Cellular proliferation in the female lower urinary tract with reference to oestrogen status

Abstract

Objective To assess cell proliferation throughout the tissues of the female lower urinary tract and to compare cell proliferation rates in women of varying oestrogen status. Design Prospective observational study. Setting A large teaching hospital. Sample Fifty-nine women undergoing surgery for urogynaecological conditions of whom 23 were premenopausal, 20 were postmenopausal and taking no oestrogen supplementation and 16 were postmenopausal and receiving some form of hormone replacement therapy. Biopsies were taken during surgery from the bladder dome, trigone, the proximal and distal urethra, vagina and vesico-vaginal fascia in the region of the bladder neck. Methods Formalin-fixed paraffin-embedded biopsies were labelled by an avidin–biotin technique with a monoclonal antibody raised against part of the nuclear matrix known as Ki-67 antigen. Main outcome measures Ki-67 expression was assessed in the epithelial, subepithelial and muscle or deep fascial regions of all tissues and related to oestrogen status. Results Ki-67 expression was only found in high levels in biopsies containing squamous epithelia. Significantly higher levels of Ki-67 expression were observed in the tissues of oestrogen replete women in the premenopausal and hormone replacement groups, compared with postmenopausal women receiving no oestrogen supplementation. Conclusions Squamous epithelia of the female lower urinary tract exhibit greater levels of cell proliferation in oestrogen replete as compared with oestrogen deficient women. As these same squamous epithelia also consistently express oestrogen receptors, the findings suggest a mechanism by which oestrogen exerts its effect on the lower urinary tract and also provide an explanation for the success of oestrogen in the treatment of some conditions causing lower urinary tract dysfunction in postmenopausal women.