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: Clinical data suggest concomitant therapy with bisphosphonates and parathyroid hormone ( PTH ) may blunt the anabolic effect of PTH ; rodent models suggest that infrequently administered bisphosphonates may interact differently . To evaluate the effects of combination therapy with an intravenous infusion of zoledronic acid 5 mg and daily subcutaneous recombinant human (rh)PTH(1 - 34 ) ( teriparatide ) 20 µg versus either agent alone on bone mineral density ( BMD ) and bone turnover markers , we conducted a 1-year multicenter , multinational , r and omized , partial double-blinded , controlled trial . 412 postmenopausal women with osteoporosis ( mean age 65 ± 9 years ) were r and omized to a single infusion of zoledronic acid 5 mg plus daily subcutaneous teriparatide 20 µg ( n = 137 ) , zoledronic acid alone ( n = 137 ) , or teriparatide alone ( n = 138 ) . The primary endpoint was percentage increase in lumbar spine BMD ( assessed by dual-energy X-ray absorptiometry [ DXA ] ) at 52 weeks versus baseline . Secondary endpoints included change in BMD at the spine at earlier time points and at the total hip , trochanter , and femoral neck at all time points . At week 52 , lumbar spine BMD had increased 7.5 % , 7.0 % , and 4.4 % in the combination , teriparatide , and zoledronic acid groups , respectively ( p < .001 for combination and teriparatide versus zoledronic acid ) . In the combination group , spine BMD increased more rapidly than with either agent alone ( p < .001 versus both teriparatide and zoledronic acid at 13 and 26 weeks ) . Combination therapy increased total-hip BMD more than teriparatide alone at all times ( all p < .01 ) and more than zoledronic acid at 13 weeks ( p < .05 ) , with final 52-week increments of 2.3 % , 1.1 % , and 2.2 % in the combination , teriparatide , and zoledronic acid groups , respectively . With combination  therapy , bone formation ( assessed by serum N-terminal propeptide of type I collagen [ PINP ] ) increased from 0 to 4 weeks , declined minimally from 4 to 8 weeks , and then rose throughout the trial , with levels above baseline from 6 to 12 months . Bone resorption ( assessed by serum β-C-telopeptide of type I collagen [ β-CTX ] ) was markedly reduced with combination therapy from 0 to 8 weeks ( a reduction of similar magnitude to that seen with zoledronic acid alone ) , followed by a gradual increase after week 8 , with levels remaining above baseline for the latter half of the year . Levels for both markers were significantly lower with combination therapy versus teriparatide alone ( p < .002 ) . Limitations of the study included its short duration , lack of endpoints beyond DXA-based BMD ( e.g. , quantitative computed tomography and finite-element modeling for bone strength ) , lack of teriparatide placebo , and insufficient power for fracture outcomes . We conclude that while teriparatide increases spine BMD more than zoledronic acid and zoledronic acid increases hip BMD more than teriparatide , combination therapy provides the largest , most rapid increments when both spine and hip sites are considered OBJECTIVE To report the histological findings of the endometrium of postmenopausal women who were r and omized to receive placebo , estrogen only , or one of three estrogen plus progestin ( E+P ) regimens in the Postmenopausal Estrogen/Progestin Interventions ( PEPI ) Trial . DESIGN A 3-year multicenter , r and omized , double-masked , placebo-controlled trial . PARTICIPANTS A total of 596 postmenopausal women aged 45 through 64 years without contraindication to hormone therapy . INTERVENTION Participants were r and omized and stratified in equal numbers to one of the following treatments in 28-day cycles : placebo , 0.625 mg/d of conjugated equine estrogens ( CEE ) , 0.625 mg/d of CEE plus 10 mg/d of medroxyprogesterone acetate ( MPA ) for the first 12 days , 0.625 mg/d of CEE plus 2.5 mg/d of MPA , or 0.625 mg/d of CEE plus 200 mg/d of micronized progesterone ( MP ) for the first 12 days . OUTCOME MEASURE Histology of endometrium collected at baseline , annual , or unscheduled visits by biopsy , curettage , or hysterectomy . ANALYSIS Intention to treat . RESULTS During follow-up women assigned to estrogen alone were more likely to develop simple ( cystic ) , complex ( adenomatous ) , or atypical hyperplasia than those given placebo ( 27.7 % vs 0.8 % , 22.7 % vs 0.8 % , and 11.8 % vs 0 % , respectively ) for the same types of hyperplasia ( P < .001 ) . Participants administered one of the three E+P regimens had similar rates of hyperplasia as those given placebo ( P = .16 ) . The occurrence of hyperplasia was distributed evenly across the 3 years of the trial . Women taking estrogens alone also had more unscheduled biopsies ( 66.4 % vs 8.4 % ; P < .001 ) and curettages ( 17.6 % vs 0.8 % ; P < .001 ) than women receiving placebo . The number of surgical procedures was similar for women receiving placebo and women receiving the E+P regimens ( P = .38 ) . Of the 45 women with complex ( adenomatous ) or atypical hyperplasia , study medications were discontinued in all , and the biopsy results of 34 ( 94 % ) of 36 women with hyperplasia reverted to normal with progestin therapy . The remainder had dilatation and curettage ( n = 2 ) or hysterectomy with ( n = 2 ) or without ( n = 6 ) prior medical therapy , or refused further biopsies ( n = 1 ) . One woman developed adenocarcinoma of the endometrium while receiving placebo . CONCLUSIONS At a dosage of 0.625 mg , the daily administration of CEE enhanced the development of endometrial hyperplasia . Combining CEE with cyclic or continuous MPA or cyclic MP protected the endometrium from hyperplastic changes associated with estrogen-only therapy The purpose of this study was to contrast the effects of conventional estrogen treatment with medroxyprogesterone on cancellous and cortical bone change in the first year following premenopausal ovariectomy .  This 1-year double-blind r and omized therapy trial was stratified by osteoporosis family history and performed in an academic medical center and community hospitals . Premenopausal women 45 + /- 5 years old , postovariectomy for benign diseases were provided 600 mg/day of calcium and r and omized to daily therapy with conjugated equine estrogen ( CEE , 0.6 mg ) or medroxyprogesterone ( MPA , 10 mg ) . The primary outcome variable was spinal quantitative computed tomography ( QCT ) bone density change over 1 year with additional outcomes of dual-energy X-ray absorptiometry ( DXA ) of proximal femur ( FN ) , whole body ( WB ) , and spine segment ( WBS ) and N-telopeptide , bone-specific alkaline phosphatase , and other bone marker , hormonal , and weight changes . Results in the 33 women completing the study , whose initial bone densities were normal ( QCT 133 mg/cm3 , femoral neck 0.94 g/cm2 , whole body DXA 1.13 g/cm2 ) , showed annual QCT loss during CEE therapy of -11.5 mg/cm3 ( p < 0.0007 ) and MPA bone loss of -19.7 mg/cm3 ( p < 0.0001 ) . Losses were marginally greater on MPA than CEE ( p = 0.04 ) . Extremely high postovariectomy ( 5 days ) and pretreatment resorption markers ( > 3 SD above premenopausal normal levels ) were significantly related to bone loss . Across the year , resorption decreased during CEE but increased on MPA treatment . Significant DXA bone losses were prevented by CEE treatment ( -1.4 % FN , -.4 % WB , and -1.5 % WBS , all NS ) . However , DXA bone loss was not prevented by MPA treatment ( -5 % FN , -2.8 % WB , and -6.1 % WBS , all p < 0.03 ) . Average weight gain was significant ( + 3.2 + /- 4.0 kg ) and greater on CEE than MPA ( + 4.7 vs. + 2.0 kg , p = 0.049 ) . In conclusion , CEE therapy did not prevent significant 8 % cancellous spinal bone loss in the first year following premenopausal ovariectomy , despite supplementation with 600 mg/day of calcium , good control of vasomotor symptoms , and nearly 5 kg of gain in weight . Significant DXA bone loss , however , was prevented by CEE , but not by MPA therapy . These unexpected results were statistically related to high bone resorption following ovariectomy , which CEE suppressed but MPA did not . Bone formation markers increased during MPA therapy but were unchanged during CEE therapy Oestrogen therapy is the gold st and ard treatment for hot flushes/night sweats , but it and oestrogen/progestin are not suitable for all women . MPA ( medroxyprogesterone acetate ) reduces hot flushes , but its effectiveness compared with oestrogen is unknown . In the present study , oral oestrogen [ CEE ( conjugated equine oestrogen ) ] and MPA were compared for their effects on hot flushes in a planned analysis of a secondary outcome for a 1-year r and omized double-blind parallel group controlled trial in an urban academic medical centre . Participants were healthy menstruating women prior to hysterectomy/ovariectomy for benign disease . A total of 41 women { age , 45 ( 5 ) years [ value is mean ( S.D. ) ] } were enrolled ; 38 women were included in this analysis of daily identical capsules containing CEE ( 0.6 mg/day ) or MPA ( 10 mg/day ) . Demographic variables did not differ at baseline . Daily data provided the number of night and day flushes compared by group . The vasomotor symptom day-to-day intensity change was assessed by therapy assignment . Hot flushes/night sweats were well controlled in both groups , one occurred on average every third day and every fourth night . Mean/day daytime occurrences were 0.363 and 0.187 with CEE and MPA respectively , but were not significantly different ( P=0.156 ) . Night sweats also did not differ significantly ( P=0.766 ) . Therapies were statistically equivalent ( within one event/24 h ) in the control of vasomotor symptoms . Day-to-day hot flush intensity decreased with MPA and tended to remain stable with CEE ( P<0.001 ) . In conclusion , this analysis demonstrates that MPA and CEE are equivalent and effective in the control of the number of hot flushes/night sweats immediately following premenopausal ovariectomy Background Progesterone is effective treatment for hot flushes/night sweats . The cardiovascular effects of progesterone therapy are unknown but evidence suggests that premenopausal normal estradiol with also normal progesterone levels may provide later cardiovascular protection . We compared the effects of progesterone to placebo on endothelial function , weight , blood pressure , metabolism , lipids , inflammation and coagulation . Methods and Results We conducted a r and omized , double-blind , 3-month placebo-controlled trial of progesterone ( 300 mg daily ) among 133 healthy postmenopausal women in Vancouver , Canada from 2003–2009 . Endothelial function by venous occlusion plethysmography was a planned primary outcome . Enrolled women were 1–11 y since last menstruation , not using hormones ( for > 6 months ) , non-smoking , without diabetes , hypertension , heart disease or their medications . R and omized ( 1∶1 ) women ( 55±4 years , body mass index 25±3 ) initially had normal blood pressure , fasting lipid , glucose and electrocardiogram results . Endothelial function ( % forearm blood flow above saline ) was not changed with progesterone ( 487±189 % , n = 18 ) compared with placebo ( 408±278 % , n = 16 ) ( 95 % CI diff [ −74 to 232 ] , P = 0.30 ) .  Progesterone ( n = 65 ) and placebo ( n = 47 ) groups had similar changes in systolic and diastolic blood pressure , resting heart rate , weight , body mass index , waist circumference , total cholesterol , low-density lipoprotein cholesterol and triglyceride levels . High-density lipoprotein was lower ( −0.14 mmol/L 
    Output:
    
agent
CONCLUSION Estrogen with an osteoblast P4R-acting progestin ( EPT ) in these five published RCT provides Level 1 evidence that MPA caused significantly greater annual percent spinal BMD gains than the same dose of ET .
***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: Clinical data suggest concomitant therapy with bisphosphonates and parathyroid hormone ( PTH ) may blunt the anabolic effect of PTH ; rodent models suggest that infrequently administered bisphosphonates may interact differently . To evaluate the effects of combination therapy with an intravenous infusion of zoledronic acid 5 mg and daily subcutaneous recombinant human (rh)PTH(1 - 34 ) ( teriparatide ) 20 µg versus either agent alone on bone mineral density ( BMD ) and bone turnover markers , we conducted a 1-year multicenter , multinational , r and omized , partial double-blinded , controlled trial . 412 postmenopausal women with osteoporosis ( mean age 65 ± 9 years ) were r and omized to a single infusion of zoledronic acid 5 mg plus daily subcutaneous teriparatide 20 µg ( n = 137 ) , zoledronic acid alone ( n = 137 ) , or teriparatide alone ( n = 138 ) . The primary endpoint was percentage increase in lumbar spine BMD ( assessed by dual-energy X-ray absorptiometry [ DXA ] ) at 52 weeks versus baseline . Secondary endpoints included change in BMD at the spine at earlier time points and at the total hip , trochanter , and femoral neck at all time points . At week 52 , lumbar spine BMD had increased 7.5 % , 7.0 % , and 4.4 % in the combination , teriparatide , and zoledronic acid groups , respectively ( p < .001 for combination and teriparatide versus zoledronic acid ) . In the combination group , spine BMD increased more rapidly than with either agent alone ( p < .001 versus both teriparatide and zoledronic acid at 13 and 26 weeks ) . Combination therapy increased total-hip BMD more than teriparatide alone at all times ( all p < .01 ) and more than zoledronic acid at 13 weeks ( p < .05 ) , with final 52-week increments of 2.3 % , 1.1 % , and 2.2 % in the combination , teriparatide , and zoledronic acid groups , respectively . With combination  therapy , bone formation ( assessed by serum N-terminal propeptide of type I collagen [ PINP ] ) increased from 0 to 4 weeks , declined minimally from 4 to 8 weeks , and then rose throughout the trial , with levels above baseline from 6 to 12 months . Bone resorption ( assessed by serum β-C-telopeptide of type I collagen [ β-CTX ] ) was markedly reduced with combination therapy from 0 to 8 weeks ( a reduction of similar magnitude to that seen with zoledronic acid alone ) , followed by a gradual increase after week 8 , with levels remaining above baseline for the latter half of the year . Levels for both markers were significantly lower with combination therapy versus teriparatide alone ( p < .002 ) . Limitations of the study included its short duration , lack of endpoints beyond DXA-based BMD ( e.g. , quantitative computed tomography and finite-element modeling for bone strength ) , lack of teriparatide placebo , and insufficient power for fracture outcomes . We conclude that while teriparatide increases spine BMD more than zoledronic acid and zoledronic acid increases hip BMD more than teriparatide , combination therapy provides the largest , most rapid increments when both spine and hip sites are considered OBJECTIVE To report the histological findings of the endometrium of postmenopausal women who were r and omized to receive placebo , estrogen only , or one of three estrogen plus progestin ( E+P ) regimens in the Postmenopausal Estrogen/Progestin Interventions ( PEPI ) Trial . DESIGN A 3-year multicenter , r and omized , double-masked , placebo-controlled trial . PARTICIPANTS A total of 596 postmenopausal women aged 45 through 64 years without contraindication to hormone therapy . INTERVENTION Participants were r and omized and stratified in equal numbers to one of the following treatments in 28-day cycles : placebo , 0.625 mg/d of conjugated equine estrogens ( CEE ) , 0.625 mg/d of CEE plus 10 mg/d of medroxyprogesterone acetate ( MPA ) for the first 12 days , 0.625 mg/d of CEE plus 2.5 mg/d of MPA , or 0.625 mg/d of CEE plus 200 mg/d of micronized progesterone ( MP ) for the first 12 days . OUTCOME MEASURE Histology of endometrium collected at baseline , annual , or unscheduled visits by biopsy , curettage , or hysterectomy . ANALYSIS Intention to treat . RESULTS During follow-up women assigned to estrogen alone were more likely to develop simple ( cystic ) , complex ( adenomatous ) , or atypical hyperplasia than those given placebo ( 27.7 % vs 0.8 % , 22.7 % vs 0.8 % , and 11.8 % vs 0 % , respectively ) for the same types of hyperplasia ( P < .001 ) . Participants administered one of the three E+P regimens had similar rates of hyperplasia as those given placebo ( P = .16 ) . The occurrence of hyperplasia was distributed evenly across the 3 years of the trial . Women taking estrogens alone also had more unscheduled biopsies ( 66.4 % vs 8.4 % ; P < .001 ) and curettages ( 17.6 % vs 0.8 % ; P < .001 ) than women receiving placebo . The number of surgical procedures was similar for women receiving placebo and women receiving the E+P regimens ( P = .38 ) . Of the 45 women with complex ( adenomatous ) or atypical hyperplasia , study medications were discontinued in all , and the biopsy results of 34 ( 94 % ) of 36 women with hyperplasia reverted to normal with progestin therapy . The remainder had dilatation and curettage ( n = 2 ) or hysterectomy with ( n = 2 ) or without ( n = 6 ) prior medical therapy , or refused further biopsies ( n = 1 ) . One woman developed adenocarcinoma of the endometrium while receiving placebo . CONCLUSIONS At a dosage of 0.625 mg , the daily administration of CEE enhanced the development of endometrial hyperplasia . Combining CEE with cyclic or continuous MPA or cyclic MP protected the endometrium from hyperplastic changes associated with estrogen-only therapy The purpose of this study was to contrast the effects of conventional estrogen treatment with medroxyprogesterone on cancellous and cortical bone change in the first year following premenopausal ovariectomy .  This 1-year double-blind r and omized therapy trial was stratified by osteoporosis family history and performed in an academic medical center and community hospitals . Premenopausal women 45 + /- 5 years old , postovariectomy for benign diseases were provided 600 mg/day of calcium and r and omized to daily therapy with conjugated equine estrogen ( CEE , 0.6 mg ) or medroxyprogesterone ( MPA , 10 mg ) . The primary outcome variable was spinal quantitative computed tomography ( QCT ) bone density change over 1 year with additional outcomes of dual-energy X-ray absorptiometry ( DXA ) of proximal femur ( FN ) , whole body ( WB ) , and spine segment ( WBS ) and N-telopeptide , bone-specific alkaline phosphatase , and other bone marker , hormonal , and weight changes . Results in the 33 women completing the study , whose initial bone densities were normal ( QCT 133 mg/cm3 , femoral neck 0.94 g/cm2 , whole body DXA 1.13 g/cm2 ) , showed annual QCT loss during CEE therapy of -11.5 mg/cm3 ( p < 0.0007 ) and MPA bone loss of -19.7 mg/cm3 ( p < 0.0001 ) . Losses were marginally greater on MPA than CEE ( p = 0.04 ) . Extremely high postovariectomy ( 5 days ) and pretreatment resorption markers ( > 3 SD above premenopausal normal levels ) were significantly related to bone loss . Across the year , resorption decreased during CEE but increased on MPA treatment . Significant DXA bone losses were prevented by CEE treatment ( -1.4 % FN , -.4 % WB , and -1.5 % WBS , all NS ) . However , DXA bone loss was not prevented by MPA treatment ( -5 % FN , -2.8 % WB , and -6.1 % WBS , all p < 0.03 ) . Average weight gain was significant ( + 3.2 + /- 4.0 kg ) and greater on CEE than MPA ( + 4.7 vs. + 2.0 kg , p = 0.049 ) . In conclusion , CEE therapy did not prevent significant 8 % cancellous spinal bone loss in the first year following premenopausal ovariectomy , despite supplementation with 600 mg/day of calcium , good control of vasomotor symptoms , and nearly 5 kg of gain in weight . Significant DXA bone loss , however , was prevented by CEE , but not by MPA therapy . These unexpected results were statistically related to high bone resorption following ovariectomy , which CEE suppressed but MPA did not . Bone formation markers increased during MPA therapy but were unchanged during CEE therapy Oestrogen therapy is the gold st and ard treatment for hot flushes/night sweats , but it and oestrogen/progestin are not suitable for all women . MPA ( medroxyprogesterone acetate ) reduces hot flushes , but its effectiveness compared with oestrogen is unknown . In the present study , oral oestrogen [ CEE ( conjugated equine oestrogen ) ] and MPA were compared for their effects on hot flushes in a planned analysis of a secondary outcome for a 1-year r and omized double-blind parallel group controlled trial in an urban academic medical centre . Participants were healthy menstruating women prior to hysterectomy/ovariectomy for benign disease . A total of 41 women { age , 45 ( 5 ) years [ value is mean ( S.D. ) ] } were enrolled ; 38 women were included in this analysis of daily identical capsules containing CEE ( 0.6 mg/day ) or MPA ( 10 mg/day ) . Demographic variables did not differ at baseline . Daily data provided the number of night and day flushes compared by group . The vasomotor symptom day-to-day intensity change was assessed by therapy assignment . Hot flushes/night sweats were well controlled in both groups , one occurred on average every third day and every fourth night . Mean/day daytime occurrences were 0.363 and 0.187 with CEE and MPA respectively , but were not significantly different ( P=0.156 ) . Night sweats also did not differ significantly ( P=0.766 ) . Therapies were statistically equivalent ( within one event/24 h ) in the control of vasomotor symptoms . Day-to-day hot flush intensity decreased with MPA and tended to remain stable with CEE ( P<0.001 ) . In conclusion , this analysis demonstrates that MPA and CEE are equivalent and effective in the control of the number of hot flushes/night sweats immediately following premenopausal ovariectomy Background Progesterone is effective treatment for hot flushes/night sweats . The cardiovascular effects of progesterone therapy are unknown but evidence suggests that premenopausal normal estradiol with also normal progesterone levels may provide later cardiovascular protection . We compared the effects of progesterone to placebo on endothelial function , weight , blood pressure , metabolism , lipids , inflammation and coagulation . Methods and Results We conducted a r and omized , double-blind , 3-month placebo-controlled trial of progesterone ( 300 mg daily ) among 133 healthy postmenopausal women in Vancouver , Canada from 2003–2009 . Endothelial function by venous occlusion plethysmography was a planned primary outcome . Enrolled women were 1–11 y since last menstruation , not using hormones ( for > 6 months ) , non-smoking , without diabetes , hypertension , heart disease or their medications . R and omized ( 1∶1 ) women ( 55±4 years , body mass index 25±3 ) initially had normal blood pressure , fasting lipid , glucose and electrocardiogram results . Endothelial function ( % forearm blood flow above saline ) was not changed with progesterone ( 487±189 % , n = 18 ) compared with placebo ( 408±278 % , n = 16 ) ( 95 % CI diff [ −74 to 232 ] , P = 0.30 ) .  Progesterone ( n = 65 ) and placebo ( n = 47 ) groups had similar changes in systolic and diastolic blood pressure , resting heart rate , weight , body mass index , waist circumference , total cholesterol , low-density lipoprotein cholesterol and triglyceride levels . High-density lipoprotein was lower ( −0.14 mmol/L 
    Output:
    