Oestrogens and lower urinary tract function.

There is increasing evidence from animal and human studies that sex steroids have an important effect on the female lower urinary tract during adult life. Oestrogen receptors have been identified throughout the brain, pontine micturition centre and in the bladder, urethra and pelvic floor. Fluctuations in the circulating level of oestrogens and progesterone occurring during the menstrual cycle and in pregnancy influence the prevalence of urinary symptoms and the results of urodynamic investigation. In addition, the menopause and subsequent oestrogen deficiency have been implicated in the aetiology of a number of urogenital complaints including incontinence, urgency and recurrent urinary tract infection (UTI). However, the use of hormone replacement therapy for these conditions has given conflicting and largely disappointing results. The aim of this paper is to discuss the role of oestrogen in the pathogenesis and treatment of lower urinary tract dysfunction.

Oestrogens for urinary incontinence in women.

BACKGROUND: It is possible that oestrogen deficiency may be an aetiological factor in the development of urinary incontinence in women. OBJECTIVES: To assess the effects of oestrogens used for the treatment of urinary incontinence. SEARCH STRATEGY: We searched the Cochrane Incontinence Group trials register (November 2002) and the reference lists of relevant articles. Date of the most recent searches: November 2002. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that included oestrogens in at least one arm, in women with symptomatic or urodynamic diagnoses of stress, urge or mixed incontinence or other urinary symptoms. DATA COLLECTION AND ANALYSIS: Trials were evaluated for methodological quality and appropriateness for inclusion by the reviewers. Data were extracted by all three reviewers and cross checked. Trial results were analysed within clinical subgroups or by intervention. Where appropriate, meta-analysis was undertaken. MAIN RESULTS: Twenty eight trials were identified which included 2926 women. Sample sizes ranged from 16 to 1525. The trials used varying combinations of type of oestrogen, dose, duration of treatment and length of follow up. Outcome data were not reported consistently and were available for only a minority of trials. In the 15 trials that compared oestrogen with placebo, 374 women received oestrogen and 344 placebo. Subjective impression of cure was higher amongst those treated with oestrogen for all categories of incontinence (36/101, 36% versus 20/96, 21%; RR for cure 1.61, 95% CI: 1.04 to 2.49). When subjective cure and improvement were considered together, a statistically higher cure and improvement rate was shown for both urge (35/61, 57% versus 16/58, 28% on placebo) and stress (46/107, 43% versus 29/109, 27%) incontinence. For women with urge incontinence, the chance of cure or improvement was approximately a quarter higher again than in women with stress incontinence. Taking all trials together, the data suggested that about 50% of women treated with oestrogen were cured or improved compared with about 25% on placebo. Overall, there were around 1 to 2 fewer voids in 24 hours amongst women treated with oestrogen. The effect again appeared to be larger amongst women with urge incontinence. There were no statistically significant differences in respect of frequency, nocturia or urgency. No serious adverse events were reported although some women experienced vaginal spotting, breast tenderness or nausea. In a large trial conducted amongst women with heart disease, data from a subset who had incontinence suggested that women treated with a combination of oestrogen and a progestogen had lower subjective cure or improvement rates compared to the placebo group (RR 0.85, 95% CI 0.76 to 0.95). The data were too few to address other questions about oestrogens compared with, or in combination with, other treatments, different types of oestrogen or different modes of delivery. REVIEWER'S CONCLUSIONS: Oestrogen treatment can improve or cure incontinence and the evidence suggests that this is more likely with urge incontinence. There was little evidence from the trials after oestrogen treatment had finished and none about long-term effects. Combined oestrogen and progesterone appeared to reduce the likelihood of cure or improvement. There were too few data to address reliably other aspects of oestrogen therapy such as oestrogen type, dose and route of administration. However, the risk of endometrial and breast cancer after long-term use suggests that oestrogen treatment should be for limited periods, especially in women with an intact uterus.

Predictors of female urinary incontinence at midlife and beyond.

Urinary incontinence (UI) is an important middle age health issue and approximately 20% of women over 40 years of age have problems with continence. Urinary incontinence poses a significant negative impact on social functioning and quality of life to many individuals. It is estimated that around three million people are regularly incontinent in the UK with a prevalence of about 40 per 1000 adults. There are various factors which can cause incontinence such as pregnancy, childbirth, obesity, menopause, or just inherent connective-tissue weakness. All of these factors can cause pathophysiology changes in the muscular and fascial structures of the pelvic floor and lead to pelvic support defects and possibly pelvic floor dysfunction. We aim with this review article to highlight predictors or predisposing factors of incontinence; in order to help clinicians during their decisions and put in place a policy of a preventive strategy to decrease the incontinence rate in the general population.

Managing postmenopausal cystitis.

Cystitis caused by prolonged estrogen deprivation may be grossly underreported. This may be why many advocates of hormone replacement therapy focus on its cardiovascular and skeletal benefits while ignoring the bladder and urethra.

The role of estrogen supplementation in lower urinary tract dysfunction.

The female lower urinary and genital tracts both arise from the primitive urogenital sinus and develop in close anatomical proximity. Sex hormones have a substantial influence on the female lower urinary tract throughout adult life, with fluctuations in their level leading to macroscopic, histological and functional changes. Urinary symptoms may therefore develop during the menstrual cycle, in pregnancy and following the menopause. Estrogen deficiency, particularly when prolonged, is associated with a wide range of urogenital complaints, including frequency, nocturia, incontinence, urinary tract infections and the 'urge syndrome'. Estrogen supplementation subjectively improves urinary stress incontinence but there is no objective benefit when given alone; however, estrogen given in combination with phenylpropanolamine may be clinically more useful. Hormone replacement therapy does appear to treat postmenopausal irritative urinary symptoms such as frequency and urgency, possibly by reversing urogenital atrophy, and there is also evidence to suggest that estrogens can provide prophylaxis against recurrent urinary tract infections. However, the 'best' type of estrogen, route of administration and duration of therapy are at present unknown.

The impact of the menstrual cycle on urinary symptoms and the results of urodynamic investigation.

Four hundred and eighty-three consecutive women referred for videocystourethrography completed a structured questionnaire about their menstrual status and urinary symptoms. Women were included in the study if they were premenopausal, had a regular menstrual cycle and were not taking hormonal therapy. One hundred and thirty-three women satisfied the inclusion criteria of whom 55 (41%) complained that their urinary symptoms were cyclical. The times at which symptoms were said to be at their worst were reported by the women as follows: during a period (n = 20; 36%); just after a period (n = 4; 7%); middle of the month (n = 8; 15%); just before a period (n = 23; 42%). The prevalence of abnormal detrusor activity on videocystourethrography increased significantly with time from the last menstrual period (chi2 for trend = 6.56, P = 0.01) and might reflect increases in the circulating level of progesterone following ovulation. This study provides further indirect evidence that progesterone could have an adverse effect on female lower urinary tract function. In addition, it might be necessary to consider the stage within the menstrual cycle when interpreting the results of urodynamic investigation.

Colposuspension after previous failed incontinence surgery: a prospective observational study.

OBJECTIVE: To evaluate the outcome of colposuspension for genuine stress incontinence in women who had previously undergone bladder neck surgery. DESIGN: Prospective observational study. SETTING: Tertiary referral urogynaecology unit. PARTICIPANTS: Fifty-two consecutive women with recurrent genuine stress incontinence operated on by one surgeon. MAIN OUTCOME MEASURES: Subjective and objective cure of stress incontinence. Complications of surgery. RESULTS: The mean age of the women was 51 years (range 28-72) and weight 72.7 kg (range 53-112). Sixty-five continence procedures had been performed previously, with 13 women (25%) having had more than one operation. Nine months post-operatively the subjective cure rate was 80% and objective cure rate 78%. Intraoperative complications were few but included two bladder injuries and one rectus muscle tear which required repair. Seven women (13%) developed voiding difficulties which required clean intermittent self-catheterisation, but only one needed to continue this for six months. None of the women developed detrusor instability. CONCLUSIONS: In this setting colposuspension after previous bladder neck surgery offers a high rate of success. However, long term follow up is needed to see if this effect is maintained.

Lower urinary tract symptoms and their impact on women with anorexia nervosa.

Anorexia nervosa is a condition which is associated with extremely low body weight and endocrine problems including persistent anovulation and a hypo-oestrogenic state. As the lower urinary tract is oestrogen sensitive, it is possible that women suffering from anorexia nervosa may experience similar distressing urinary problems. Of 29 anorexic women assessed, the majority had significant irritative urinary symptoms of which frequency, urgency and nocturia were the most common. These symptoms also had an unfavorable impact on their quality of life.

Does the menopause influence the risk of bacteriuria?

The objective of this study was to test the hypothesis that the risk of bacteriuria is increased as a result of estrogen deprivation following the menopause. All midstream urine samples (MSU) sent to the King's College Hospital department of microbiology by general practitioners in 1997 were assessed. Bacteriuria was diagnosed when the bacterial count was >10(5) organisms/ml. Logistic regression analysis was performed to investigate the effects of age and sex on the likelihood of having a positive result. Non-linear effects of age were investigated, with interest focusing in particlar on the time around the menopause. There were 15,392 MSU samples analyzed; 11,811 (77%) were from women and 3581 (23%) from men. In both sexes the proportion of positive results increased with increasing age (P<0.0001). The specimens taken from women were significantly more likely to be positive than those taken from a man of the same age (P<0.0001). In women there was no evidence of any non-linear relationship between age and the log odds of a positive result. A plot of the proportion of positive results versus age did not suggest any departure from a linear relationship at or following the menopause. In conclusion, the increased risk of bacteriuria which occurs as women get older appears to happen gradually as a result of the aging process, rather than as the result of pathophysiological changes in the urogenital tract that take place at or following the menopause.

Pregnancy following a single lung transplant.

Successful pregnancy in a single lung transplant recipient has not been reported previously. The long term effect of pregnancy on graft function and management of deteriorating pulmonary function is not defined. This case describes the management, outcome, and problems encountered when a single lung transplant recipient developed a progressive deterioration in pulmonary function during pregnancy, attributed to accelerated obliterative bronchiolitis.

Videocystourethrography with a ring pessary in situ. A clinically useful preoperative investigation for continent women with urogenital prolapse?

The aim of the study was to evaluate the use of a vaginal pessary in the detection of genuine stress incontinence (GSI) in women with urogenital prolapse undergoing urodynamic investigation. Continent women with urogenital prolapse, with or without associated urinary symptoms, were studied. All underwent videocystourethrography using a standardized protocol. None had evidence of incontinence on provocative testing in the upright position. A well-fitting vaginal ring pessary was inserted to reduce the prolapse and mimic a vaginal repair. The provocative tests were then repeated while the bladder was screened. Seventy women with a mean age 59.0 years (range 34-83) were recruited over a 21-month period: 15 women complained of prolapse alone and 55 had concurrent urinary symptoms; 19 women (27%) developed GSI only following the insertion of a vaginal pessary. The women who became incontinent were significantly older (mean age 63.9 years) than those who remained continent (mean age 56.8 years) (P < 0.020). The use of a vaginal pessary increases the detection rate of GSI in continent women with urogenital prolapse undergoing videocystourethrography. These findings are important because women with prolapse and coexisting incontinence should be offered a continence procedure rather than a simple vaginal repair.

Mucosal concentration and excretion of clindamycin by the human stomach.

Each of 12 patients undergoing routine diagnostic upper gastrointestinal endoscopy received a single iv infusion of clindamycin phosphate 300 mg over 10 min. During the endoscopy, mucosal biopsies of the gastric antrum and fundus were obtained at varying times following the infusion. The clindamycin concentrations in the biopsies and in serum samples also taken after the infusion were determined. In addition, six healthy volunteers participated in a cross-over study on two different days. On both days, each subject received a single iv infusion of clindamycin phosphate 300 mg, immediately after which, gastric secretion was stimulated by iv pentagastrin (2 micrograms/kg/h) which was infused continuously over 150 min. On one of the study days, acid secretion by the stomach was inhibited by a slow iv infusion of ranitidine 50 mg. Clindamycin concentrations in gastric aspirates and serum samples collected after the infusion were determined. Concentrations of clindamycin in the fundal mucosa were significantly higher than the simultaneous serum concentrations (median ratio of tissue concentration to serum concentration, 2.0; P < 0.005) while concentrations in the antral mucosa were similar to those in serum (median ratio, 1.2; P = 0.65). Ranitidine significantly inhibited pentagastrin-stimulated acid secretion as demonstrated by a decrease in the volume of gastric aspirate when ranitidine was administered compared with when it was not administered (P < 0.01). Clindamycin concentrations in gastric juice were approximately one and one-half times higher than those in serum samples obtained simultaneously, both during stimulation of gastric acid secretion with pentagastrin and during inhibition of pentagastrin-stimulated acid secretion with ranitidine. Gastric juice concentrations of clindamycin were significantly higher following administration of ranitidine than after stimulation of gastric secretion by pentagastrin alone. Fundal mucosal and gastric juice concentrations of clindamycin exceeded the hypothetical maximum serum concentrations, indicating that accumulation in the stomach occurred against a concentration gradient.