目的:本研究的目的是证明拉索福昔芬是否能改善更年期泌尿生殖系统综合征的阴道体征/症状。
方法:两个相同,3期试验将绝经后有中重度阴道症状的妇女随机分为口服拉索福昔芬0.25或0.5mg/d,或安慰剂,12周。最烦人的症状从基线到第12周的变化,阴道pH,并评估了阴道旁和浅表细胞的百分比。这些共同终点使用协方差分析进行分析,除了表面细胞,通过非参数分析,基于等级的Kruskal-Wallis测试。
结果:两项研究招募了444和445名女性(平均年龄,~60y),分别。与安慰剂相比,拉索福昔芬在12周时的共同主要终点为0.25和0.5mg/d(全部P<0.0125)。研究1:最麻烦的症状(与安慰剂的最小平方平均差:0.25和0.5mg/d的-0.4和-0.5,分别),阴道pH(-0.65,-0.58),和阴道浅表(5.2%,5.4%),和副鼻部(-39.9%,-34.9%)细胞;研究2:最令人讨厌的症状(-0.4,-0.5),阴道pH(-0.57,-0.67),和阴道浅表(3.5%,2.2%)和副鼻部(-34.1%,-33.5%)细胞。早在第2周就出现了一些改善。大多数治疗引起的不良事件是轻度或中度,并且最常报告潮热(拉索福昔芬vs安慰剂:13%-23%vs9%-11%)。严重不良事件很少发生,没有死亡发生。
结论:在两项3期试验中,口服拉索福昔芬0.25和0.5mg/d可显著改善阴道体征/症状,并具有良好的安全性,具有临床意义,提示拉索福昔芬对更年期泌尿生殖系统综合征的有益作用。
OBJECTIVE: The aim of this study was to demonstrate whether lasofoxifene improves vaginal signs/symptoms of genitourinary syndrome of menopause.
METHODS: Two identical, phase 3 trials randomized postmenopausal women with moderate to severe vaginal symptoms to oral lasofoxifene 0.25 or 0.5 mg/d, or placebo, for 12 week. Changes from baseline to week 12 in most bothersome symptom, vaginal pH, and percentages of vaginal parabasal and superficial cells were evaluated. These coprimary endpoints were analyzed using analysis of covariance, except superficial cells, which were analyzed by the nonparametric, rank-based Kruskal-Wallis test.
RESULTS: The two studies enrolled 444 and 445 women (mean age, ~60 y), respectively. Coprimary endpoints at week 12 improved with lasofoxifene 0.25 and 0.5 mg/d greater than with placebo ( P < 0.0125 for all). Study 1: most bothersome symptom (least square mean difference from placebo: -0.4 and -0.5 for 0.25 and 0.5 mg/d, respectively), vaginal pH (-0.65, -0.58), and vaginal superficial (5.2%, 5.4%), and parabasal (-39.9%, -34.9%) cells; study 2: most bothersome symptom (-0.4, -0.5), vaginal pH (-0.57, -0.67), and vaginal superficial (3.5%, 2.2%) and parabasal (-34.1%, -33.5%) cells. Some improvements occurred as early as week 2. Most treatment-emergent adverse events were mild or moderate and hot flushes were most frequently reported (lasofoxifene vs placebo: 13%-23% vs 9%-11%). Serious adverse events were infrequent and no deaths occurred.
CONCLUSIONS: In two phase 3 trials, oral lasofoxifene 0.25 and 0.5 mg/d provided significant and clinically meaningful improvements in vaginal signs/symptoms with a favorable safety profile, suggesting beneficial effects of lasofoxifene on genitourinary syndrome of menopause.