The effect of ovariectomy and long-term estrogen replacement on bladder structure and function in the rat

Purpose: The use of estrogen replacement therapy for treating postmenopausal urinary incontinence is a controversial topic. We examined the behavioral, cystometric and histological changes that occur with long-term estrogen depletion and supplementation in rat bladders to determine the role of menopause in lower urinary tract dysfunction. Materials and Methods: A total of 40 female Sprague-Dawley rats were placed into 1 of 3 groups, including bilateral ovariectomy, bilateral ovariectomy plus estrogen replacement and control. The estrogen replaced group received a 0.25 mg. 16-week sustained release pellet (Innovative Research of America, Sanasota, Florida) placed subcutaneously. After surgery voiding frequency and volume were measured in 24-hour periods by placing animals in metabolic cages. After 16 weeks the rats underwent catheterization and continuous cystometry. The bladder was then removed and stained with Gomori trichrome. The collagen-to-smooth muscle density ratio was calculated for each specimen using current imaging software. Results: There was no significant difference in voiding patterns in the 3 groups, as measured by volume and voiding frequency. Cystometric data showed a trend toward higher voiding pressure, threshold pressure, baseline pressure and mean inter-voiding pressure in the ovariectomy group compared with the estrogen and control groups, although there was no statistical significance. Histological studies showed a higher mean collagen-to-smooth muscle ratio plus or minus standard deviation in the ovariectomy group (0.807 +/- 0.204) than in the ovariectomy plus estrogen replacement (0.709 +/- 0.118) and control (0.700 +/- 0.129) groups (p < 0.05). Furthermore, when histological and cystometric data were compared for individual samples, we found a direct correlation of mean inter-voiding pressure (a measure of bladder instability) with the collagen-to-smooth muscle ratio (p < 0.05). Conclusions: Long-term estrogen replacement is beneficial for treating postmenopausal urinary incontinence.