Efficacy of intradermal injection of tranexamic acid and ascorbic acid versus tranexamic acid and placebo in the treatment of melasma: A split‐face comparative trial

Abstract

Background and Aims
Melasma is a common dermatologic disorder characterized by symmetrical hyperpigmented lesions on the face. Although various therapeutic options are available for melasma, its treatment remains challenging. The present study evaluated the safety and efficacy of intradermal microinjection of tranexamic acid (TA) plus ascorbic acid in treating melasma lesions compared with TA and placebo.

Methods
From September 2019 to May 2020, 24 patients with symmetrical melasma were enrolled in a prospective, double‐blind, split‐face, randomized controlled clinical trial. Each patient received 50 mg/ml TA and 50 mg/ml ascorbic acid for one side of the face (A) and 50 mg/ml TA and placebo for the other side (B) every 2 weeks for 12 weeks. The Melasma Area and Severity Index (MASI) score, Physician Global Assessment, and pain were measured at baseline and at 4, 8, 12, and 24 weeks. Statistical analysis was done using SPSS software version 16, and data were reported as mean ± standard deviation or median and interquartile range. χ² and Fisher's exact tests were used to test differences between the groups.

Results
Both groups experienced a significant decrease in MASI scores compared with the baseline. The MASI score was significantly less in the intervention group than the placebo group at the 8th and 12th weeks. However, burning pain was significantly more prominent in the intervention group.

Conclusion
Intradermal injection of ascorbic acid combined with TA can be beneficial in treating melasma. Currently, there are numerous treatment modalities for melasma. However, the results still vary, and satisfactory outcomes are yet to be reached.

Full text

Received: 18 June 2021
|
Revised: 23 November 2021
|
Accepted: 7 December 2021
DOI: 10.1002/hsr2.537
ORIGINAL RESEARCH
Efficacy of intradermal injection of tranexamic acid and
ascorbic acid versus tranexamic acid and placebo in the
treatment of melasma: A split‐face comparative trial
Nader Pazyar
1
|Seyedeh Nasrin Molavi
2
|Parisa Hosseinpour
3
|
Maryam Hadibarhaghtalab
4
|Seyedeh Yasamin Parvar
4,5
|
Motahareh Babazadeh Dezfuly
1
1
Dermatology Department, Ahvaz
Jundishapur University of Medical Sciences,
Ahvaz, Iran
2
Dermatology Department, Emam Hospital,
School of Medicine, Ahvaz Jundishapur
University of Medical Sciences, Ahvaz, Iran
3
School of Medicine, Islamic Azad University,
Kazeroun Branch, Kazeroun, Iran
4
Molecular Dermatology Research Center,
Shiraz University of Medical Sciences,
Shiraz, Iran
5
Student Research Committee, Shiraz
University of Medical Sciences, Shiraz, Iran
Correspondence
Maryam Hadibarhaghtalab, Molecular
Dermatology Research Center,
Shiraz University of Medical Sciences,
Shiraz 1433671348, Iran.
Email: Maryam_hadibarhaghtalab@yahoo.com
Funding information
Nutrition and Metabolic Disease Research
Center of Ahvaz Jundishapur University of
Medical Sciences, Grant/Award Number:
NRC‐9604
Abstract
Background and Aims: Melasma is a common dermatologic disorder characterized
by symmetrical hyperpigmented lesions on the face. Although various therapeutic
options are available for melasma, its treatment remains challenging. The present
study evaluated the safety and efficacy of intradermal microinjection of tranexamic
acid (TA) plus ascorbic acid in treating melasma lesions compared with TA and
placebo.
Methods: From September 2019 to May 2020, 24 patients with symmetrical mel-
asma were enrolled in a prospective, double‐blind, split‐face, randomized controlled
clinical trial. Each patient received 50 mg/ml TA and 50 mg/ml ascorbic acid for one
side of the face (A) and 50 mg/ml TA and placebo for the other side (B) every
2 weeks for 12 weeks. The Melasma Area and Severity Index (MASI) score, Physician
Global Assessment, and pain were measured at baseline and at 4, 8, 12, and 24
weeks. Statistical analysis was done using SPSS software version 16, and data were
reported as mean ± standard deviation or median and interquartile range. χ
2
and
Fisher's exact tests were used to test differences between the groups.
Results: Both groups experienced a significant decrease in MASI scores compared
with the baseline. The MASI score was significantly less in the intervention group
than the placebo group at the 8th and 12th weeks. However, burning pain was
significantly more prominent in the intervention group.
Conclusion: Intradermal injection of ascorbic acid combined with TA can be bene-
ficial in treating melasma. Currently, there are numerous treatment modalities for
melasma. However, the results still vary, and satisfactory outcomes are yet to be
reached.
KEYWORDS
ascorbic acid, MASI score, melasma, split‐face injection, tranexamic acid
Health Sci. Rep. 2022;5:e537. wileyonlinelibrary.com/journal/hsr2
|
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https://doi.org/10.1002/hsr2.537
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC

1|INTRODUCTION
Melasma is a common skin issue that results from melanogenesis
dysfunction. It is particularly prominent in middle‐aged women and is
characterized by dark, hyperpigmented patches. The exact etiology of
the disease is still unknown. However, factors like oral contraceptives,
steroids, exposure to sunlight, pregnancy, hormone replacement
therapy, ovarian tumors, and a stressful lifestyle may promote the
development of the disease.
1,2
Therefore, the emergence of melasma
is influenced by various factors and depends on environmental inter-
actions, hormonal effects, and genetic susceptibility. Although mel-
asma is found in all races, it is more prevalent in darker skin phototypes
(Fitzpatrick skin III−V); it mainly affects people of Asian, Middle
Eastern, Latin American, African, or Hispanic descent.
3
Even though melasma is primarily a cosmetic concern, this con-
dition can dramatically impact the quality of life of affected patients
and causes depression and frustration, reducing their psychosocial
quality of life. In 2003, Balkrishnan and colleagues developed and
evaluated the Melasma Quality of Life Index. It was reported that
65% of patients felt discomfort due to spots on their face, while 55%
felt frustrated and 57% felt ashamed of their skin condition.
4
A lit-
erature review by Pawaskar et al.
5
also found that melasma has a
severe impact on health‐related quality of life and deleteriously af-
fects patients' emotional wellbeing, social life, and physical health.
Nowadays, various treatment modalities are used to eliminate
the lesions and prevent recurrences, including systematic and topical
agents along with light‐based therapies and lasers.
6
Broad‐spectrum
sunscreens, retinoic acid (tretinoin), azelaic acid, ascorbic acid, tra-
nexamic acid (TA),
7
and chemical peels (such as salicylic acid and
glycolic acid) are other treatment options have been described in the
literature.
8
TA acts as an antifibrinolytic agent by inhibiting the tissue
plasminogen activator. It has been shown to reduce blood loss and
transfusion requirements in surgical procedures, including emergency
trauma surgery, cardiovascular and spinal cord surgery, and hip and
knee arthroplasty procedures. TA is also the only FDA‐approved drug
for heavy menstrual bleeding. The amount of TA used to treat mel-
asma is much less than the antifibrinolytic dose. The hypo-
pigmentation effect of TA is due to its antiplasmin activity.
9–12
According to the comparative study of the efficacy of in-
tradermal and topical TA versus a triple combination of tretinoin
0.025%, hydroquinone 2%, and fluocinolone acetonide 0.01%, in-
tradermal TA led to a significant decrease in the Melasma Area and
Severity Index (MASI) score compared with the other groups.
13
In a
split‐face controlled trial by Saki et al.,
14
a monthly intradermal in-
jection of TA was associated with significantly reduced melanin
content compared with topical hydroquinone during the first 4 weeks
of treatment. However, after 20 weeks, the overall changes were not
significant.
Topical and intradermal injection of ascorbic acid is another
option for treating melasma lesions. Espinal‐Perez et al. conducted a
double‐blind, randomized controlled trial evaluating the effect of 5%
ascorbic acid versus 4% hydroquinone in treating melasma. In this
study, both treatments showed satisfactory results without statistical
differences in colorimetric measures. Nevertheless, those who re-
ceived hydroquinone reported more side effects than those who
received ascorbic acid (68.7% vs. 6.2% of patients).
15
The present study aimed to compare the efficacy and adverse
effects of administering 50 mg/ml TA and 50 mg/ml ascorbic acid
intradermally versus TA and placebo in treating facial melasma
lesions. It should be noted that while TA has direct interactions with
aspirin, epinephrine, acetaminophen, and 30 other drugs, it does not
directly interact with ascorbic acid according to the Medscape and
other approved websites.
16
2|MATERIALS AND METHODS
This prospective, double‐blind, randomized split‐face controlled trial
was conducted on patients diagnosed with melasma referring to the
dermatology clinic of Ahvaz Imam Khomeini Hospital affiliated with
Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. The
sample size was measured as 24 patients in each group according to
the formula below and a related study by Iraji et al.
17
(95% con-
fidence interval, 80% power, α: 0.02, β: 0.04, S
1
: 0.8, S
2
:1.3, mean 1:
1.5, mean 2: 2.8).
()
N
zz σσ
d
=
(+)×+
.
β
1−() 1−21
22
2
2
α2
We included all females aged 18−50 years who had symmetrical
melasma with Fitzpatrick II−IV skin types. To reduce the possibility of
selection bias, one side of the face was randomly treated with TA and
ascorbic acid, while the other was treated with a placebo. We ex-
cluded patients with a history of melasma treatment within the last
month; pregnant or lactating women; those who were sensitive to
the studied drugs; patients with coagulation disorders; patients using
oral contraceptives, anticonvulsants (phenytoin), or anticoagulant
medications since the past year; and patients with active herpetic
lesions and warts on the face.
This controlled trial was conducted in line with the CONSORT
statement from September 2019 to May 2020, and the Ahvaz Jun-
dishapur University of Medical Sciences Ethics Committee approved
the study. Participants were given necessary information regarding
the study, and written informed consent was obtained before com-
mencing the investigation.
2.1 |Study implementation
In the beginning, all participants were examined using a wood lamp to
determine the melasma type (dermal, epidermal, or mixed). Demo-
graphic characteristics including sex, age, predisposing factors
(pregnancy, exposure to ultraviolet rays, and oral contraceptives),
family history of melasma, skin phenotypes, duration of the disease,
type of melasma, affected body parts, and history of previous
treatments were recorded.
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In the following step, after administering a local anesthetic (lido-
caine/prilocaine) and dressing on the face for 60 min, an intradermal
injection was performed using a 1 ml syringe with intervals of 1 cm. To
keep the distance of injections at 1 cm intervals, we measured the dis-
tances with a ruler and marked them with a pen. Thirty minutes after the
procedure, the spots were cleaned with an alcohol pad. Each site was
injected with 0.1 ml of the solution. Intradermal injection of drugs was
performed by injecting the needle at an angle of 5−15° into the skin,
leading to the formation of a wheal‐like area on the skin.
18
TA and
ascorbic acid were available in vials of 500 mg per 5 ml solution. In Group
A, one side of the face was injected with 0.5 ml of TA (50 mg) and 0.5 ml
of normal saline. In Group B, the other side of the face was injected with
0.5 ml of TA (50 mg) and 0.5 ml of ascorbic acid (50 mg). After the in-
jection, patients were advised to apply a cold compress and use sunsc-
reen. Injections were performed in 2‐week intervals for 12 weeks.
2.2 |Outcome measures
Based on standard guidelines, the MASI was used to evaluate the in-
volved area, darkness, and homogeneity of hyperpigmentation. For
calculating the involved area (A), the right side of the forehead, the
cheek, and the chin were calculated as 15%, 30%, and 5% of the whole
face, respectively. Similar areas on the left side of the face were calcu-
lated in the same way, reaching a total of 100%. The final score ranged
between 0 and 6 (0=no involvement, 1=0%−9%, 2=10%−29%,
3=30%−49%, 4 = 50%−69%, 5=70%−89% and 6 = 90%−100%). Dark-
ness (D) is evaluated based on a 0−4 scale: scale 0 means the absence of
any darkness; scale 1 is a light brown color; scale 2 is a brown color; scale
3 is a dark brown color; scale 4 means black. Homogeneity (H) is mea-
sured on a 0−4 scale, from the minimal to the maximal grade of
homogeneity. At last, the MASI score is calculated by multiplying the A
score by the sum of D and H for each of the six regions. The maximum
score for each side is 24, and the minimum is zero.
MASI score: 0.15(A)(D + H) + 0.3(A)(D + H) + 0.05(A)(D + H).
Patients were visited, and the MASI score and potential side effects
were evaluated at baseline and after 4, 8, 12, and 24 weeks of treatment.
The Dynamic Physician Global Assessment (Dynamic PGA) was
also used to evaluate the response to treatment by taking photographs
of the lesions with a digital camera (Samsung Galaxy Note10+) at the
FIGURE 1 Flow chart of the clinical trial (each number represents one face side of the participants)
PAZYAR ET AL.
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beginning and end of the study. In this scale, 0%−25% improvement
was reported as poor improvement, 26%−50% and 51%−75% were
reported as fair and good improvement, respectively, and 76%−100%
improvement in lightening was reported as an excellent improvement.
The patients' pain score was also recorded on a scale of 0−10, where
0 indicates no pain and 10 indicates the most severe pain.
2.3 |Statistical analysis
Statistical analysis was done using SPSS software version 16 (SPSS
Inc.). A descriptive analysis was done on the demographic informa-
tion, and data were reported as mean ± standard deviation (SD) or
median and interquartile range (IQR) in case of nonparametric vari-
ables (e.g., duration of melasma). Frequencies were presented as
numbers and percentages. χ
2
and Fisher's exact tests were used to
test the differences between the categorical variables. A pvalue less
than 0.05 was considered significant.
3|RESULTS
Thirty female patients with bilateral symmetrical melasma lesions
were eligible for the study (Figure 1). One patient was excluded from
the study due to pregnancy, while another was excluded due to using
other treatment modalities. Twenty‐eight patients were enrolled in
each group. Furthermore, two participants were also lost to follow‐up
due to transportation issues and the COVID‐19 pandemic, and two
participants discontinued the treatment due to injection pain.
Therefore, a total number of 24 patients with 24 sides of the face in
each group were injected and analyzed.
The mean age of the studied patients was 35.54 ± 5.26 years, ran-
ging from 28 to 46 years; most patients were in their forties (62.5%). The
median duration of the disease in the studied patients was 4.0 (IQR
2.0−6.0) years, ranging from 1 to 12 years. Seventeen patients (70.8%)
had a positive family history of melasma, and 16 patients (66.7%) had a
positive history of previous treatment. According to the distribution of
melasma, eight patients (33.3%) had centrofacial lesions, and the other
16 patients had malar patterns. Eighteen patients (75%) had epidermal
melasma 1, 9, and 14 participants had Fitzpatrick skin types II, III, and IV,
respectively. Demographic data of patients and melasma features are
shown in Table 1.
Evaluation of melasma exacerbating factors showed that one
(4.2%) of the patients had no aggravating factors, five (20.8%) had the
pregnancy factor. Also, six patients (25%) had the ultraviolet (UV)
light exposure factor, four (16.7%) had a history of taking oral con-
traceptive pills (OCP), five (20.8%) had both pregnancy and UV ex-
posure, and two (8.3%) had both factors of OCP pills and UV
exposure. Finally, one person (4.2%) had prior pregnancy, OCP, and
UV exposure as exacerbating factors.
A comparison of the effectiveness of treatment according to the
MASI score is shown in Table 2.During the study intervals, the MASI
score significantly decreased (pvalue between groups < 0.001) from
the eighth week onwards (8th, 12th, and 24th weeks compared with
the baseline). In general, the average MASI score of patients in Group
A decreased by 1.29 points, falling from 4.49 (SD 1.48) at the
baseline to 3.20 (SD 1.21) 24 weeks later. This is while the average
MASI score of patients in the intervention group decreased by 2
points from 4.61 (SD 1.54) at the baseline to 2.61 (SD 1.14) 24 weeks
later. It is also worth mentioning that there were statistically sig-
nificant differences in both groups in each follow‐up compared with
the last one (p< 0.001). Figures 2and 3show both sides of the face
of two patients before treatment and 24 weeks later.
The Physician Global Assessment (PGA) rated the improvement in
lesions in the tranexamic acid (TA) plus placebo group as excellent in 1
patient, good in 7, fair in 13, and poor in 3 patients. Improvement in
the TA plus ascorbic acid group was rated excellent in 3, good in 14,
fair in 6, and poor in 1 patient (Figure 4). The results showed a sta-
tistically significant difference between the two groups (p=0.003).
TABLE 1 Demographic data and melasma features of the study
population
Variable Category
Frequency, N(%) or
Median [IQR]
Age 20−30 4 (16.7)
30−40 15 (62.5)
40−50 5 (20.8)
Duration of melasma
(years)
Median (IQR) 4.0 [2.0−6.0]
Family history of
melasma, N(%)
Positive 17 (70.8)
Negative 7 (29.2)
Fitzpatrick skin type Type I 0 (0%)
Type II 1 (4.2)
Type III 9 (37.5)
Type IV 14 (58.3)
Distribution of
melasma
Centrofacial 8 (33.3)
Malar 16 (66.7)
Type of melasma Epidermal 18 (75.0)
Mixed 6 (25.0)
Previous treatment Positive 16 (66.7)
Negative 8 (33.3)
Predisposing factors Pregnancy 5 (20.8
UV 6 (25)
OCP 4 (16.7)
OCP + UV 2 (8.3)
Pregnancy + UV 5 (20.8)
Pregnancy + UV + OCP 1 (4.2)
Negative 1 (4.2)
Note: Frequencies are reported as number (%) and median [interquartile
range (IQR)].
Abbreviation: OCP, oral contraceptive pills.
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TABLE 2 Comparison of the effectiveness of the intervention
according to the Melasma Area and Severity Index (MASI) score in
groups A (tranexamic acid plus normal saline) and B (tranexamic acid
plus ascorbic acid)
Timeline Group (N= 24) Mean ± SD pvalue
Baseline A 4.49 ± 1.48 0.30
B 4.61 ± 1.54
4th week A 4.29 ± 1.44 0.63
B 4.34 ± 1.51
8th week A 3.66 ± 1.35 <0.001
B 2.40 ± 1.25
12th week A 2.82 ± 1.29 <0.001
B 2.40 ± 1.25
24th week A 3.20 ± 1.21 <0.001
B 2.61 ± 1.14
Note: Bold pvalues are statistically significant at 0.05%.
Abbreviation: SD, standard deviation.
According to the treatment complications in the studied patients,
all patients in both groups reported pain and burning sensation in the
injection site despite topical anesthesia. The mean pain score of
patients in the ascorbic acid group was significantly higher at
0.82 (SD 0.11), while in the placebo group, the mean pain score was
0.50 (SD 0.10) (p= 0.01).
4|DISCUSSION
Melasma is an acquired condition of the facial skin that mainly affects
childbearing women. Clinically, it commonly affects the face in a
centrofacial pattern of patches and macules with irregular borders.
The course of the disease is resistant to treatment and has a high
recurrence rate; therefore, treatment of melasma still requires more
evidence and a combination of effective pharmacological and non-
pharmacological interventions.
6
Ascorbic acid is one of the suggested supplements in managing
patients with melasma. It acts by chelating copper ions used in the
cellular pigmentation process, thereby inhibiting melanogenesis.
19
This study aimed to evaluate the effectiveness of intradermal in-
jection of a combination of TA with ascorbic acid on one side of the
face and compared it with the intradermal injection of TA plus
placebo on the opposite side in the treatment of melasma. The
findings showed that intracutaneous injection of a combination of
TA with ascorbic acid could significantly reduce the patients' MASI
scores from the eighth week onward compared with the pre‐
intervention condition.
FIGURE 2 Photographs of the same patient:
(A) Before treatment; (B) after treatment with
tranexamic acid and placebo; (C) before
treatment; (D) after treatment with tranexamic
acid and ascorbic acid
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In the present study, we injected ascorbic acid intradermally for its
accelerated effect, whereas topical ascorbic acid has limited penetration
in the skin and may cause extreme dryness.
20
In another study, Ismail
et al. conducted a clinical trial on 30 female patients in Greece on
microneedling with topical ascorbic acid in treating melasma. Micro-
needling followed by applying topical L‐ascorbic acid 20% in each ses-
sion resulted in a significant decrease in the MASI score from three
sessions onward without any serious side effects, especially in patients
with Fitzpatrick skin phototypes I−III. In line with our study, the men-
tioned study tested ascorbic acid with higher concentrations.
21
To date, no single therapy has been proven to be effective in
treating melasma. In contrast, combination therapies (e.g., tretinoin
plus corticosteroids plus hydroquinone) appear to be more beneficial
than monotherapy.
22,23
Ali Balvei et al., in a clinical trial in Australia,
evaluated the effect of a combination of mesotherapy with ascorbic
acid and salicylic acid (as a peeling agent) in one group and salicylic
acid alone in the other group. After 2 months of therapy with 2‐week
intervals between sessions, those who received ascorbic acid me-
sotherapy experienced a greater decrease in MASI scores than those
who received only the peeling agent. However, the reduction was not
statistically significant. The authors suggested that long‐term inter-
mittent maintenance therapy and additional treatment sessions could
be more effective in prolonging the activity of ascorbic acid in the
treatment of melasma.
20
A clinical trial by Surabhi Dayal et al. on
patients with epidermal melasma evaluated 20% trichloroacetic acid
versus combination therapy of 5% ascorbic acid cream and tri-
chloroacetic acid. The researchers showed that although both study
groups experienced a significant reduction in MASI score, combina-
tion therapy also led to a significant reduction in MASI score.
Furthermore, those who received trichloroacetic acid experienced
more side effects, though this was not significant.
7
Although the
study used ascorbic acid topically, a finding similar to the present
study was the effectiveness of adding ascorbic acid to the patient's
medication regimen and using a combination treatment.
FIGURE 3 Photographs of the same patient:
(A) before treatment; (B) after treatment with
tranexamic acid and placebo; (C) before
treatment; (D) after treatment with tranexamic
acid and ascorbic acid
FIGURE 4 Physicians Global Assessment (PGA) in melasma
patients injected with tranexamic acid (TA) plus placebo versus TA
plus ascorbic acid
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Recent studies conducted in Iran share a similar population to
that of ours and facilitate a more accurate comparison. Iraji and his
colleagues, in a comparative study conducted on 30 patients with
melasma, evaluated the effect of mesotherapy with ascorbic acid and
TA with and without glutathione. At the end of the study, both
groups experienced a significant decrease in the MASI score relative
to the baseline scores.
17
Like other injection methods, pain and burning were common
side effects of our treatment in all patients, though the ascorbic acid
group reported significantly more degrees of pain. In contrast, a study
by Liliana Elizabeth Espinal Perez et al. comparing the effect of
standard hydroquinone treatment with vitamin C found that vitamin
C had fewer adverse effects.
15
A mild to moderate burning sensation,
erythema, ecchymosis, and edema are other reported adverse effects
of vitamin C in the literature.
17,20
Our study had several limitations. First of all, if the sample size
had been larger, the results would be more accurate. Since enroll-
ment in the study required consent and multiple sessions of in‐person
visits were mandatory, access to a larger sample size was challenging.
Furthermore, some patients did not show up for the last follow‐up.
Secondly, there may be selection bias in assessing patients with facial
melasma. Another limitation of this study was that we only used the
MASI score for evaluating melasma. This is while other modalities,
including Visioface
®
photography and the Mexameter
®
, can allow a
more comprehensive analysis of melasma lesions.
5|CONCLUSION
The intradermal injection of a combination of TA and ascorbic acid
could significantly reduce patients' MASI scores, and this improve-
ment was sustained until 3 months. Currently, there are numerous
treatment modalities for melasma. However, the results still vary, and
satisfactory outcomes are yet to be reached. Thus, more research is
needed to find the most efficient treatment.
ACKNOWLEDGMENTS
This study was extracted from the thesis of dermatology resident Dr.
Seyedeh Nasrin Molavi. This study was financially supported by the
Nutrition and Metabolic Disease Research Center of Ahvaz Jun-
dishapur University of Medical Sciences (grant number: NRC‐9604).
CONFLICTS OF INTEREST
The authors declare no conflicts of interest.
ETHICS STATEMENT
The Ethics Committee of the Ahvaz Jundishapur University
of Medical Sciences approved the present study under code
number IR.AJUMS.REC.1398.623. The study was also enrolled
in and approved by the Iranian Registry of Clinical Trials
(IRCT20191213045719N1). Written informed consent was
obtained from all patients before initiating the trial. All patients
were guaranteed that their information would be kept confidential.
AUTHOR CONTRIBUTIONS
Conceptualization, supervision: Nader Pazyar. Conceptualization and
formal analysis: Seyedeh Nasrin Molavi. Methodology and writing—
original draft: Parisa Hosseinpour and Maryam Hadibarhaghtalab.
Supervision, writing—original draft and writing—review and editing:
Seyedey Yasamin Parvar. Methodology and supervision: Motahareh
Babazadeh Dezfuly.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the
corresponding author upon reasonable request.
ORCID
Seyedeh Yasamin Parvar http://orcid.org/0000-0002-3027-1843
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How to cite this article: Pazyar N, Molavi SN, Hosseinpour P,
Hadibarhaghtalab M, Parvar SY, Dezfuly MB. Efficacy of
intradermal injection of tranexamic acid and ascorbic acid
versus tranexamic acid and placebo in the treatment of
melasma: a split‐face comparative trial. Health Sci Rep. 2022;5:
e537. doi:10.1002/hsr2.537
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