Topical clobetasol superior to progesterone in premenopausal women with vulvar Lichen sclerosus: Study
Lichen sclerosus (LS) is a chronic, localized, lymphocyte-mediated inflammatory skin disease which predominantly affects the anogenital region of women. The estimated prevalence of LS is about 1.7% in patients of gynecological private practices and it is usually diagnosed in peri- or postmenopausal women. LS clusters in families, which suggests genetic predisposition. The etiology is probably multifactorial, but individual factors have not yet been identified. Trauma, injury, and sexual abuse have been suggested as possible triggers of symptoms in genetically predisposed people, which might be due to the Koebner phenomenon. The long delays between disease onset and appropriate diagnosis may be caused by unfamiliarity with LS, inappropriate genital skin examination, and patients' reticence and embarrassment. LS lowers patient quality of life, and is associated with higher risk of squamous cell cancer (SCC) of the vulva, therefore, early diagnosis and treatment are important.
Current standard treatments include topical steroids like clobetasol propionate 0.05%, or, as a second line treatment, calcineurin inhibitors, but the effects of therapy on the risk of VIN or SCC are unknown. Long-term use of very potent steroids like clobetasol propionate may have the adverse effect of secondary atrophy of the skin, and this may make it hard to differentiate the atrophy sites from primary signs of progressive LS.
This randomized double-blind trial by A.R. Günthert et al published in European Journal of Obstetrics & Gynecology determined Topical progesterone 8% ointment was inferior to standard therapy with topical clobetasol propionate 0.05% in previously untreated premenopausal women with vulvar LS after 12 weeks treatment.
It was a Randomized, double-blind, 2-arm, single center superiority trial in premenopausal women with histologically confirmed vulvar LS who were randomized in a 1:1 ratio to receive clobetasol propionate 0.05% ointment or progesterone 8% ointment. The primary outcome was the clinical severity LS score after 12 weeks, which consists of six clinical features assessed by the physician. Secondary outcomes were the symptom severity LS score, which consists of three symptoms rated by the patient, the Short Form SF-12 physical and mental health scores, and adverse events. Response to medication was assessed by biopsy at the end of the treatment to evaluate inflammatory parameters.
Overall, 105 women were screened, 102 underwent vulvar biopsy and 37 received a histologically confirmed diagnosis of LS and were randomized: 17 to progesterone and 20 to clobetasol propionate.
At 12 weeks, the mean clinical LS scores improved from 4.6 to 4.5 in the progesterone arm, and from 4.6 to 2.9 in the clobetasol propionate arm (difference in favor of clobetasol p = 0.009), and the mean symptom severity LS scores improved from 4.5 to 3.1 in the progesterone arm, and from 4.7 to 1.9 in the clobetasol propionate arm (difference in favor of clobetasol p = 0.095).
LS was in complete remission in 6 out of 10 patients (60%) with available biopsy in the progesterone arm, and in 13 out of 16 patients (81.3%) in the clobetasol propionate arm (odds ratio in favor of clobetasol p = 0.234). No drug-related serious adverse event occurred during the trial.
In this randomized double-blind superiority pilot trial in women with LS the progesterone 8% ointment was found to be inferior to clobetasol propionate 0.05% in controlling clinical signs and symptoms at 12 weeks as measured by the clinical LS score and the symptom LS score, respectively. Women who received topical progesterone 8% ointment had no improvement at 12 weeks post-randomization. Conversely, those treated with clobetasol propionate 0.05% improved in clinical and symptom severity scores at 12 weeks after randomization. Both therapies were well tolerated.
Source: A.R. Günthert et al.; European Journal of Obstetrics & Gynecology and Reproductive Biology 272 (2022) 88–95
