Context: Pelvic organ prolapse (POP) increases in prevalence with age; recurrence after surgical repair is common.
Objective: To determine the effects of local estrogen treatment on connective tissue synthesis and breakdown in the vaginal wall of postmenopausal women planning surgical repair of POP.
Design: Randomized trial.
Setting: Academic tertiary medical center.
Patients or Other Participants: Postmenopausal women with a uterus and symptomatic anterior and/or apical prolapse ≥stage 2.
Intervention: Estrogen (Premarin®) or placebo cream for 6 weeks preoperatively.
Main Outcome Measures: Full thickness anterior apical vaginal wall biopsies were obtained at time of hysterectomy and analyzed for mucosa and muscularis thickness, connective tissue synthesis and degradation. Serum levels of estrone and 17β-estradiol were analyzed at baseline and day of surgery using highly sensitive liquid chromatography-tandem mass spectrometry.
Results: Fifteen women per group (n=30 total) were randomized; 13 per group underwent surgery. Among drug-adherent participants (n=8 Estrogen, n=13 Placebo), epithelial and muscularis thickness was increased 1.8- and 2.7-fold (p=0.002 and 0.088, respectively) by estrogen. Collagen types 1α1 and 1α2 mRNA increased 6.0 and 1.8-fold in the vaginal muscularis (p< 0.05 for both); collagen type Ia protein increased 9-fold in the muscularis (p=0.012) whereas collagen III was not changed significantly. MMP-12 (human macrophage elastase) mRNA was suppressed in the vaginal mucosa from estrogen-treated participants (p=0.011), and MMP-9 activity was decreased 6-fold in the mucosa and 4-fold in the muscularis (p=0.02). Consistent with menopausal norms, serum estrone and 17β-estradiol were low and did not differ among the two groups.
Conclusions: Vaginal estrogen application for 6-weeks preoperatively increased synthesis of mature collagen, decreased degradative enzyme activity, and increased thickness of the vaginal wall, suggesting this intervention improves both the substrate for suture placement at the time of surgical repair and maintenance of connective tissue integrity of the pelvic floor.
Written by:
Rahn DD, Good MM, Roshanravan SM, Shi H, Schaffer JI, Singh RJ, Word RA. Are you the author?
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX.
Reference: J Clin Endocrinol Metab. 2014 Jun 20:jc20141216.
doi: 10.1210/jc.2014-1216
PubMed Abstract
PMID: 24947034
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