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. The use of oestradiol therapy in postmenopausal women after TVT-O anti-incontinence surgery. Efficacy of sustained-release vaginal oestriol in alleviating urogenital and systemic climacteric complaints. Effects of two different regimens of continuous hormone replacement therapy on endometrial histopathology and postmenopausal uterine bleeding. Results from the Estonian postmenopausal hormone therapy trial [ISRCTN35338757]. Oestradiol-releasing vaginal ring versus oestriol vaginal pessaries in the treatment of bothersome lower urinary tract symptoms. Effects of "natural oestrogen" replacement therapy on menopausal symptoms and blood clotting. Effects of oral estrogen and progestin on the lower urinary tract among female nursing home residents. A two-year double-blind controlled study of the clinical effect of combined and sequential postmenopausal replacement therapy and steroid metabolism during treatment. [Comparative study on two different dosages of conjugated equine estrogen continuously combined with medroxyprogesterone in prevention of postmenopausal osteoporosis]. Gonadotropin-releasing hormone analogue plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial. Hormone replacement therapy plus pelvic floor muscle exercise for postmenopausal stress incontinence. A randomized, controlled trial. Vaginal estrogen therapy and overactive bladder symptoms in postmenopausal patients after a tension-free vaginal tape procedure: a randomized clinical trial. A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence.
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. To investigate whether patients who were treated with TVT-O procedure for urodynamic stress incontinence had a significant improvement in their urodynamic findings and their post-operative symptoms (frequency, urgency, nocturia) if they were treated post-operatively with vaginal oestradiol for 6 months compared to the non-treated group.
                Prospective randomised study. 190 patients were asked to participate in our study. Finally, a total of 92 patients in group 1 and 91 patients in group 2 completed the study. In group 1, which was the treatment group, patients having the TVT-O procedure for urodynamic stress incontinence were instructed to use post-operatively oestradiol tablets, 25 micrograms (Vagifem, Novo Nordisk) vaginally, once daily, nocte, for 2 weeks and then twice weekly for 6 months. The patients in group 2 (control group) had the TVT-O procedure only. All patients were reviewed in 2 months and again in 6 months time.
                There was no statistically significant difference between the two groups concerning pre-operative and post-operative haemoglobin, operative time, hospital stay or return to work. The within group analysis did not show significant differences between pre-operative and post-operative urodynamic data in both groups. Patients treated with vaginal estradiol post-operatively showed a statistically significant reduction in relation to the symptoms of urgency and frequency but not in relation to nocturia and urge incontinence compared to the non-treated group. There is no difference in relation to the efficacy of TVT-O procedure between the groups at 6 months follow-up.
                It appears that vaginal oestradiol treatment could be offered to postmenopausal patients after a TVT-O procedure having the symptoms of frequency and urgency provided they are aware of the lack of evidence regarding long term benefit.
                Copyright 2010. Published by Elsevier Ireland Ltd. In a double-blind, placebo-controlled study, 109 patients suffering from local and vasomotor postmenopausal complaints were randomly assigned to treatment with either depot vaginal suppositories containing 3.5 mg oestriol (E3) or a placebo. The treatment schedule comprised one vaginal suppository twice weekly for 3 weeks initially, followed by maintenance therapy with one vaginal suppository weekly for the 6-month study period. The effectiveness of the therapy was assessed on the basis of questionnaires (Kupperman index for vasomotor complaints and an original urogenital index for local complaints) and gynaecological examinations which included assessments of vaginal cytology, vaginal pH and Döderlein bacilli. To rule out induced endometrial proliferation, endometrial biopsies were performed in 50 women before and after the study. The vaginal depot (E3) formulation showed highly significant superiority over the placebo with respect to therapeutic effect on local urogenital complaints and alleviation of vasomotor complaints, including hot flushes. Analysis of the endometrial biopsies indicated that the monotherapy used caused no endometrial stimulation. Taking into account the minimal rate of adverse effects, the 3.5 mg E3 depot formulation studied represents a useful variant in the range of preparations available for the treatment of post-menopausal complaints. To compare the effects of frequently used two different regimens of combined continuous hormone replacement therapy; 0.625 mg conjugated equine estrogen (CEE) + 2.5 mg medroxyprogesterone acetate (MPA) and 1 mg 17beta estradiol (E2) + 0.5 mg norethindrone acetate (NETA), on endometrial histopathology and postmenopausal uterine bleeding.
                Two hundred and forty-six outpatient subjects aged 41-57 years were enrolled in the study conducted at the menopause clinic between November 2003 and November 2004. One hundred and thirty-nine patients were assigned to receive 0.625 mg conjugated equine estrogen + 2.5 mg medroxyprogesterone acetate (CEE/MPA), whereas 107 patients were to receive 17beta estradiol + 0.5 mg norethindrone acetate (E2/NETA). Inclusion criteria of the study were: normal values of endometrial thickness at basal evaluation, women with intact uterus, at least 12 months of amenorrhea, normal vaginal smear, bilateral mammography and biochemical blood parameters. All women were questioned every 3 months for vaginal bleeding/spotting. Endometrial sampling was performed by Pipelle catheter in the 12th month of therapy.
                For the first 3 months, vaginal bleeding/spotting rate for the CEE/MPA group was 38.7%, whereas it was higher (45%) in the E2/NETA group. For the second 3-month period, vaginal bleeding/spotting frequencies were 41.1 and 37.8%, respectively. In the third 3-month period 30.6 and 29.6%, and in the fourth 3-month period, 18.5 and 12.5% of the patients reported vaginal bleeding or spotting. None of the results of endometrial sampling have shown findings of cancer histopathology.
                Compared to CEE/MPA regimen, E2/NETA therapy has not shown more favorable effects on postmenopausal bleeding abnormalities. Irregular endometrial proliferation was seen more with the E2/NETA regimen. At present the Women's Health Initiative trial is the only reported randomised controlled trial studying the effects of hormone therapy among healthy postmenopausal women. The Women's Health Initiative reports have been criticized for lacking in generalisability, due to the characteristics of the trial population. We aimed to compare the health effects of oral continuous combined hormone therapy with a placebo and non-treatment among healthy Estonian women.
                Eligible women were randomised into a blind group of hormone therapy versus placebo and into a non-blind group of open label hormone therapy versus non-treatment. One thousand seven hundred and seventy-eight postmenopausal women aged 50-64 at the time of sampling were recruited in 1999-2001 at three clinical centers in Estonia. Participants received conjugated equine oestrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5mg/d, or conjugated equine oestrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 5mg/d, if less than 3 years had passed since menopause at recruitment, or matched placebo or non-treatment. Trial treatment was stopped gradually from 1 January 2004 to 31 May 2004.
                After a follow-up period from 2.0 to 5.0 years the combined hazard ratio, stratified by blinding and adjusted for age at recruitment and former oral contraceptive use was 1.12 (95% confidence interval [CI]: 0.90-1.40) for coronary heart disease, 1.24 (95% CI: 0.85-1.82) for cerebrovascular disease, 1.36 (95% CI: 0.73-2.52) for total cancer, and 0.61 (95% CI: 0.42 to 0.89) for bone fractures.
                The results from the Estonian Postmenopausal Hormone Therapy randomised trial are consistent with the Women's Health Initiative findings. To assess the efficacy of an oestradiol-releasing vaginal ring and oestriol pessaries in the alleviation of lower urinary tract symptoms occurring after the menopause.
                Randomised, parallel group, controlled trial.
                Twenty-six clinics of practising gynaecologists and one outpatient clinic at a department of obstetrics and gynaecology.
                Two hundred and fifty-one postmenopausal women, with a mean age of 66 years, reporting at least one bothersome lower urinary tract symptom.
                One hundred and thirty-four women were treated with the oestradiol-releasing ring for 24 weeks; 117 women were treated with oestriol pessaries 0.5 mg every second day for 24 weeks.
                Subjective scores of urgency, frequency, nocturia, dysuria, stress incontinence and urge incontinence.
                The two treatments were equally efficacious in alleviating urinary urgency (51% vs 56%), urge incontinence (58% vs 58%), stress incontinence (53% vs 59%) and nocturia (51% vs 54%). Dysuria was alleviated in 76% vs 67%, equivalence was not demonstrated. No statistically significant difference was found for any primary efficacy endpoint. Sixty percent of the participants rated the form of administration via the vaginal ring as excellent, compared with 14% for the pessaries (P < 0.0001).
                Low dose vaginally administered oestradiol and oestriol are equally efficacious in alleviating lower urinary tract symptoms which appear after the menopause. The form of administration of the vaginal ring, seems to be more acceptable than oestriol pessaries. In a double-blind study on the value of equine ("natural") oestrogens 30 patients presenting with menopausal symptoms in a group practice were monitored for possible adverse effects on blood clotting, weight, and blood pressure. The women were randomly allocated to two groups and given either three months' hormone treatment followed by three months' placebo or vice versa. An appreciable amelioration of all symptoms on placebo made it difficult to asses the genuine value of oestrogen treatment during the period of study. Both groups made a dramatic clinical improvement during the first three months. Nevertheless, the symptoms of the 15 women who received oestrogen first returned after the cross-over to placebo without any suggestion of a placebo response. In contrast, the other group who took placebo first did not deteriorate after changing to oestrogen. The menopausal index and the karyopyknotic index were not reliable guides to the need for oestrogen treatment. Hot flushes, however, were proportionately reduced on oestrogen and they seemed to be more readily eliminated in individual cases by oestrogen. The results of blood clotting studies indicated that natural oestrogen administration raised the levels of the extrinsic clotting factors VII and X and accelerated the prothrombin time. The findings were similar to those observed after three months synthetic oestrogen administration with oral contraception. Long-term studies and epidemiological surveys of the clinical incidence of thrombotic and other sequelae are needed before large-scale oestrogen replacement treatment can be recommended. To examine the effects of oral estrogen/progestin on incontinence and related lower urinary tract conditions among female nursing home (NH) residents.
                Randomized placebo-controlled trial.
                Five NHs.
                Thirty-two incontinent female residents of average age 88.
                Subjects were randomized to receive either oral estrogen (0.625 mg) combined with progesterone (2.5 mg) or placebo, daily for 6 months. Measures of incontinence severity, the clinical appearance of the vagina, vaginal and urethral cytology, and urine and vaginal cultures were made at baseline, 3 months, and 6 months. In addition to active drug or placebo, all subjects received regular toileting assistance (prompted voiding) by trained research aides during 3-day data-collection periods to compensate for mobility and cognitive impairments.
                At 3 and 6 months there were no significant differences between the groups in the severity of incontinence, the prevalence of bacteriuria, or the results of vaginal cultures. Several clinical findings associated with atrophic vaginitis improved more in the active than the placebo group and vaginal pH and vaginal and urethral cytology exhibited a partial estrogenic effect.
                Our results must be interpreted with caution because of the size and the select nature of our subject sample. Up to 6 months of oral estrogen had only a partial estrogenic effect on vaginal and urethral epithelium and no clinical effects in this patient population. We believe that future studies of estrogen for urinary incontinence in frail NH residents should utilize a topical preparation and consider targeting urinary tract infection as an additional outcome measure. A total of 151 postmenopausal women were randomly allocated to 3 groups for treatment with hormone replacement therapy. One group received combined therapy (2 mg oestradiol (E2) and 1 mg norethisterone acetate (NETA) daily), the second group was placed on sequential therapy (2 mg E2 for 12 days, 2 mgE2 and 1 mg NETA for 10 days and 1 mg E2 for 6 days), while the third was given placebo. Treatment was administered over 24 cycles of 28 days. The two active treatments were equally effective in relieving climacteric symptoms. In the combined therapy group, 62% of the women experienced spotting and/or breakthrough bleeding during the first 3 cycles; thereafter this proportion decreased to between 3 and 18% in each of the following three-cycle periods. Sixty-four percent (64%) of these women had no more bleeding after the first 3 cycles. Endometrial atrophy was detected in 93% of the women in this group after 24 cycles of therapy. Bleeding irregularities occurred during the first 3 cycles in 27% of the patients treated with sequential therapy and in 21% of those receiving placebo. In the subsequent 3-cycle periods these figures fell to below 10% in the 2 groups. In all 3 groups weight remained stable but blood pressure increased equally in the actively treated groups and the placebo group. The levels of follicle-stimulating hormone (FSH), sex-hormone-binding globulin (SHBG) and the free fraction of E2 in serum were significantly lower in the combined therapy group than in the sequential therapy group. The higher level of free E2 in the latter group may have been caused by a decrease in metabolism associated with the increased SHBG concentration. It was concluded that combined treatment with E2 and NETA might provide an alternative to sequential treatment in postmenopausal women willing to tolerate the initial high risk of breakthrough bleeding/spotting in order to avoid subsequent regular bleeding. In the subgroup of women in whom bleeding irregularities continue, sequential treatment should be considered. To investigate the effects of two dosages of conjugated equine estrogen (CEE) in preventing bone loss in early postmenopausal women.
                Two hundreds and thirty six early postmenopausal women were randomly given one of the following regimens for two years. Groups A (GA): CEE 0.625 mg + medroxyprogesterone (MPA domestic made) 2 mg + caltrate-D (Ca-D) 1 tablet daily; Group B (GB): CEE 0.3 mg + MPA 2 mg + Ca-D 1 tablet daily; Group C (GC): Ca-D 1 tablet daily alone. The observation endpoints included: (1) bone mineral density (BMD) of lumbar 2 - 4 (L(2 - 4)) measured by duel energy X-ray absorptiometry (DEXA, Lunar DPX-L) before and 1, 2 years after treatment; (2) vaginal bleeding recorded daily and endometrium thickness yearly by transvaginal ultrasonography. Endometrium biopsies were performed if its thickness greater than 5 mm.
                Two hundreds and thirteen (90%) cases completed 1-year study, 176 (75%) 2 year study. In GA L(2 - 4) BMD significantly increased both after 1 and 2 year treatment as compared with pretreatment value (P < 0.001). While in GB, L(2 - 4) BMD significantly elevated only after 1 year treatment, but did not reach significance during the end of 2 year therapy. In contrast, L(2 - 4) BMD decreased by 0.4% and 1.6% respectively after 1, 2 year of GC although without significance. Compared among the three group, the increments of mean L(2 - 4) BMD after 1 year treatment in GA and GB were significantly different from, that in GC (+2.3%, +2.7% versus -0.4%, P < 0.001, P < 0.05 respectively). So were the values after 2 year treatment (+3.7%, +0.7% versus -1.6%, P < 0.001, P < 0.05 respectively). As compared the mean L(2 - 4) BMD between GA and GB, the difference reached significance only after 2 year (P < 0.01), but not after 1 year treatment (P > 0.05). The vaginal bleeding rate in GA during the first month and 1, 2 year after treatment were higher than those in GB and GC (52% versus 16%, 9%; 43% versus 12%, 2.8%; 34% versus 8%, 3.3%). Endometrium biopsies were carried in 153 cases (27 had endometrium thicker than 5 mm) in GA and GB. No atypical hyperplasia was found, but 2 cases showed simple hyperplasia in the GA. One case in GA developed superficial thromphlebitis during the 1 year treatment.
                Both 0.625 mg and 0.3 mg daily of CEE continuously combined with domestic MPA are effective in preventing postmenopausal osteoporosis. The former has more stronger effect than the latter, but needs higher dose of MPA when combined continuously in order to decrease the vaginal bleeding rate and preventing endometrium hyperplasia. The aim of this study was to determine whether or not continuous combined HRT used with GnRH-a for the treatment of endometriosis can prevent hypoestrogenic side effects associated with GnRH-a.
                Forty premenopausal women with laparoscopically proven endometriosis entered the study. The patients were randomized into two groups. Group I (n = 19) received 3.75 mg i.m. leuprolide acetate (LA) every 4 weeks for 24 weeks. Group II (n = 21) received 3.7 mg LA combined with 1.25 mg oral conjugated equine estrogen (CEE) and 5 mg oral medroxyprogesterone acetate (MA).
                Total revised AFS score as well as total pelvic pain scores decreased significantly (P < .001) in both groups. However, a statistically significant difference of hot flushes and sweating was reported by women receiving LA + HRT as compared to those treated with LA alone (P < .001). Furthermore, the bone loss at the lumbar spine was 4.2% in group I compared to 0.9% in group II at the end of the study.
                This study suggests that 1.25 mg CEE + 5 mg MA is effective in preventing hypoestrogenic side effects caused by GnRH-a, while the treatment of endometriosis is not impaired. To investigate the effects of the combination of pelvic floor muscle exercise (PFME) and estriol on postmenopausal stress incontinence (SI).
                Sixty-six patients with postmenopausal SI were randomized to a group treated with a combination of estriol (1 mg/d) and PFME (group A, n = 32) and a group treated with PFME alone (group B, n = 34). Efficacy was evaluated every three months based on stress scores obtained from a urinary incontinence (UI) questionnaire.
                A significant decrease in stress score was observed in mild and moderate UI patients in both groups three months after the commencement of therapy (A and B, P < .0001). The therapeutic effect in group A was more prominent for up to 18 months in mild UI and for up to 12 months in moderate UI (A vs. B, P < .05). Kaplan-Meier analysis showed that the cumulative morbidity rate in mild SI patients was significantly lower in group A (0%) than in group B (12%, P < .005).
                Combination therapy with estriol plus PFME was effective and is capable of serving as first-line treatment for mild SI. To evaluate whether the frequency of overactive bladder (OAB) symptoms increases in menopause patients after a tension-free vaginal tape (TVT) procedure, and to determine if topical estrogen therapy can help prevent these symptoms.
                After undergoing a preoperative assessment, enrolled patients were randomly allocated to receive TVT plus postoperative vaginal estrogen therapy (ET group) or TVT without adjunctive medical treatment (No ET group). The pre- and postoperative assessments included: acquisition of a urogynecologic history with standardized questions regarding urinary function (including a 10-grade visual analogue scale score), urogynecologic clinical examination, and urodynamic assessment. Follow-up assessments were performed at 1, 3, and 6 months after surgery.
                Fifty-six of 59 patients were evaluable; 28 received topic vaginal estrogen after surgery (ET group) and 28 did not receive adjunctive medical treatment (No ET group). The overall OAB syndrome rate in menopause patients (No ET group) was 7% (2 of 28 patients) at baseline and 32% (9 of 28 patients) 6 months after surgery (P = 0.04). At the 6-month follow-up assessment, the incidence of urinary urgency was 4% (1 of 28 patients) and 29% (8 of 28 patients) in the ET and No ET groups, respectively (P = 0.01). Differences in frequency and nocturia were not statistically significant. Analysis of the visual analogue scale scores revealed that at the 6-month follow-up assessment, urgency significantly improved in the ET group compared with the No ET group (0.23 +/- 1.0 vs 2.30 +/- 3.7, respectively; P = 0.02).
                The TVT procedure seems to increase the frequency of OAB syndrome in menopause patients. Vaginal estriol therapy significantly reduces symptoms of urinary urgency, has a high rate of patient satisfaction, and can be used to treat postmenopausal women for at least 6 months after a TVT procedure. We compared the short-term efficacy, safety and tolerability of transdermal versus oral oxybutynin in adults with urge urinary incontinence.
                Volunteers with detrusor instability currently responding to oral immediate release oxybutynin were enrolled in our study. Those patients presenting with recurrence of incontinent symptoms after a 2-week washout underwent confirmatory cystometrogram with subsequent randomization to transdermal or oral treatment. Matching active and placebo medications included matrix patches applied twice weekly and capsules taken 2 or 3 times daily. Dose titration was based on anticholinergic symptoms. Outcome measures included comparison of baseline to 6 week changes in incontinence episodes on a 3 day urinary diary, a visual analog scale for efficacy and anticholinergic symptoms reported on a questionnaire. Safety monitoring included adverse events and skin tolerability of the transdermal system.
                A total of 76 patients were enrolled and 74 completed at least 4 weeks of treatment. Mean age in the transdermal and oral groups was 64 and 63 years, and 87% and 97% were female, respectively. Daily incontinent episodes decreased in the transdermal and oral groups (7.3 to 2.4 [66%] and 7.4 to 2.6 [72%], respectively, p = 0.39). The visual analog scale reduction in urinary leakage improved from washout in both groups (p <0.0001) with no difference between them (p = 0.9). Dry mouth occurred in significantly fewer patients in the transdermal (38%) compared with those in the oral group (94%, p <0.001). Of the patients in the transdermal group 67% noticed a reduction in dry mouth severity compared with previous oral treatment, and 90% had none or mild skin erythema.
                Transdermal delivery of oxybutynin resulted in comparable efficacy and a significantly improved anticholinergic side effect profile compared with oral administration in adults with urge urinary incontinence.
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.