***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: CONTEXT The effects of continuous combined hormone therapy on gynecologic cancers have not been investigated previously in a r and omized trial setting . OBJECTIVE To determine the possible associations of estrogen plus progestin on gynecologic cancers and related diagnostic procedures . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 16 608 postmenopausal women , who had not had a hysterectomy at baseline and who had been recruited from 40 US clinical centers between September 1993 and October 1998 ( average follow-up , 5.6 years ) . INTERVENTION One tablet per day containing 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOME MEASURE Incident invasive cancer of the ovary and endometrium . RESULTS In 5.6 years of follow-up , there were 32 cases of invasive ovarian cancer , 58 cases of endometrial cancer , 1 case of nonendometrial uterine cancer , 13 cases of cervical cancer , and 7 cases of other gynecologic cancers . The hazard ratio ( HR ) for invasive ovarian cancer in women assigned to estrogen plus progestin compared with placebo was 1.58 ( 95 % confidence interval [ CI ] , 0.77 - 3.24 ) . The HR for endometrial cancer was 0.81 ( 95 % CI , 0.48 - 1.36 ) . No appreciable differences were found in the distributions of tumor histology , stage , or grade for either cancer site . The incidence of other gynecologic cancers was low and did not differ by r and omization assignment . More women taking estrogen plus progestin required endometrial biopsies ( 33 % vs 6 % ; P<.001 ) . CONCLUSIONS This r and omized trial suggests that continuous combined estrogen plus progestin therapy may increase the risk of ovarian cancer while producing endometrial cancer rates similar to placebo . The increased burden of endometrial biopsies required to assess vaginal bleeding further limits the acceptability of this regimen . These data provide additional support for caution in the use of continuous combined hormones CONTEXT The timing of initiation of hormone therapy may influence its effect on  cardiovascular disease .  OBJECTIVE To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began . DESIGN , SETTING , AND PARTICIPANTS Secondary analysis of the Women 's Health Initiative ( WHI ) r and omized controlled trials of hormone therapy in which 10,739 postmenopausal women who had undergone a hysterectomy were r and omized to conjugated equine estrogens ( CEE ) or placebo and  16,608 postmenopausal women who had not had a hysterectomy  were r and omized to CEE plus medroxyprogesterone acetate ( CEE + MPA ) or placebo .  Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998 . MAIN OUTCOME MEASURES Statistical test for trend of the effect of hormone therapy on coronary heart disease ( CHD ) and stroke across categories of age and years since menopause in the combined trials . RESULTS In the combined trials , there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 370 [ corrected ] cases of CHD and 239 cases of stroke in the placebo group . For women with less than 10 years since menopause began , the hazard ratio ( HR ) for CHD was 0.76 ( 95 % confidence interval [ CI ] , 0.50 - 1.16 ) ; 10 to 19 years , 1.10 ( 95 % CI , 0.84 - 1.45 ) ; and 20 or more years , 1.28 ( 95 % CI , 1.03 - 1.58 ) ( P for trend = .02 ) . The estimated absolute excess risk for CHD for women within 10 years of menopause was -6 per 10,000 person-years ; for women 10 to 19 years since menopause began , 4 per 10,000 person-years ; and for women 20 or more years from menopause onset , 17 per 10,000 person-years . For the age group of 50 to 59 years , the HR for CHD was 0.93 ( 95 % CI , 0.65 - 1.33 ) and the absolute excess risk was -2 per 10,000 person-years ; 60 to 69 years , 0.98 ( 95 % CI , 0.79 - 1.21 ) and -1 per 10,000 person-years ; and 70 to 79 years , 1.26 ( 95 % CI , 1.00 - 1.59 ) and 19 per 10,000 person-years ( P for trend = .16 ) . Hormone therapy increased the risk of stroke ( HR , 1.32 ; 95 % CI , 1.12 - 1.56 ) . Risk did not vary significantly by age or time since menopause . There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women ( HR of 0.70 for 50 - 59 years ; 1.05 for 60 - 69 years , and 1.14 for 70 - 79 years ; P for trend = .06 ) . CONCLUSIONS Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause , but this trend test did not meet our criterion for statistical significance . A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause . These data should be considered in regard to the short-term treatment of menopausal symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611 Background The grading of recommendation , assessment , development and evaluation ( GRADE ) approach is widely implemented in health technology assessment and guideline development organisations throughout the world . GRADE provides a transparent approach to reaching judgements about the quality of evidence on the effects of a health care intervention , but is complex and therefore challenging to apply in a consistent manner . Methods We developed a checklist to guide the research er to extract the data required to make a GRADE assessment . We applied the checklist to 29 meta-analyses of r and omised controlled trials on the effectiveness of health care interventions . Two review ers used the checklist for each paper and used these data to rate the quality of evidence for a particular outcome . Results For most ( 70 % ) checklist items , there was good agreement between review ers . The main problems were for items relating to indirectness where considerable judgement is required . Conclusions There was consistent agreement between review ers on most items in the checklist . The use of this checklist may be an aid to improving the consistency and reproducibility of GRADE assessment s , particularly for inexperienced users or in rapid review s without the re sources to conduct assessment s by two research ers independently CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women .  All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD OBJECTIVES Early age at natural menopause has been associated with increased all-cause mortality in several studies , although the literature is not consistent . This relation has not been examined among African American women . STUDY DESIGN Data were from the Black Women 's Health Study , a follow-up study of African-American women enrolled in 1995 . Among 11,212 women who were naturally menopausal at entry to the study or during follow-up through 2008 , we assessed the relation of age at natural menopause to all-cause and cause-specific mortality . At baseline and biennially , participants reported on reproductive and medical history , including gynecologic surgeries and exogenous hormone use .  Mortality data were obtained from the National Death Index . Multivariable Cox proportional hazard models were used to estimate mortality rate ratios ( MRR ) and 95 % confidence intervals ( CI ) for categories of age at menopause . RESULTS Of 692 deaths identified during 91,829 person years of follow-up , 261 were due to cancer , 199 to cardiovascular diseases and 232 to other causes . Natural menopause before age 40 was associated with increased all-cause mortality ( MRR=1.34 , 95 % CI 0.96 - 1.84 , relative to menopause at 50 - 54 years ; P-trend=0.04 ) and with the subcategories of death considered - cancer , cardiovascular disease , and all other causes . The associations were present among never and ever users of postmenopausal female hormones and among never and ever smokers . CONCLUSIONS In this large prospect i ve cohort of African-American women , natural menopause before age 40 was associated with a higher rate of all-cause and cause-specific mortality . These findings provide support for the theory that natural menopause before age 4 
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Hormone replacement therapy may slightly improve overall survival in women who have undergone surgical treatment for EOC , but the certainty of the evidence is low .
There may be little or no effect of HRT use on progression-free survival .
Future well- design ed RCTs are required as this is an important area to women experiencing  menopausal symptoms following surgical treatment for ovarian cancer , especially as doctors are often reluctant to prescribe HRT in this scenario .
The evidence in this review is too limited to support or refute that HRT is very harmful in this population