Treatment of lichen sclerosus with topical dihydrotestosterone. Androgens in the topical treatment of lichen sclerosus. Topical testosterone in the treatment of vulvar lichen sclerosus. The response of balanitis xerotica obliterans to local steroid application compared with placebo in children. Clinical and histologic effects of topical treatments of vulval lichen sclerosus. A critical evaluation. Testosterone maintenance therapy. Effects on vulvar lichen sclerosus treated with clobetasol propionate. A double-blind, randomized controlled trial of clobetasol versus pimecrolimus in patients with vulvar lichen sclerosus.
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. Testosterone propionate has been shown repeatedly to be effective in the treatment of vulvar lichen sclerosus, yet studies of androgens in serum of women with untreated vulvar lichen sclerosus suggested an abnormal activity of 5-alpha reductase in these patients. If impairment of 5-alpha reductase in women with untreated vulvar lichen sclerosus is a proximate cause of this disease, then dihydrotestosterone should be more effective than testosterone propionate in the treatment of the condition.
                To test this hypothesis, five women with vulvar lichen sclerosus received topically either dihydrotestosterone or testosterone propionate in a double-blind cross-over study.
                These androgens appear to be equally effective in inducing objective improvement of the vulvar lichen sclerosus by both gross and microscopic criteria.
                Impairment of 5-alpha reductase may not be germane to the pathogenesis of vulvar lichen sclerosus. Comparison between 2% testosterone propionate and petrolatum ointment in the treatment of vulvar lichen sclerosus in a randomized, double-blind, controlled clinical study.
                Fifty-eight consecutive patients with histologically confirmed vulvar lichen sclerosus were enrolled. They underwent a 1-year period of topical treatment with either medication, with clinical evaluations of symptoms and gross appearance at 2-month intervals, followed by histological evaluation at the end of the treatment period. Statistical analysis was performed according to the chi-squared test and the Student-Newman-Keuls test.
                A substantial improvement in symptoms was achieved in 20 (66.6%) patients in the testosterone group and in 21 (75%) patients in the placebo group. No statistical differences were observed between the two groups. Gross changes were observed in a few cases and no case demonstrated histologic modifications.
                Petrolatum ointment is as effective as 2% testosterone in the treatment of vulvar lichen sclerosus. We evaluated the clinical effectiveness of topical steroid application for balanitis xerotica obliterans in children and analyzed the association of any clinical response with histological findings.
                Our double-blind, placebo controlled, randomized study included 40 boys in whom balanitis xerotica obliterans was diagnosed clinically by cicatricial phimosis. The severity of phimosis was graded into 4 groups. Patients were randomized to receive the topical application of 0.05% mometasone furoate or placebo. After 5 weeks phimosis severity was reevaluated and all patients underwent circumcision. Surgical specimens were histologically typed as an early, intermediate or late form of balanitis xerotica obliterans.
                Seven patients were withdrawn from the study. In the steroid group 7 boys had clinical improvement and 10 had no change. Histological study showed an early, intermediate and late form of balanitis xerotica obliterans in 5, 5 and 7 cases, respectively. Of cases with clinical improvement 5 were the early and 2 the intermediate type. In the placebo group 5 cases worsened clinically and 11 did not change. Histological evaluation revealed an early, intermediate and late form of balanitis xerotica obliterans in 3, 7 and 6 boys, respectively. Of the 5 cases with histological worsening, disease was the early, intermediate and late type in 2, 2 and 1, respectively.
                Applying a potent topical steroid affects improvement in balanitis xerotica obliterans in the histologically early and intermediate stages of disease, and may inhibit further worsening in the late stage. A randomized study was conducted on 79 patients with vulval lichen sclerosus who were treated for three months with four topical drugs including testosterone (2%), progesterone (2%), clobetasol propionate (.05%) and a cream based preparation. To evaluate the efficacy of the treatments, patients were examined before and after therapy for symptoms, gross appearance of the lesions and histopathologic features. Patients treated with clobetasol had a better response than responses recorded in the other groups. Remission of symptoms occurred in 75% of patients treated with clobetasol compared to 20% treated with testosterone, 10% treated with progesterone and 10% treated with a cream based preparation. The clobetasol group was the only group with gross changes and histologic evaluations before and after treatment, that showed a highly significant difference (P < .001). In a condition characterized by epidermal atrophy, we observed a significant reduction in epidermal atrophy after treatment. This study suggests that clobetasol propionate (.05%) (a very potent topical steroid) is the therapy of choice in vulval lichen sclerosus. To evaluate the possible effects of topical testosterone as maintenance therapy after clobetasol propionate treatment.
                Thirty-two patients with biopsy-proven vulvar lichen sclerosus (LS), after 24 weeks of treatment with 0.05% clobetasol propionate cream, were randomly distributed into two groups of 16 each and treated for a further length of time (24 weeks) with testosterone 2% ointment or a cream-based preparation (placebo). The patients were examined before and after treatment for symptoms, gross aspects and histologic features.
                With clobetasol propionate all patients had a marked improvement (P < .001) in both clinical and histologic parameters. After clobetasol propionate therapy, the 16 testosterone-treated patients had significant worsening of their symptoms (P < .05%) and no evident changes in gross aspects (P = NS). The placebo-treated group had good symptomatic control of their disease, with no significant changes in symptoms or gross aspects (P = NS).
                After the good results obtained with clobetasol propionate, treatment with testosterone appeared to have a negative effect, while a regularly provided emollient cream was useful in symptom control. Lichen sclerosus (LS) is a lymphocyte-mediated chronic cutaneous disorder with a predilection for the vulva. The current gold standard treatment is topical ultrapotent corticosteroids such as clobetasol.
                We sought to compare the safety and efficacy of clobetasol and pimecrolimus in the treatment of vulvar LS.
                This double-blind, randomized trial enrolled 38 women with biopsy-proven vulvar LS. This study consisted of a 2-week screening period and a 12-week treatment period. The primary efficacy variable was the change in inflammation, as determined by a dermatopathologist, on the biopsy specimens obtained at screening and at the week 12 visit. Secondary efficacy variables included the change from baseline in pruritus and burning/pain as assessed by patients using a visual analog scale and a clinical evaluation by the investigator.
                Clobetasol was found to be superior in improving inflammation when compared with pimecrolimus (P = .015). Both groups showed improvement in pruritus and burning/pain but this difference was not statistically significant (P = .32 and .93, respectively). Both clobetasol and pimecrolimus were found to be effective in decreasing both the total score on the Investigator Global Assessment (P = .001) and all 3 subscales. Serum levels of pimecrolimus and clobetasol did not approach levels of concern during the study period. No adverse events were reported.
                This study was limited by the relatively short study duration.
                Both clobetasol and pimecrolimus appear efficacious and well tolerated for the treatment of vulvar LS; however, clobetasol is more effective than pimecrolimus and should remain first-line therapy for LS.
                Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
The current limited evidence demonstrates the efficacy of clobetasol propionate, mometasone furoate, and pimecrolimus in treating genital lichen sclerosus. Further RCTs are needed to determine the optimal potency and regimen of topical corticosteroids, examine other topical interventions, assess the duration of remission or prevention of flares, evaluate the reduction in the risk of genital squamous cell carcinoma or genital intraepithelial neoplasia, and examine the efficacy in improving the quality of the sex lives of people with this condition.