ABSTRACT

Introduction

Vulvar and vaginal atrophy (VVA) affects up to two thirds of postmenopausal women, with symptoms of vaginal dryness, dyspareunia, and vulvar/vaginal irritation. Despite the availability of various treatments, women express dissatisfaction with their options. An estradiol (E2; 4-µg and 10-µg) softgel vaginal insert was approved by the Food and Drug Administration (FDA) to treat moderate to severe dyspareunia, a symptom of VVA, due to menopause. These inserts were designed to treat VVA effectively and safely while avoiding some of the drawbacks of other administration methods.

Areas covered

This article reviews the physical characteristics and pharmacokinetic data of the E2 softgel vaginal insert. Primary and secondary efficacy endpoints and safety data are reviewed from the pivotal REJOICE trial (NCT02253173), and substudies that explore response rates, changes in vaginal epithelium by visual assessment, efficacy in patient subgroups, effects on sexual function, and patient satisfaction compared with other treatments.

Expert opinion

The E2 insert shows that vaginal drug delivery is an optimal route of administration for locally treating VVA. This E2 softgel vaginal insert is a safe and effective treatment for symptoms of postmenopausal VVA. The E2 insert’s pharmacokinetic characteristics are related to its unique formulation, rapid dissolution, and minimal systemic absorption.

Abbreviations

AE: adverse event; AUC: area under the concentration-time curve; BMI: body mass index; C_avg: average concentration; CI: confidence interval; C_max: maximum concentration; C_min: minimum concentration; E2: estradiol; FDA: Food and Drug Administration; FSFI: Female Sexual Function Index; GSM: genitourinary symptoms of menopause: MBS: most bothersome symptom; NAMS: North American Menopause Society; OR: odds ratio; PI: pulsatility index; PK: pharmacokinetic; REVIVE: Real Women’s Views of treatment options for menopausal Vaginal changEs; RI: resistance index; ROC: receiver operating characteristic; TEAE: treatment-emergent adverse event; t_max: time to maximum concentration; VVA: vulvar and vaginal atrophy.

中文翻译：

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雌二醇软胶囊插入物用于治疗VVA症状：专家意见。

摘要

介绍

外阴和阴道萎缩（VVA）最多影响三分之二的绝经后妇女，伴有阴道干燥，性交困难和外阴/阴道刺激症状。尽管有各种治疗方法，妇女对她们的选择仍然不满意。食品和药物管理局（FDA）批准使用雌二醇（E2； 4-µg和10-µg）阴道软胶囊插入剂，用于治疗由于绝经而引起的中度至重度的性交困难，这是VVA的症状。这些插入物旨在有效安全地治疗VVA，同时避免了其他给药方法的某些缺点。

覆盖区域

本文回顾了E2软凝胶阴道插入物的物理特性和药代动力学数据。从关键的REJOICE试验（NCT02253173）中回顾了主要和次要的疗效终点和安全性数据，以及研究了反应率，通过视觉评估阴道上皮的变化，对患者亚组的疗效，对性功能的影响以及与其他方法相比患者满意度的子研究治疗。

专家意见

E2插页显示阴道给药是局部治疗VVA的最佳给药途径。这种E2软胶囊阴道插入物是绝经后VVA症状的安全有效治疗方法。E2插件的药代动力学特性与其独特的配方，快速溶解和最小的全身吸收有关。

缩略语

AE：不良事件；AUC：浓度-时间曲线下的面积；BMI：体重指数；C _avg：平均浓度；CI：置信区间；C _max：最大浓度；C _min：最低浓度；E2：雌二醇；FDA：食品药品管理局；FSFI：女性性功能指数；GSM：更年期的泌尿生殖系统症状：MBS：最讨厌的症状；NAMS：北美更年期协会；OR：比值比；PI：搏动指数；PK：药代动力学；回顾：真正的女性对更年期阴道变化的治疗选择的看法；RI：电阻指数；ROC：接收机工作特性；TEAE：治疗紧急不良事件；t _max：达到最大浓度的时间；VVA：外阴和阴道萎缩。