***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 
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    Input: OBJECTIVE To determine the effects of four doses of a 7-day transdermal 17beta-estradiol ( E2 ) delivery system , including 0.025 mg/day , on bone loss in postmenopausal women . METHODS This was a multicenter , double-masked , r and omized , placebo-controlled study of the effects of transdermal E2 at doses of 0.025 , 0.05 , 0.06 , and 0.1 mg/day for the prevention of postmenopausal osteoporosis . Efficacy was evaluated from bone mineral density of lumbar vertebrae L2-L4 , radius , proximal femur , and total hip measured with dual-energy x-ray absorptiometry . Serum osteocalcin and urinary pyridinoline and deoxypyridinoline concentrations were measured . RESULTS At 24 months , E2 doses of 0.025 , 0.05 , 0.06 , and 0.1 mg/day result ed in mean increases in bone mineral density of the lumbar spine of 2.37 % , 4.09 % , 3.28 % , and 4.70 % , respectively , and increased bone mineral density of the total hip by 0.26 % , 2.85 % , 3.05 % , and 2.03 % , respectively . All increases were statistically significantly greater than placebo , which decreased bone mineral density by 2.49 % at the spine and 2.04 % at the hip . Consistent and significant improvements in biochemical markers of bone turnover also were noted at various intervals in all treatment groups . The most frequent adverse events were local reactions from the transdermal drug-delivery system , effects of estrogen , and menopausal symptoms . CONCLUSION Transdermal E2 at doses of 0.025 , 0.05 , 0.06 , and 0.1 mg/day effectively prevented bone loss in postmenopausal women A 10-year , double-blind prospect i ve study was undertaken to evaluate the effects of  estrogen replacement therapy .  The sample population consisted of 84 pairs of r and omly chosen postmenopausal patients who were matched for age and diagnosis . One half of the patients received conjugated estrogens and cyclic progesterone , while the other half received placebo . Estrogen-treated patients whose therapy started within 3 years of menopause showed improvement or no increase in osteoporosis . Control patients demonstrate an increase in their osteoporosis Postmenopausal hormone replacement therapy is associated with a reduction in the incidence of coronary heart disease . However , inconclusive results have been reported with respect to the risk of stroke , and recent studies consistently showed an increased risk of venous thromboembolism in postmenopausal women using oral estrogen .  There are surprisingly few interventional studies to assess the true effects of estrogen-progestin regimens on blood coagulation and fibrinolysis , and the impact of the route of estrogen administration on hemostasis has not been well documented . Therefore , we investigated the effects of oral and transdermal estradiol/progesterone replacement therapy on hemostatic variables . Forty-five healthy postmenopausal women , aged 45 to 64 years , were assigned r and omly to one of the three following groups : cyclic oral or transdermal estradiol , both combined with progesterone , or no hormonal treatment .  Hemostatic variables were assayed at baseline and after a 6-month period . Pairwise differences in the mean change between the three groups were compared using nonparametric tests . Oral but not transdermal estradiol regimen significantly increased the mean value of prothrombin activation peptide ( F1 + 2 ) and decreased mean antithrombin activity compared with no treatment . Differences in fragment F1 + 2 levels between active treatments were significant . The oral estrogen group was associated with a significant decrease in both mean tissue-type plasminogen ( t-PA ) concentration and plasminogen activator inhibitor ( PAI-1 ) activity and a significant rise in global fibrinolytic capacity ( GFC ) compared with the two other groups . A transdermal estrogen regimen had no significant effect on PAI-1 , t-PA , and GFC levels . There were no significant changes in mean values of fibrinogen , factor VII , von Willebr and factor , protein C , fibrin D-dimer , and plasminogen between and within the three groups . We conclude that oral estrogen/progesterone replacement therapy may result in coagulation activation and increased fibrinolytic potential , whereas opposed transdermal estrogen appears without any substantial effects on hemostasis . Whereas these results may account for an increased risk of venous thromboembolism in users of oral postmenopausal estrogen  , they emphasize the potential importance of the route of estrogen administration in prescribing hormone replacement therapy to postmenopausal women , especially to those at high risk of thrombotic disease CONTEXT Therapy with individual antiresorptive agents has been shown to be effective for prevention and treatment of postmenopausal osteoporosis , but whether combination antiresorptive therapy with hormones and bisphosphonates is safe or efficacious or how these agents compare in elderly women is unknown . OBJECTIVE To determine whether hormone replacement and the bisphosphonate alendronate sodium in combination are efficacious and safe , and how they compare with monotherapy in community-dwelling elderly women . DESIGN R and omized , double-blind , placebo-controlled , clinical trial . SETTING AND PARTICIPANTS Five hundred seventy-three community-dwelling women age 65 years or older were screened : 485 completed screening and 373 ( aged 65 to 90 years ) were r and omized following a 3-month , open-label , run-in phase with hormone replacement and alendronate placebo . The trial was conducted at a single academic US medical center from January 1996 to May 2001 . INTERVENTIONS Participants were r and omly assigned in a 2 x 2 factorial design to receive hormone replacement ( conjugated equine estrogen , 0.625 mg/d , with or without medroxyprogesterone , 2.5 mg/d ) and alendronate , 10 mg daily , both agents , or neither . All participants received calcium and vitamin D supplements . MAIN OUTCOME MEASURES Annualized change in bone mineral density of the hip and spine and occurrence of adverse events . RESULTS Bone mineral density at 3 years was significantly greater at all femoral and vertebral sites in women treated with combination therapy than with monotherapy , with mean ( SD ) increases of 5.9 % ( 3.8 ) at the total hip , 10.4 % ( 5.4 ) at the posteroanterior lumbar spine , and 11.8 % ( 6.8 ) at the lateral lumbar spine . Mean ( SD ) increases in bone mass at the hip in women treated with alendronate alone were significantly greater than in those treated with hormone replacement therapy alone ( 4.2 % [ 3.8 ] vs 3.0 % [ 4.9 ] ; P<.05 , respectively ) , and alendronate result ed in more responders to therapy . All therapies were well tolerated and participant retention was 90 % at 3 years . CONCLUSIONS Combination therapy with hormone replacement and alendronate was efficacious and well tolerated in this cohort . Alendronate was superior to hormone replacement , and combination therapy was superior to either therapy alone . Combination therapy may represent an option for women with more severe disease or for those who have failed to achieve an adequate response to monotherapy BACKGROUND Long-term treatment of patients with asymptomatic primary hyperparathyroidism remains controversial , but the presence of osteoporosis is regarded as an indication for parathyroidectomy . Hormone replacement therapy ( HRT ) is a possible alternative therapy in osteopenic postmenopausal women with the disorder , and results of short-term studies suggest a beneficial effect on bone mass comparable to that achieved by parathyroidectomy . Longer-term data are required to further assess the efficacy of this treatment in chronic stable primary hyperparathyroidism . METHODS We report the results of the extension from 2 to 4 years of a r and omized , placebo-controlled trial of HRT in postmenopausal women with primary hyperparathyroidism . Of 23 postmenopausal women with primary hyperparathyroidism , 11 received active HRT with conjugated equine estrogen , 0.625 mg/d , and medroxyprogesterone acetate , 5 mg/d , and 12 received placebo .  Bone mineral density was measured throughout the skeleton at 6-month intervals using dual-energy x-ray absorptiometry in these women and in 50 normocalcemic age-matched control subjects . None of the 23 patients withdrew during the extension period . RESULTS Changes in bone mineral density were more positive in those taking HRT than placebo , with the between-group differences at 4 years being 4.6 % in the total body , 7.5 % in the lumbar spine , 7.4 % in the femoral neck , 8.2 % in the femoral trochanter , 6.8 % in the legs , and 7.0 % in the forearm ( P<.01 ) . At skeletal sites composed predominantly of cortical bone , there was a progressive divergence of the 2 groups . Biochemical markers of bone turnover remained lower throughout the study in women taking HRT . When rates of bone loss were compared between the placebo group and healthy women of comparable age , bone loss tended to be more marked throughout the skeleton in women with hyperparathyroidism , but only in the total body and its legs subregion was this difference significant . CONCLUSIONS Hormone replacement therapy is efficacious in the long-term management of osteopenia in postmenopausal women with primary hyperparathyroidism and thus represents an important new therapeutic option for asymptomatic patients who do not have other indications for surgery .  Bone loss seems to be accelerated in untreated primary hyperparathyroidism BACKGROUND We conducted a 3-year , double-blind , r and omized , placebo-controlled study to determine whether the positive effects of hormone/estrogen replacement therapy ( H/ERT ) on postcranial bone density are accompanied by similar positive effects on oral bone mass . METHODS A total of 135 postmenopausal women ( aged 41 - 70 years ) with no evidence of moderate or severe periodontal disease were r and omized to receive daily oral conjugated estrogen ( Premarin ; 0.625 mg ) alone or in combination with medroxyprogesterone acetate ( Prempro ; 0.625 and 2.5 mg , respectively ) or placebo . All subjects received calcium carbonate ( 1000 mg/d ) and cholecalciferol ( 400 [ corrected ] IU/d ) supplements . The primary efficacy end points were the changes in alveolar crest height and alveolar bone density . Alveolar crest height was measured on bite-wing radiographs , and changes in alveolar bone mass were assessed by means of digital-subtraction radiography . Postcranial bone density was measured in the lumbar spine and left proximal femur by means of dual-energy x-ray absorptiometry . RESULTS Hormone/estrogen replacement therapy significantly increased alveolar bone mass compared with placebo ( + 1.84 % vs + 0.95 % [ P = .04 ] ) , and tended to improve alveolar crest height ( + 4.83 % vs + 3.46 % [ P = .34 ] ) . Bone mineral density of the proximal femur significantly increased in the H/ERT compared with the placebo group ( total proximal femur , + 3.59 % vs + 0.22 % [ P = .001 ] ; neck , + 2.05 % vs -0.34 % [ P = .02 ] ; trochanter , + 3.49 % vs + 0.08 % [ P<.001 ] ) , but not the lumbar spine ( + 1.01 % vs + 0.17 % [ P = .39 ] ) . Changes in alveolar bone mass correlated with bone density changes in the total femur ( r = 0.28 [ P = .02 ] ) and femoral trochanter ( r = 0.25 [ P = .04 ] ) in the H/ERT but not in the placebo group . CONCLUSIONS Postcranial and oral bone mass were increased in postmenopausal women receiving H/ERT . Improvement in oral bone health constitutes an additional benefit of H/ERT OBJECTIVE To determine the relative risk for sustaining a  first hip fracture after hormone replacement therapy .  DESIGN Prospect i ve population -based cohort study with an average observation period of 5.7 years . SETTING A prescription-based cohort in the Uppsala health care region in Sweden . PARTICIPANTS The cohort ( 23 246 women ) comprised virtually all women of 35 years of age and older who received noncontraceptive estrogens from April 1977 through March 1980 . Comparisons were made with women in the background population . MEASUREMENTS Follow-up through 1983 was done with regard to hospital admissions for a first cervical or trochanteric hip fracture . The observed number of cases was compared with that expected on the basis of person-years of observation in the cohort and incidence rates in the background population . Analyses were made in exposure categories , based solely on prescription data . MAIN RESULTS During 133 022 person-years of observation , 163 cases of first 
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No increase in the incidence of total cancer events but an increase in the incidence of thrombus was found to be associated with HT .
Conclusions : HT is associated with a reduced risk of total , hip , and vertebral fractures , with a possible attenuation of this protection effect after it is stopped or when it is begun after 60 years .
However , there may be an increase in the incidence of thrombus formation associated with HT