Clinical trial

Efficacy of dioic acid compared with hydroquinone in the

treatment of melasma
Andrés Tirado-Sánchez, MD, MSc, Aleida Santamarı́a-Román, MD, and
Rosa Marı́a Ponce-Olivera, MD, MSc

From the Servicio de Dermatologı́a, Hospital Abstract

General de México, México
Correspondence
Andrés Tirado-Sánchez, MD, MSc
Servicio de Dermatologı́a
Hospital General de México
O.D., Dr Balmis 148, Col. Doctores
Deleg. Cuauhtemoc
México, D.F., C.P. 06720
E-mail: andrestiradosanchez@hotmail.com
Background Melasma is a common disorder of pigmentation characterized by relatively
symmetric, brown or gray–brown patches on sun-exposed facial areas. Hydroquinone, the most
effective agent in melasma, is known to irritate the skin, and so new alternatives in the treatment
of melasma are required. We sought to assess the clinical response of a new depigmenting
agent in melasma.
Methods Ninety-six Mexican female patients with melasma were enrolled in this open,
comparative, 12-week study. The patients received 1% dioic acid cream (twice daily) or 2%
hydroquinone cream (twice daily).
Results There was a significant difference in the Melasma Area Severity Index (MASI) scores
from baseline to the end of the study using treatment with dioic acid (baseline, 14.52 3.4; after
12 weeks of treatment, 6.05 ± 1.2; P ¼ 0.001) and hydroquinone (baseline, 15.22 ± 2.4; after
12 weeks of treatment, 6.34 ± 1.3; P ¼ 0.001); however, there were no significant differences
between treatments (baseline, P ¼ 0.311; after 12 weeks of treatment, P ¼ 0.287). The side-
effects were similar with both medications; however, pruritus was more common in patients
using hydroquinone.
Conclusions Dioic acid is an effective and highly tolerated skin product, although further
controlled, blind, multicenter studies are required to support these results.

(which regulates tyrosinase transcription) and by inhibiting

Introduction
Melasma is a common disorder of pigmentation characterized
by relatively symmetric, brown or gray–brown patches on
sun-exposed facial areas. The condition is commonly seen on
the faces of women with Fitzpatrick skin types IV–VI;
however, in Latin women, melasma is common in skin types
III–IV. Conventional treatment for melasma includes
elimination of any possible causative problem, the use of an
adequate sunscreen and depigmenting agents, with and
without the combination of other therapies, such as tretinoin,
topical corticosteroids, or superficial peeling agents.1,2 Hydro-
quinone (HQ) is the most effective agent in the treatment of
melasma, although it is quite aggressive in its action and is
known to irritate the skin;3 therefore, new alternatives for the
treatment of melasma are required. Dioic acid (DA) is a
monounsaturated dicarboxylic acid derived by biofermenta-
tion from oleic acid with an efficient whitening effect,4 which
interferes with cellular melanosynthesis by binding as an
agonist to nuclear peroxisome proliferator-activated receptor
melanosome transfer.5 We sought to assess the clinical
response of this new depigmenting agent in melasma.
Materials and Methods
Ninety-six Mexican female patients suffering from melasma were
enrolled in this open, comparative, 12-week study. Patients with
melasma aged 32–45 years, with Fitzpatrick skin type III, and with
mild to moderate bilateral and symmetric or mixed melasma,
confirmed with Wood’s lamp, were included. The exclusion criteria
included pregnancy, the use of HQ or other topical treatments
within 3 months of the study, and the use of oral contraceptives.
All participants provided written informed consent prior to
enrollment into the study. The study was performed with the
approval of the Investigation and Ethics Committee at our hospital.
Standard and UV photographs and the Melasma Area Severity
Index (MASI) score (to accurately quantify the severity of
melasma and changes during therapy, according to the procedure
modified by Kimbrough-Green et al.6) for the clinical examination 893

ª 2009 The International Society of Dermatology International Journal of Dermatology 2009, 48, 893–895
894 Clinical trial Dioic acid vs. hydroquinone for melasma Tirado-Sánchez, Santamarı́a-Román, and Ponce-Olivera

Table 1 Patient demographics Table 2 Side-effects observed in the study

Variable 1% DA (n ¼ 66) (%) 2% HQ (n ¼ 30) (%) Side-effect 1% DA (n ¼ 66) (%) 2% HQ (n ¼ 30) (%) P

Age (years) 43 ± 3.55 45 ± 4.22 Erythema 4 (6) 4 (13) 0.425

Duration of melasma (years) 9 ± 4.36 8 ± 3.33 Burning 8 (12) 2 (6) 0.652
Type of melasma Pruritus 2 (3) 6 (20) 0.039*
Centrofacial 9 (14) 2 (7) Acneiform reaction 20 (30) 3 (10) 0.057
Malar 16 (24) 10 (33)
Mandibular 6 (9) 3 (10) 2
*v statistically significant.
Mixed 35 (53) 15 (50)

Discussion
Melasma is one of the most common dermatoses in clinical
practice, and can have a severe effect on a patient’s quality of
were recorded at baseline and week 12. Chromametry and other
life.1 HQ is the most popular and effective treatment for
studies were not assessed.
melasma; however, certain side-effects, such as contact der-
The patients received 1% DA cream (twice daily) or 2% HQ
matitis and ochronosis, even at low concentrations,3 limit its
cream (twice daily). The type of treatment used by each patient
use, and have led to the search for a new, effective, and more
was determined by a computer-generated randomization code.
secure alternative.
Only gentle cleansing was required before application; no further
The results of our study clearly demonstrate the efficacy
degreasing was performed.
and safety of DA. We did not find any statistically significant
difference in the results between the DA and HQ groups (both
Statistical analysis
1% DA and 2% HQ showed the same efficacy in the treat-
The data obtained from MASI tests were analyzed using the par-
ment of mild to moderate facial melasma). After 12 weeks of
ametric Student’s t-test; the other data were analyzed using a
treatment, we observed a decrease in the MASI scores by
paired t-test. All tests were one-sided because improvement is
more than 40%. These results can be compared with the data
directional in nature.
obtained in other clinical trials. Topical retinoids decreased
MASI scores by 20% (tretinoin 0.05%)7 to 32% (tretinoin
Results 0.1%)6 after 40 weeks of treatment. Kligman and Willis’
formula8 (4% HQ, 0.05% tretinoin and hydrocortisone)
Ninety-six patients were enrolled in the study (four were lost
reduced the MASI score by 69–75% after 8 weeks of treat-
to follow-up). The demographic data are given in Table 1.
ment. These effective schemes have some side-effects that
Sixty-six patients were enrolled in the DA group and 30 in the
limit their use; however, DA did not show serious side-effects
HQ group. Four patients (three in the DA group and one in
or discomfort to the patients.
the HQ group) did not follow the study completely because of
Data provided by Scherdin et al.9 showed that the MASI
causes unrelated to the study products (two patients lived far
score decreased by 42.3% from baseline to the end of the
away from the study center, one became pregnant, and the
study with DA after 8 weeks of treatment, comparable with
other used another depigmenting product). The average age
the results of 2% HQ. This was the first study on the efficacy
of the patients was 43 ± 3.55 years (38–52 years) in the DA
of DA in melasma, and demonstrated that DA is an effective
group and 45 ± 4.22 years (37–56 years) in the HQ group;
and highly skin-tolerable product.
the average duration of melasma was 9 years (3–12 years) for
Our study showed that DA was clearly as effective and
both groups.
tolerable as 2% HQ; however, further controlled, blind,
There were significant differences between the MASI scores
multicenter studies are required to support these results.
from baseline to the end of the study using treatment with
DA (14.52 ± 3.4 vs. 6.05 ± 1.2, P ¼ 0.001) (Fig. 1) and HQ
(15.22 ± 2.4 vs. 6.34 ± 1.3, P ¼ 0.001); however, there were References
no significant differences between treatments (baseline,
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similar for both medications, although pruritus was more treatment update. Dermatol Clin 2005; 23: 209–226.
common in patients with HQ. Acneiform reaction was more 3 Picardo M, Carrera M. New and experimental treatments of
prevalent in patients with DA; this was probably caused by chloasma and other hypermelanoses. Dermatol Clin 2007;
the oilier vehicle. 25: 352–362.

International Journal of Dermatology 2009, 48, 893–895 ª 2009 The International Society of Dermatology
Tirado-Sánchez, Santamarı́a-Román, and Ponce-Olivera
Figure 1 Photographs taken before (a, c)
and after (b, d) treatment with dioic acid
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ª 2009 The International Society of Dermatology
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International Journal of Dermatology 2009, 48, 893–895