Female stress incontinence and uterovaginal prolapse : collagen turnover and hormone sensitivity in urogenital tissue
Author: Edwall, Lena
Date: 2009-01-23
Location: Föreläsningssalen R64, Karolinska Universitetssjukhuset, Huddinge
Time: 09.00
Department: Institutionen för klinisk vetenskap / Department of Clinical Sciences
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thesis.pdf (839.1Kb)
Abstract
Background: Prevalence of both stress urinary incontinence (SUI) and
uterovaginal prolapse (UP) is high and rising with age. Risk factors
include multiparity, obesity, chronic obstructive lung disease and
previous gynecological surgery. The underlying pathology is still unknown
but may include defective connective tissue.
Aims: To study collagen turnover markers in urogenital tissue, in order to gain insight regarding a possible altered collagen synthesis or metabolism in SUI and UP, if circulating sex steroids have any influence on collagen turnover and if there are any differences in sex steroids between women with or without SUI.
Methods: A total of 126 women were consecutively enrolled and classified according to urogenital status into three groups: SUI without UP, N=71; UP without incontinence, N=24; urologically healthy controls without UP, N=31. Urogenital tissue biopsies and serum was collected for analysis of the tissue and serum collagen turnover markers carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of type I collagen (ICTP) and the amino-terminal propeptide of procollagen III (PIIINP) and serum steroids, steroid binding proteins and IGF-I.
Result: Compared to controls tissue (T-)PIIINP and T-ICTP were significantly lower in SUI and T-PICP and T-PIIINP significantly higher in UP. Tissue collagen turnover markers were positively correlated to serum estradiol-17beta, especially at physiological serum estrone levels, in the controls but not in SUI patients except to a certain degree in premenopausal subjects. Instead of being related to serum estradiol- 17beta, tissue collagen turnover markers in SUI patients were negatively correlated to serum total and free testosterone. There were no significant differences between comparable subgroups of SUI patients and controls in circulating sex steroids.
Conclusions: Our findings indicate a reduced collagen breakdown in SUI and an increased collagen turnover in UP, both which may negatively tissue elasticity and strength. Urogenital tissue collagen turnover may be stimulated by estrogen in urologically healthy women but not in SUI patients in general but to a certain degree in premenopausal subjects. The latter finding may indicate menopause related changes as one underlying factor behind SUI. At supraphysiological concentrations estrone may act as a partial estradiol-17B antagonist also in vivo. Urogenital tissue collagen turnover in SUI patients may be inhibited by testosterone, perhaps by inhibition of matrix metalloprotease activity. Our findings emphasize the fact that SUI and UP have two distinctly different etiologies and shall be studied using »clean« patient materials
Aims: To study collagen turnover markers in urogenital tissue, in order to gain insight regarding a possible altered collagen synthesis or metabolism in SUI and UP, if circulating sex steroids have any influence on collagen turnover and if there are any differences in sex steroids between women with or without SUI.
Methods: A total of 126 women were consecutively enrolled and classified according to urogenital status into three groups: SUI without UP, N=71; UP without incontinence, N=24; urologically healthy controls without UP, N=31. Urogenital tissue biopsies and serum was collected for analysis of the tissue and serum collagen turnover markers carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of type I collagen (ICTP) and the amino-terminal propeptide of procollagen III (PIIINP) and serum steroids, steroid binding proteins and IGF-I.
Result: Compared to controls tissue (T-)PIIINP and T-ICTP were significantly lower in SUI and T-PICP and T-PIIINP significantly higher in UP. Tissue collagen turnover markers were positively correlated to serum estradiol-17beta, especially at physiological serum estrone levels, in the controls but not in SUI patients except to a certain degree in premenopausal subjects. Instead of being related to serum estradiol- 17beta, tissue collagen turnover markers in SUI patients were negatively correlated to serum total and free testosterone. There were no significant differences between comparable subgroups of SUI patients and controls in circulating sex steroids.
Conclusions: Our findings indicate a reduced collagen breakdown in SUI and an increased collagen turnover in UP, both which may negatively tissue elasticity and strength. Urogenital tissue collagen turnover may be stimulated by estrogen in urologically healthy women but not in SUI patients in general but to a certain degree in premenopausal subjects. The latter finding may indicate menopause related changes as one underlying factor behind SUI. At supraphysiological concentrations estrone may act as a partial estradiol-17B antagonist also in vivo. Urogenital tissue collagen turnover in SUI patients may be inhibited by testosterone, perhaps by inhibition of matrix metalloprotease activity. Our findings emphasize the fact that SUI and UP have two distinctly different etiologies and shall be studied using »clean« patient materials
List of papers:
I. Edwall L, Carlström K, Jonasson AF (2005). "Markers of collagen synthesis and degradation in urogenital tissue from women with and without stress urinary incontinence." Neurourol Urodyn 24(4): 319-24
Pubmed
II. Edwall L, Carlström K, Jonasson AF (2007). "Endocrine status and markers of collagen synthesis and degradation in serum and urogenital tissue from women with and without stress urinary incontinence." Neurourol Urodyn 26(3): 410-5
Pubmed
III. Edwall L, Carlström K, Fianu Jonasson A (2008). "Markers of collagen synthesis and degradation in urogenital tissue and serum from women with and without uterovaginal prolapse." Mol Hum Reprod 14(3): 193-7. Epub 2008 Jan 28
Pubmed
IV. Edwall L, Carlström K, Fianu Jonasson A (2008). "Different estrogen sensitivity of urogenital tissue from women with and without stress urinary incontinence." Neurourology and Urodynamics (Submitted)
I. Edwall L, Carlström K, Jonasson AF (2005). "Markers of collagen synthesis and degradation in urogenital tissue from women with and without stress urinary incontinence." Neurourol Urodyn 24(4): 319-24
Pubmed
II. Edwall L, Carlström K, Jonasson AF (2007). "Endocrine status and markers of collagen synthesis and degradation in serum and urogenital tissue from women with and without stress urinary incontinence." Neurourol Urodyn 26(3): 410-5
Pubmed
III. Edwall L, Carlström K, Fianu Jonasson A (2008). "Markers of collagen synthesis and degradation in urogenital tissue and serum from women with and without uterovaginal prolapse." Mol Hum Reprod 14(3): 193-7. Epub 2008 Jan 28
Pubmed
IV. Edwall L, Carlström K, Fianu Jonasson A (2008). "Different estrogen sensitivity of urogenital tissue from women with and without stress urinary incontinence." Neurourology and Urodynamics (Submitted)
Issue date: 2009-01-02
Rights:
Publication year: 2009
ISBN: 978-91-7409-292-9
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