***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: Purpose To evaluate the relative efficiency of leuprolide 3.75 mg , leuprolide 7.5 mg , and goserelin 3.6 mg in relation to the reduction in serum testosterone , regarding the levels of castration . Material s and methods We evaluated prospect ively 60 r and omized patients with advanced prostate carcinoma , with indication for hormone blockade . The patients were divided into 3 groups of 20 : Group ( 1 ) received leuprolide 3.75 mg ; Group ( 2 ) received leuprolide 7.5 mg ; and Group ( 3 ) received goserelin 3.6 mg . All groups were treated with monthly application of the respective drugs . The patients ’ levels of serum testosterone were evaluated in two moments : before the treatment and 3 months after the treatment . Results The patients ’ ages were similar within the three groups , with a median of 72 , 70 , and 70 in groups 1 , 2 , and 3 , respectively . Of the patients that received leuprolide 3.75 mg , leuprolide 7.5 mg , and goserelin 3.6 mg , 26.3 , 25 , and 35 % , respectively , did not reach castration levels , considering a testosterone cutoff ≤ 50 ng/dl . And 68.4 , 30 , and 45 % , respectively , did not reach castration levels , considering a testosterone cutoff ≤ 20 ng/dl . Conclusions There were no statistically significant differences in the levels of castration when comparing leuprolide 3.75 mg , leuprolide 7.5 mg , and goserelin 3.6 mg , altogether . When compared in groups of two , there was a statistically significant difference between leuprolide 3.75 mg and leuprolide 7.5 mg , the latter presented better results in reaching castration levels , cutoff ≤ 20 ng/dl . The importance of this difference , however , must be measured with caution , since the comparison of the three groups simultaneously did not reach the established significance level , even though it came close Bone mineral density ( BMD ) and bone mineral content ( BMC ) were measured in the femoral neck area , trochanteric area and Wards triangle , and in the distal radius of the left forearm before and after 1 year of endocrine treatment in 27 patients with prostatic cancer . Eleven of the patients were treated with orchidectomy and 16 with combined oral and intramuscular estrogens . The patients were free from metastases during the entire observation period . In the orchidectomized patients , BMD and BMC of the distal radius decreased significantly following treatment , whereas no changes were observed in the estrogen-treated patients . These preliminary results demonstrate that estrogens may protect bone in male subjects also and may merit further investigations on larger groups of patients Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more PURPOSE Patients with stage D2 prostate carcinoma are often treated initially with hormones to decrease endogenous testosterone . Therapy with diethylstilbestrol ( DES ) , leuprolide , or bilateral orchiectomy has been reported to be equivalent . DES is the cheapest preparation , but has the potential for serious cardiovascular or thromboembolic complications .  Flutamide is a novel anti and rogen with fewer side effects . PATIENTS AND METHODS The Eastern Cooperative Oncology Group ( ECOG ) conducted a double-blind , r and omized study to compare the efficacy of flutamide ( 250 mg three times daily ) to DES ( 1 mg three times daily ) as the primary hormonal therapy for patients with stage D2 prostate cancer . Patients were stratified by performance status , disease sites , and history of cardiovascular disease at r and omization . RESULTS Forty-eight patients received DES and 44 flutamide . Patient characteristics were evenly distributed between the two treatments . The overall response rate was similar ( DES , 62 % ; flutamide , 50 % ) . Grade III or worse cardiovascular or thromboembolic toxicity developed in 33.3 % of patients on DES and in 17.6 % on flutamide ( P = .051 ) . Other toxicities were similar between the two treatment arms . However , DES produced significantly longer time to treatment failure ( 26.4 v 9.7 months , P = .016 ) and longer survival than flutamide ( 43.2 v 28.5 months , P = .040 ) . CONCLUSION As the primary hormonal therapy for stage D2 prostate cancer , DES caused more serious cardiovascular or thromboembolic complications than flutamide . Despite this , flutamide was not as active an initial agent as DES . However , the effectiveness of flutamide in conjunction with other agents compared with DES remains undetermined , and the optimal initial hormone therapy of stage D2 prostate cancer requires further studies Objective : To compare the efficacy of diethylstilboestrol ( DES ) with bicalutamide in the treatment of hormone refractory prostate cancer in relation to its effect on prostate-specific antigen ( PSA ) and survival . Methods : Patients on LHRH analogues for prostate carcinoma with evidence of biochemical or clinical progression were r and omized into one of the treatment arms ( n = 58 ) . The first group ( group A , n = 26 ) received 1 mg of DES with 75 mg of aspirin per day in addition to the primary hormonal treatment . The second group ( group B , n = 32 ) received bicalutamide at a dose of 50 mg/day in addition to the primary treatment . Patients were followed up every 3 months with their PSA being checked and were also monitored for any clinical progression and adverse effects as a result of treatment . Any adverse event occurring after patients were started on treatment was attributed to the drug and patients were clinical ly assessed at each visit . Failure of treatment was defined as a 50 % or greater increase in PSA after commencing treatment . Once r and omized , all patients were followed up for survival regardless of failure of second-line hormonal manipulation . Results : The mean age of the patients was 76.7 years ( 60–88 , SD 7.4 ) in group A and 76 years ( 67–86 , SD 6.9 ) in group B. Twelve patients in each group had metastatic disease .  The median follow-up periods for both groups were 24 months ( range 6–48 in group A , range 3–54 in group B ) . 65 % of the patients in group A ( 17/26 ) and 43.5 % ( 14/32 ) in group B had a fall in their PSA levels ( p = 0.08 , Fisher ’s exact test ) with 23 % ( 6/26 ) and 31 % ( 10/32 ) having a > 50 % response respectively ( p = 0.34 , Fisher ’s exact test ) . Mean PSA nadir in those who responded were 20.6 ng/ml ( range 1.6–59.4 ) and 7.41 ng/ml ( range 0.1–42.6 ) in groups A and B respectively . The median duration of response was 9 months ( 3–18 months ) for group A and 12 months ( 3–18 months ) for group B. Seven patients in group A and 6 in group B experienced adverse events . Three of the 7 in the group A experienced cardiovascular related adverse effects ( 1 congestive cardiac failure , 1 pulmonary embolism and 1 stroke ) . At the end of the study period , 14 ( 54 % ) of group A patients were alive and 12 ( 46 % ) were dead . In group B , 15 ( 47 % ) were alive , 16 ( 50 % ) were dead and 1 ( 3 % ) lost to follow-up . At the completion of the study , 3 patients in each group were still on treatment . Conclusion : Low-dose DES and 50 mg of bicalutamide per day are equally effective in  hormone refractory prostate carcinoma  with respect to biochemical response , although DES has more severe adverse effects . This is a small sample and larger multicentre trials are needed to give us a definite conclusion Luteinizing hormone releasing hormone agonists presently are being evaluated in the treatment of patients with metastatic prostatic cancer . To determine the comparative benefits of a specific luteinizing hormone releasing hormone agonist [ 6-leu ( 1 - 9 ) luteinizing hormone releasing hormone nonapeptide ethylamide ] relative to conventional estrogen therapy  23 patients with stage D2 prostatic cancer were r and omized to receive either 1 mg . luteinizing hormone releasing hormone agonist daily ( 12 ) or 3 mg . diethylstilbestrol per day ( 11 ) . Both agents were effective in inducing a remission in all patients , although diethylstilbestrol was slightly faster . The early phase of treatment with the luteinizing hormone releasing hormone agonist was dominated by a transient reversible deterioration ( the flare ) of the patient , which was believed to be related to the agonist-induced increase in serum and rogens . At 1 year of followup adverse effects in both groups have been minor but the proportion of patients with progression in the luteinizing hormone releasing hormone agonist group ( 6 of 12 ) was significantly higher than that in the diethylstilbestrol group ( 0 of 11 ) . Further investigation is required to determine the role of luteinizing hormone releasing hormone agonist in the treatment of patients with advanced prostatic cancer In a controlled , prospect i ve , r and omized clinical trial , we evaluated the safety and efficacy of leuprolide , a superactive analog of luteinizing hormone releasing hormone , given in a single subcutaneous injection dose of 1 mg per day , versus diethylstilbestrol ( DES ) 3 mg per day by mouth in patients with previously untreated Stage D2 prostatic adenocarcinoma . Eleven leuprolide patients and 10 DES patients were evaluated for therapeutic response . Eighty per cent of patients in each group experienced subjective improvement in bone pain and urinary obstructive signs and symptoms . Although the pooled percentages of complete , partial , and stable objective responses were greater for the leuprolide group than the DES group , the sums of the percentages of complete and partial objective responses were comparable for both treatment groups during the first forty-eight and sixty weeks of the study , respectively . In addition , patients not responding to leuprolide generally experienced no benefit with crossover to DES , and vice versa . Serious adverse reactions were more common in the DES group and included fatal myocardial infa rct ion , arrhythmia , deep venous thrombosis , and gynecomastia . Vasomotor flushing , disease flare , and injection site irritation occurred most often in leuprolide patients , but did not require modification or discontinuation of treatment Two multicenter , open , r and omized phase III clinical trials were conducted in the United Kingdom to compare the effectiveness and safety of the depot formulation of the luteinizing hormone-releasing hormone ( LHRH ) agonist goserelin ( Zoladex , ICI Pharma , Wilmington , Delaware ) , 3.6 mg sc/28 d , with orchiectomy and with diethylstilbestrol ( DES ) , 1 mg tid , in the treatment of advanced prostatic cancer . In the Zoladex versus orchiectomy trial , there was no significant difference between the treatment groups with regard to subjective and objective responses ( British Prostate Group criteria ) , endocrine responses , clinical effects and side effects , time to treatment failure and death , or survival after similar median follow-up periods . It was concluded that depot Zoladex had behaved as a truly medical alternative to orchiectomy . In the Zoladex versus DES trial , subjective and objective responses ( British Prostate Group and National Prostatic Cancer Project criteria ) , response duration and survival were similar . However , there was a more rapid response to treatment in the depot Zoladex group . Side effects from Zoladex such as flare symptoms during the initial stages of treatment required no discontinuation of therapy ; in contrast , 15 percent of patients receiving DES required cessation of therapy during the first three months because of side effects . It was concluded that depot Zoladex was superior to DES in its attainment of an early objective response and in its absence of side effects , and that Zoladex was comparable with DES in terms of response rates and survival The aim of this study was to predict cardiovascular complications in patients with prostatic cancer treated with oestrogen .  A r and omised prospect i ve study of oestrogen therapy versus orchiectomy was performed . Patients with pre-existing cardiovascular morbidity were excluded ( 16 % ) . Prior to the initiation of therapy , patients were subjected to exercise stress tests , physiological evaluation of peripheral circulation , blood volume estimation , chest X-ray , blood test , including hormones , lipoproteins , and antithrombin III , and a physical examination and history by a cardiologist . The oestrogen treatment and the orchiectomy group did not differ with regard to these pretreatment variables ; 25 % of the patients given oestrogen therapy had cardiovascular complications during the initial treatment year compared with none in the orchiectomy group . Three statistical discriminating techniques were employed and they allowed us to identify 2 strong discriminating variables for cardiovascular complications if oestrogen therapy is instituted in patients with prostatic cancer but without overt clinical cardiovascular disease . These 2 discriminators were luteinising hormone ( LH ) and ST-segment depression 
    Output:
    
Although trials showed DES as similarly effective to another forms of ADT , evidence s about cardiovascular toxicity in out of date high doses have discouraged its use .
In doses of 1 mg , DES has been used as secondary line PCa treatment with safety .
Conclusions DES might be similarly effective to other forms of ADT on advanced PCa patients , with potential important roles .
Intriguingly , the burden of severe cardiovascular toxicity is mainly related to old-fashioned doses of 5.0 and 3.0 mg .