PURPOSE: Genital lichen sclerosus is a chronic inflammatory and fibrosclerotic disease associated with substantial morbidity. Acitretin has been reported to be of benefit in many dermatological indications including lichen sclerosus. We evaluated the efficacy and tolerability of acitretin for biopsy confirmed, severe lichen sclerosus of the male genitalia.MATERIALS AND METHODS: A randomized, double-blind, placebo controlled study was performed in which 52 male patients with severe, long-standing lichen sclerosus were randomized in a 2:1 ratio to receive daily acitretin (35 mg) or placebo for 20 consecutive weeks. Followup lasted for 36 weeks from baseline. The primary end point was complete response of active lichen sclerosus as well as improvement of patient quality of life. Secondary end points were partial response and recurrence rates after treatment discontinuation.RESULTS: A total of 49 patients completed the study and were eligible for statistical analysis. Complete response was achieved by 36.4% (12 of 33) of the acitretin group vs 6.3% (1 of 16) of the controls, while 36.4% (12 of 33) vs 12.5% (2 of 16) achieved partial resolution, respectively. Mean total clinical score of the acitretin group was significantly lower than that of the controls at week 20 [t (47) = -4.146, p = 0.00 < 0.5], which was also accompanied by a significant improvement in mean Dermatology Life Quality Index score [t (32) = 6,441, p = 0.000 < 0.05]. Acitretin was well tolerated and only minimal transient side effects were recorded.CONCLUSIONS: Acitretin is safe and effective for the management of severe, long-standing lichen sclerosus of the male genitalia. Study limitations included bias during clinical evaluation considering the expected side effects of acitretin.