Prospective, randomized, double-blind clinical study of split-body comparison of topical hydroquinone and hexylresorcinol for skin pigment appearance

Dyspigmentation is a common cosmetic concern in dermatology. Currently, the first line topical medication in the United States is hydroquinone. Hydroquinone use is associated with potential safety concerns including cytotoxicity to melanocytes, systemic absorption, metabolism in distant organs, and production of potentially carcinogenic metabolites. Hexylresorcinol is an ingredient that has been used in food preservation and as antiseptic has been shown to inhibit tyrosinase in vitro and has been studied as a novel skin-lightening agent. To perform a double-blind randomized split-body investigation of comparison on topical hexylresorcinol and hydroquinone on face and hands to assess for change in the appearance of skin tone and pigmentation. Thirty-two healthy female participants ages 35–65 (50.93 ± 7.37) years old with skin type I–IV were randomized to using either topical 1% hexylresorcinol or 2% hydroquinone on the left or right side of the face and corresponding hand over 12 weeks. The topical preparation was applied twice a day to assigned areas. Standardized photos were taken of the face and colorimetric measurements were taken of both sides of the forehead, cheeks and each hand at baseline (Day 0), week 4, and week 12. Of the 32 participants, 3 were lost to follow-up and the remaining were included in the final analysis. Pigmentation measured by colorimeter and clinical grading were significantly decreased at 4 and 12 weeks relative to baseline with no difference between the HR and HQ groups. No adverse effects were noted with either intervention. Hexylresorcinol 1% is well-tolerated and equivalent to hydroquinone 2% in reducing the appearance of facial and hand pigment. Further studies with an expanded population and longer time course are warranted. Registration No.: NCT04345094.