OBJECTIVE: To determine whether oestrogen replacement will produce an improvement in the quantity, or quality, of pelvic collagen in postmenopausal women. DESIGN: A prospective double-blind placebo controlled trial of oestrogen therapy. SETTING: Southmead Hospital, Bristol, UK. POPULATION: Fifty-five postmenopausal women with a urodynamic diagnosis of genuine urinary stress incontinence. METHODS: Randomisation to a six-month, double-blind, placebo-controlled, trial of oestradiol valerate 2mg once daily. A 10mg-30mg periurethral biopsy was taken from the vaginal epithelium before and after treatment. Tissue was analysed for total collagen content, intermolecular cross-links, advanced glycation end-products, collagen type ratios and matrix metalloproteinase (MMP) activity. RESULTS:Forty-nine women completed the trial of whom 26 received oestrogen and 23 receivedplacebo. When compared with placebo, oestrogen treatment resulted in significant decreases in total collagen (P = 0.0054), the mature cross-link HHL (P = 0.0009) and the advanced glycation end-product NFC-1 (P = 0.0009). There was a significant rise in the immature cross-link HLKNL (P = 0.0191). Oestrogen produced a significant increase in MMP-2 expression (Pro MMP-2, P = 0.0017). CONCLUSIONS: Six months treatment with oestrogen has profound effects upon pelvic collagen metabolism, stimulating collagen degradation via increased proteinase activity. While aged collagen is being lost, new collagen is synthesised as witnessed by the increase in the immature cross-links and the decrease in both mature cross-links and advanced glycation end-products. Collagen loss contradicts previous reports; perhaps aged collagen degradation is merely an early response to oestrogen stimulation. We have evidence of new collagen synthesis, and it may be that a longer treatment interval would show total collagen content increasing. Further studies within this field are warranted.
RCT Entities:
OBJECTIVE: To determine whether oestrogen replacement will produce an improvement in the quantity, or quality, of pelvic collagen in postmenopausal women. DESIGN: A prospective double-blind placebo controlled trial of oestrogen therapy. SETTING: Southmead Hospital, Bristol, UK. POPULATION: Fifty-five postmenopausal women with a urodynamic diagnosis of genuine urinary stress incontinence. METHODS: Randomisation to a six-month, double-blind, placebo-controlled, trial of oestradiol valerate 2mg once daily. A 10mg-30mg periurethral biopsy was taken from the vaginal epithelium before and after treatment. Tissue was analysed for total collagen content, intermolecular cross-links, advanced glycation end-products, collagen type ratios and matrix metalloproteinase (MMP) activity. RESULTS: Forty-nine women completed the trial of whom 26 received oestrogen and 23 received placebo. When compared with placebo, oestrogen treatment resulted in significant decreases in total collagen (P = 0.0054), the mature cross-link HHL (P = 0.0009) and the advanced glycation end-product NFC-1 (P = 0.0009). There was a significant rise in the immature cross-link HLKNL (P = 0.0191). Oestrogen produced a significant increase in MMP-2 expression (Pro MMP-2, P = 0.0017). CONCLUSIONS: Six months treatment with oestrogen has profound effects upon pelvic collagen metabolism, stimulating collagen degradation via increased proteinase activity. While aged collagen is being lost, new collagen is synthesised as witnessed by the increase in the immature cross-links and the decrease in both mature cross-links and advanced glycation end-products. Collagen loss contradicts previous reports; perhaps aged collagen degradation is merely an early response to oestrogen stimulation. We have evidence of new collagen synthesis, and it may be that a longer treatment interval would show total collagen content increasing. Further studies within this field are warranted.
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