***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: Sixty-nine women with a convincing complaint of menorrhagia took part in a double-blind treatment trial . Menstrual blood loss was measured and the subject 's own perception was carefully recorded . Only 38 % had objective menorrhagia with a measured loss greater than 80 ml although 59 % would qualify with an upper limit of normal of 60 ml . Overall the measured loss in the " heaviest " periods ( 69.6 + /- 7.3 ml ; mean + /- SEM ) were significantly greater than that of the " lightest " periods ( 42.7 + /- 4.7 ml ; p less than 0.001 ) , but there were many major errors in perception by individuals . Perceived daily blood loss volume on a 4-point rating scale gave the following group means and ranges : spotting , 2.5 ml ( 0.1 to 15.5 ) ; light , 5.7 ml ( 0.1 to 63.1 ) ; moderate , 16.1 ml ( 0.5 to 108.6 ) ; very heavy , 22.0 ml ( 1.4 to 215.8 ) ; very wide individual ranges of assessment are illustrated . As a whole the group was also able to distinguish between a day-to-day volume increase or decrease , but again there were many major errors . Some subjects who experienced a reduction in measured blood loss from one day to the next actually perceived this as a large increase . Menstrual pain and duration of bleeding were not found to influence perception of blood loss volume , whereas younger subjects ( 26 and under ) were significantly more likely than older women ( 37 and over ) to regard a moderate loss as very heavy . There was no significant correlation between the number of pads/tampons used and the measured menstrual loss , and some individuals showed extreme variations between blood loss and pad usage . This study suggests that the only reliable assessment of menstrual blood loss volume and changes in volume in women complaining of menorrhagia is obtained by objective measurement of blood loss by a technique such as alkaline hematin extraction OBJECTIVE To investigate the management of menorrhagia in primary care and its impact on referral and hysterectomy rates . DESIGN Prospect i ve observational study . SETTING 11 general practice s from the Somerset Morbidity Project . SUBJECTS 885 women consulting their general practitioner with menorrhagia over four years . MAIN OUTCOME MEASURES Proportions of these women investigated and treated with drugs in primary care , referred to a gynaecologist and undergoing operative procedures . The relation between investigation and prescribing in primary care and referral to and surgery in secondary care . RESULTS Less than half of women had a vaginal examination ( 42 % , 95 % CI 39 % to 45 % ) , or a full blood count ( 39 % , 95 % CI 36 % to 43 % ) . Almost a quarter of women , 23 % ( 95 % CI 20 % to 26 % ) , received  no drugs  and 37 % ( 95 % CI 34 % to 40 % ) received  norethisterone .  Over a third , 38 % ( 95 % CI 34 % to 40 % ) , of women were referred , and once referred 43 % ( 95 % CI 38 % to 48 % ) of women were operated on . Women referred to a gynaecologist were significantly more likely to have received  tranexamic acid and /or mefenamic acid  in primary care ( chi(2)=16.4 , df=1 , p<0.001 ) . There were substantial between practice variations in management , for example in prescribing of  tranexamic acid and /or mefenamic acid  ( range 16 % to 72 % ) and referral to gynaecology ( range 24 % to 52 % ) . There was a significant association between high referral and high operative rates ( Spearman 's correlation coefficient=0.86 , p=0.001 ) . CONCLUSIONS Substantial differences in management exist between practice s when investigating and prescribing for menorrhagia in primary care . Rates of prescribing of effective medical treatment remain low . The decision to refer a woman impacts markedly on her chances of subsequently being operated on . Effective management in primary care may not reduce referral or hysterectomy rates 44 women with heavy menstrual bleeding participated in a six months r and omised , double blind , cross over clinical trial . The objective was to use simple methods to study whether treatment of menorrhagia with tranexamic acid has an effect that can be detected by the women themselves . The effect was evaluated by means of diaries and a visual analog scale . The bleeding during each period of treatment was compared with the bleeding during untreated periods . Bleeding during the different periods of treatment was also compared directly . The results indicate that tranexamic acid was more effective than placebo . This difference was not disclosed , however , in the laboratory data . After the study , 75 % of the women wished to continue treatment with tranexamic acid 22 patients complaining of primary menorrhagia or menorrhagia associated with an intrauterine device ( I.U.C.D. ) were studied in a double blind trial with crossover of ethamsylate and placebo . Acutal menstrual blood-losses were calculated from the iron content of used sanitary material during one pre-trail menstrual period and four trial menstrual periods , during which patients received ethamsylate ( " Dicynene " ) treatment during two menstrual cycles and placebo during two cycles . During ethamsylate treatment the mean menstrual blood-loss was reduced by 50 % in patients with primary menorrhagia and by 19 % in patients with an I.U.C.D. This difference between the two groups is probably accounted for by the differing values of initial blood-loss which was significantly higher in the group with primary menorrhagia . Tampon usage and the duration of bleeding were not significantly altered by ethamsylate treatment . Reported side-effects , which were not serious , were equally common during ethamsylate and placebo treatment Abstract Objective : To determine whether an educational package could influence the management of menorrhagia  , increase the appropriateness of choice of non-hormonal treatment , and reduce referral rates from primary to secondary care . Design : R and omised controlled trial . Setting : General practice s in East Anglia . Subjects : 100 practice s ( 348 doctors ) in primary care were recruited and r and omised to intervention ( 54 ) and control ( 46 ) . Interventions : An educational package based on principles of “ academic detailing ” with independent academics was given in small practice based interactive groups with a visual presentation , a printed evidence based summary , a graphic management flow chart , and a follow up meeting at 6 months . Outcome measures : All practice s recorded consultation details , treatments offered , and outcomes for women with regular heavy menstrual loss ( menorrhagia )  over 1 year . Results : 1001 consultation data sheets for menorrhagia were returned . There were significantly fewer referrals ( 20 % v 29 % ; odds ratio 0.64 ; 95 % confidence interval 0.41 to 0.99 ) and a significantly higher use of  tranexamic acid  ( odds ratio 2.38 ; 1.61 to 3.49 ) in the intervention group but no overall difference in  norethisterone treatment compared with controls . There were more referrals when tranexamic acid was given with norethisterone than when it was given alone . Those practice s reporting fewer than 10 cases showed the highest increase in prescribing of tranexamic acid .  Conclusions : The educational package positively influenced referral for menorrhagia and treatment with appropriate non-hormonal drugs Abstract Objective : To compare the efficacy and acceptability of ethamsylate , mefenamic acid , and tranexamic acid for treating menorrhagia .  Design : R and omised controlled trial . Setting : A university department of obstetrics and gynaecology . Subjects : 76 women with dysfunctional uterine bleeding . Interventions : Treatment for five days from day 1 of menses during three consecutive menstrual periods . 27 patients were r and omised to take ethamsylate 500 mg six hourly , 23 patients to take mefenamic acid 500 mg eight hourly , and 26 patients to take tranexamic acid 1 g six hourly . Main outcome measures : Menstrual loss measured by the alkaline haematin method in three control menstrual periods and three menstrual periods during treatment ; duration of bleeding ; patient 's estimation of blood loss ; sanitary towel usage ; the occurrence of dysmenorrhoea ; and unwanted events . Results : Ethamsylate did not reduce mean menstrual blood loss whereas mefenamic acid reduced blood loss by 20 % ( mean blood loss 186 ml before treatment , 148 ml during treatment ) and tranexamic acid reduced blood loss by 54 % ( mean blood loss 164 ml before treatment , 75 ml during treatment ) . Sanitary towel usage was significantly reduced in patients treated with mefenamic acid and tranexamic acid . Conclusions : Tranexamic acid given during menstruation is a safe and highly effective treatment for excessive bleeding .  Patients with dysfunctional uterine bleeding should be offered medical treatment with tranexamic acid before a decision is made about surgery . Key messages In any year around 5 % of women aged 30 - 49 years visit their general practitioners with menor-rhagia Every year in the United Kingdom around 45 000 hysterectomies and a further 10 000 endometrial ablations are performed for menorrhagia The commonest drug prescribed in the British Isles for menorrhagia ( norethisterone ) has little or no effect in reducing menstrual bleeding  Tranexamic acid ( an antifibrinolytic ) 1 g six to eight hourly reduces menstrual blood loss by over half and should be offered to women with dysfunctional bleeding before a decision is made about Objective To compare the effect of Kabi 2161 ( a prodrug of tranexamic acid ) and placebo on the reduction of menstrual blood loss in women suffering from idiopathic menorrhagia and to evaluate tolerance and effectiveness in a two‐dose regimen In a double-blind trial tranexamic acid ( Cyclokapron ) 1 g. four times a day for the first four days of menstruation , significantly decreased menstrual blood loss in women with menorrhagia for which no organic cause had been found . No difference in side-effects was noted between the active and placebo treatment Objective To compare the efficacy and safety of tranexamic acid and norethisterone in the treatment of ovulatory menorrhagia A double-blind study of 65 women , aged 15 - 44 , was performed to determine if IUD use caused menorrhagia , and if so , if the menorrhagia could be prevented with Cyclocaprone . IUDs were inserted and the women were given pills to take during their menstrual periods . The pills were given at r and om ; 34 received Cyclocaprone and 31 received placebos . The volume of menstrual bleeding was measured during 1 menstrual period before the experiment , which served as a control , and for up to 4 menstrual periods after the insertion of the IUD and administration of the pills . The average volume of blood loss during the control period was about 35.75 ml ; during the following menstrual periods this increased 11.5 % among the women who had received Cyclocaprone and 82.7 % among those who had received placebos . The difference between the 2 groups was statistically significant ( p less than .001 ) . The majority of the women subjectively reported an increase in menstrual bleeding . The cyclocaprone users may have experienced an abnormally heavy bleeding during the menstrual period which caused them to report an increase in menstrual bleeding . In 13 of the menstrual cycles , blood loss exceeded 100 ml ; all of these cases were among women who had received placebos . The greatest increase in blood loss occurred in the menstrual cycle after the insertion of the IUD ; blood loss decreased in each subsequent menstrual period . 3 women who had received placebos had a hemoglobin concentration of less than 10.5 gm% . There were 5 cases of side effects among the women using Cyclocaprone and 2 among the women taking placebos . The results suggest that the IUD causes an activation of plasminogen in the endometrium early in the menstrual cycle ; cyclocaprone prevents this activation and the result ing menorrhagia abnormality in the giant platelet syndrome of Bernard-Soulierl 8 and also in von Willebr and 's disease , in which the abnormality is probably secondary to a deficiency or defect of a plasma protein related to factor VIIII-the factor VII I-related protein . ' 9 In our patient the defective ristocetin platelet aggregation seemed to be due to a plasma defect rather than to a primary platelet abnormality because aggregation was corrected partially or completely by the addition of normal plasma , cryoprecipitate , or a plasma fraction rich in factor VIII-related in protein . On the other h and the level of factor VIII-related protein in the infant 's plasma was normal , which suggested that either there was a functional abnormality of this protein or the patient lacked another substance necessary for ristocetin platelet aggregation . This did not seem to be fibrinogen , which , it has been suggested , is a co-factor for ristocetin aggregation,20 because the thrombin clotting times and fibrinogen levels were normal . The small volumes of blood obtainable from the infant precluded more detailed in-vitro studies , and it is possible that the vitamin E deficiency was directly responsible for the defective platelet ristocetin aggregation or that the deficiency result ed in the synthesis of an abnormal factor VIII-related protein . The normal bleeding time , the lack of family history , and the results of treatment , however , did not suggest that the infant was suffering from von Willebr and 's disease . The role of iron or folate deficiency in the pathogenesis of the patient 's haematological status is difficult to assess . It has been suggested that folate deficiency 
    Output:
    
AUTHORS ' CONCLUSIONS Antifibrinolytic treatment ( such as TXA ) appears effective for treating HMB compared to placebo , NSAIDs , oral luteal progestogens , ethamsylate , or herbal remedies , but may be less effective than LIUS .
There were too few data for most comparisons to determine whether antifibrinolytics were associated with increased risk of adverse events , and most studies did not specifically include thromboembolism as an outcome