***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Silicone vaginal rings for the continuous release of 17 beta-oestradiol ( E2 ) with 2 constant in vitro release rates were used for the treatment of symptoms of urogenital atrophy in 2 groups of postmenopausal women . The very low dose of 7 micrograms/24 h was found to alleviate atrophic symptoms effectively and to induce significant maturation of vaginal and urethral epithelium . After a brief initial peak , the serum levels of E2 over 3 mth of treatment remained close to the detection limit . The ' undetectable ' E2 release pattern was reflected only in increased levels of oestrone sulphate . There was no evidence of a systemic metabolic response and patient acceptance of the method was excellent . Continuous low-dose release of E2 via vaginal rings consequently offers an alternative means of administering local oestrogen therapy which may be particularly suitable for geriatric patients The objective of the study was to assess the effects of low-dose vaginal treatment with oestradiol before vaginal operation . In a double-blind r and omized study including 43 postmenopausal women scheduled for vaginal repair operation for genital descensus , it was found that 7 patients suffered from concomitant urinary stress incontinence .  Vagifem ( 25 micrograms oestradiol ) or placebo was administered as vaginal pessaries daily , 3 weeks prior to surgery and the clinical effects evaluated . One month postoperatively the prevalence of bacteriuria ( > 100,000 CFU/ml urine ) was significantly lower when using oestradiol than in the placebo group . At follow-up 3 years later 40 women ( 93 % ) answered the question naires . None received hormone replacement therapy . Nineteen percent in the preoperative oestradiol group and 11 % in the preoperative placebo group had had more than two episodes of cystitis treated with antibiotics . This difference is not statistically significant ( p > 0.05 ) . Recurrent cystitis was not correlated to bacteriuria postoperatively . Seventy-nine percent of the women with genital prolapse but only 29 % of the women with concomitant urinary stress incontinence were cured ( p < 0.05 ) . Neither preoperative  oestradiol  treatment nor body weight had any influence on relapse . Preoperative low-dose vaginal oestradiol treatment may reduce the incidence of bacteriuria in the immediate postoperative period but no long-lasting effects on recurrent cystitis or relapse were seen . Longer-lasting hormone replacement therapy may be necessary to achieve lasting effects Importance Nearly half of postmenopausal women report bothersome vulvovaginal symptoms , but few data support the efficacy of 2 commonly recommended treatments . Objective To compare the efficacy of a low-dose vaginal estradiol tablet and a vaginal moisturizer , each vs placebo , for treatment of moderate-to-severe postmenopausal vulvovaginal symptoms . Design , Setting , and Participants This 12-week multicenter r and omized clinical trial enrolled postmenopausal women with moderate to severe symptoms of vulvovaginal itching , pain , dryness , irritation , or pain with penetration . Interventions Vaginal 10-&mgr;g estradiol tablet ( daily for 2 weeks , then twice weekly ) plus placebo gel ( 3 times a week ) ( n = 102 ) vs placebo tablet plus vaginal moisturizer ( n = 100 ) vs dual placebo ( n = 100 ) . Main Outcomes and Measures The main outcome was decrease in severity ( 0 - 3 ) of most bothersome symptom ( MBS ) between enrollment and 12 weeks . Additional measures included a composite vaginal symptom score , Female Sexual Function Index ( FSFI ) score ( 2 - 36 ) , modified Female Sexual Distress Score – Revised item 1 , treatment satisfaction and meaningful benefit , Vaginal Maturation Index , and vaginal pH. Results The 302 women had a mean ( SD ) age of 61 ( 4 ) years and were primarily white ( 267 [ 88 % ] ) , college educated ( 200 [ 66 % ] ) , and sexually active ( 245 [ 81 % ] ) . Most women ( 294 [ 97 % ] ) provided data for the primary analysis . The most commonly reported MBS was pain with vaginal penetration ( 182 [ 60 % ] ) , followed by vulvovaginal dryness ( 63 [ 21 % ] ) . Mean baseline MBS severity was similar between treatment groups : estradiol , 2.4 ( 95 % CI , 2.3 to 2.6 ) ; moisturizer , 2.5 ( 95 % CI , 2.3 to 2.6 ) ; placebo , 2.5 ( 95 % CI , 2.4 to 2.6 ) . All treatment groups had similar mean reductions in MBS severity over 12 weeks : estradiol , −1.4 ( 95 % CI , −1.6 to −1.2 ) ; moisturizer , −1.2 ( 95 % CI , −1.4 to −1.0 ) ; and placebo , −1.3 ( 95 % CI , −1.5 to −1.1 ) . No significant differences were seen between estradiol ( P = .25 ) or moisturizer ( P = .31 ) compared with placebo . Mean total FSFI improvement was similar between estradiol ( 5.4 ; 95 % CI , 4.0 to 6.9 ) and placebo ( 4.5 ; 95 % CI , 2.8 to 6.1 ) ( P = .64 ) , and between moisturizer ( 3.1 ; 95 % CI , 1.7 to 4.5 ) and placebo ( P = .17 ) . Conclusions and Relevance Our results suggest that neither prescribed vaginal estradiol tablet nor over-the-counter vaginal moisturizer provides additional benefit over placebo vaginal tablet and gel in reducing postmenopausal vulvovaginal symptoms . Trial Registration clinical trials.gov Identifier : OBJECTIVE : To evaluate the efficacy of two vaginal doses of estradiol ( E2 ) compared with placebo in the treatment of atrophic vaginitis . METHODS : In a multi-center , r and omized , double-blind , parallel-group study , 230 postmenopausal women received treatment with 25 mcg or 10 mcg E2 or placebo for 12 weeks . Efficacy was measured through composite score of three vaginal symptoms and grading of vaginal health . Additional analyses included maturation of vaginal and urethral mucosa . Safety assessment s included endometrial biopsy , adverse events , changes in laboratory tests , and physical examinations . After 12 weeks of treatment , all patients were switched to the open-label extension and received treatment with 25 mcg E2 up to week 52 . RESULTS : Vaginal tablets with 25 mcg and 10 mcg E2 showed significant ( P<.001 ) improvement in composite score of vaginal health . Other results with 10 mcg E2 were not entirely consistent with those for 25 mcg E2 . Over 12 weeks , both active treatments result ed in greater decreases in vaginal pH than placebo . There were no significant differences between the 25 mcg and 10 mcg E2 groups in terms of improvements in maturation value or composite score of three vaginal symptoms . The efficacy was maintained to week 52 with 25 mcg E2 . CONCLUSION : Vaginal tablets with 25 mcg and 10 mcg E2 provided relief of vaginal symptoms , improved urogenital atrophy , decreased vaginal pH , and increased maturation of the vaginal and urethral epithelium . Those improvements were greater with 25 mcg than with 10 mcg E2 . Both doses were effective in the treatment of atrophic vaginitis . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00465192 and NCT00464971 LEVEL OF EVIDENCE : Objective : The aim of this study was to evaluate the efficacy and safety of low-dose conjugated estrogens ( CE ) cream for treatment of atrophic vaginitis . Methods : Postmenopausal women ( N = 423 ) with moderate-to-severe vaginal atrophy were r and omized to CE cream 0.3 mg or placebo once daily ( 21 days on/7 days off ) or twice weekly for 12 weeks , followed by open-label treatment with CE cream for 40 weeks consistent with their prior regimen . Primary endpoints were changes in vaginal maturation index ( VMI ; percentage of superficial cells ) , vaginal pH , and severity of participant-reported most bothersome symptom ( vaginal dryness , itching , burning , or dyspareunia ) at week 12 . Endometrial safety was assessed by transvaginal ultrasound and endometrial biopsy for 52 weeks . Results : At week 12 , improvements in VMI with daily and twice-weekly use of low-dose CE cream ( 27.9 % and 25.8 % , respectively ) were significantly greater compared with placebo ( 3.0 % and 1.0 % , respectively ; P < 0.001 ) . Improvements in vaginal pH with daily and twice-weekly CE cream ( −1.6 for both ) were also significantly greater relative to placebo ( −0.4 and −0.3 , respectively ; P < 0.001 ) . VMI and vaginal pH responses were sustained through 52 weeks . Both CE cream regimens significantly reduced most bothersome symptom scores compared with placebo ( P ≤ 0.001 ) , including those for dyspareunia ( P ≤ 0.01 ) . There was no report of endometrial hyperplasia or carcinoma . Adverse events occurred with similar frequency among the active and placebo groups during the double-blind phase . Conclusions : Daily and twice-weekly use of low-dose CE cream was equally effective in relieving symptoms of vulvovaginal atrophy  . Both regimens showed endometrial safety and sustained efficacy during 1 year of therapy PURPOSE To evaluate the clinical efficacy and safety of intravaginal application of 25 microg micronized oestradiol in postmenopausal women from the Greek population suffering from symptoms related to vaginal atrophy . MATERIAL S AND METHODS 91 women suffering from vaginal dryness , vaginal itching and dyspareunea were treated with 25 microg 17beta-oestradiol vaginal tablets . The duration of treatment was 12 weeks . During the first two weeks the women inserted one vaginal tablet intravaginally once daily . Thereafter , the women inserted one tablet twice per week with at least a 3-day interval between treatments to maintain therapeutic response for ten weeks . Efficacy was evaluated by the relief of vaginal symptoms and safety by the concentrations of serum oestradiol ( E2 ) and follicular-stimulating hormone ( FSH ) . Pretreatment and post-treatment findings were compared and each patient served as her own control . RESULTS The rates of symptoms of vaginal dryness , vaginal itching and dyspareunea showed statistically significant differences over the course of the trial ( Cochran Q test , p < 0.001 ) . No one complained of vaginal dryness and vaginal itching after four and six weeks of treatment respectively , while in one patient the sensation of dyspareunea remained constant after the fourth week of treatment . Despite the statistically significant increase in blood oestradiol levels in relation to baseline values ( ANOVA model of repeated measures , p < 0.001 ) , these levels were within the normal range for postmenopausal women . Also , serum FSH levels were statistically significantly reduced from 47.4 mIU/ml at entry into the study to 45.5 mIU/ml after two weeks of treatment ( dependent sample s t-test , p < 0.003 ) , but were clearly within the postmenopausal range . CONCLUSIONS The twice-weekly local single treatment with vaginal tablets containing 25 microg of 17beta-oestradiol was effective and safe for the relief of symptoms related to atrophic vaginitis in postmenopausal women from the Greek population Background : Vaginal atrophy is a common complication in menopause which does not improve with time and , if untreated , can affect the quality of life for women . The aim of this study was to compare the effectiveness of the vaginal cream of hyaluronic acid and conjugated estrogen ( Premarin ) in treatment of vaginal atrophy . Methods : This study was a r and omized controlled clinical trial on 56 menopausal women with symptoms of vaginal atrophy ; they were r and omly allocated to two groups ( recipient conjugated estrogen and hyaluronic acid ) . The severity of each sign of atrophy was evaluated by visual analog signals ( VAS ) and on the basis of a four point scale . Also to recognize the cellular maturation with pap smear and the maturation degree were calculated according to the formula and scores 0 - 100 . As to the vaginal PH , we used PH marker b and , the rate of which was divided into 4 degrees . Data were analyzed using SPSS , version 20 , and P≤0.05 was considered as significant . Results : The results of this study showed that the symptoms of v 
    Output:
    
Compared with placebo , all vaginal estrogens demonstrated superiority in objective endpoints and subjective endpoints of GSM , whereas some trials demonstrated superiority versus placebo in urogenital symptoms .
No significant difference was observed between various dosages and dosage forms of vaginal estrogen products .
Vaginal estrogen showed superiority over vaginal lubricants and moisturizers for the improvement of objective clinical endpoints of vulvovaginal atrophy but not for subjective endpoints .
Unopposed vaginal estrogens seemed safe , although studies were not powered to detect a long-term estrogenic side effect .
Conclusion : Estrogen products were found to be clinical ly effective for the treatment of GSM with doses as low as 4 & mgr;g .
Vaginal estrogen products seem to be safe with few adverse effects , although there is a lack of long-term controlled clinical trial safety data .