***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: PURPOSE In this study , we sought to 1 ) describe elements of the financial and quality -of-life burden of dysfunctional uterine bleeding ( DUB ) from the perspective of women who agreed to obtain surgical treatment ; 2 ) explore associations between DUB symptom characteristics and the financial and quality -of-life burden ; 3 ) estimate the annual dollar value of the financial burden ; and 4 ) estimate the most that could be spent on surgery to eliminate DUB symptoms for which medical treatment has been unsuccessful that would result in a $ 50,000/ quality -adjusted life-year incremental cost-effectiveness ratio . METHODS We collected baseline data on DUB symptoms and aspects of the financial and quality -of-life burden for 237 women agreeing to surgery for DUB in a r and omized trial comparing hysterectomy with endometrial ablation . Measures included out-of-pocket pharmaceutical expenditures , excess expenditures on pads or tampons , the value of time missed from paid work and home management activities , and health utility . We used chi2 and t tests to assess the statistical significance of associations between DUB characteristics and the financial and quality -of-life burden . The annual financial burden was estimated . RESULTS Pelvic pain and cramps were associated with activity limitations and tiredness was associated with a lower health utility . Excess pharmaceutical and pad and tampon costs were $ 333 per patient per year ( 95 % confidence interval [ CI ] , $ 263-$403 ) . Excess paid work and home management loss costs were $ 2,291 per patient per year ( 95 % CI , $ 1847-$2752 ) . Effective surgical treatment costing $ 40,000 would be cost-effective compared with unsuccessful medical treatment . CONCLUSION The financial and quality -of-life effects of DUB represent a substantial burden 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 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 Background In r and omised trials , rather than comparing r and omised groups directly some research ers carry out a significance test comparing a baseline with a final measurement separately in each group . Methods We give several examples where this has been done . We use simulation to demonstrate that the procedure is invalid and also show this algebraically . Results This approach is biased and invalid , producing conclusions which are , potentially , highly misleading . The actual alpha level of this procedure can be as high as 0.50 for two groups and 0.75 for three . Conclusions R and omised groups should be compared directly by two- sample methods and separate tests against baseline are highly misleading To compare the effect of naproxen on idiopathic and myomainduced menorrhagia , 11 women with myomatosus uterus and 14 women with idiopathic menorrhagia ( menstrual blood loss greater than 80 mL ) were treated in a doubleblind trial with placebo or naproxen during four consecutive menstruations . Placebo had no effect on menstrual blood loss .  Naproxen ( 500 to 1000 mg daily for five days ) reduced menstrual blood loss by 35.7 % in women with idiopathic menorrhagia , but it had no consistent effect on myomainduced menorrhagia . No side effects occurred during naproxen use . Thus , naproxen may prove a suitable treatment for idiopathic but not for myoma-induced menorrhagia A well controlled double blind prospect i ve trial was undertaken to determine the efficacy of mefenamic acid in the treatment of menorrhagia . Eighty patients who had unexplained cyclical menorrhagia with secretory endometrium received mefenamic acid orally in a dose of 500 mg 8 hourly or a placebo tablet thrice daily starting from day-one of the cycle for 5 days or till cessation of menses . Mefenamic acid administration caused a statistically significant reduction in the number of days of bleeding from 9.7 + /- 3.1 days before treatment to 4.1 + /- 0.6 days after treatment . It also brought about significant reduction in the amount of bleeding in terms of number of pads used per day , that is from 15.2 + /- 3.1 before treatment to 6.5 + /- 0.02 after treatment . Eighty-six percent patients in the treatment group had control of menorrhagia with the drug compared to 20 % in the control group without drugs and this difference was statistically significant . Mefenamic acid proved to be a potent and efficacious agent in the control of unexplained menorrhagia Summary : A series of 45 ovulatory women with a complaint of menorrhagia were r and omized into 3 treatment groups , before receiving therapy with mefenamic acid in 2 cycles and 1 of 3 other agents in 2 cycles : naproxen ( group 1 ; n = 14 ) , a low dose monophasic combined oral contraceptive ( group 2 ; n = 12 ) or low dose danazol ( group 3 ; n = 12 ) . Menstrual blood loss was measured in 2–4 control cycles and during therapy . Mefenamic acid  reduced measured blood loss by 20 % ; 38 % ; and 39 % in groups 1–3 respectively . Naproxen  reduced blood loss by 12 % ; the oral contraceptive by 43 % ; and danazol by 49 % . There was no statistically significant difference in blood loss reduction ( mean of 2 cycles ) between any of the treatments , although women on danazol experienced a dramatic and highly significant further reduction in blood loss after the first treatment cycle ( p < 0.003 ) . These were all effective therapies in a majority of women , but some ‘ non‐responders ’ were seen in each group . The ‘ non‐responders ’ had a significantly lower pretreatment blood loss than responders . Several women in group 1 showed anomalous responses to prostagl and in inhibitors with consistent and substantial exacerbation of menorrhagia during therapy . A number of reasonable therapies exist for the medical treatment of menorrhagia , but because none is suitable for everyone management needs to be individualized for each patient This paper review s the various theories offered to explain excessive menstrual blood losses whether these are of primary origin or induced by IUD . An increased concentration of prostagl and ins in endometrial tissue at the onset of menstruation may contribute to heavy menstrual bleeding . The mechanism of action is not clear , but prostagl and ins may affect the stability of lysosomes which in turn lead to increased release of various proteinases . These in turn may disturb the hemostatic mechanism of the endometrium . Prostagl and ins may also affect platelet aggregation and /or various coagulation factors and cause vasodilation - all mechanisms may theoretically alter the hemostasis of the endometrium . Treatment of menorrhagia with a prostagl and in synthetase inhibitor , naproxen , result ed in a significant reduction in menstrual blood loss in women with primary menorrhagia as well as with IUD-induced  excessive menstrual blood loss . The reduction amounted to about 30 % , which is lower than the reduction obtained by treatment with antifibrinolytic agents or oral contraceptives A double-blind , placebo-controlled crossover trial was undertaken to determine the efficacy of meclofenamate sodium in the treatment of menorrhagia . Twenty-nine patients who had a baseline menstrual blood loss greater than 60 ml received 2 months ' each of  meclofenamate sodium , 100 mg by mouth , three times a day , or a placebo . The mean menstrual blood loss was reduced from 141.6 + /- 15.9 ml at baseline to 69.0 + /- 6.3 ml during treatment cycles but remained increased during placebo cycles ( 135.6 + /- 11.3 ml ) . The symptoms of dysmenorrhea , backache , and headache were significantly reduced only during active drug periods . The number of days of flow and pads or tampons used was also reduced during drug cycles but not during placebo cycles . Overall , 26 of the 29 patients evaluated had a reduction in menstrual blood loss with the use of meclofenamate sodium . It appears that many women with unexplained menorrhagia may benefit from this treatment 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 Sixty-nine patients with a convincing history of menorrhagia completed a 4-cycle double-blind r and omized placebo- controlled crossover trial of mefenamic acid taken during menstruation . Only 30 of these patients demonstrated objective menorrhagia with a measured menstrual loss greater than 80 ml during the placebo cycles , but the remainder reported passing clots and /or using 2 pads at a time . Fourteen of these women ( 20 % ) had a loss of less than 35 ml while taking placebos . This raises serious questions about the establishment of menorrhagia based on history alone . Overall , there was a mean reduction of 28.1 % in menstrual blood loss between placebo and mefenamic acid cycles ( P<.001 ) . The greatest reduction recorded was 80 % , and most of the large percentage reductions were seen in patients with high loss during placebo cycles . Significant reductions in blood loss ( P<.001 ) were seen in patients with ovulatory dysfunctional uterine bleeding and menorrhagia that developed after tubal interruption . There was also an indication based on small sample sizes that mefenamic acid reduced blood loss in women with anovulatory dysfunctional uterine bleeding , fibroids , intrauterine devices , and von Willebr and disease . No reduction was seen during the mefenamic acid cycle in the group with a loss of less than 35 
    Output:
    
MAIN RESULTS As a group , NSAIDs were more effective than placebo at reducing HMB but less effective than either  tranexamic acid , danazol or the levonorgestrel-releasing intrauterine system ( LNG IUS ) .
Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs but this did not appear to affect the acceptability of treatment .
There was no evidence of a difference between the individual NSAIDs ( naproxen and mefenamic acid ) in reducing HMB .
AUTHORS ' CONCLUSIONS NSAIDs  reduce HMB when compared with placebo but are less effective than tranexamic acid , danazol or LNG IUS .
However , adverse events are more severe with danazol therapy .
In the limited number of small studies suitable for evaluation , no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral luteal progestogen , ethamsylate , OCC or another type of intrauterine system , Progestasert