Efficacy of estrogen supplementation in the treatment of urinary incontinence. The Continence Program for Women Research Group. Treatment with oral piperazine oestrone sulphate for genuine stress incontinence in postmenopausal women. The effect of oestrogen supplementation on post-menopausal urinary stress incontinence: a double-blind placebo-controlled trial. Efficacy of low-dose intravaginal estriol on urogenital aging in postmenopausal women. [Transvaginal estrogen therapy in urinary stress incontinence]. Combined behavioral and individualized drug therapy versus individualized drug therapy alone for urge urinary incontinence in women. Effects of estrogen with and without progestin on urinary incontinence. Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women. A comparative study of safety and efficacy of continuous low dose oestradiol released from a vaginal ring compared with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy.
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. The use of oestrogens in the treatment of genuine stress incontinence was assessed by a double-blind prospective trial in 36 postmenopausal women with genuine stress incontinence who received 3 months of cyclical treatment with either piperazine oestrone sulphate or a matching placebo. Patients were assessed subjectively and objectively before and after treatment by 7-day bladder charts, urethral pressure profiles (UPP), the Urilos nappy test, vaginal cytology and hormone assays (plasma oestrogens and gonadotrophins). There was no statistical difference in the subjective response to treatment between the two groups. After 6 weeks of treatment there was a greater reduction in the number of pad changes/24 h in the oestrogen-treated patients that approached statistical significance but, because of a marked response in the placebo group, this difference was not significant after 3 months of treatment. There were also no significant differences between the two groups with respect to the UPP or Urilos measurements but the vaginal cytology and hormone profiles were significantly affected by oestrogens. In view of the possible risks of oestrogen therapy its use in genuine stress incontinence is limited. To investigate the effect of hormone replacement therapy on post-menopausal urinary stress incontinence.
                Double-blind, placebo-controlled, randomised trial.
                University associated teaching hospital.
                Post-menopausal women with genuine stress incontinence, not taking hormone replacement therapy.
                Randomisation to six months therapy with oestradiol valerate 2 mg daily or placebo. Assessment prior to treatment and upon study completion with the SF-36 health status questionnaire, the Bristol Female Lower Urinary Tract Symptoms questionnaire, a one week urinary diary, one hour perineal pad test, cystometry and urethral profilometry.
                Sixty-seven women consented to participate, 33 were randomised to receive oestradiol. Mean age was 63 years. Five women failed to undergo repeat assessment, three of whom were receiving oestrogen. Six women receiving oestradiol experienced breakthrough bleeding during the six months and were subsequently treated with additional monthly progestogen. No significant effect of oestrogen over placebo was observed for any subjective or objective clinical outcome.
                This trial is one of the largest controlled studies yet reported, with the longest duration of treatment. No improvement in post-menopausal stress incontinence was demonstrated after six months therapy with oestradiol. This concurs with another study reported recently; it seems unlikely that oestrogen has a significant role to play in this condition. To assess the efficacy and safety of intravaginal estriol administration on urinary incontinence, urogenital atrophy, and recurrent urinary tract infections in postmenopausal women.
                Eighty-eight postmenopausal women with urogenital aging symptoms were enrolled in this prospective, randomized, placebo-controlled study. Participants were randomly divided into two groups, with each group consisting of 44 women. Women in the treatment group received intravaginal estriol ovules: 1 ovule (1 mg) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy. Women in the control group received inert placebo vaginal suppositories in a similar regimen. We evaluated urogenital symptomatology, urine cultures, colposcopic findings, urethral cytologic findings, urethral pressure profiles, and urethrocystometry before as well as after 6 months of treatment.
                After therapy, the symptoms and signs of urogenital atrophy significantly improved in the treatment group in comparison with the control group. Thirty (68%) of the treated participants, and only seven (16%) of the control participants registered a subjective improvement of their incontinence. In the treated participants, we observed significant improvements of colposcopic findings, and there were statistically significant increases in mean maximum urethral pressure, in mean urethral closure pressure as well as in the abdominal pressure transmission ratio to the proximal urethra. Urethrocystometry showed positive but not statistically significant modifications.
                Our results show that intravaginal administration of estriol may represent a satisfactory therapeutic choice for those postmenopausal women with urogenital tract disturbances who have contraindications or refuse to undergo standard hormone therapy. Thirty-four postmenopausal stress incontinence patients were divided in two groups: 17 were treated with 0.5 mg oestriol vaginal cream for 90 days, 17 controls were treated with moisturizing cream. All had low urethral pressures and dystrophy. Treated patients showed improvement of maximum urethral pressure, urethral closure pressure, and volume at first sensation of fullness. Dystrophy was cured in most patients; in 17% incontinence was cured and in 41% subjectively improved. We tested whether individualized drug therapy enhanced with behavioral training would result in better outcomes than individualized drug therapy alone.
                Participants were community dwelling women with urge predominant incontinence. Using a randomized clinical trial design women were randomized to 8 weeks (4 visits) of drug therapy alone (32) or drug therapy plus behavioral training (32). Drug therapy was individually titrated, extended release oxybutynin with proactive management of side effects. Behavioral training included pelvic floor muscle training and urge suppression techniques. The primary outcome measure was reduction in frequency of incontinence episodes on bladder diary at 8 weeks (with followup at 6 and 12 months). Secondary outcomes included patient satisfaction, global perception of improvement, Urogenital Distress Inventory and Incontinence Impact Questionnaire.
                In intent to treat analysis frequency of incontinence was reduced a mean of 88.5% in the drug alone group and 78.3% in the combined therapy group (p = 0.16). Outcomes were not significantly different between the groups in the analysis of completers (91.5% vs 86.2%, p = 0.34), or in either analysis at 6 or 12 months. The groups also did not differ significantly on secondary outcomes at any point. Participants in the drug alone group tended to be taking higher doses of oxybutynin at 8 weeks but the final dose did not differ significantly between the groups. Based on a conditional power calculation the trial was stopped early for futility.
                When drug therapy is implemented with frequent individualized dose titration, daily bladder diaries and careful management of side effects, initiating concurrent behavioral training does not enhance outcomes for urge incontinence in women.
                Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved. Menopausal hormone therapy has long been credited with many benefits beyond the indications of relieving hot flashes, night sweats, and vaginal dryness, and it is often prescribed to treat urinary incontinence (UI).
                To assess the effects of menopausal hormone therapy on the incidence and severity of symptoms of stress, urge, and mixed UI in healthy postmenopausal women.
                Women's Health Initiative multicenter double-blind, placebo-controlled, randomized clinical trials of menopausal hormone therapy in 27,347 postmenopausal women aged 50 to 79 years enrolled between 1993 and 1998, for whom UI symptoms were known in 23,296 participants at baseline and 1 year.
                Women were randomized based on hysterectomy status to active treatment or placebo in either the estrogen plus progestin (E + P) or estrogen alone trials. The E + P hormones were 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate (CEE + MPA); estrogen alone consisted of 0.625 mg/d of conjugated equine estrogen (CEE). There were 8506 participants who received CEE + MPA (8102 who received placebo) and 5310 who received CEE alone (5429 who received placebo).
                Incident UI at 1 year among women without UI at baseline and severity of UI at 1 year among women who had UI at baseline.
                Menopausal hormone therapy increased the incidence of all types of UI at 1 year among women who were continent at baseline. The risk was highest for stress UI (CEE + MPA: relative risk [RR], 1.87 [95% confidence interval {CI}, 1.61-2.18]; CEE alone: RR, 2.15 [95% CI, 1.77-2.62]), followed by mixed UI (CEE + MPA: RR, 1.49 [95% CI, 1.10-2.01]; CEE alone: RR, 1.79 [95% CI, 1.26-2.53]). The combination of CEE + MPA had no significant effect on developing urge UI (RR, 1.15; 95% CI, 0.99-1.34), but CEE alone increased the risk (RR, 1.32; 95% CI, 1.10-1.58). Among women experiencing UI at baseline, frequency worsened in both trials (CEE + MPA: RR, 1.38 [95% CI, 1.28-1.49]; CEE alone: RR, 1.47 [95% CI, 1.35-1.61]). Amount of UI worsened at 1 year in both trials (CEE + MPA: RR, 1.20 [95% CI, 1.06-1.36]; CEE alone: RR, 1.59 [95% CI, 1.39-1.82]). Women receiving menopausal hormone therapy were more likely to report that UI limited their daily activities (CEE + MPA: RR, 1.18 [95% CI, 1.06-1.32]; CEE alone: RR, 1.29 [95% CI, 1.15-1.45]) and bothered or disturbed them (CEE + MPA: RR, 1.22 [95% CI, 1.13-1.32]; CEE alone: RR, 1.50 [95% CI, 1.37-1.65]) at 1 year.
                Conjugated equine estrogen alone and CEE + MPA increased the risk of UI among continent women and worsened the characteristics of UI among symptomatic women after 1 year. Conjugated equine estrogen with or without progestin should not be prescribed for the prevention or relief of UI. To assess the long term risks and benefits of hormone replacement therapy (combined hormone therapy versus placebo, and oestrogen alone versus combined hormone therapy).
                Multicentre, randomised, placebo controlled, double blind trial.
                General practices in UK (384), Australia (91), and New Zealand (24).
                Postmenopausal women aged 50-69 years at randomisation. At early closure of the trial, 56,583 had been screened, 8980 entered run-in, and 5692 (26% of target of 22,300) started treatment.
                Oestrogen only therapy (conjugated equine oestrogens 0.625 mg orally daily) or combined hormone therapy (conjugated equine oestrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily). Ten years of treatment planned.
                Primary outcomes: major cardiovascular disease, osteoporotic fractures, and breast cancer. Secondary outcomes: other cancers, death from all causes, venous thromboembolism, cerebrovascular disease, dementia, and quality of life.
                The trial was prematurely closed during recruitment, after a median follow-up of 11.9 months (interquartile range 7.1-19.6, total 6498 women years) in those enrolled, after the publication of early results from the women's health initiative study. The mean age of randomised women was 62.8 (SD 4.8) years. When combined hormone therapy (n=2196) was compared with placebo (n=2189), there was a significant increase in the number of major cardiovascular events (7 v 0, P=0.016) and venous thromboembolisms (22 v 3, hazard ratio 7.36 (95% CI 2.20 to 24.60)). There were no statistically significant differences in numbers of breast or other cancers (22 v 25, hazard ratio 0.88 (0.49 to 1.56)), cerebrovascular events (14 v 19, 0.73 (0.37 to 1.46)), fractures (40 v 58, 0.69 (0.46 to 1.03)), and overall deaths (8 v 5, 1.60 (0.52 to 4.89)). Comparison of combined hormone therapy (n=815) versus oestrogen therapy (n=826) outcomes revealed no significant differences.
                Hormone replacement therapy increases cardiovascular and thromboembolic risk when started many years after the menopause. The results are consistent with the findings of the women's health initiative study and secondary prevention studies. Research is needed to assess the long term risks and benefits of starting hormone replacement therapy near the menopause, when the effect may be different.
                Current Controlled Trials ISRCTN 63718836. To compare the safety, efficacy and acceptability of a continuous low dose oestradiol releasing vaginal ring with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy.
                An open, parallel, comparative multicentre trial.
                Sydney and Melbourne, Australia.
                One hundred and ninety-four postmenopausal women with symptoms and signs of urogenital atrophy were randomised on a 2:1 basis to 12 weeks of treatment with an oestrogen vaginal ring versus an oestrogen cream.
                Equivalence (95% CI) was demonstrated between the two treatments for relief of vaginal dryness and dyspareunia, resolution of atrophic signs, improvement in vaginal mucosal maturation indices and reduction in vaginal pH. No significant difference was demonstrated in endometrial response to a progestogen challenge test and equivalence was demonstrated in the incidence of intercurrent bleeding episodes. The vaginal ring was significantly more acceptable than the cream P < 0.0001), and was preferred to the cream (P < 0.001).
                With equivalent efficacy and safety and superior acceptability to vaginal cream, the low dose oestradiol vaginal ring is an advance in vaginal delivery systems for the treatment of urogenital atrophy.
Urinary incontinence may be improved with the use of local oestrogen treatment. However, there was little evidence from the trials on the period after oestrogen treatment had finished and no information about the long-term effects of this therapy was given. Conversely, systemic hormone replacement therapy using conjugated equine oestrogen may worsen incontinence. There were too few data to reliably address other aspects of oestrogen therapy, such as oestrogen type and dose, and no direct evidence comparing routes of administration. The risk of endometrial and breast cancer after long-term use of systemic oestrogen suggests that treatment should be for limited periods, especially in those women with an intact uterus.