Is Topical Zinc Effective in the Treatment of Melasma? A Double-Blind Randomized Comparative Study ALIREZA YOUSEFI, MD,* ZAHRA KHANI KHOOZANI, MD, † SAEED ZAKERZADEH FOROOSHANI, MD, † NOOSHIN OMRANI, MD, ‡ AMIR MANSOOR MOINI, MD, † AND YASAMAN ESKANDARI, MD † BACKGROUND AND OBJECTIVES Zinc plays a role in skin health, and preliminary data have shown its beneficial effects for melasma. We compared the effect of topical zinc with that of hydroquinone as the standard treatment on severity of melasma. PATIENTS AND METHODS Ninety-three women with melasma were randomized to receive zinc sulfate 10% or hydroquinone 4% solutions once daily for 2 months. They were followed for an additional 3 months while using sunscreen. The severity of melasma was assessed at baseline and at 2 and 5 months using the Melasma Area and Severity Index (MASI). RESULTS Eighty-two patients completed the study. The MASI score fell significantly in both groups, but a greater decrease was seen in those who received hydroquinone (43.5  15.5% vs 18.6  20.8%, p < .001). Postinflammatory pigmentation occurred in 5.2% of the zinc group and irritation in 30.9% of the hydroquinone group. CONCLUSION Topical zinc therapy is not highly effective in reducing the severity of melasma, but further trials are needed to determine whether adding zinc to current topical treatments could improve treatment response. The authors have indicated no significant interest with commercial supporters. M elasma is one of the most common and disturbing cosmetic disorders with skin darkening. Pigmentation is brown to gray and usually affects the cheeks, forehead, nose, and upper lip. Melasma is more common in women; other known risk factors are pregnancy, sun exposure, and some medications such as hormones and anti- epileptic medication. 1 It is more common in Asian population than in other races. 2 In Iran, there have not been enough population based studies to deter- mine the prevalence of melasma, although Moin and colleagues reported a prevalence of 15.8% for melasma in pregnant women. 3 Current treatments have not been successful at completely correcting the skin pigmentation of melasma. 4 Suggested medications include sunscreen, bleaching creams (e.g., hydroquinone (HQ)), acne creams (e.g., azelaic acid), and topical retinoids alone or in combination. 4,5 Other suggested treat- ment strategies are lasers, intense pulse light, and chemical peels. According to a review of randomized trials by Rajaratnam and colleagues, tretinoin and triple-combination creams are the most-effective treatments for melasma. 4 Taylor and colleagues reported a maximum efficacy of 26.1% for complete resolution, 6 but combination therapies are associ- ated with more side effects (erythema, desquama- tion, burning, dryness, and pruritus), which are most common in patients receiving tretinoin and hydroquinone (80%), followed by tretinoin and fluocinolone acetonide. 6 *Department of Dermatology, Najafabad Branch, Islamic Azad University, Najafabad, Iran; † School of Medicine, Najafabad Branch, Islamic Azad University, Najafabad, Iran; ‡ School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran © 2013 by the American Society for Dermatologic Surgery, Inc.  Published by Wiley Periodicals, Inc.  ISSN: 1076-0512  Dermatol Surg 2014;40:33–37  DOI: 10.1111/dsu.12296 33