***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: CONTEXT St and ard therapy for hot flashes has been hormone replacement with estradiol or progestational agents , but recent data suggest that antidepressants inhibiting serotonin reuptake may also be effective . OBJECTIVE To evaluate a selective serotonin reuptake inhibitor ( paroxetine controlled release [ CR ] ) in treating the vasomotor symptoms displayed by a general cross-section of menopausal women . DESIGN AND SETTING R and omized , double-blind , placebo-controlled , parallel group study conducted across 17 US sites , including urban , suburban , and rural clinics . PATIENTS A total of 165 menopausal women aged 18 years or older experiencing at least 2 to 3 daily hot flashes and must have discontinued any hormone replacement therapy for at least 6 weeks . Women were excluded if they had any signs of active cancer or were undergoing chemotherapy or radiation therapy . INTERVENTION After a 1-week placebo run-in phase , study participants were r and omized to receive placebo or receive 12.5 mg/d or 25.0 mg/d of paroxetine CR ( in a 1:1:1 ratio ) for 6 weeks . MAIN OUTCOME MEASURES Mean change from baseline to week 6 in the daily hot flash composite score ( frequency x severity ) . RESULTS Fifty-six participants were r and omly assigned to receive placebo and 51 to receive 12.5 mg/d and 58 to receive 25.0 mg/d of paroxetine CR . The mean reductions in the hot flash frequency composite score from baseline to week 6 were statistically significantly greater for those receiving paroxetine CR than for those receiving placebo . By week 6 , the mean daily hot flash frequency went from 7.1 to 3.8 ( mean reduction , 3.3 ) for those in the 12.5-mg/d and from 6.4 to 3.2 ( mean reduction , 3.2 ) for those in the 25-mg/d paroxetine CR groups and from 6.6 to 4.8 ( mean reduction , 1.8 ) for those in the placebo group . Mean placebo-adjusted reduction in hot flash composite scores were -4.7 ( 95 % confidence interval , - 8.1 to -1.3 ; P = .007 ) comparing 12.5-mg/d paroxetine CR with placebo ; and -3.6 ( 95 % confidence interval , -6.8 to -0.4 ; P = .03 ) comparing 25.0-mg/d paroxetine CR with placebo . This corresponded to median reductions of 62.2 % for those in the 12.5-mg/d and 64.6 % for those in the 25.0-mg/d paroxetine CR groups compared with 37.8 % for those in the placebo group . CONCLUSION Paroxetine CR may be an effective and acceptable alternative to hormone replacement and other therapies in treating menopausal hot flash symptoms Objective To assess the effect of daily dietary supplementation of soy protein isolate powder on hot flushes in post-menopausal women . Methods We carried out a double-blind , parallel , multi-center , r and omized  placebo-controlled trial of 104 post-menopausal women . Fifty-one patients ( age range 48–61 years ) took 60 g of isolated soy protein daily and 53 patients ( age range 45–62 years ) took 60 g of placebo ( casein ) daily . The study lasted 12 weeks . Using analysis of covariance , we analyzed changes from baseline in mean number of moderate to severe hot flushes ( including night sweats ) during treatment . Results Soy was significantly superior to placebo ( P < .01 in reducing the mean number of hot flushes per 24 hours after 4 , 8 , and 12 weeks of treatment . In particular , women taking soy had a 26 % reduction in the mean number of hot flushes by week 3 and a 33 % reduction by week 4 ( P < .001 by the Wilcoxon exact test ) . By the end of the 12th week , patients taking soy had a 45 % reduction in their daily hot flushes versus a 30 % reduction obtained with the placebo ( P < .01 ) . The overall rates of adverse effects were similar for soy and casein-placebo .  Twenty-five patients dropped out of the study : 11 in the soy group and 14 in the  placebo group . Gastrointestinal side effects were the most common cause of premature withdrawal from the study ( seven patients in each group ) . Conclusion Soy protein isolate added daily to the diet substantially reduced the frequency of hot flushes in climacteric women IMPORTANCE Estrogen therapy is the gold st and ard treatment for hot flashes and night sweats , but some women are unable or unwilling to use it because of associated risks . The serotonin-norepinephrine reuptake inhibitor venlafaxine hydrochloride is used widely as a nonhormonal treatment . While the clinical impression is that serotonin-norepinephrine reuptake inhibitors are less effective than estrogen , these medications have not been simultaneously evaluated in one clinical trial to date . OBJECTIVE To determine the efficacy and tolerability of low-dose oral 17β-estradiol and low-dose venlafaxine extended release in alleviating vasomotor symptoms ( VMS ) . DESIGN , SETTING , AND PARTICIPANTS In total , 339 perimenopausal and postmenopausal women with at least 2 bothersome VMS per day ( mean , 8.1 per day ) were recruited from the community to MsFLASH ( Menopause Strategies : Finding Lasting Answers for Symptoms and Health ) clinical network sites between December 5 , 2011 , and October 15 , 2012 . INTERVENTIONS Participants were r and omized to double-blind treatment with low-dose oral 17β-estradiol ( 0.5 mg/d ) ( n = 97 ) , low-dose venlafaxine hydrochloride extended release ( 75 mg/d ) ( n = 96 ) , or placebo ( n = 146 ) for 8 weeks . MAIN OUTCOMES AND MEASURES The primary outcome was the mean daily frequency of VMS after 8 weeks of treatment . Secondary outcomes were VMS severity , bother , and interference with daily life . Intent-to-treat analyses compared the change in VMS frequency between each active intervention and placebo and between the 2 active treatments . RESULTS Compared with baseline , the mean VMS frequency at week 8 decreased to 3.9 ( 95 % CI , 2.9 - 4.9 ) VMS per day ( 52.9 % reduction ) in the estradiol group , to 4.4 ( 95 % CI , 3.5 - 5.3 ) VMS per day ( 47.6 % reduction ) in the venlafaxine group , and to 5.5 ( 95 % CI , 4.7 - 6.3 ) VMS per day ( 28.6 % reduction ) in the placebo group . Estradiol  reduced the frequency of symptoms by 2.3 more per day than placebo ( P < .001 ) , and venlafaxine  reduced the frequency of symptoms by 1.8 more per day than placebo ( P = .005 ) . The results were consistent for VMS severity , bother , and interference . Low-dose estradiol reduced the frequency of symptoms by 0.6 more per day than venlafaxine ( P = .09 ) . Treatment satisfaction was highest ( 70.3 % ) for estradiol ( P < .001 vs placebo ) , lowest ( 38.4 % ) for placebo , and intermediate ( 51.1 % ) for venlafaxine ( P = .06 vs placebo ) . Both interventions were well tolerated . CONCLUSIONS AND RELEVANCE Low-dose oral estradiol and venlafaxine are effective treatments for VMS in women during midlife . While the efficacy of low-dose estradiol may be slightly superior to that of venlafaxine , the difference is small and of uncertain clinical relevance . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01418209 OBJECTIVES Guidelines recommend using the lowest effective dose of oestrogen for the management of vasomotor symptoms in postmenopausal women . The primary aim of this double-blind , multi-centre , r and omised study was to assess the efficacy of oral ultra-low dose continuous combined hormone replacement therapy with 17β-oestradiol and dydrogesterone . STUDY DESIGN 313 women with ≥50 moderate to severe hot flushes during the previous week were r and omised to 0.5 mg 17β-oestradiol/2.5 mg dydrogesterone ( E 0.5 mg/D 2.5 mg ) , 1 mg 17β-oestradiol/5 mg dydrogesterone ( E 1mg/D 5 mg ) or placebo for 13 weeks . The placebo group then switched to E 0.5 mg/D 2.5 mg for a further 39 weeks , whilst the other groups continued on the same treatment . RESULTS After 13 weeks , the reduction in the number of moderate to severe hot flushes/day in the E 0.5 mg/D 2.5 mg group was greater than in the placebo group ( -6.4 vs. -4.9 , p<0.001 ) and comparable to that in the 1/5 mg group ( -6.3 ) . E 0.5 mg/D 2.5 mg and E 1mg/D 5 mg significantly improved the total Menopause Rating Scale score . The number of bleeding/spotting days was lower with E 0.5 mg/D 2.5 mg than with E 1 mg/D 5 mg . The overall amenorrhoea rate with E 0.5 mg/D 2.5 mg was 81 % ; this increased to 91 % in months 10 - 12 . CONCLUSIONS Continuous combined 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone was effective in alleviating vasomotor symptoms and improving quality of life , and was associated with a high amenorrhoea rate and a good tolerability profile Objective To evaluate the efficacy of two ultra-low-dose 17β-estradiol plus norethisterone acetate ( NETA ) treatment regimens for relieving  menopausal symptoms . Design A total of 577 postmenopausal women were enrolled , in three treatment groups in a double-blind , r and omized , placebo-controlled study of 0.5 mg 17β-estradiol + 0.1 mg NETA or 0.5 mg 17β-estradiol + 0.25 mg NETA or placebo . Participants returned at weeks 4 , 8 , 12 and 24 for climacteric complaint evaluation based on a daily diary vasomotor symptom record . Patients were assessed by the Greene Climacteric Scale and urogenital symptoms were also evaluated . Results Treatment with ultra-low-dose 0.5 mg 17β-estradiol + 0.1 mg NETA ( 0.1 Group ) or 0.5 mg 17β-estradiol + 0.25 mg NETA ( 0.25 Group ) effectively reduced the severity and number of hot flushes within the initial weeks of therapy . Compared to placebo , a rapid , statistically significant decrease in the frequency and severity of hot flushes was achieved by week 3 , followed by further improvement which continued throughout the study . There were no statistically significant differences between the active treatment arms . Conclusions The data show that both ultra-low-dose regimens are effective in reducing the severity and number of hot flushes compared to placebo , with good safety profiles Objectives Drospirenone is a novel progestogen that , combined with 17β-estradiol , reduces the frequency and severity of menopausal vasomotor symptoms ( VMS ) in different population s. This double-blind , multicenter study compared the efficacy , safety and tolerability of 2 mg drospirenone/1 mg estradiol ( DRSP/E2 ) vs. placebo in Chinese postmenopausal women with moderate to severe VMS . Methods Women , aged 45–65 years , were r and omized to  DRSP/E2  ( n = 183 ) or placebo ( n = 61 ) once daily for four 28-day cycles . Changes in the frequency and severity of hot flushes were analyzed as primary variables , together with other climacteric and urogenital symptoms , clinical global improvement , adverse events and physical/gynecological parameters . Results Relative changes in numbers of hot flushes/week were −80.4 % for DRSP/E2 vs. −51.9 % for placebo ( treatment difference −28.5 % , p < 0.0001 ) . There were trends toward a greater reduction in severity of hot flushes with DRSP/E2 treatment . Patients treated with DRSP/E2 were more often free from sweating episodes ( p < 0.0001 ) and vaginal dryness ( p = 0.0008 ) . Other climacteric symptoms , including nervousness and pollakisuria , followed a trend of greater response with DRSP/E2 . Similar to other combination HRT regimens , DRSP/E2  increased occurrences of bleeding , but these decreased over time . Adverse events in patients treated with DRSP/E2 were mostly m 
    Output:
    
Isoflavones and black cohosh were more effective than placebo , although not significantly better than O+P. Not only were selective serotonin reuptake inhibitors ( SSRIs ) or serotonin-norepinephrine reuptake inhibitors ( SNRIs ) found to be ineffective in relieving VMSs , but they also had significantly higher odds of discontinuation than placebo .
For women who have not undergone hysterectomy , transdermal O+P was the most effective treatment for VMS relief .