title: Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial.
abstract: BACKGROUND
  Pelvic organ prolapse (POP) increases in prevalence with age; recurrence after surgical repair is common.
  
  
  OBJECTIVE
  The objective of the study was 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.
  
  
  METHODS
  This was a randomized trial.
  
  
  METHODS
  The study was conducted at an academic tertiary medical center.
  
  
  METHODS
  Postmenopausal women with a uterus and symptomatic anterior and/or apical prolapse at stage 2 or greater participated in the study.
  
  
  METHODS
  Estrogen (Premarin) or placebo cream for 6 weeks preoperatively was the intervention.
  
  
  METHODS
  Full-thickness anterior apical vaginal wall biopsies were obtained at the 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 the 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 = .002 and P =.088, respectively) by estrogen. Collagen types 1α1 and 1α2 mRNA increased 6.0- and 1.8-fold in the vaginal muscularis (P < .05 for both); collagen type Ia protein increased 9-fold in the muscularis (P = .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 = .011), and matrix metalloprotease-9 activity was decreased 6-fold in the mucosa and 4-fold in the muscularis (P = .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.
authors.affiliation: Department of Obstetrics and Gynecology (D.D.R., M.M.G., S.M.R., H.S., J.I.S., R.A.W.), University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032; and Department of Laboratory Medicine and Pathology (R.J.S.), Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: David D
authors.initials: DD
authors.lastname: Rahn
authors.forename: Meadow M
authors.initials: MM
authors.lastname: Good
authors.forename: Shayzreen M
authors.initials: SM
authors.lastname: Roshanravan
authors.forename: Haolin
authors.initials: H
authors.lastname: Shi
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Schaffer
authors.forename: Ravinder J
authors.initials: RJ
authors.lastname: Singh
authors.forename: R Ann
authors.initials: RA
authors.lastname: Word
mesh_terms: D000282:Administration, Intravaginal; D001706:Biopsy; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000008:administration & dosage*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D004970:Estrone / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007430:Intraoperative Care / Q000379:methods; D055118:Medication Adherence; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D017698:Postmenopause; D014596:Uterine Prolapse / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D014622:Vaginal Creams, Foams, and Jellies
chemical_list: D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D014622:Vaginal Creams, Foams, and Jellies; D004970:Estrone; D004958:Estradiol; D003094:Collagen; D017364:Collagenases