title: Paraurethral connective tissue in stress-incontinent women after menopause.
abstract: OBJECTIVE
  To study whether stress urinary incontinence after menopause is correlated to changes in the paraurethral connective tissue ultrastructure and metabolism.
  
  
  METHODS
  Transvaginal biopsies were obtained from the paraurethral connective tissue in stress urinary incontinent women after menopause with and without estrogen replacement therapy, and from comparable controls. All the stress-incontinent women underwent urodynamic investigation. In the specimens, collagen concentration, measured as hydroxyproline, and the degree of extractability by pepsin digestion, were quantified. Proteoglycan composition and concentration were analyzed using Alcian Blue precipitation, followed by electro-phoretic separation and quantification. Using Northern blots, mRNA levels for the collagens I and III, the small proteoglycans decorin and biglycan, and the large proteoglycan versican, were quantified. Collagen structure was examined with transmission electron microscopy, and the diameters of collagen fibrils were analyzed with an interactive image analysis system (IBAS, Zeiss/Kontron).
  
  
  RESULTS
  No significant difference in paraurethral connective tissue biochemistry or ultrastructure was registered between women with stress incontinence and controls. Estrogen replacement therapy resulted in a lower collagen concentration both between the controls (p = 0.02) and between the incontinent women (0.02). In the women with stress incontinence also the extractability by pepsin digestion was higher in the group with estrogen treatment (p = 0.004), indicating a decrease in cross-linking. The proteoglycan/collagen ratio was higher in the control group with estrogen treatment compared to untreated (p = 0.02), but no difference was found between estrogen treated and untreated incontinent women. The median collagen fibril diameter was 15% larger in the incontinent group of women without estrogen therapy compared to the control group and 5% larger when comparing the incontinent group on estrogen replacement therapy to the corresponding control group.
  
  
  CONCLUSIONS
  The extracellular matrix of paraurethral connective tissue in stress urinary incontinent women after menopause reacted differently to estrogen replacement therapy compared to continent controls. In contrast to incontinent women of fertile age no major changes in collagen metabolism were found in stress urinary incontinent women after menopause.
authors.affiliation: Karolinska Institutet, Division of Obstetrics and Gynecology, Danderyd Hospital, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Falconer
authors.forename: G
authors.initials: G
authors.lastname: Ekman-Ordeberg
authors.forename: B
authors.initials: B
authors.lastname: Blomgren
authors.forename: O
authors.initials: O
authors.lastname: Johansson
authors.forename: U
authors.initials: U
authors.lastname: Ulmsten
authors.forename: G
authors.initials: G
authors.lastname: Westergren-Thorsson
authors.forename: A
authors.initials: A
authors.lastname: Malmström
mesh_terms: D000368:Aged; D003094:Collagen / Q000032:analysis / Q000648:ultrastructure*; D003238:Connective Tissue / Q000737:chemistry / Q000473:pathology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000032:analysis; D008875:Middle Aged; D017698:Postmenopause; D011509:Proteoglycans / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D014521:Urethra / Q000737:chemistry / Q000473:pathology*; D014550:Urinary Incontinence, Stress / Q000378:metabolism / Q000473:pathology*
chemical_list: D011509:Proteoglycans; D012333:RNA, Messenger; D003094:Collagen; D006909:Hydroxyproline