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: BACKGROUND tibolone at usual doses of 2.5 mg/day in postmenopausal women has been shown to improve climacteric complaints , without affecting endometrial thickness and lipid profile or blood glucose . However , the potentially similar efficacy , but better tolerability , of a low dose of this drug ( 1.25 mg ) has never been established . METHODS 162 healthy , non-obese , post-menopausal women , aged 40 - 65 years , with an intact uterus were enrolled in a national , single centre , r and omised , double blind , placebo controlled , parallel group trial . After 1 week of runin , patients were treated for 24 weeks with placebo , tibolone 1.25 mg or 2.5 mg/day . During the study laboratory tests , endometrial ultrasound scans and mammography were performed . Occurrence of menopausal signs and symptoms , including vaginal bleeding , and quality of sexual life were also checked . RESULTS in the 120 patients terminating the study without major protocol violations , climacteric symptoms were similarly improved by tibolone 1.25 and 2.5 mg ( 78 % and 90 % reduction at week 24 for hot flushes , 36 % and 34 % for sweating episodes and 44 % and 51 % for vaginal dryness ) , but not by placebo . Benefits occurred earlier in the group treated with tibolone 2.5 mg . Quality of sexual life was almost invariably improved by tibolone as compared to placebo , but improvement occurred earlier in the tibolone 1.25 mg group . Severity of vaginal bleeding was not different between placebo and active treatment groups , except at week 12 when was higher . At the end of treatment vaginal bleeding occurred in 15 % of patients treated with placebo , 14 % treated with tibolone 1.25 mg and 12 % treated with tibolone 2.5 mg . Endometrial thickness and breast density were not changed by treatment , as well as FSH , 17-beta-estradiol , total cholesterol , HDL and LDL cholesterol , triglycerides and blood glucose . Adverse events were reported by 14.7 % , 26.7 % and 24.4 % of patients treated with placebo , tibolone 1.25 mg and tibolone 2.5 mg/day , respectively . CONCLUSIONS tibolone at doses of 1.25 or 2.5 mg/day given for 24 weeks to postmenopausal women displayed similar efficacy and safety profiles , though were more effective than placebo . Tibolone 1.25 mg induced a more gradual relief from climacteric symptoms and a more prompt improvement of sexual function In this report we evaluated the action of conjugated equine estrogens ( CEE ) on vaginal symptoms , cytology , pH , and flora in late postmenopausal women without any previous hormone therapy . The study was a r and omized , double-blind , placebo-controlled trial with 48 late postmenopausal women who received placebo or unopposed CEE ( 0.625mg/day of CEE orally ) during three months of treatment .  Vaginal and sexual complaints were evaluated through daily diary cards . We analyzed vaginal changes through cytology and pH measurements . After three months of treatment , 20 % of placebo-treated patients and 80 % of the CEE-treated patients reported improvement in vaginal dryness and irritation . In the latter group , the vaginal cells and Lactobacillus increased and the vaginal pH decreased , without other changes in sexual complaints . We concluded that estrogen ameliorated the genital tract of late postmenopausal women without any previous hormone therapy OBJECTIVE In some women , hot flashes and other symptoms attributed to menopause persist for many years after the cessation of menses . The frequency and severity of such symptoms and response to hormone therapy in older women have not been well documented . METHODS We used data from the Heart and Estrogen/Progestin Replacement Study , a blinded , clinical trial among 2763 women with documented coronary disease and a uterus who were r and omized to receive either conjugated estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg in one tablet or placebo .  Participants were queried at baseline and annually regarding menopausal symptoms . Breast symptoms were self‐reported , and uterine bleeding was recorded on a daily diary . RESULTS Symptoms associated with menopause were relatively common among Heart and Estrogen/Progestin Replacement Study participants , whose average age was 67 years and who averaged 18 years since menopause . At baseline , 16 % of women reported frequent hot flashes , 26 % vaginal dryness , 10 % genital irritation , 55 % trouble sleeping , and 53 % early awakening . Women assigned to hormone therapy reported less frequent hot flashes , vaginal dryness , and trouble sleeping compared with women assigned to placebo , but more frequent vaginal discharge , genital irritation , uterine bleeding , and breast symptoms . The reporting of breast symptoms among women in the hormone group decreased from 40 % at 1 year to 13 % by the 4th year . Uterine bleeding was reported by 31 % and spotting by an additional 33 % of women in the hormone group during the 1st year of treatment ; by the 4th year , these proportions had fallen to 11 % and 20 % , respectively . CONCLUSION Symptoms typically attributed to menopause are common in elderly women .  Postmenopausal hormone therapy  reduces hot flashes , trouble sleeping , and vaginal dryness , but at st and ard doses in elderly women is associated with vaginal discharge , genital irritation , uterine bleeding , and breast symptoms Objective : To determine the effects of raloxifene on sexual function in postmenopausal women with pre-existing vaginal atrophy treated with vaginal estrogen cream . Methods : A total of 187 naturally postmenopausal women , 42 - 80 years of age , with signs of genitourinary atrophy were enrolled in this 6-month , multicenter , parallel-group study . Subjects were r and omized to oral raloxifene HCl 60 mg daily or matching placebo ; the same subjects were also r and omized to receive one application of either vaginal conjugated estrogen cream 0.5 g twice weekly for 6 months or non-hormonal vaginal moisturizer twice weekly for 3 months , followed by conjugated estrogen cream for 3 months . Both investigators and subjects were masked to the identity of the oral medication . The vaginal preparations were administered in an open-label fashion . The Sexual Activity Question naire ( SAQ ) was administered at baseline and at 3 and 6 months . Safety was assessed throughout the study . Results : A total of 102 women were sexually active at baseline and , of these , 82 were also sexually active at the 6-month end-point . At 6 months , raloxifene and placebo , in the presence of vaginal conjugated estrogen cream , were both associated with improvement from baseline in vaginal dryness and reduced discomfort during sexual activity . There were no significant differences between raloxifene and placebo groups in any SAQ item . Enjoyment of sexual activity significantly increased from baseline with raloxifene but not with placebo . No difference in adverse events was observed between groups . Conclusion : Raloxifene had no negative effects on sexual function in postmenopausal women with vaginal atrophy who were treated concomitantly with vaginal estrogen cream The women in this study were either post-menopausal or ovariectomised for at least 1 yr prior to the study . They had also been treated for cancer of the cervix ( 27 women ) , endometrium ( 5 ) , ovaries ( 5 ) or breast ( 1 ) . All women presented with sexual troubles , mainly genital discomfort ( dyspareunia or vaginism ) . In a double-blind fashion , gynaecological capsules containing either an oestradiol diether ( ICD : promestriene ) or only the excipient were administered for 40 consecutive days . At the end of the treatment , the FSH , LH , oestrone ( E1 ) and oestradiol ( E2 ) plasma levels were not found to be significantly different from the pre-therapeutic values . These results suggest that promestriene acts on the vaginal mucosa , therefore not being converted back into the hormone from which it was derived . Also , in its dietheroxide form , promestriene is incapable of crossing the malpighian ( vaginal or epidermal ) epithelium and of reaching the general blood circulation . This discrepancy between the local anti-atrophic effects and the inability to exert systemic oestrogen activities singles out promestriene and justifies its therapeutic use when hormonally active oestrogens are contra-indicated , as in patients who have an oestrogen-sensitive cancer in their medical history Objective To assess the effect of  combined hormone replacement therapy ( HRT )  on health related quality of life . Design R and omised placebo controlled double blind trial . Setting General practice s in United Kingdom ( 384 ) , Australia ( 94 ) , and New Zeal and ( 24 ) . Participants Postmenopausal women aged 50 - 69 at r and omisation ; 3721 women with a uterus were r and omised to combined oestrogen and progestogen  ( n=1862 ) or placebo  ( n=1859 ) . Data on health related quality of life at one year were available from 1043 and 1087 women , respectively . Interventions Conjugated equine oestrogen 0.625 mg plus medroxyprogesterone acetate 2.5/5.0 mg or matched placebo orally daily for one year . Main outcome measures Health related quality of life and psychological wellbeing as measured by the women ’s health question naire . Changes in emotional and physical menopausal symptoms as measured by a symptoms question naire and depression by the Centre for Epidemiological Studies depression scale ( CES-D ) . Overall health related quality of life and overall quality of life as measured by the European quality of life instrument ( EuroQol ) and visual analogue scale , respectively . Results After one year small but significant improvements were observed in three of nine components of the women ’s health question naire for those taking combined HRT compared with those taking placebo :  vasomotor symptoms ( P<0.001 ) , sexual functioning ( P<0.001 ) , and sleep problems ( P<0.001 ) . Significantly fewer women in the combined HRT group reported hot flushes ( P<0.001 ) , night sweats ( P<0.001 ) , aching joints and muscles ( P=0.001 ) , insomnia ( P<0.001 ) , and vaginal dryness ( P<0.001 ) than in the placebo group , but greater proportions reported breast tenderness ( P<0.001 ) or vaginal discharge ( P<0.001 ) . Hot flushes were experienced in the combined HRT and placebo groups by 30 % and 29 % at trial entry and 9 % and 25 % at one year , respectively . No significant differences in other menopausal symptoms , depression , or overall quality of life were observed at one year . Conclusions Combined HRT started many years after the menopause can improve health related quality of life . Trial registration IS RCT N 63718836 Aim . To evaluate with vali date d instruments changes in quality of life and sexuality in women receiving hormonal replacement therapy ( AHT ) .  Design . R and omised , double-blind , double-dummy study with two parallel treatment arms . Patients and methods . Forty-seven healthy post-menopausal women , aged 45–64 years , were evaluated using the Female Sexual Function Index ( FSFI ) and the menopause-specific quality of life question naire ( MENQOL ) . Of them , 40 diagnosed with sexual dysfunction were r and omised ( 1:1 ) to receive daily 0.625 mg of conjugated estrogens plus 1.25 mg of methyl-testosterone and 100 mg of micronised progesterone or placebo . After 3 months follow-up , FSFI and MENQOL question naires were administered for a second time . Results . Quality of life was unchanged in the placebo group whereas AHT significantly improved scores of vasomotor , psychological , physical and sexual symptoms . As expected , FSFI was not modified in the placebo group while in AHT group the FSFI score improved significantly . In addition , at the end of the study , 68.7 % of subjects of the AHT group did not fit did not fit the criteria for sexual dysfunction as per the FSFI ( p < 0.0001 ) . Conclusions . Adding methyl-testosterone to hormone therapy  improves quality of life and sexuality in post-menopausal women with sexual dysfunction 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 dydrogester 
    Output:
    
agent
HT treatment with estrogens alone or in combination with progestogens was associated with a small to moderate improvement in sexual function , particularly in pain , when used in women with menopausal symptoms or in early postmenopause ( within five years of amenorrhoea ) , but not in unselected postmenopausal women .
The current evidence does not suggest an important effect of tibolone or of SERMs alone or combined with estrogens on sexual function .
***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: BACKGROUND tibolone at usual doses of 2.5 mg/day in postmenopausal women has been shown to improve climacteric complaints , without affecting endometrial thickness and lipid profile or blood glucose . However , the potentially similar efficacy , but better tolerability , of a low dose of this drug ( 1.25 mg ) has never been established . METHODS 162 healthy , non-obese , post-menopausal women , aged 40 - 65 years , with an intact uterus were enrolled in a national , single centre , r and omised , double blind , placebo controlled , parallel group trial . After 1 week of runin , patients were treated for 24 weeks with placebo , tibolone 1.25 mg or 2.5 mg/day . During the study laboratory tests , endometrial ultrasound scans and mammography were performed . Occurrence of menopausal signs and symptoms , including vaginal bleeding , and quality of sexual life were also checked . RESULTS in the 120 patients terminating the study without major protocol violations , climacteric symptoms were similarly improved by tibolone 1.25 and 2.5 mg ( 78 % and 90 % reduction at week 24 for hot flushes , 36 % and 34 % for sweating episodes and 44 % and 51 % for vaginal dryness ) , but not by placebo . Benefits occurred earlier in the group treated with tibolone 2.5 mg . Quality of sexual life was almost invariably improved by tibolone as compared to placebo , but improvement occurred earlier in the tibolone 1.25 mg group . Severity of vaginal bleeding was not different between placebo and active treatment groups , except at week 12 when was higher . At the end of treatment vaginal bleeding occurred in 15 % of patients treated with placebo , 14 % treated with tibolone 1.25 mg and 12 % treated with tibolone 2.5 mg . Endometrial thickness and breast density were not changed by treatment , as well as FSH , 17-beta-estradiol , total cholesterol , HDL and LDL cholesterol , triglycerides and blood glucose . Adverse events were reported by 14.7 % , 26.7 % and 24.4 % of patients treated with placebo , tibolone 1.25 mg and tibolone 2.5 mg/day , respectively . CONCLUSIONS tibolone at doses of 1.25 or 2.5 mg/day given for 24 weeks to postmenopausal women displayed similar efficacy and safety profiles , though were more effective than placebo . Tibolone 1.25 mg induced a more gradual relief from climacteric symptoms and a more prompt improvement of sexual function In this report we evaluated the action of conjugated equine estrogens ( CEE ) on vaginal symptoms , cytology , pH , and flora in late postmenopausal women without any previous hormone therapy . The study was a r and omized , double-blind , placebo-controlled trial with 48 late postmenopausal women who received placebo or unopposed CEE ( 0.625mg/day of CEE orally ) during three months of treatment .  Vaginal and sexual complaints were evaluated through daily diary cards . We analyzed vaginal changes through cytology and pH measurements . After three months of treatment , 20 % of placebo-treated patients and 80 % of the CEE-treated patients reported improvement in vaginal dryness and irritation . In the latter group , the vaginal cells and Lactobacillus increased and the vaginal pH decreased , without other changes in sexual complaints . We concluded that estrogen ameliorated the genital tract of late postmenopausal women without any previous hormone therapy OBJECTIVE In some women , hot flashes and other symptoms attributed to menopause persist for many years after the cessation of menses . The frequency and severity of such symptoms and response to hormone therapy in older women have not been well documented . METHODS We used data from the Heart and Estrogen/Progestin Replacement Study , a blinded , clinical trial among 2763 women with documented coronary disease and a uterus who were r and omized to receive either conjugated estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg in one tablet or placebo .  Participants were queried at baseline and annually regarding menopausal symptoms . Breast symptoms were self‐reported , and uterine bleeding was recorded on a daily diary . RESULTS Symptoms associated with menopause were relatively common among Heart and Estrogen/Progestin Replacement Study participants , whose average age was 67 years and who averaged 18 years since menopause . At baseline , 16 % of women reported frequent hot flashes , 26 % vaginal dryness , 10 % genital irritation , 55 % trouble sleeping , and 53 % early awakening . Women assigned to hormone therapy reported less frequent hot flashes , vaginal dryness , and trouble sleeping compared with women assigned to placebo , but more frequent vaginal discharge , genital irritation , uterine bleeding , and breast symptoms . The reporting of breast symptoms among women in the hormone group decreased from 40 % at 1 year to 13 % by the 4th year . Uterine bleeding was reported by 31 % and spotting by an additional 33 % of women in the hormone group during the 1st year of treatment ; by the 4th year , these proportions had fallen to 11 % and 20 % , respectively . CONCLUSION Symptoms typically attributed to menopause are common in elderly women .  Postmenopausal hormone therapy  reduces hot flashes , trouble sleeping , and vaginal dryness , but at st and ard doses in elderly women is associated with vaginal discharge , genital irritation , uterine bleeding , and breast symptoms Objective : To determine the effects of raloxifene on sexual function in postmenopausal women with pre-existing vaginal atrophy treated with vaginal estrogen cream . Methods : A total of 187 naturally postmenopausal women , 42 - 80 years of age , with signs of genitourinary atrophy were enrolled in this 6-month , multicenter , parallel-group study . Subjects were r and omized to oral raloxifene HCl 60 mg daily or matching placebo ; the same subjects were also r and omized to receive one application of either vaginal conjugated estrogen cream 0.5 g twice weekly for 6 months or non-hormonal vaginal moisturizer twice weekly for 3 months , followed by conjugated estrogen cream for 3 months . Both investigators and subjects were masked to the identity of the oral medication . The vaginal preparations were administered in an open-label fashion . The Sexual Activity Question naire ( SAQ ) was administered at baseline and at 3 and 6 months . Safety was assessed throughout the study . Results : A total of 102 women were sexually active at baseline and , of these , 82 were also sexually active at the 6-month end-point . At 6 months , raloxifene and placebo , in the presence of vaginal conjugated estrogen cream , were both associated with improvement from baseline in vaginal dryness and reduced discomfort during sexual activity . There were no significant differences between raloxifene and placebo groups in any SAQ item . Enjoyment of sexual activity significantly increased from baseline with raloxifene but not with placebo . No difference in adverse events was observed between groups . Conclusion : Raloxifene had no negative effects on sexual function in postmenopausal women with vaginal atrophy who were treated concomitantly with vaginal estrogen cream The women in this study were either post-menopausal or ovariectomised for at least 1 yr prior to the study . They had also been treated for cancer of the cervix ( 27 women ) , endometrium ( 5 ) , ovaries ( 5 ) or breast ( 1 ) . All women presented with sexual troubles , mainly genital discomfort ( dyspareunia or vaginism ) . In a double-blind fashion , gynaecological capsules containing either an oestradiol diether ( ICD : promestriene ) or only the excipient were administered for 40 consecutive days . At the end of the treatment , the FSH , LH , oestrone ( E1 ) and oestradiol ( E2 ) plasma levels were not found to be significantly different from the pre-therapeutic values . These results suggest that promestriene acts on the vaginal mucosa , therefore not being converted back into the hormone from which it was derived . Also , in its dietheroxide form , promestriene is incapable of crossing the malpighian ( vaginal or epidermal ) epithelium and of reaching the general blood circulation . This discrepancy between the local anti-atrophic effects and the inability to exert systemic oestrogen activities singles out promestriene and justifies its therapeutic use when hormonally active oestrogens are contra-indicated , as in patients who have an oestrogen-sensitive cancer in their medical history Objective To assess the effect of  combined hormone replacement therapy ( HRT )  on health related quality of life . Design R and omised placebo controlled double blind trial . Setting General practice s in United Kingdom ( 384 ) , Australia ( 94 ) , and New Zeal and ( 24 ) . Participants Postmenopausal women aged 50 - 69 at r and omisation ; 3721 women with a uterus were r and omised to combined oestrogen and progestogen  ( n=1862 ) or placebo  ( n=1859 ) . Data on health related quality of life at one year were available from 1043 and 1087 women , respectively . Interventions Conjugated equine oestrogen 0.625 mg plus medroxyprogesterone acetate 2.5/5.0 mg or matched placebo orally daily for one year . Main outcome measures Health related quality of life and psychological wellbeing as measured by the women ’s health question naire . Changes in emotional and physical menopausal symptoms as measured by a symptoms question naire and depression by the Centre for Epidemiological Studies depression scale ( CES-D ) . Overall health related quality of life and overall quality of life as measured by the European quality of life instrument ( EuroQol ) and visual analogue scale , respectively . Results After one year small but significant improvements were observed in three of nine components of the women ’s health question naire for those taking combined HRT compared with those taking placebo :  vasomotor symptoms ( P<0.001 ) , sexual functioning ( P<0.001 ) , and sleep problems ( P<0.001 ) . Significantly fewer women in the combined HRT group reported hot flushes ( P<0.001 ) , night sweats ( P<0.001 ) , aching joints and muscles ( P=0.001 ) , insomnia ( P<0.001 ) , and vaginal dryness ( P<0.001 ) than in the placebo group , but greater proportions reported breast tenderness ( P<0.001 ) or vaginal discharge ( P<0.001 ) . Hot flushes were experienced in the combined HRT and placebo groups by 30 % and 29 % at trial entry and 9 % and 25 % at one year , respectively . No significant differences in other menopausal symptoms , depression , or overall quality of life were observed at one year . Conclusions Combined HRT started many years after the menopause can improve health related quality of life . Trial registration IS RCT N 63718836 Aim . To evaluate with vali date d instruments changes in quality of life and sexuality in women receiving hormonal replacement therapy ( AHT ) .  Design . R and omised , double-blind , double-dummy study with two parallel treatment arms . Patients and methods . Forty-seven healthy post-menopausal women , aged 45–64 years , were evaluated using the Female Sexual Function Index ( FSFI ) and the menopause-specific quality of life question naire ( MENQOL ) . Of them , 40 diagnosed with sexual dysfunction were r and omised ( 1:1 ) to receive daily 0.625 mg of conjugated estrogens plus 1.25 mg of methyl-testosterone and 100 mg of micronised progesterone or placebo . After 3 months follow-up , FSFI and MENQOL question naires were administered for a second time . Results . Quality of life was unchanged in the placebo group whereas AHT significantly improved scores of vasomotor , psychological , physical and sexual symptoms . As expected , FSFI was not modified in the placebo group while in AHT group the FSFI score improved significantly . In addition , at the end of the study , 68.7 % of subjects of the AHT group did not fit did not fit the criteria for sexual dysfunction as per the FSFI ( p < 0.0001 ) . Conclusions . Adding methyl-testosterone to hormone therapy  improves quality of life and sexuality in post-menopausal women with sexual dysfunction 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 dydrogester 
    Output:
    