Stress urinary incontinence in women : Pathophysiological aspects

Abstract: STRESS URINARY INCONTINENCE IN WOMEN Pathophysiological Aspects Christian Falconer. MD, Dissertation from, Karolinska Institutet Danderyd Hospital, Division of Obstetrics and Gynaecology, S-182 88 Danderyd, Sweden Objective: The pathophysiology of female stress urinary incontinence (SUI) is multifactorial. In this thesis biochemical and ultrastructural changes in the paraurethral supporting connective tissue and changes in the innervation of the vaginal wall in relation to SUI have been focused upon. Methods: Skin and paraurethral biopsies were obtained from pre- and postmenopausal SUI women, with or without estrogen replacement therapy (ERT) and from comparable healthy women. Collagen and proteoglycan composition and concentration were analysed. The mRNA levels for collagens I and III, the small proteoglycans decorin and biglycan, and the large proteoglycan versican were quantified. Difference in collagen metabolism in skin biopsies between comparable SUI and continent women was also analysed. The ultrastructure of the collagen was examined with transmission electron microscopy and the diameters of collagen fibrils were analysed.The immunohistochemical marker protein gene product 9.5 (PGP 9.5) was used in staining all axons and nerve terminals in biopsies from the vaginal mucosa at different locations. In a two-year follow-up study the clinical outcome and changes in connective tissue metabolism after intravaginal slingplasty (IVS) in SUI women were analysed. Results and discussion: The major findings in the present studies were a significantly higher collagen concentration in combination with an increase in cross-linking of the paraurethral connective tissue in incontinent women of fertile age compared to continent controls. These changes were accompanied by increase in the mRNA levels for collagens I and III. The biochemical findings were related to a significant increase in collagen fibril diameter. In addition to the biochemical and ultrastructural changes a decrease in sensory innervation of the vaginal epithelium was found, indicating a decrease in sensibility for urinary leakage. The changes resulted in considerable impairment of the mechanical properties of the tissue. After menopause no such differences were found. On the other hand, the collagen concentration was greater and combined with lower collagen cross-linking in healthy women after menopause than in premenopausal women. These changes were counteracted by ERT. Fibroblast cultures from skin biopsies in SUI women after menopause accumulated 30% less collagen than comparable controls, suggesting an altered collagen metabolism. The IVS procedure resulted in a significant change in paraurethral collagen extractability, still present two years after surgery. This finding indicates a changed metabolism, most likely induced by the implanted sling, resulting in a restoration of the elastic properties of the connective tissue. Conclusion: SUI in women of fertile age is related to significant changes in the paraurethral extracellular matrix composition and ultrastructure and a decrease in the sensory innervation of the vaginal epithelium. In women after menopause, the pathophysiology of SUI is different, with no major changes in the extracellular matrix. The two-year cure rate of SUI after the IVS procedure is competitive with other surgical methods, and is probably related to changes in the paraurethral collagen organization. Key words: menopause, paraurethral connective tissue, extracellular matrix, collagen. proteoglycans, sensory innervation, intravaginal slingplasty. ISBN 9 1-628-2345-0