The effect of ovariectomy and long-term estrogen replacement on bladder structure and function in the rat.
ABSTRACT 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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ABSTRACT: To assess the efficacy of cyclic postmenopausal hormone replacement in treating urinary incontinence in hypoestrogenic women. Eighty-three hypoestrogenic women complaining of urinary incontinence were included. All patients were community-dwelling, age 45 years or older, with involuntary loss of urine occurring at least once a week and urodynamic evidence of genuine stress incontinence and/or detrusor instability. Evaluation consisted of a comprehensive clinical and urodynamic research protocol. The hypoestrogenic entry criterion was a plasma estradiol level of 30 pg/mL or less. Parabasal cells on vaginal smears were also monitored. The primary outcome was the number of incontinent episodes per week, as documented on a standardized urinary diary. Secondary outcomes were the quantity of fluid loss, voluntary diurnal and nocturnal micturition frequency, generic and condition-specific health-related quality of life measurements, and patient satisfaction. A randomized, placebo-controlled, double-blind design was used. Subjects in the treatment group were given conjugated equine estrogens (0.625 mg) and medroxyprogesterone (10 mg) cyclically for 3 months. Controls received placebo tablets. (All results are presented as mean +/- standard deviation.) Subjects were 67 +/- 9 years old. The menopause duration was 18 +/- 11 years. The duration of incontinence was 9 +/- 9 years. Estradiol level at baseline was 9 +/- 9 pg/mL, and the parabasal cell count was 42 +/- 44%. The number of incontinent episodes at baseline was 13 +/- 10 for the treatment group and 16 +/- 4 for controls. No significant changes occurred in the number of incontinent episodes after treatment: 10 +/- 10 for the treatment group, and 13 +/- 14 for the controls (P = .7). Also, fluid loss was not changed: 176 +/- 106 g for the treatment group and 64 +/- 88 g for the control group at baseline, and 101 +/- 150 and 51 +/- 69 g after treatment, respectively (P = .7). There were no significant differences for either diurnal or nocturnal voluntary micturition, quality of life measures, or patient's perception of improvement. Three-month cyclic hormone replacement therapy did not affect either clinical or quality of life variables of incontinent, hypoestrogenic women. Long-term effects are unlikely to be substantially different. The use of estrogen supplementation as preventive or adjuvant therapy was not evaluated in this study.Obstetrics and Gynecology 12/1996; 88(5):745-9. · 4.80 Impact Factor
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ABSTRACT: Female Fischer 344 rats were ovariectomized or sham operated and treated with oil or estradiol cypionate (100 mg./100 gm./month) for two or four months. Rats were then placed in metabolism cages for measurement of micturition characteristics, and bladders were removed for bladder strip studies. Ovariectomy had no effects on micturition characteristics. However, estradiol treatment of ovariectomized rats caused significant increases in water consumption and urine excretion, and in mean and maximal micturition volumes compared to both ovariectomized and sham-operated rats. These effects were more pronounced at four months. Estradiol treatment also caused significant increases in bladder body mass, while ovariectomy was without effect. Two months after ovariectomy and/or estradiol treatment, there were no differences in contractile responses of bladder body or base strips to contractile agents when compared to shams. However, after four months, ovariectomy caused significant decreases in contractile responsiveness to nerve stimulation. ATP, carbachol, and KCl compared to sham-operated rats. Estradiol treatment caused increased responsiveness to nerve stimulation, ATP, carbachol, and KCl compared to ovariectomized rats, and to carbachol compared to sham operated rats. Possible causes for the effects of ovariectomy on bladder contractility include decreases in calcium influx. Although estradiol reversed the effects of ovariectomy on bladder function, in addition we observed some indirect effects which were probably the result of estradiol-induced polyuria and increases in bladder mass.The Journal of Urology 10/1992; 148(3):915-9. · 3.70 Impact Factor
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ABSTRACT: 1. The effect of oestradiol pretreatment was investigated on the response of rat isolated detrusor muscle to cholinergic, electrical and 5-hydroxytryptamine (5-HT) stimulation with and without diethylstilbestrol (DES) (2 microM) in the organ bath. 2. Virgin female Wistar rats were injected subcutaneously for 8 days with oestradiol benzoate 150 micrograms kg-1. Control rats received no injections or injection only with the vehicle, ethyl oleate. 3. Detrusor muscle from treated rats showed a decreased sensitivity to acetylcholine (ACh) and carbachol-induced contractile responses. The dose-response curves to these agonists showed a 44% reduction in maximum contractile response for ACh (P < 0.001), and a 38% reduction in maximum contractile response for carbachol (P < 0.05). The addition of 2 microM DES to the bathing medium further significantly reduced the maximum contractile response by 56 and 57% of control respectively. 4. Electrically stimulated detrusor muscle from treated rats showed a significant 49% reduction in the maximum contractile response (P < 0.001). The addition of 2 microM DES to the bathing medium further significantly reduced the maximum contractile response by 66% of control. The tetrodotoxin resistant responses were smaller in pretreated rats, suggesting a reduced sensitivity of the smooth muscle to direct electrical stimulation. 5. The response to 5-HT stimulation by detrusor muscle samples from oestradiol-treated rats showed a non-significant reduction in maximum contractile response, but the addition of 2 microM DES to the bath chamber resulted in a 67% reduction in the response (P < 0.001). 6. Oestradiol pretreatment did not affect the potassium dose-response curve.7. Oestradiol pretreatment reduced the rat detrusor muscle sensitivity to the blocking effect of atropine on the response to electrical field stimulation. Pretreatment also reduced the potentiating effect of physostigmine on the same response.8. These results suggest that oestradiol pretreatment had a modulating effect on cholinergic responses.The addition of oestrogen to the tissue environment enhances this inhibitory effect.British Journal of Pharmacology 11/1992; 107(3):766-70. · 5.07 Impact Factor