Changes in paraurethral connective tissue at menopause are counteracted by estrogen

Abstract

To study whether the transition to menopause is accompanied by changes in the paraurethral connective tissue and if these changes are modified by estrogen replacement therapy. Biopsies were obtained from the paraurethral tissue from 34 women; 12 menstruating, 14 postmenopausal without estrogen treatment, and 8 with estrogen treatment. Collagen concentration and collagen extractability by pepsin digestion were measured. Proteoglycan composition and concentration were analysed using Alcian blue. The mRNA levels for collagen I and III, the small proteoglycans (PGS) decorin and biglycan, and the large proteoglycan versican, were estimated. The paraurethral biopsies consisted of fibrous connective tissue, with collagen fibers as dominating structure. Several proteoglycans were identified; versican, heparansulphate proteoglycans, biglycan and decorin. The small proteoglycan decorin represented 85% of all proteoglycans. The collagen concentration was almost doubled in postmenopausal biopsies compared to premenopausal. The collagen fibril organization was also changed with higher cross-linking after menopause whereas the amount and the composition of the proteoglycans were unchanged. The proteoglycan/collagen ratio was significantly decreased. Estrogen replacement therapy resulted in decreased collagen concentration, decreased cross-linking of the collagen and reversal of the PGS/collagen ratio to almost premenopausal level. The therapy resulted in increased levels of mRNA for collagen I and III which suggests that the changes are due to an increased turnover. The decrease in estrogen levels at menopause results in a connective tissue with different qualities after menopause. Estrogen replacement therapy tends to restore the metabolism of the genitourinary connective tissue to premenopausal conditions.