CHANGES IN PARAURETHRAL CONNECTIVE-TISSUE AT MENOPAUSE ARE COUNTERACTED BY ESTROGEN

Objective: 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. Study design: Biopsies were obtained from the paraurethral tissue from 34 women; 12 menstruat ing, 14 postmenopausal without estrogen treatment, and 8 with estrogen treatment. Collagen concentration and collagen extractability by peps in digestion were measured. Proteoglycan composition and concentration were analysed using Alcian blue. The mRNA levels for collagen I and I II, the small proteoglycans (PGS) decorin and biglycan, and the large proteoglycan versican, were estimated. Results: The paraurethral biops ies consisted of fibrous connective tissue, with collagen fibers as do minating structure. Several proteoglycans were identified; versican, h eparansulphate proteoglycans, biglycan and decorin. The small proteogl ycan decorin represented 85% of all proteoglycans. The collagen concen tration was almost doubled in postmenopausal biopsies compared to prem enopausal. The collagen fibril organization was also changed with high er cross-linking after menopause whereas the amount and the compositio n 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 coll agen and reversal of the PGS/collagen ratio to almost premenopausal le vel. The therapy resulted in increased levels of mRNA for collagen I a nd III which suggests that the changes are due to an increased turnove r. Conclusion: The decrease in estrogen levels at menopause results in a connective tissue with different qualities after menopause. Estroge n replacement therapy tends to restore the metabolism of the genitouri nary connective tissue to premenopausal conditions.