human
***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: Twenty-six postmenopausal women participated in a double-blind trial involving treatment according to a Latin square design with either ( i ) dl-norgestrel alone ( 0.075 mg/day ) continuously for two cycles , ( ii ) estradiol-17 beta alone ( 1 mg on 25 of 28 days ) for two cycles , or ( iii ) the combined hormones for six cycles . A placebo control cycle followed each hormonal treatment . Plasma triglycerides decreased by an average 22 % during treatment with either dl-norgestrel alone ( 123 + /- 11 vs. 160 + /- 10 mg/dl , n = 25 , P < 0.005 ) or combination therapy ( 126 + /- 11 vs. 162 + /- 11 , n = 25 , P < 0.005 ) as compared with control . Plasma total cholesterol fell by 5 % during two cycles of treatment with either dl-norgestrel alone ( 229 + /- 11 vs. 242 + /- 10 mg/dl , n = 25 , P < 0.02 ) or combination therapy ( 233 + /- 11 vs. 246 + /- 10 , n = 25 , P < 0.05 ) versus placebo . During the fifth and sixth cycles of combination therapy 94 % of cycles were free of flushing ( vs. 31 % for control , P < 0.01 ) , 64 % of cycles were free of spotting not requiring protection ( control 75 % ) , 96 % of cycles were free of vaginal bleeding ( control 100 % ) , endometrial biopsy showed inactive endometrium in nine of the 10 subjects re-biopsied , fasting blood pyruvate decreased by 20 % ( P < 0.05 ) and diastolic blood pressure fell by 4 % compared with control ( P < 0.05 ) , whereas glucose tolerance was unchanged . There was a significant reduction in vasomotor flushing beginning with the third to fourth cycles of combination therapy New estradiol ( E2 ) transdermal matrix patches developed for once-a-week application , releasing 25 μg E2 ( 7D-25 ) or 50 μg E2 ( 7D-50 ) daily , were investigated in comparison with a placebo patch and the twice-weekly parent patch releasing 50 μg E2 ( Derm-50 ) daily . Three hundred and eleven postmenopausal patients suffering at least seven hot flushes daily were r and omly assigned to the four parallel groups and treated continuously for 12 weeks without progestin opposition . The daily number of hot flushes significantly decreased in all groups . At the 12th week the decrease from a baseline average of eight to nine episodes per day was 78 % with 7D-25 , 93 % and 97 % respectively with 7D-50 and Derm-50 , and significantly ( p < 0.001 ) lower with placebo ( 59 % ) . Comparable efficacy was observed in terms of severity of hot flushes , Kupperman Index and patient self-rated overall efficacy . Minor systemic adverse events occurred in 10.0 % , 8.8 % , 16.9 % ) and 13.5 % patients in the placebo , 7D-25 , 7D-50 and Derm-50 groups respectively . Occasional mild and transient itching and /or erythema at the site of application was reported by a few patients , with no difference between groups or between once-weekly or twice-weekly application . In conclusion all E2 patches were significantly more effective than placebo in relieving climacteric symptoms in a dose-dependent fashion and all were well tolerated Background For postmenopausal women , the main reason to start hormone therapy ( HT ) is to reduce menopausal symptoms and to improve quality of life ( QOL ) . The aim of this study was to analyse the impact of HT on different aspects of symptom experience and QOL during a r and omised trial . A total of 1823 postmenopausal women were recruited into the Estonian Postmenopausal Hormone Therapy ( EPHT ) trial in 1999–2001 . Women were r and omised to blind HT , open-label HT , placebo or non-treatment arm . After one year in the trial , a question naire was mailed and 1359 women ( 75 % ) responded , 686 in the HT arms and 673 in the non-HT arms . Mean age at filling in the question naire was 59.8years . The question naire included Women 's Health Question naire ( WHQ ) to assess menopause specific QOL of middle-aged women together with a 17-item question naire on symptoms related to menopause , a question about painful intercourse , and a question about women 's self-rated health . Results After one year in the trial , fewer women in the HT arms reported hot flashes , trouble sleeping , and sweating on the symptom question naire . According to WHQ , women in the HT arms had fewer vasomotor symptoms , sleep problems , and problems with sexual behaviour , but more menstrual symptoms ;  HT had no effect on depression , somatic symptoms , memory , attractiveness , or anxiety . A smaller proportion of women reported painful intercourse in the HT arms . There were no significant differences between the trial arms in women ’s self-rated subjective health . Conclusions The results from the EPHT trial confirm that HT is not justified for treating symptoms , other than vasomotor symptoms , among postmenopausal women . WHQ proved to be a useful and sensitive tool to assess QOL in this age group of women OBJECTIVES We sought to compare the effects of estrogen/transvaginal progesterone gel with estrogen/medroxyprogesterone acetate ( MPA ) on exercise-induced myocardial ischemia in postmenopausal women with coronary artery disease or previous myocardial infa rct ion , or both . BACKGROUND Estrogen therapy beneficially affects exercise-induced myocardial ischemia in postmenopausal women ; however , women with an intact uterus also take progestin to protect against uterine malignancies . The effects of combination estrogen/progestin therapy on myocardial ischemia are unknown . METHODS Eighteen postmenopausal women ( mean + /- SD age 59+/-7 years ) were given 17-beta-estradiol in single-blinded manner for four weeks ( 1 mg/day for three weeks then 2 mg/day for one week ) . Estradiol ( 2 mg/day ) was then continued , and the patients were r and omized ( double-blind ) for 12 days to either transvaginal progesterone gel ( 90 mg on alternate days ) and oral MPA placebo ( 10 mg/day ) , or vice versa . After another two weeks on estradiol alone , the patients crossed over to progestin treatment and repeated the protocol on the opposite treatment . Patients underwent treadmill exercise testing after each estradiol phase and at day 10 of each progestin phase . RESULTS Exercise time to myocardial ischemia increased after the first estrogen phase as compared with baseline ( mean difference with 95 % confidence interval [ CI ] : 72 s [ 34 to 110 ] , p = 0.001 ) , and was increased by combination estradiol/progesterone therapy as compared with estradiol/MPA therapy ( 92 s [ 35 to 149 ] , p = 0.001 ) ) . Two patients ( 11 % ) were withdrawn while taking estradiol/MPA owing to unstable angina . CONCLUSIONS Combination estrogen/transvaginal progesterone gel increases exercise time to myocardial ischemia , as compared with estrogen/MPA . These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration The aim of this study was to compare the pharmacodynamic response to a neuroactive steroid , pregnanolone , before and during different hormonal setting s of postmenopausal hormone replacement therapy ( HRT ) , using natural progesterone . A second aim was to investigate whether the response to pregnanolone was associated with cyclicity in negative mood symptoms during treatment . Twenty six postmenopausal women with climacteric symptoms were administered HRT in a r and omized , double blinded , placebo-controlled , crossover study . The women received 2 mg oral estradiol ( E(2 ) ) continuously during two 28-day cycles and 800 mg of vaginal progesterone or placebo sequentially for the last 14 days of each treatment cycle . Pharmacodynamic response to pregnanolone was assessed before treatment , and during the last week of each treatment cycle , by comparing the effects of intravenous pregnanolone ( 3alpha-hydroxy-5beta-pregnan-20-one ) on saccadic eye velocity ( SEV ) , saccade acceleration , saccade latency and self-rated sedation . Throughout the study daily symptom rating scales were kept . According to the daily symptom rating scales , patients were divided into two groups ; one group who displayed a significant variance in negative mood symptoms during HRT ( cyclicity ) and one group with no cyclical changes in negative mood symptoms during treatment . During treatment with either E(2 ) alone or E(2)+progesterone the response in saccadic eye movement parameters and in self-rated sedation to pregnanolone was enhanced compared to pretreatment values . The SEV , saccade acceleration and sedation responses to pregnanolone was also increased in women expressing cyclicity in negative mood symptoms compared to women with no cyclical changes in negative mood during HRT . In conclusion , during treatment with either E(2 ) alone , or E(2)+progesterone , pregnanolone  sensitivity was increased . Women expressing cyclicity in negative mood symptoms were more sensitive to pregnanolone than women without symptom cyclicity during HRT 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 To investigate two different doses of oral estradiol to reduce the number of hot flushes in Japanese women with climacteric symptoms . Methods Women ( n = 211 ) aged 40–64 years who had experienced natural menopause or bilateral oophorectomy , with ≥ three moderate/severe hot flushes per day in the week before study , were r and omized to receive micronized estradiol ( E2 ) 0.5 or 1.0 mg or placebo once daily for 8 weeks . The primary efficacy endpoint was percentage change in mean daily number of hot flushes over 7 days from baseline to final examination . Results Percentage change in mean daily number of hot flushes at final examination was similar for E2 0.5 mg and E2 1.0 mg ( −79.58 ± 28.29 % vs. −82.49 ± 25.31 % , p = 0.555 ) but was significantly lower with placebo ( −57.89 ± 34.15 % , p < 0.001 vs. E2 , both doses ) . There was no significant difference in number of treatment-related adverse events occurring in the E2 0.5 and 1.0 mg groups ( 25 % and 36.6 % , respectively ) . The higher E2 dose showed more pronounced effects on symptom severity . Conclusions The dose of 0.5 mg/day was effective as the oral E2 starting dose for treatment of hot flushes in Japanese women Abstract Objective : To analyze the short-term efficacy and safety over menopausal symptoms of three low-dose continuous sequential 17β-estradiol (E)/progesterone ( P ) parental monthly formulations using novel non-polymeric microspheres . Methods : This was a multicenter , r and omized , single blinded study in which peri- and postmenopausal women were assigned to receive a monthly intramuscular injection of 0.5 mg E + 15 mg P ( Group A , n = 34 ) , 1 mg E + 20 mg P ( Group B , n = 24 ) or 1 mg E + 30 mg P ( Group C , n 
    Output:
    
agent
Subgroup analysesSubgroup analyses by dose of BHT suggested that higher doses of BHT may be associated with more effectiveness but also higher risk of adverse effects .
There was low to moderate quality evidence that BHT in various forms and doses is more effective than placebo for treating moderate to severe menopausal hot flushes .
There was some evidence to suggest that higher doses of BHT are associated with greater effectiveness but also with higher risk of adverse effects .
No data are yet available about the safety of BHT with regard to long-term outcomes such as heart attack , stroke and breast cancer .
***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: Twenty-six postmenopausal women participated in a double-blind trial involving treatment according to a Latin square design with either ( i ) dl-norgestrel alone ( 0.075 mg/day ) continuously for two cycles , ( ii ) estradiol-17 beta alone ( 1 mg on 25 of 28 days ) for two cycles , or ( iii ) the combined hormones for six cycles . A placebo control cycle followed each hormonal treatment . Plasma triglycerides decreased by an average 22 % during treatment with either dl-norgestrel alone ( 123 + /- 11 vs. 160 + /- 10 mg/dl , n = 25 , P < 0.005 ) or combination therapy ( 126 + /- 11 vs. 162 + /- 11 , n = 25 , P < 0.005 ) as compared with control . Plasma total cholesterol fell by 5 % during two cycles of treatment with either dl-norgestrel alone ( 229 + /- 11 vs. 242 + /- 10 mg/dl , n = 25 , P < 0.02 ) or combination therapy ( 233 + /- 11 vs. 246 + /- 10 , n = 25 , P < 0.05 ) versus placebo . During the fifth and sixth cycles of combination therapy 94 % of cycles were free of flushing ( vs. 31 % for control , P < 0.01 ) , 64 % of cycles were free of spotting not requiring protection ( control 75 % ) , 96 % of cycles were free of vaginal bleeding ( control 100 % ) , endometrial biopsy showed inactive endometrium in nine of the 10 subjects re-biopsied , fasting blood pyruvate decreased by 20 % ( P < 0.05 ) and diastolic blood pressure fell by 4 % compared with control ( P < 0.05 ) , whereas glucose tolerance was unchanged . There was a significant reduction in vasomotor flushing beginning with the third to fourth cycles of combination therapy New estradiol ( E2 ) transdermal matrix patches developed for once-a-week application , releasing 25 μg E2 ( 7D-25 ) or 50 μg E2 ( 7D-50 ) daily , were investigated in comparison with a placebo patch and the twice-weekly parent patch releasing 50 μg E2 ( Derm-50 ) daily . Three hundred and eleven postmenopausal patients suffering at least seven hot flushes daily were r and omly assigned to the four parallel groups and treated continuously for 12 weeks without progestin opposition . The daily number of hot flushes significantly decreased in all groups . At the 12th week the decrease from a baseline average of eight to nine episodes per day was 78 % with 7D-25 , 93 % and 97 % respectively with 7D-50 and Derm-50 , and significantly ( p < 0.001 ) lower with placebo ( 59 % ) . Comparable efficacy was observed in terms of severity of hot flushes , Kupperman Index and patient self-rated overall efficacy . Minor systemic adverse events occurred in 10.0 % , 8.8 % , 16.9 % ) and 13.5 % patients in the placebo , 7D-25 , 7D-50 and Derm-50 groups respectively . Occasional mild and transient itching and /or erythema at the site of application was reported by a few patients , with no difference between groups or between once-weekly or twice-weekly application . In conclusion all E2 patches were significantly more effective than placebo in relieving climacteric symptoms in a dose-dependent fashion and all were well tolerated Background For postmenopausal women , the main reason to start hormone therapy ( HT ) is to reduce menopausal symptoms and to improve quality of life ( QOL ) . The aim of this study was to analyse the impact of HT on different aspects of symptom experience and QOL during a r and omised trial . A total of 1823 postmenopausal women were recruited into the Estonian Postmenopausal Hormone Therapy ( EPHT ) trial in 1999–2001 . Women were r and omised to blind HT , open-label HT , placebo or non-treatment arm . After one year in the trial , a question naire was mailed and 1359 women ( 75 % ) responded , 686 in the HT arms and 673 in the non-HT arms . Mean age at filling in the question naire was 59.8years . The question naire included Women 's Health Question naire ( WHQ ) to assess menopause specific QOL of middle-aged women together with a 17-item question naire on symptoms related to menopause , a question about painful intercourse , and a question about women 's self-rated health . Results After one year in the trial , fewer women in the HT arms reported hot flashes , trouble sleeping , and sweating on the symptom question naire . According to WHQ , women in the HT arms had fewer vasomotor symptoms , sleep problems , and problems with sexual behaviour , but more menstrual symptoms ;  HT had no effect on depression , somatic symptoms , memory , attractiveness , or anxiety . A smaller proportion of women reported painful intercourse in the HT arms . There were no significant differences between the trial arms in women ’s self-rated subjective health . Conclusions The results from the EPHT trial confirm that HT is not justified for treating symptoms , other than vasomotor symptoms , among postmenopausal women . WHQ proved to be a useful and sensitive tool to assess QOL in this age group of women OBJECTIVES We sought to compare the effects of estrogen/transvaginal progesterone gel with estrogen/medroxyprogesterone acetate ( MPA ) on exercise-induced myocardial ischemia in postmenopausal women with coronary artery disease or previous myocardial infa rct ion , or both . BACKGROUND Estrogen therapy beneficially affects exercise-induced myocardial ischemia in postmenopausal women ; however , women with an intact uterus also take progestin to protect against uterine malignancies . The effects of combination estrogen/progestin therapy on myocardial ischemia are unknown . METHODS Eighteen postmenopausal women ( mean + /- SD age 59+/-7 years ) were given 17-beta-estradiol in single-blinded manner for four weeks ( 1 mg/day for three weeks then 2 mg/day for one week ) . Estradiol ( 2 mg/day ) was then continued , and the patients were r and omized ( double-blind ) for 12 days to either transvaginal progesterone gel ( 90 mg on alternate days ) and oral MPA placebo ( 10 mg/day ) , or vice versa . After another two weeks on estradiol alone , the patients crossed over to progestin treatment and repeated the protocol on the opposite treatment . Patients underwent treadmill exercise testing after each estradiol phase and at day 10 of each progestin phase . RESULTS Exercise time to myocardial ischemia increased after the first estrogen phase as compared with baseline ( mean difference with 95 % confidence interval [ CI ] : 72 s [ 34 to 110 ] , p = 0.001 ) , and was increased by combination estradiol/progesterone therapy as compared with estradiol/MPA therapy ( 92 s [ 35 to 149 ] , p = 0.001 ) ) . Two patients ( 11 % ) were withdrawn while taking estradiol/MPA owing to unstable angina . CONCLUSIONS Combination estrogen/transvaginal progesterone gel increases exercise time to myocardial ischemia , as compared with estrogen/MPA . These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration The aim of this study was to compare the pharmacodynamic response to a neuroactive steroid , pregnanolone , before and during different hormonal setting s of postmenopausal hormone replacement therapy ( HRT ) , using natural progesterone . A second aim was to investigate whether the response to pregnanolone was associated with cyclicity in negative mood symptoms during treatment . Twenty six postmenopausal women with climacteric symptoms were administered HRT in a r and omized , double blinded , placebo-controlled , crossover study . The women received 2 mg oral estradiol ( E(2 ) ) continuously during two 28-day cycles and 800 mg of vaginal progesterone or placebo sequentially for the last 14 days of each treatment cycle . Pharmacodynamic response to pregnanolone was assessed before treatment , and during the last week of each treatment cycle , by comparing the effects of intravenous pregnanolone ( 3alpha-hydroxy-5beta-pregnan-20-one ) on saccadic eye velocity ( SEV ) , saccade acceleration , saccade latency and self-rated sedation . Throughout the study daily symptom rating scales were kept . According to the daily symptom rating scales , patients were divided into two groups ; one group who displayed a significant variance in negative mood symptoms during HRT ( cyclicity ) and one group with no cyclical changes in negative mood symptoms during treatment . During treatment with either E(2 ) alone or E(2)+progesterone the response in saccadic eye movement parameters and in self-rated sedation to pregnanolone was enhanced compared to pretreatment values . The SEV , saccade acceleration and sedation responses to pregnanolone was also increased in women expressing cyclicity in negative mood symptoms compared to women with no cyclical changes in negative mood during HRT . In conclusion , during treatment with either E(2 ) alone , or E(2)+progesterone , pregnanolone  sensitivity was increased . Women expressing cyclicity in negative mood symptoms were more sensitive to pregnanolone than women without symptom cyclicity during HRT 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 To investigate two different doses of oral estradiol to reduce the number of hot flushes in Japanese women with climacteric symptoms . Methods Women ( n = 211 ) aged 40–64 years who had experienced natural menopause or bilateral oophorectomy , with ≥ three moderate/severe hot flushes per day in the week before study , were r and omized to receive micronized estradiol ( E2 ) 0.5 or 1.0 mg or placebo once daily for 8 weeks . The primary efficacy endpoint was percentage change in mean daily number of hot flushes over 7 days from baseline to final examination . Results Percentage change in mean daily number of hot flushes at final examination was similar for E2 0.5 mg and E2 1.0 mg ( −79.58 ± 28.29 % vs. −82.49 ± 25.31 % , p = 0.555 ) but was significantly lower with placebo ( −57.89 ± 34.15 % , p < 0.001 vs. E2 , both doses ) . There was no significant difference in number of treatment-related adverse events occurring in the E2 0.5 and 1.0 mg groups ( 25 % and 36.6 % , respectively ) . The higher E2 dose showed more pronounced effects on symptom severity . Conclusions The dose of 0.5 mg/day was effective as the oral E2 starting dose for treatment of hot flushes in Japanese women Abstract Objective : To analyze the short-term efficacy and safety over menopausal symptoms of three low-dose continuous sequential 17β-estradiol (E)/progesterone ( P ) parental monthly formulations using novel non-polymeric microspheres . Methods : This was a multicenter , r and omized , single blinded study in which peri- and postmenopausal women were assigned to receive a monthly intramuscular injection of 0.5 mg E + 15 mg P ( Group A , n = 34 ) , 1 mg E + 20 mg P ( Group B , n = 24 ) or 1 mg E + 30 mg P ( Group C , n 
    Output:
    