J Skin Stem Cell. 2017 March; 4(1):e62113. Published online 2016 December 20. doi: 10.5812/jssc.62113. Research Article A Double Blind Randomized Trial of Efficacy and Safety of 5% Methimazole Versus 2% Hydroquinone in Patients with Melasma Najmolsadat Atefi, 1 Elham Behrangi, 1 Somayyeh Nasiripour, 1 Golnaz Mehran, 1 Sedighe Naeji, 1, * Mahba Azizi, 2 Parvaneh Hassani, 1 and Zahra Azizian 2 1 Department of Dermatology, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran 2 Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran * Corresponding author: Sedighe Naeji, Dermatology Resident, MD, Department of Dermatology, Rasoul Akram Hospital, Niayesh Street, Sattarkhan Street, Iran University of Medical Sciences, Tehran, Iran. Tel: +98-9127462987, E-mail: drnaeji@gmail.com Received 2016 October 06; Revised 2016 November 23; Accepted 2016 December 10. Abstract Background: Melasma is an acquired facial hyperpigmentation that is chronic and resistant to treatment. This study aimed at comparing the therapeutic response and safety of 5% methimazole cream versus 2% hydroquinone cream in Iranian females with melasma. Methods: This was a randomized, controlled, double-blind clinical trial. Fifty-eight patients aged 18 to 50, and who had been clini- cally diagnosed with melasma were enrolled. They were randomly divided to 2 groups: those treated with 5% methimazole cream and those treated with 2% hydroquinone once nightly for 8 weeks. Their responses to treatment were evaluated using the Melasma area and severity index (MASI), the ΔE score obtained using VisioFace digital photography, and the patients’ own satisfaction. Safety was assessed by measuring thyroid-stimulating hormone (TSH) levels. For statistical analysis, the SPSS version 16.0 for Windows (SPSS Inc., Chicago, IL) was used. Results: The subjective assessments of methimazole and hydroquinone (patient satisfaction) were as follows: excellent and good, 67.7% for methimazole vs. 70.3% for hydroquinone, and moderate and mild, 32.2% for methimazole versus 29.6% for hydroquinone. The assessments showed no statistical differences between the 2 groups (P = 0.942). At the end of treatment, MASI scores were signif- icantly lower in the methimazole group than in the hydroquinone group (P = 0.042). The VisioFaceΔE scores were also significantly lower in the methimazole group than in the hydroquinone group (P = 0.049). Serum thyroid stimulating hormone (TSH) levels showed no statistical differences between the 2 groups (P = 0.613). Conclusions: Compared with 2% hydroquinone, topical methimazole was more effective for improving melasma and had no effect on serum TSH levels. Therefore, methimazole could be considered as a first-line or combination therapy for melasma. Keywords: Melasma, Methimazole, Hydroquinone, Thyroid-Stimulating Hormone 1. Background Melasma is a commonly acquired hypermelanosis on sun-exposed regions and is characterized by symmetric hyperpigmentation with irregular margins that involve the cheeks, forehead, nose, upper lips, and chin, although other sun-exposed regions may also be involved (1, 2). Sun exposure is the most important predisposing factor. Sev- eral studies have proposed other predisposing factors, e.g., genetic factors, female gender, skin phototype III-V, sexual hormone levels, pregnancy, thyroid disorders, cosmetics, and drugs; however, the exact etiology remains unknown 1. Because of frequent relapses, treating melasma is diffi- cult and frustrating. Hydroquinone has been considered as a first-line therapy as it moderately decreases pigmenta- tion in almost all patients. Other treatment modalities in- clude tretinoin (3-5), corticosteroids (6), kojic acid (7), aze- laic acid (8, 9), and third mixture (10, 11). Intense pulsed light, lasers, and dermabrasion have been considered as adjuvant therapies (12-14). The efficacy of 5% methima- zole cream has been recently reported in 2 patients with treatment-resistant melisma (15). This suppresses melanin synthesis by inhibiting peroxidase (16-22) and thyrosinase (23, 24). Unlike hydroquinone, methimazole does not lead to the death of melanocytes (18) and has no cytotoxic or mutagenic effects (25, 26). This study aimed at evaluating the therapeutic effect of topical 5% methimazole versus 2% hydroquinone in fe- males with melasma. Copyright © 2016, Journal of Skin and Stem Cell. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.