Günthert Andreas R, Limacher Andreas, Beltraminelli Helmut, Krause Elke, Mueller Michael D, Trelle Sven, Bobos Pavlos, Jüni Peter
Department of Gynecology and Obstetrics, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland; gyn-zentrum ag, Lucerne, Switzerland.
CTU Bern, University of Bern, Bern, Switzerland.
Eur J Obstet Gynecol Reprod Biol. 2022 May;272:88-95. doi: 10.1016/j.ejogrb.2022.03.020. Epub 2022 Mar 10.
Lichen sclerosus (LS) is a chronic inflammatory skin disease that mostly affects the anogenital region of women and lowers patients' quality of life. Current standard treatment of LS is topical steroids.
To evaluate the efficacy of topical progesterone 8% ointment and compare to standard therapy with topical clobetasol propionate 0.05% in premenopausal women presenting with previously untreated early onset LS.
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 (SD 2.0) to 4.5 (SD 1.7) in the progesterone arm, and from 4.6 (SD 2.8) to 2.9 (SD 2.2) in the clobetasol propionate arm (difference in favor of clobetasol 1.61; 95% CI 0.44 to 2.77, p = 0.009), and the mean symptom severity LS scores improved from 4.5 (SD 3.8) to 3.1 (SD 3.0) in the progesterone arm, and from 4.7 (SD 2.8) to 1.9 (SD 1.8) in the clobetasol propionate arm (difference in favor of clobetasol 1.32; 95% CI -0.25 to 2.89, 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 0.35; 95% CI 0.06 to 2.06, p = 0.234). No drug-related serious adverse event occurred during the trial.
Topical progesterone 8% ointment is inferior to standard therapy with topical clobetasol propionate 0.05% in previously untreated premenopausal women with vulvar LS after 12 weeks treatment.
硬化性苔藓（LS）是一种慢性炎症性皮肤病，主要影响女性的肛门生殖器区域，降低患者的生活质量。目前LS的标准治疗方法是外用类固醇。
评估8%外用黄体酮软膏的疗效，并与0.05%丙酸氯倍他索标准疗法在既往未治疗的早发性LS的绝经前女性中的疗效进行比较。
一项针对组织学确诊为外阴LS的绝经前女性的随机、双盲、双臂、单中心优效性试验，这些女性按1:1的比例随机接受0.05%丙酸氯倍他索软膏或8%黄体酮软膏治疗。主要结局是12周后的临床严重程度LS评分，该评分由医生评估的六个临床特征组成。次要结局是症状严重程度LS评分，由患者对三种症状进行评分，简短健康调查简表SF - 12身心健康评分以及不良事件。在治疗结束时通过活检评估药物反应，以评估炎症参数。
总体而言，共筛查了105名女性，102名接受了外阴活检，37名经组织学确诊为LS并被随机分组：17名接受黄体酮治疗，20名接受丙酸氯倍他索治疗。12周时，黄体酮组的平均临床LS评分从4.6（标准差2.0）改善至4.5（标准差1.7），丙酸氯倍他索组从4.6（标准差2.8）改善至2.9（标准差2.2）（丙酸氯倍他索组优势差值为1.61；95%置信区间0.44至2.77，p = 0.009），黄体酮组的平均症状严重程度LS评分从4.5（标准差3.8）改善至3.1（标准差3.0），丙酸氯倍他索组从4.7（标准差2.8）改善至1.9（标准差1.8）（丙酸氯倍他索组优势差值为1.32；95%置信区间 - 0.25至2.89，p = 0.095）。在黄体酮组有活检结果的10名患者中，6名（60%）LS完全缓解，在丙酸氯倍他索组16名患者中有13名（81.3%）完全缓解（丙酸氯倍他索组优势比为0.35；95%置信区间0.06至2.06，p = 0.234）。试验期间未发生与药物相关的严重不良事件。
在既往未治疗的绝经前外阴LS女性中，治疗12周后，8%外用黄体酮软膏的疗效低于0.05%丙酸氯倍他索标准疗法。
