Lichen sclerosus typically affects the vulva of postmenopausal women. Because serum levels of dihydrotestosterone are low in women with vulvar lichen sclerosus and because dihydrotestosterone is an effector androgen in vulvar skin, this double-blind cross-over study assessed five women with vulvar lichen sclerosus to determine the response to treatment with dihydrotestosterone. Objective gross and microscopic improvement in lichen sclerosus accompanied sustained treatment with topical dihydrotestosterone, but not with vehicle alone. However, there was no change in symptoms (itching and dyspareunia) in these women, although dihydrotestosterone did improve some of the features of vulvar lichen sclerosus and may represent a new treatment for this disease.