The Effect of Ovariectomy and Long-term Estrogen Replacement on Bladder Structure and Function in the Rat

Division of Urologic Research, Albert Einstein College of Medicine, The Bronx, New York, USA.
The Journal of Urology (Impact Factor: 4.47). 09/2002; 168(3):1265-8. DOI: 10.1097/01.ju.0000023406.93873.08
Source: PubMed


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.

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    • "The latter effect has been attributed to a decrease in ACh release from nerve fibers (Yoshida et al., 2007). Axonal degeneration in the detrusor, including disrupted axolemma, depleted synaptic vesicles, and disrupted neuronal mitochondria, as well as an ϳ25% reduction in the smooth muscle mass at 4 months after OVX in aged (13–14 months) female Fisher rats may account for the reduction in efferent nerve-evoked responses (Zhu et al., 2001; Fleischmann et al., 2002). Taken together, the results suggest that the facilitatory effect of OVX is less likely due to enhancement of the excitatory efferent neurotransmission or increase in bladder smooth muscle excitability but may be related to changes in either peripheral sensory mechanisms (urothelium or afferent nerves) or central neural pathways controlling bladder reflexes. "
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