***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: A comparison of cycle control , efficacy and tolerability of two oral contraceptive preparations containing 20 microg ethinylestradiol combined with either 100 microg levonorgestrel ( EE/LNG 20/100 ) or 500 microg norethisterone ( EE/NET 20/500 ) was conducted . These results were compared to a st and ard reference preparation , containing 30 microg ethinylestradiol combined with 150 microg levonorgestrel ( EE/LNG 30/150 ) . Efficacy data from 8,544 treatment cycles were obtained from 767 women .  Good cycle control and effective contraception was achieved with the two LNG preparations , however , the cycle control results were less favorable with EE/NET 20/500 . The cumulative incidence of women with at least one episode of intermenstrual bleeding from cycles 2 to 7 ( primary target variable ) was 43.9 % for EE/LNG 20/100 , 72.7 % for EE/NET 20/500 , and 15.7 % for the st and ard EE/LNG 30/150 . The difference between the 2 20 microg of EE preparations , which favored EE/LNG 20/100 , was statistically significant ( p = 0.001 ) . The overall spotting rates ( cycles 1 - 13 ) were 9.3 % for EE/LNG 20/100 , 21.7 % for EE/NET 20/500 , and 3.3 % for the st and ard EE/LNG 30/150 . Amenorrhea was reported in 7.1 % ( EE/LNG 20/100 ) , 20.6 % ( EE/NET 20/500 ) , and 0.9 % ( st and ard EE/LNG 30/150 ) , respectively . Intermenstrual bleeding episodes were shorter with EE/LNG 20/100 and EE/LNG 30/150 of the 13 treatment cycles . The study Pearl indices were 0.9 for EE/LNG 20/100 , 1.9 for EE/NET 20/500 , and 0.0 for EE/LNG 30/150 . All three treatments were well tolerated . However , tolerability was somewhat less favorable with EE/NET 20/500 . A total of 160 women prematurely discontinued the study for various reasons ( EE/LNG 20/100 : 7 % ; EE/NET 20/500 : 18 % ; EE/LNG 30/150 : 4 % ) . The overall adverse event incidence rate during the trial was low in all groups . Blood pressure remained largely unaffected . Thirteen serious adverse events were recorded for all treatment groups , all but one were assessed as not related to the treatments . There were no remarkable treatment related differences in mean body weight throughout the study and the laboratory values were largely unaffected in all three treatments groups In a parallel , multicenter study in Norway and Finl and involving a total of 196 healthy women ( mean age 22.4 years , range 18–30 ) , the effects on serum lipids and lipoproteins of two multiphasic oral contraceptives containing ethinyl estradiol ( EE ) but different progestins were examined . One formulation contained EE 35 μg and norethisterone ( NET ) 0.5 mg on days 1–7 and days 17–21 and elevated NET 1.0 mg during the midphase ( days 8–16 ) . The other formulation contained EE 30 μg on days 1–6 and days 12–21 and 40 μg on days 7–11 and phased levonorgestrel ( LGN ) : 50 μg ( days 1–6 ) , 75 μg ( days 7–11 ) and 125 μg ( days 12–21 ) . Both formulations induced significant elevation of total cholesterol ( 6.7 and 4.1 % ) , Apo B ( 8.1 and 7.0 % ) as well as HDL ( 6.4 and 3.7 % ) for the EE/NET and EE/LGN formulation respectively . Mean serum levels of triglycerides were significantly elevated ( 58 and 47 % ) . However , all mean serum lipid and lipoprotein values remained within the normal range , and no change in the calculated cholesterol ratio ( HDL/total cholesterol ) nor lipoprotein ratio ( HDL/(HDL+LDL ) ) was observed . No significant difference between the formulations could be detected with respect to the effect on serum lipids and lipoproteins measured . The change in total cholesterol was smaller than reported in many studies of monophasic preparations . Taken together , these data suggest that only small alterations in lipid metabolism are elicited by these oral contraceptives In an open , r and omized study in an outpatient clinic of a large teaching hospital , thirty-one female volunteers with regular cycles and established ovulation by ultrasonography were given one of two triphasic oral contraceptives containing ethinylestradiol combined with levonorgestrel or desogestrel during six cycles of treatment . The main outcome measures were transvaginal ultrasonography and serum E2 and P measurements in pill cycles 1 , 3 and 6 . No ovarian activity was found in 10 subjects . Among the remaining 21 women who showed ovarian activity , most follicle-like structures developed in the pill-free week and decreased in size or disappeared in the first pill week . One women taking triphasic desogestrel had evidence of a luteinized unruptured follicle and one women taking triphasic levonorgestrel had a possible ovulation . The latter women also showed symptoms of lower abdominal pain . A statistically significant difference in ovarian activity between the two oral contraceptives could not be established . The two triphasic oral contraceptives suppressed ovarian activity to the same degree . A trend was seen towards increasing ovarian activity with duration of use in both treatment groups 398 new users of oral contraceptives at the Research Clinic of the Southwest Foundation Texas were asked if they experienced nausea vomiting headache or breast discomfort nervousness or depression and had weight and blood pressure recorded in the pretreatment cycle and at monthly visits . Each received placebo Oracon ( sequential ) Ovulen-21 ( combination ) Norinyl-1 or .5 mg chlormadinone acetate in a double-blind protocol incorporating a pretreatment placebo cycle crossover to an active pill for 4 cycles and 2 more crossovers for Cyles 5 and 6 . The only symptoms significantly higher than in the pretreatment ( placebo ) cycle were nausea and vomiting with Oracon ( p greater than .05 ) and headache with Ovulen ( p greater than .05 ) . Pointing out that the highest incidence of complaints occurred in the placebo cycle the authors conclude that controls are necessary in contraceptive trials but the first cycle is not valid for comparison A phase III clinical study was carried out among 5680 fertile Chinese women to evaluate efficacy and side effects of three monthly  injectable contraceptives : Mesigyna , Cyclofem and Chinese Injectable No. 1 . When used in a once-a-month treatment schedule ( part 1 of study ) , the effectiveness of Chinese Injectable No. 1 was unacceptably low ; 36 pregnancies occurred during the first 1743 women-months of use , 16 before the second injection . The study was restarted with a revised injection schedule for Injectable No. 1 : two injections separated by 9 + /- 1 days during the first month and subsequent injections given 10 - 12 days after the onset of bleeding , or if no bleeding occurred , 28 days after previous injection . In part 2 of the study , 988 , 990 and 992 subjects were provided Mesigyna , Cyclofem and Injectable No. 1 , respectively . Life-table pregnancy rates at one year were 0.41 % , 0 % and 0.77 % ( p < 0.05 ) , respectively ; the overall discontinuation rates at one year were 13.9 % , 19.1 % and 20.4 % ( p < 0.001 ) . Discontinuation rates for bleeding problems were significantly different between the groups : discontinuation rates for amenorrhea were 0.58 % , 3.71 % and 0.68 % ( p < 0.001 ) for Mesigyna , Cyclofem and Injectable No. 1 ; for other bleeding problems , the rates were 4.88 % , 8.38 % and 12.64 % ( p < 0.001 ) . There were no significant differences between the groups regarding discontinuation for other medical or non-medical reasons . Mean weight changes after one year of use were small : 0.73 , 0.86 and 0.17 kg for the three groups , respectively . Both Mesigyna and Cyclofem were very effective for contraception , but Mesigyna appeared to be tolerated slightly better with regard to cycle control ; the modified dose regimen for Injectable No. 1 also gave a low pregnancy rate but was associated with higher rates of discontinuation The efficacy and acceptability of two third generation oral contraceptives in Thai women were evaluated in a prospect i ve , open , group-comparative , r and omized , multicenter trial of women asking for contraception . In six Family Planning Centers and Outpatient Gynaecological Clinics in urban areas in Thail and , 783 healthy women who were at risk for pregnancy and did not have contraindications to oral contraceptive use were r and omly allocated to one of the two study groups . An oral contraceptive containing 30 mcg ethinylestradiol and 150 mcg desogestrel was given to 394 women and an oral contraceptive with the same amount of ethinylestradiol and 75 mcg gestodene to 389 women during 6 cycles . Criteria of cycle control , side effects and the presence and severity of acne vulgaris were assessed and blood pressure and body weight measured at pretreatment and after cycles 1 , 3 and 6 . Furthermore , the efficacy was evaluated after the last cycle . No pregnancies occurred with either of the contraceptives . The incidences of irregular bleeding and minor side effects in both groups were very low and decreased after an initial increase in the first cycle . Acne improved in both groups . Blood pressure and body weight remained unchanged . The two oral contraceptives were found to be effective and acceptable in Thai women . Compared to Caucasian women , the incidences of irregular bleeding and side effects were apparently lower in these Asian women . Furthermore , the effects of both oral contraceptives were comparable Blinding embodies a rich history spanning over two centuries . Most research ers worldwide underst and blinding terminology , but confusion lurks beyond a general comprehension . Terms such as single blind , double blind , and triple blind mean different things to different people . Moreover , many medical research ers confuse blinding with allocation concealment . Such confusion indicates misunderst and ings of both . The term blinding refers to keeping trial participants , investigators ( usually health-care providers ) , or assessors ( those collecting outcome data ) unaware of the assigned intervention , so that they will not be influenced by that knowledge . Blinding usually reduces differential assessment of outcomes ( information bias ) , but can also improve compliance and retention of trial participants while reducing biased supplemental care or treatment ( sometimes called co-intervention ) . Many investigators and readers naïvely consider a r and omised trial as high quality simply because it is double blind , as if double-blinding is the sine qua non of a r and omised controlled trial . Although double blinding ( blinding investigators , participants , and outcome assessors ) indicates a strong design , trials that are not double blinded should not automatically be deemed inferior . Rather than solely relying on terminology like double blinding , research ers should explicitly state who was blinded , and how . We recommend placing greater credence in results when investigators at least blind outcome assessment s , except with objective outcomes , such as death , which leave little room for bias . If investigators properly report their blinding efforts , readers can judge them . Unfortunately , many articles do not contain proper reporting . If an article cl aims blinding without any accompanying clarification , readers should remain sceptical about its effect on bias reduction The aim of this study was to compare contraceptive reliability , cycle control , and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol ( EE2 ) and 75 micrograms gestodene ( GSD ) , with a reference preparation containing a similar dose of gestodene but in combination with 30 micrograms ethinylestradiol . A higher incidence of intermenstrual bleeding was apparent under the 20 micrograms EE2 oral contraceptive . For the 20 micrograms EE2 preparation , 47.4 % of all women reported spotting at least once over a period of 12 treatment cycles , whereas this figure was 35.5 % for the 30 micrograms EE2 pill ( p < 0.05 ) . However , the incidence was within a range that corresponds to that of other OCs . The cumulative breakthrough bleeding rates ( at least once during the one year of treatment ) of 14.5 % ( 20 micrograms EE2 ) and 11.8 % ( 30 micrograms EE2 ) of women were not significantly different . In relation to all cycles , the intermenstrual bleeding rates were remarkably lower , indicating that the majority of the volunteers experienced such events only in few cycles under treatment : the spotting rate was 11.5 % ( 20 micrograms EE2 ) and 7.2 % ( 30 micrograms EE2 ) of all cycles , and the breakthrough bleeding rate was 
    Output:
    
The 3 placebo-controlled , r and omized trials did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight gain .
In addition , discontinuation of combination contraceptives because of weight gain did not differ between groups when this factor was studied .
: Available evidence is insufficient to determine the effect of  combination contraceptives on weight , but no large effect is evident