Perioperative Vaginal Estrogen as Adjunct to Native Tissue Vaginal Apical Prolapse Repair

Abstract

ImportanceSurgical 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.ObjectiveTo compare the efficacy of perioperative vaginal estrogen vs placebo cream on prolapse recurrence following native tissue surgical prolapse repair.Design, Setting, and ParticipantsThis 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.InterventionsThe 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).Main Outcomes and MeasuresThe 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.ResultsOf 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.Conclusions and RelevanceAdjunctive perioperative vaginal estrogen application did not improve surgical success rates after native tissue transvaginal prolapse repair.Trial RegistrationClinicalTrials.gov Identifier: NCT02431897

Characteristics Associated With Surgical Failure After Native Tissue Apical Prolapse Repair

“…This was a planned ancillary analysis of a randomized superiority trial (NCT02431897), the design and primary outcome report of which have been previously published. 7,8 IMPROVE (Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen) aimed to determine whether perioperative use of vaginal estrogen cream, compared with placebo, would improve tissue quality in postmenopausal patients with prolapse and affect recurrence rates after surgical repair. The application of estrogen cream did not improve recurrence rates; the adjusted hazard ratio (HR) of failure for vaginal estrogen compared with placebo was 1.97 (95% CI, 0.92-4.22; P5.08).…”

“…At 12 months, the model-estimated failure was 19% (95% CI, 9-27%) (n520) for the vaginal estrogen group and 9% (95% CI, 2-15%) (n510) for the placebo group. 8 Three U.S. clinical sites enrolled participants between December 2016 and February 2020. The statistical analysis plan and protocol were approved by IRBs at each site and by an independent data and safety monitoring board assembled by the National Institute on Aging.…”

Renewed call for action: Highlight negative results to improve science

“… 1 In the meantime, on August 15, 2023, JAMA also published three consecutive articles with negative findings in the same issue. 2 , 3 , 4 Many researchers have been encouraged by the publication of several articles with negative results in a row. In this scenario, the authors would need to call on more researchers and journals to pay attention to the publication of studies with negative results.…”