. both the lesional MI and EI scores decreased significantly.9% of the sub. The mean MASI . Sen. using the physician’s global assessment and MASI scores were per- ment. 54% good. Sample sizes ranged of improvement like Wu et al study17. Only English language articles were study.8% excellent.

Color Scale and 100% in 16 weeks.4% worsened. Oral TA is an effective and safe photo. therapy mean improvement in scores was 69%. Aamir and Naseem 65 Clinical and 500mg daily for 6 months No No Patients rating for excellent. 10. ments and those who did not.500 mg daily for 2 No No The MI and EI scores decreased TA decreased epidermal pigmenta- scores months significantly. (2012) 25 MI and EI 1.1% asma. (2011) 32 Clinical and 750 mg daily for the first Yes No There was no significant difference Oral TA may not be effective for colorimetric 1 month after QSRL in the incidence of PIH between preventing PIH after Q-switched assess.63%.T A B LE 1 Oral TA in treatment of melasma TARAZ Patient Assessment Placebo ET AL.01%. number and increased numbers of mast cells. and 4. MI 5 melanin index. improvement in the treatment of and hydroquinone 2% nificant at 4 weeks and 8 weeks melasma once daily for 2 months Tan et al. | TA 5 Tranexamic acid. No No The mean MASI scores after TA Low-dose oral TA can serve as a safe tion to pre-existing treatment were significantly lower and useful adjunct in the treat- combination topical than those prior to treatment.05%. tretinoin 0. Oral TA seems to be a potentially ing system months tients accounted for 85% in 4 new and promising therapeutic in Skin Tone weeks. (2014) 35 5-point scor.7% patients had documented Oral TA may be an effective adjunct Global for median of 4 months improvement. 97% in 8 and 12 weeks. The ment of refractory melasma. vessel dermal changes. the results were statistically sig. and 0. 3 of 8 . (2016) 561 Physician TA 250 mg twice a day No No 89.500 mg daily for 4 No No They found that the improved pa. Wu et al. Karn et al. ma. combination group as compared based triple combination cream cinolone acetonide to topical group was shown and results in a faster and sustained 0. EI 5 erythema index.1%. (2012) 74 Clinical and 500 mg daily for 6 No No Patients rating for excellent. treatment participants who received oral TA ruby laser. Oral TA is a safe and effective (2014) photo. (2012) 260 MASI 500 mg daily for 3 Yes No Significant decrease in the mean Addition of oral TA provides rapid months MASI from baseline to 8 and 12 and sustained improvement in the treatment of melasma. fair. assessment respectively Na et al. months fair.54%. PIH 5 postinflammatory hyperpigmentation. Study number tool Dose and duration Control group group Result Conclusion Kato et al. 1. Histological analysis tion associated with melasma and showed significant reduction of also reversed melasma-related epidermal pigmentation.8% . mMASI 5 Modified Melasma Area and Severity Index. assessment spectively Li et al. and 1.0% remained for refractory melasma Assessment unchanged. option. 12%. 31. such as vessel numbers and mast cell counts.5% re. and poor outcome accounted treatment in patients with melas- graphic 23% . good. (2016) 25 MASI TA 500 mg daily in addi. Lee et al. and poor outcome accounted therapy for the treatment of mel- graphic 10. good. Padhi and Pradhan 40 MASI 500 mg daily and topical Yes No Faster reduction in pigmentation in Addition of oral TA to fluocinolone- (2015) cream containing fluo.

cation of 3% TA cream twice a day (group A. Both MASI and MI improved signifi- combination group and 21 in the laser group completed the study. good. 66. A total of 51 hydroquinone and 0. there was significant improvement with no difference between 3. 0–25%. 6. and no of oral TA. Pigmentation chloric acid) three times per day. n 5 8) or intradermal Patients without family history of melasma had better response rates injections of TA 0. IPL and laser. while Shin. For the MASI.2% poor). 39. Patients were divided in group A a day.5% versus 66. 89. In objective evaluation both treatments were effective. n 5 10). randomized. 72% of the patients had a relapse of melasma within efficacy of topical TA in treatment of melasma.3% vs. alone group.5% of patients rated mel- asma improvement as good and 50% as imperceptible in group A. such as patients graded as having improved more than 75% in the laser. 30. 40 mg vehicle for treatment of melasma. 27. Five clinical studies 2 months of ceasing TA. Patients have been on oral TA for at least 2 months (dur. Photographic evolution. Two blinded dermatologists eval- and erythema were measured using MASI and Mexameter. months (range 1–48 months). Park.The dosage prescribed was 250 mg twice Steiner et al. than laser treatment alone. 30% of patients using TA versus 39. 51–75%. Choi. Based on patients’ evaluated by two investigators using digital photographs. Twenty uated patients using the mMASI.1%. (2009) enrolled 18 female with melasma in an open- a day. with no oral TA combined with low-fluence 1064-nm quality-switched neo- statistical difference between groups. Oh. All patients were treated with two sessions of involving 25 women by Kanechorn Na Ayuthaya. The degree of improvement was based on Physician Global pigs.4 of 8 | TARAZ ET AL. Moreover. Ebrahimi and Naeini (2014) enrolled 50 patients with melasma in a In 2013. The resulting data showed that a treatment regimen combining laser However. Twenty three patients in the one patients completed the study.7 months. 21. Manos- laser. change in 37.3% good. In each self-assessment. A significant decreasing trend was observed in the MASI score of both ing treatments) and up to 8 months. vs. Niumphradit. 53 mg coated ascorbic acid.8–6 months).7% of patients had docu- label trial and randomly assigned them to receive either at home appli- mented improvement. and topical solution of 3% intense pulsed light (IPL) and laser treatment in melasma.05 ml (4 mg/ml) in 1 cm interval once per week for than those with family history.1% excellent. The (n 5 24) that received oral TA 500 mg daily during IPL therapy and patient’s self-assessment of melasma improvement was graded along three or four times of low fluence QSNY laser treatments at 1–2 four scales: excellent. vessel number and increased numbers of mast cells. patients were found. and 0. Histological analysis on skin biopsies revealed that melanin con- Assessment. These differences were not . 26–50% weeks interval and group B (n 5 27) those who were treated with only and poor. Duration of treatment was a median of 4 months (range tent in the basal layer of UV-exposed epidermis is significantly reduced 0.3 | Topical tranexamic acid onset of lightening at 1.7%. 4 mg calcium pantothenate. the results did not reach statistical difference. worsening in 50% versus 11. 10% remained unchanged. the number of patients As previously mentioned Na et al. In terms of treatment response. In 1998. and Lee (2013) carried a controlled trial double-blind. and 39. Patients applied topical TA or vehicle L-cysteine. About the self-assessment. Maeda and Naganuma (1998) were Lee. with oral TA led to a significantly greater reduction in mMASI score the EI at 12 weeks on the TA-treated side was higher than the vehicle. dymium-doped yttrium aluminum garnet (QSNY) laser for the treat- In 2012.2 | Oral tranexamic acid with laser treatments.7% rated improvement as good and 33. fair. The MASI was evaluated at baseline and every 4 weeks.4% worsened. cantly at 12 weeks as opposed to baseline in two groups of patients. The follow-up period was up to 6 Table 2 summarizes the clinical studies that have been evaluated the months. MASI and self- was seen within 2 months of TA initiation (range 0. 12-week split-face trial. Of the 503 who improved. 37. and Nakakes (2012) assessed the efficacy of topical 5% TA versus TA-based medication(125 mg TA.3% group A than group B. a 12-weeks randomized double blind split-face trial ment of melasma. scores after TA treatment was 69% lower than at baseline with mean 3. Thng.2% with a median duration of 7 months on cessation in 12. >75% lightening. and Goh (2016) conducted a retrospective analysis of found that post-exposure applications of 2 and 3% solutions of TA patients who received oral TA for melasma. 33.4% of patients group.3% as impercep- trial among 48 patients to evaluate the clinical efficacy and safety of tible. Cho. and patients in the combination group took 8 weeks of oral roi. Cho. and 1 mg pyridoxine hydro- blindly to the designated sides of the face twice daily.01% dexamethasone on the other side two times patients were included in the study. Modified MASI scores were blindly groups with no significant difference between them.4% fair. (2013) showed that combination of graded as achieving improvements of greater than 50% and 75% oral and topical TA decreased epidermal pigmentation associated with that was significantly higher in the combination group.03–22 months) whereas the duration of follow-up was a median of 7 in the regions to which TA solutions have been applied.2% in group A versus group B. with no melasma and also reversed melasma-related dermal changes. In all. However. Photographic evaluation showed improvement relapse rate of 27.4% vs. Thirty-nine patients successfully completed the trial. Reduction of mMASI score was significantly higher in after 12 weeks (3% vs. changes in the mMASI score were statistically significant after using combination solution possessed a favorable therapeutic response treatments. Patients applied 3% to evaluate the clinical efficacy and safety of oral TA as an adjuvant to TA topical solution on one side of the face. 561 patients were could prevent hyperpigmentation induced by UV exposure in guinea enrolled.5% versus 22. and Lee (2013) conducted a prospective randomized in group B. response 12 weeks (group B. Conversely. with a assessment were used. despite continuing topical combination skin with total of 144 patients and sample sizes ranged from 18 to 50 lightening agents.

Kim et al. superiority of injection treatment. and treatments were effective. | 5 of 8 . mMASI 5 Modified Melasma Area and Severity Index. provement. TARAZ ET AL. (2016) 23 mMASI 2% TA formulation to the No No The mMASI scores significantly im. with no 22.7% of patients showed im. How. Topical TA is effective as a treatment whole face twice daily proved in 22 of 23 participants for melasma. 30 MASI 5% TA topical liposomeor Yes No The mean MASI scores significantly Topical liposomal TA can be used as (2015) 4% hydroquinone reduced in both treated sides after an effective and safe therapeutic cream twice daily for 12 week. Although lightening of pigmentation Ayuthaya et al. In group B. MI 5 melanin index. the results were not (2012) weeks. 50 MASI 3% TA topical solution or Yes No A significant decreasing trend was The topical TA as an effective and (2014) topical solution of 3% observed in the MASI score of safe medication for the treatment hydroquinone 1 0. for 12 weeks after 12 weeks application TA 5 Tranexamic acid. No dif- daily for 12 weeks.1% worsening.01% both groups with no significant of melasma. ferences were seen in patients’ and investigator’s satisfaction of melasma improvement between two groups. T A B LE 2 Topical TA in treatment of melasma Patient Control Placebo Study number Assessment tool Dose and duration group group Result Conclusion Steiner et al. 18 Photographic. For statistical difference between the MASI. lightening of pigmentation mens induced by TA gel was neither superior nor different compared to its vehicle although erythema was significant on the TA-applied site Ebrahimi et al. dexamethasone twice difference between them. MASI. with TA 0. 11. in objective evaluation both / ml) for 12 weeks. A greater decrease was agent in melasma.2% remained unchanged. Banihashemi et al. worsening in 50%.05 ml (4 mg 66. in 12. TA 3% cream twice a day Yes No In group A there was improvement Although the subjective clinical eva- (2009) colorimetry or once weekly of in. 12 weeks observed with 5% liposomal TA. there was significant groups improvement with no difference between treatments Kanechorn Na 23 MI score and MASI 5% TA gel or vehicle Yes Yes MI and MASI scores were signifi. and luation has demonstrated the evolution tradermal injections no change in 37. twice daily for 12 cantly reduced on both tested was obtained. sides compare to baseline. significant between the two regi- ever. although this difference was not statistically significant.5%.5%.

The authors found that at the basal layer containing 2% TA three times a week. of combined solution were significantly prominent compared with TA.4 | Topical tranexamic acid with IPL more than 50% improvement. Endothelin (ET)21 was found to be downregulated with TA. Clinical cantly from baseline to 12 weeks after the last IPL treatment on the efficacy was categorized based on reduction in mMASI into five as topical TA side but not on the vehicle side. and no response (no change). significantly decreased the mMASI score from the baseline to the end of the treatment but it was less effective than silymarin cream and gly- 3. and 12 weeks. showed 3. Fujiwara.1% as poor (0 to 25% separately for each side at the baseline and every month until one lightening). Jaafari. The procedures baseline and week 4. The efficacy of topical TA in excellent (if > 75%). The localized microinjection of TA revealed a statistically significant improvement on the topical TA side. weeks was observed.38%) in the microneedling group. and 12 but the melanin content was significantly lowered. Thirty women were enrolled in a split.05 mL TA (4 mg/mL) was injected intradermally at 1 cm intervals. In oral ment of melasma.500 mg . poor (< preventing rebound pigmentation after 12 weeks of the last IPL also 25%). or intralesional) used in treatment of melasma. Histological evaluation of skin ment was performed at monthly intervals.09%) in the microinjections group. Six patients (26. Based on MASI and colorimetric evaluation both treatment TA. were evaluated using the mMASI at baseline and weeks 4. Budamakuntla et al. (2010) used intradermal TA (5 mg/mL) on guinea pigs. Li et al. asma. 4. 8. it has been mostly used at dosage of 500 to 1. The mean MASI scores significantly reduced in both treated cacy of topical 3% TA to intradermal injection of TA in 18 women with sides after 12 week. ment of melasma. The lightness values were done three times at monthly intervals (0. and glycolic acid peeling 50% (n 5 20) in treat- Patients were followed up for 12 weeks after the last 4th IPL treatment. effects and mechanism of action of topical TA in the treatment of mel. 9. Topical 2% TA or vehicle was to compare the efficacy of intradermal injection of TA (n 5 20). 15 women who received a total of four sessions of IPL treatment on a Elfar and El-Maghraby (2015) enrolled 60 female in a clinical study monthly basis to both sides of the face. MASI scoring and patient global assess- lesional and perilesional normal skin. line and at 4. topical applied to a randomly assigned side during and after IPL treatment. Twenty-three patients completed the As previously mentioned. there was 35. Clinical effects of exposed epidermis. significantly improved melasma with no difference between Kim.5 | Tranexamic acid microinjection colic acid peeling. and Jabari (2015) com. the two groups. 4 | DISCUSSION In 2006. (2013) in a prospective open-label study ran- meter. Salehi. to the designated sides of the face assessment. domly assigned 60 patients in ratio of 1:1 to localized microinjections pants after application. and Lee (2015) conducted a randomized. According to the patients’ self- TA and 4% hydroquinone cream. Among 85 patients who completed the pare therapeutic effects of liposomal TA and conventional hydroqui. A greater decrease was observed with liposomal melasma. as compared to 12 patients (41. and 14. statistically significant between two groups. good (25–50%). Patients blindly applied 5% topical liposomal that during the first 4 weeks. month after treatment course. Injection was performed face twice a day and the nonwoven fabric mask immersed in skin lotion every day for another month.05 ml (4 mg/ml) into MI scores and mMASI were determined. trial. The mMASI scores significantly improved in 22 of 23 partici. the side effects 0. split-face study in although the difference was not statistically significant. Among 13 patients who com- the melasma lesion at 1 cm interval weekly for 12 weeks. and 8 weeks) and fol- were increased and the erythema values were decreased in both lowed up for further 3 months. although this difference was not statistically significant. from 18 to 100 patients that evaluated the effect of TA microinjection or microneedling on melasma were found. and between weeks 4 and 8. a significant decrease in the mean MASI from baseline to 8 and 12 none dosage form on melasma. the number of melanocytes was not reduced. Skin pigmentation was measured using MASI at each visit 76. and no response in four patients Four clinical studies with total of 238 patients and sample sizes ranged (20%) were detected in TA treatment group. poor and microneedling response in eight patients (40%).4% rated improvement as good (51 to 75% lightening). This was repeated weekly for 12 weeks. Steiner et al. Improvement after week 4 was more rapid than face trial lasting 12 weeks. The improvement was significant between of TA (4 mg/mL) or TA with microneedling (4 mg/mL).72% improvement in the MASI score compared to tent in the epidermis. Shibata. Park. silymarin cream (n 5 20). Good response in eight patients (40%). (2009) compared the effi- study. twice daily. Lee. In the microinjection group. biopsies from 10 patients showed a significant decrease in melanin con. The number of CD31-positive vessels and the 44. for 12 weeks. the mean MI and mMASI scores decreased signifi- were followed up monthly for 3 months after the last session. topical.41% in the microneedling group. However. Twenty three patients applied a 2% TA emulsion to the whole which had been exposed to UVB for 1 month. The scores revealed better improvement in patients treated with microneedling than with microinjections Chung. Lee et al (2006) conducted a prospective open-label study to assess the efficacy of localized microinjection of TA for the treat. A total of 100 women were enrolled in study and administration. 8. and Kang (2016) investigated the treatments.6 of 8 | TARAZ ET AL. TA (oral. MASI was calculated at base- Banihashemi. The patients pleted the study. at the end of third follow-up visit. Zabolinejad.5% as fair (26 to 50% lightening). and skin pigmentation and erythema were measured using a chroma. TA was injected intradermaly 0. very good (50–75%). expression of the vascular endothelial growth factor both tended to There was no significant difference in the mean MASI scores between decrease.

.. 217–223. & El-Maghraby. Kuno.. (2012).. Li. N.. M. Elfar.. Journal of Clinical Experi- sion. & Yan. (2014).. melasma in Pakistani population: A pilot study. A. Fu. 41. T. E. Y. M. Y. M. Park. size of this study or momentous effect of sun protection in melasma Gupta. J. M. 6.. be effective as well as topical hydroquinone alone. A randomised.. Journal of Photochemistry and Photobiology B. 35–43.. 753–757. . H. G.. (1995). Yoshimura. 385–392. 198–203. ent studies ranging from 1 month to 6 months. Chow. G. C. L. P. K. . Journal of Cutaneous and Aesthetic Surgery. other topical treatment such as IPL and laser. M. Journal of The Ameri- Aamir. Park. tion of ranexamic acid. Topical tranexamic acid as an well tolerates and common side effects include gastrointestinal discom- adjuvant treatment in melasma: Side-by-side comparison clinical fort and menstrual irregularities (Aamir & Naseem. Karn et al.. 4.. it is possible that the small sample ing pregnancy. Lee. S. M. M. Salehi. 11.. He. 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