Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas.
Department of Obstetrics and Gynecology, University of Alabama at Birmingham.
JAMA. 2023 Aug 15;330(7):615-625. doi: 10.1001/jama.2023.12317.
Surgical repairs of apical/uterovaginal prolapse are commonly performed using native tissue pelvic ligaments as the point of attachment for the vaginal cuff after a hysterectomy. Clinicians may recommend vaginal estrogen in an effort to reduce prolapse recurrence, but the effects of intravaginal estrogen on surgical prolapse management are uncertain.
To compare the efficacy of perioperative vaginal estrogen vs placebo cream on prolapse recurrence following native tissue surgical prolapse repair.
DESIGN, SETTING, AND PARTICIPANTS: This randomized superiority clinical trial was conducted at 3 tertiary US clinical sites (Texas, Alabama, Rhode Island). Postmenopausal women (N = 206) with bothersome anterior and apical vaginal prolapse interested in surgical repair were enrolled in urogynecology clinics between December 2016 and February 2020.
The intervention was 1 g of conjugated estrogen cream (0.625 mg/g) or placebo, inserted vaginally nightly for 2 weeks and then twice weekly to complete at least 5 weeks of application preoperatively; this continued twice weekly for 12 months postoperatively. Participants underwent a vaginal hysterectomy (if uterus present) and standardized apical fixation (either uterosacral or sacrospinous ligament fixation).
The primary outcome was time to failure of prolapse repair by 12 months after surgery defined by at least 1 of the following 3 outcomes: anatomical/objective prolapse of the anterior or posterior walls beyond the hymen or the apex descending more than one-third of the vaginal length, subjective vaginal bulge symptoms, or repeated prolapse treatment. Secondary outcomes included measures of urinary and sexual function, symptoms and signs of urogenital atrophy, and adverse events.
Of 206 postmenopausal women, 199 were randomized and 186 underwent surgery. The mean (SD) age of participants was 65 (6.7) years. The primary outcome was not significantly different for women receiving vaginal estrogen vs placebo through 12 months: 12-month failure incidence of 19% (n = 20) for vaginal estrogen vs 9% (n = 10) for placebo (adjusted hazard ratio, 1.97 [95% CI, 0.92-4.22]), with the anatomic recurrence component being most common, rather than vaginal bulge symptoms or prolapse repeated treatment. Masked surgeon assessment of vaginal tissue quality and estrogenization was significantly better in the vaginal estrogen group at the time of the operation. In the subset of participants with at least moderately bothersome vaginal atrophy symptoms at baseline (n = 109), the vaginal atrophy score for most bothersome symptom was significantly better at 12 months with vaginal estrogen.
Adjunctive perioperative vaginal estrogen application did not improve surgical success rates after native tissue transvaginal prolapse repair.
ClinicalTrials.gov Identifier: NCT02431897.
在子宫切除术后，使用阴道固有组织的骨盆韧带作为阴道袖口的附着点，通常进行阴道顶端/阴道前壁脱垂的手术修复。临床医生可能会建议阴道雌激素，以努力减少脱垂复发，但阴道雌激素对手术脱垂管理的影响尚不确定。
比较围手术期阴道雌激素与安慰剂乳膏对固有组织手术脱垂修复后脱垂复发的疗效。
设计、地点和参与者：这是一项在美国 3 个三级临床地点（德克萨斯州、阿拉巴马州、罗得岛州）进行的随机优势临床试验。2016 年 12 月至 2020 年 2 月期间，在泌尿科诊所招募了有困扰的前阴道和阴道顶端脱垂且对手术修复感兴趣的绝经后妇女（n=206）。
干预措施为每晚阴道内插入 1 克共轭雌激素乳膏（0.625mg/g）或安慰剂，持续 2 周，然后每周两次，至少提前 5 周应用；术后继续每周两次应用 12 个月。参与者接受阴道子宫切除术（如果存在子宫）和标准化的阴道顶端固定术（子宫骶骨或骶棘韧带固定术）。
主要结局是术后 12 个月时，至少出现以下 3 种结果之一的脱垂修复失败时间：前壁或后壁的解剖学/客观脱垂超过处女膜，或顶端下降超过阴道长度的三分之一，阴道膨出症状，或反复脱垂治疗。次要结局包括尿和性功能、泌尿生殖萎缩的症状和体征以及不良事件的测量。
在 206 名绝经后妇女中，199 名被随机分组，186 名接受了手术。参与者的平均（SD）年龄为 65（6.7）岁。与安慰剂相比，接受阴道雌激素治疗的女性在 12 个月时的主要结局没有显著差异：阴道雌激素组的 12 个月失败发生率为 19%（n=20），安慰剂组为 9%（n=10）（调整后的危险比，1.97[95%置信区间，0.92-4.22]），解剖学复发是最常见的原因，而不是阴道膨出症状或脱垂反复治疗。在手术时，阴道雌激素组的阴道组织质量和雌激素化的盲法外科医生评估明显更好。在基线时至少有中度困扰性阴道萎缩症状的参与者亚组（n=109）中，阴道雌激素组的最困扰症状的阴道萎缩评分在 12 个月时显著改善。
围手术期阴道内应用雌激素并不能提高固有组织经阴道脱垂修复后的手术成功率。
ClinicalTrials.gov 标识符：NCT02431897。
