***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 Reliable estimates of cancer risk are critical for guiding management of BRCA1 and BRCA2 mutation carriers . The aims of this study were to derive penetrance estimates for breast cancer , ovarian cancer , and contralateral breast cancer in a prospect i ve series of mutation carriers and to assess how these risks are modified by common breast cancer susceptibility alleles . METHODS Prospect i ve cancer risks were estimated using a cohort of 978 BRCA1 and 909 BRCA2 carriers from the United Kingdom . Nine hundred eighty-eight women had no breast or ovarian cancer diagnosis at baseline , 1509 women were unaffected by ovarian cancer , and 651 had been diagnosed with unilateral breast cancer .  Cumulative risks were obtained using Kaplan-Meier estimates . Associations between cancer risk and covariables of interest were evaluated using Cox regression . All statistical tests were two-sided . RESULTS The average cumulative risks by age 70 years for BRCA1 carriers were estimated to be 60 % ( 95 % confidence interval [ CI ] = 44 % to 75 % ) for breast cancer , 59 % ( 95 % CI = 43 % to 76 % ) for ovarian cancer , and 83 % ( 95 % CI = 69 % to 94 % ) for contralateral breast cancer . For BRCA2 carriers , the corresponding risks were 55 % ( 95 % CI = 41 % to 70 % ) for breast cancer , 16.5 % ( 95 % CI = 7.5 % to 34 % ) for ovarian cancer , and 62 % ( 95 % CI = 44 % to 79.5 % ) for contralateral breast cancer . BRCA2 carriers in the highest tertile of risk , defined by the joint genotype distribution of seven single nucleotide polymorphisms associated with breast cancer risk , were at statistically significantly higher risk of developing breast cancer than those in the lowest tertile ( hazard ratio = 4.1 , 95 % CI = 1.2 to 14.5 ; P = .02 ) . CONCLUSIONS Prospect i ve risk estimates confirm that BRCA1 and BRCA2 carriers are at high risk of developing breast , ovarian , and contralateral breast cancer . Our results confirm findings from retrospective studies that common breast cancer susceptibility alleles in combination are predictive of breast cancer risk for BRCA2 carriers Objective : To investigate levels of  follicle stimulating hormone ( FSH )  , as a measure of ovarian function and menopausal symptoms prior to and following  hysterectomy in women under the age of 45 years . Design : This was a prospect i ve controlled study . Sample : A total of 56 hysterectomy patients and 34 controls , up to the age of 42 years , were recruited . Methods : Women undergoing hysterectomy were recruited prior to their operation and were matched , where possible , with controls for age , parity and smoking . Five blood sample s were taken over 2 years , two before the operation ( or at a 1-month interval in the control group ) and then at 6 months , 1 year and 2 years . Question naires were completed at each sampling to assess symptoms associated with reduced estrogen secretion . Results : No significant differences in FSH levels between patients and controls were found . Modest differences in FSH levels between different time-points were identified ( p = 0.03 ) , but this disappeared if age and smoking were included as covariates . For the question naire data , there were no significant differences between the two groups on the somatic and vasomotor scales , but for psychological symptoms the patients scored significantly higher than the controls ( p = 0.007 ) , particularly at the pre-operation time-point . Conclusion : The study found no evidence of compromise of ovarian function , as reflected in FSH levels , within 2 years of hysterectomy . Psychological symptoms were higher in women undergoing hysterectomy both before and after the operation OBJECTIVE To evaluate the subsequent pelvic sonographic characteristics as well as the clinical outcome following hysterectomy with and without oophorectomy . STUDY DESIGN A prospect i ve study of sonographic evaluation of 164 women , aged 29 - 72 years , with a history of hysterectomy was performed . Ninety-one patients underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and 73 women had either hysterectomy ( abdominal or vaginal ) only or hysterectomy with unilateral salpingo-oophorectomy .  RESULTS The mean time interval between surgery and sonographic evaluation was 4.3 years ( range , 1 - 25 years ) . Out of the 73 women with left ovaries , 37 ( 50.7 % ) were found to have pelvic lesions and four women underwent re-operations following these findings . The histologic finding were cystadenoma , hydrosalpinx with periovarian adhesions and two paraovarian cysts . In comparison , only five of the 91 women ( 5.5 % ) following bilateral salpingo-oophorectomy were found to have pelvic lesions ( P < 0.0005 ) . None of the women with prophylactic oophorectomy were operated upon following these findings . CONCLUSIONS In comparison to patients after total hysterectomy and bilateral salpingo-oophorectomy , women with prior hysterectomy and ovarian preservation are prone to subsequent pelvic lesions . They need to be closely followed with clinical , laboratory and sonographic means , and may undergo reoperations in order to rule out the possibility of neoplasia Reporting harms may cause more trouble and discredit than the fame and glory associated with successful reporting of benefits ( 1 ) . The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement , a checklist ( Table 1 ) flow diagram first published in 1996 and revised 5 years later ( 2 , 3 ) , is an effort to st and ardize , and thereby improve , published reports of r and omized , controlled trials ( RCTs ) . One of the additions to the 2001 revision was an item about reporting adverse events . This single item did not do full justice to the importance of harms-related issues . The CONSORT Group met in September 2001 to discuss how to correct this deficiency . We aim ed to provide evidence -based guidance on the reporting of harms in RCTs . First , we search ed MEDLINE , EMBASE , Web of Science , and the Cochrane Library using a wide array of terms related to harms and identified pertinent evidence . We also communicated with experts and review ed bibliographies of identified articles to find additional studies . At a meeting in Montebello , Quebec , Canada , in May 2003 , CONSORT Group members , including several journal editors and additional experts in related fields , held a structured discussion of recommendations about reporting of harms-related issues in RCTs . The discussion s led to a written document that we circulated among the team members for comment . The present manuscript describes our recommendations on the appropriate reporting of harms in RCTs . Table 1 . Original CONSORT Checklist The terminology of harms-related issues in RCTs is confusing and often misleading or misused ( see Glossary ) ( 4 , 5 ) . Safety is a reassuring term that may obscure the real and potentially major harms that drugs and other interventions may cause . We encourage authors to use the term harms instead of safety . In addition to misused terminology , reporting of harms in RCTs has received less attention than reporting of efficacy and effectiveness and is often inadequate ( 6 - 14 ) . In short , both scientific evidence and ethical necessity call for action to improve the quality of reporting of harms in RCTs ( 15 , 16 ) . Here , we present a set of recommendations and accompanying explanations for the proper reporting of harms in RCTs . These recommendations should complement the existing CONSORT statement ( Table 2 ) . Examples are presented on the Annals and CONSORT ( www.consort-statement.org ) Web sites . Table 2 . Checklist of Items To Include When Reporting Harms in R and omized , Controlled Trials Recommendations Title and Abstract Recommendation 1 . If the study collected data on harms and benefits , the title or abstract should so state . The title should mention harms if the study of harms was a key trial objective . Many phase I and phase II trials , some phase II/III trials , and most phase IV trials ( 17 , 18 ) target harms as primary outcomes . Yet , the title and abstract seldom contain the word harm . Among 375143 entries in the Cochrane Central Register of Controlled Trials ( Cochrane Library , issue 3 , 2003 ) , search ing titles with the search terms harm or harms yielded 337 references ( compared with 55374 for efficacy and 23415 for safety ) . Of the 337 , excluding several irrelevant articles on self-harm or harm reduction , only 3 trial reports and 2 abstract s contained the word harm in their titles . Authors should present information on harms in the abstract . If no important harms occurred , authors should so state . Explicit reference to the reporting of adverse events in the title or abstract is also important for appropriate data base indexing and information retrieval ( 19 ) . Introduction Background Recommendation 2 . If the trial addresses both harms and benefits , the introduction should so state . The introduction states the scientific background and rationale of an RCT . This requires a balanced presentation whereby the possible benefits of the intervention under investigation are outlined along with the possible harms associated with the treatment . R and omized , controlled trials that focus primarily on harms should clearly state this interest when describing the study objectives in the Introduction and in defining these objectives in the Methods . Methods Outcomes Recommendation 3 . List addressed adverse events with definitions for each ( with attention , when relevant , to grading , expected vs. unexpected events , reference to st and ardized and vali date d definitions , and description of new definitions ) . The Methods section should succinctly define the recorded adverse events ( clinical and laboratory ) . Authors should clarify whether the reported adverse events encompass all the recorded adverse events or a selected sample . They should explain how , why , and who selected adverse events for reporting . In trials that do not mention harms-related data , the Methods section should briefly explain the reason for the omission ( for example , the design did not include the collection of any information on harms ) . Authors should also be explicit about separately reporting anticipated and unexpected adverse events . Expectation may influence the incidence of reported or ascertained adverse events . Making participants aware in the consent form of the possibility of a specific adverse event ( priming ) may increase the reporting rate of the event ( 20 ) . Another example of priming is the finding that the rates of withdrawals due to adverse events and the rates of specific adverse events were significantly higher in trials of aspirin , diclofenac , or indomethacin with comparator drugs compared with placebo-controlled trials ( 21 ) . Presumably , participants were more eager to come forth and report an adverse event or to withdraw from treatment when they knew they could not be receiving inactive placebo . Authors should report whether they used st and ardized and vali date d measurement instruments for adverse events . Several medical fields have developed st and ardized scales ( 22 - 32 ) . Use of nonvali date d scales is common . The source document for well-established definitions and scales should be referenced . New definitions for adverse events should be explicit and clear . Authors should describe how they developed and vali date d new scales . For interventions that target healthy individuals ( for example , many preventive interventions ) , any harm , however minor , may be important to capture and report because the balance of harms and benefits may easily lean toward harms in a low-risk population . For other population s and for interventions that improve major outcomes ( for example , survival ) , severe and life-threatening adverse events may be the only ones that are important in the balance of benefits and harms . Recommendation 4 . Clarify how harms-related information was collected ( mode of data collection , timing , attribution methods , intensity of ascertainment , and harms-related monitoring and stopping rules , if pertinent ) . It is important to describe the question naires , interviews , and tests used to collect information on harms , as well as their timing during follow-up . Passive surveillance of harms leads to fewer recorded adverse events than active surveillance ( 4 ) . Open-ended questions may yield different information , both quantitatively and qualitatively , than structured question naires ( 33 ) . Studies of nonsteroidal , anti-inflammatory drugs ( NSAIDs ) exemplify how data collection methods can affect the detection and reporting of harms . When selective NSAIDs with fewer gastrointestinal adverse events became available , trials reported more than 10 times as many ulcers when comparing these drugs with older NSAIDs as when older NSAIDs were compared with placebo . In the newer trials , more ulcers were detected because participants had regular endoscopy , and the case definition of ulcers was more sensitive ( 34 ) . Authors should specify the time frame of surveillance for adverse events . Some investigators stop recording adverse events at the end of the intervention period or a certain number of days afterward ( for example , 30 days after discontinuation of drug therapy ) and miss events with long latency ( 35 ) . Surgical trials often capture only the adverse events that occur intraoperatively . Several important surgical complications are likely to occur later . Finally , in crossover trials , delayed events might occur while the patient is taking a subsequent assigned treatment . Attribution is the process of deciding whether an adverse event is related to the intervention . Whenever authors filter events through an attribution process , they should state who makes the attribution ( investigators , participants , sponsors , or combinations ) , whether the process is blinded to assigned treatment , and what definitions of adverse events they use ( 4 ) . Discontinuations and withdrawals due to adverse events are especially important because they reflect the ultimate decision of the participant and /or physician to discontinue treatment . Although treatment may occasionally be discontinued for mild or moderate adverse events , attributing discontinuation to a specific reason ( to toxicity , lack 
    Output:
    
Although no evidence is available from RCTs , there is growing evidence from observational studies that surgical menopause may impact negatively on cardiovascular health and all cause mortality