***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 
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    ***EXAMPLES*** 
    Input: Purpose To further investigate the efficacy of progesterone in the treatment of the symptoms of premenstrual syndrome ( PMS ) .  Material s and Methods From an initial cohort of 25 subjects diagnosed with moderate to severe PMS , 17 reproductive age females completed the 7-month , doubleblind , placebo controlled trial using 200-mg vaginal progestone suppositories . Multiple modalities for evaluating symptoms were employed , including the Spielberger self-evaluation rating , the Beck depression inventory , and the Hamilton anxiety scale . In addition , each subject was interviewed by a psychiatrist on a monthly basis ; ovulation was determined monthly using a basal body temperature chart ; serum hormonal assays included beta endorphin , progesterone , follicle stimulating hormone , luteinizing hormone , estradiol , and prolactin . Results Hormonal assays confirmed no differences between treatment and control groups . Overall scores on all test vehicles were likewise not significantly different between the two groups ; however , in the subcategory of nervous symptoms , a significant improvement was found in symptoms relating to tension , mood swings , irritability , anxiety and lack of control . Conclusions Metabolites of progesterone ( pregnanolone and allopregnanolone ) may play a physiologic role as anxiolytic agents , perhaps modifying mood and anxiety ; the current study confirms the utility of twice daily , 200-mg progesterone vaginal suppositories , in the alleviation of some PMS symptoms relating to anxiety and irritability . Further evaluation may be warranted to ascertain which patients in the known heterogeneous PMS population may be most likely to benefit from such treatment Background Given an observed test statistic and its degrees of freedom , one may compute the observed P value with most statistical packages . It is unknown to what extent test statistics and P values are congruent in published medical papers . Methods We checked the congruence of statistical results reported in all the papers of volumes 409–412 of Nature ( 2001 ) and a r and om sample of 63 results from volumes 322–323 of BMJ ( 2001 ) . We also tested whether the frequencies of the last digit of a sample of 610 test statistics deviated from a uniform distribution ( i.e. , equally probable digits ) . Results 11.6 % ( 21 of 181 ) and 11.1 % ( 7 of 63 ) of the statistical results published in Nature and BMJ respectively during 2001 were incongruent , probably mostly due to rounding , transcription , or type- setting errors . At least one such error appeared in 38 % and 25 % of the papers of Nature and BMJ , respectively . In 12 % of the cases , the significance level might change one or more orders of magnitude . The frequencies of the last digit of statistics deviated from the uniform distribution and suggested digit preference in rounding and reporting . Conclusions This incongruence of test statistics and P values is another example that statistical practice is generally poor , even in the most renowned scientific journals , and that quality of papers should be more controlled and valued CONTEXT Over the years , different hypotheses involving the ovarian steroid hormones have been proposed to explain the luteal phase occurrence of severe premenstrual syndrome symptoms . Although it had been strongly suspected that differences in the concentrations of the ovarian steroids may underlie the mood and psychological imbalance of this disorder , the evidence for this hypothesis has been inconsistent and remains controversial . OBJECTIVE Our objective was to measure the ovarian steroid hormones across the menstrual cycle in women with and without luteal phase symptoms consistent with premenstrual dysphoric disorder ( PMDD ) . DESIGN We measured  estradiol ( E2 ) , progesterone , and SHBG  in women with and without PMDD using a cross-sectional and prospect i ve experimental design . Participating women underwent 2-month self- assessment symptom screening and 1-month hormonal evaluation . RESULTS Overall means for LH , progesterone , E2 , peak E2 , and free E2 were not different between groups . Across the menstrual cycle , overall percent free E2 was significantly lower and SHBG significantly greater in the PMDD group compared with controls ( 1.39 + /- 0.26 vs. 1.50 + /- 0.28 , P = 0.03 ; 61.4 + /- 25.1 vs. 52.4 + /- 21.3 nmol/liter , P = 0.046 , respectively ) . During the luteal phase , free E2 was significantly lower in the PMDD group compared with controls ( PMDD 7.6 + /- 7.0 vs. controls 8.9 + /- 8.4 pmol/liter ; P = 0.032 ) . For both follicular and luteal phases , SHBG was significantly higher in the PMDD group ( follicular phase 60.5 + /- 31.7 vs. 51.4 + /- 38.2 nmol/liter , P = 0.047 ; luteal phase 65.1 + /- 32.3 vs. 55.1 + /- 38.9 nmol/liter , P = 0.03 ) . In both groups , SHBG significantly increased from the follicular to luteal phase . CONCLUSION Luteal phase concentrations of free E2 , percent free E2 , and SHBG differ significantly between women with and without PMDD The present study extends a previous report of lower plasma ACTH levels in women with premenstrual syndrome ( PMS ) compared with asymptomatic controls .  Plasma levels of estradiol and progesterone were measured daily in 10 women with confirmed PMS and 8 asymptomatic women . Daily symptom reports were maintained during the same menstrual cycle . Both estradiol and progesterone levels were consistently , but not significantly , higher throughout the cycle in PMS subjects compared with controls . From the follicular to the early luteal phase , estradiol levels were significantly higher in a previously defined PMS subgroup 2 with more severe symptoms throughout the cycle compared with both the less severe PMS subgroup 1 and controls . Progesterone levels were significantly and positively correlated with PMS symptoms along the entire menstrual cycle , preceding the symptoms by 5 - 7 days . These preliminary results provide support for the hypothesis that the presence of progesterone at early luteal phase levels is required for PMS symptoms to occur A covert method of assessing perception of health in relation to menstruation was applied prospect ively to a group of women aged 20 to 40 years . Of the 1386 r and omly selected women contacted , 838 ( 60 % ) provided information for the full study period of six weeks and 608 of these respondents menstruated during that time . A clear excess of women demonstrated premenstrual deterioration in perceived health . This rose to a peak at the onset of menstruation and subsided rapidly during menstruation , thus reflecting the conventionally defined pattern of the premenstrual syndrome . When , on completion of prospect i ve recording , the same women were asked to return an overt and retrospective assessment of paramenstrual symptoms , the overall pattern of results was similar but , for individual women , there was little correspondence between similar data obtained by the two different methods A double blind , r and omised , crossover trial of oral micronised progesterone ( two months ) and placebo ( two months ) was conducted to determine whether progesterone alleviated premenstrual complaints . Twenty three women were interviewed premenstrually before treatment and in each month of treatment . They completed Moos 's menstrual distress question naire , Beck et al 's depression inventory , Spielberger et al 's state anxiety inventory , the mood adjective checklist , and a daily symptom record . Analyses of data found an overall beneficial effect of being treated for all variables except restlessness , positive moods , and interest in sex . Maximum improvement occurred in the first month of treatment with progesterone . Nevertheless , an appreciably beneficial effect of progesterone over placebo for mood and some physical symptoms was identifiable after both one and two months of treatment . Further studies are needed to determine the optimum duration of treatment OBJECTIVES To explore the possible role of natriuretic peptides and vasopressin in luteal phase fluid retention in premenstrual syndrome ( PMS ) and to determine the effect of progesterone therapy on these hormones . DESIGN Self-controlled prospect i ve study . SETTING University-based medical research centre . PATIENTS Six patients with PMS were studied during the symptomatic luteal and asymptomatic follicular phases . The follicular phase response was used as the control for each subject . INTERVENTIONS An intravenous infusion of 3 % saline solution was administered on an early follicular and a late luteal phase day in 2 menstrual cycles . Progesterone was administered orally during the second luteal phase . OUTCOME MEASURES Osmolality , arginine vasopressin ( AVP ) , atrial natriuretic factor ( ANF ) , and brain natriuretic peptide ( BNP ) levels in plasma , osmolality , sodium , potassium , cyclic adenosine monophosphate ( cAMP ) and cyclic guanosine 5'-phosphate ( cGMP ) concentrations in urine , and thirst sensation . RESULTS Mean basal plasma ANF and osmolality levels and the threshold for AVP release and thirst were lower , and mean urinary cyclic nucleotide levels and AVP sensitivity ( amount of AVP secreted per unit rise in plasma osmolality ) were higher , in the luteal phase than in the follicular phase . With saline loading , there was an increase in plasma osmolality , AVP and ANF and in urinary sodium and cyclic nucleotide levels . Plasma ANF and osmolality levels remained lower in the luteal phase compared with the follicular phase , but AVP levels at the end of the saline infusion were higher in the luteal phase than in the follicular phase . Progesterone therapy caused an increase in plasma ANF and osmolality levels and the AVP threshold and a decrease in AVP levels and sensitivity and urinary cyclic nucleotide levels . BNP levels did not change with phase or treatment . The differences in AVP threshold with phase and treatment were statistically significant ( p < 0.001 ) . There was a significant phase effect for plasma ANF ( p = 0.02 ) and a significant or near-significant interaction effect of phase and treatment for plasma ANF ( p = 0.06 ) and urinary cAMP ( p = 0.047 ) and cGMP ( p = 0.066 ) . The effect of phase and treatment was not significant for the other measurements . CONCLUSIONS Luteal phase fluid retention may be due to a relative deficiency of ANF and a lower threshold for AVP release . The symptomatic improvement produced by progesterone treatment may be due to its stimulation of ANF and inhibition of AVP release or synthesis BACKGROUND A variety of definitions have been applied to premenstrual syndrome . The severity of the syndrome is also variable . AIM A study was undertaken to compare progesterone pessaries with placebo in the relief of symptoms of  premenstrual syndrome . In this study the condition was characterized by a wide range of symptoms recurring in the late luteal phase but absent in the follicular phase ( that is , the specific definition published by Dalton in 1953 ) . METHOD A multicentre , prospect i ve , double-blind , r and omized , parallel group study was undertaken by 45 general practitioners . Patients were deemed eligible after two prospect i ve menstrual cycles of observation ( selection phase ) in which a precise definition of symptoms was applied . Patients were r and omized to use either progesterone pessaries ( 400 mg twice a day ) or matching placebo , by vaginal or rectal administration , from 14 days before the expected onset of menstruation until the onset of vaginal bleeding , for four consecutive cycles . Baseline data for the outcome variables were determined in the selection phase . The main outcome variables were changes in the severity ( categorized as none , mild , moderate or severe ) of each patient 's most severe symptom , and in the average score of all the patient 's symptoms characteristic of premenstrual syndrome . Spontaneous reports of adverse events were recorded . RESULTS A total of 281 patients were screened for premenstrual syndrome ; of these , 141 patients were r and omized to treatment or placebo groups . Efficacy was evaluated in 93 patients . Reductions in the scores of the highest scoring , most severe , symptoms and in the average symptom score , were consistently observed in patients receiving progesterone pessaries and in those receiving placebo . The response to progesterone was greater than to placebo during each cycle ; the differences were clinical ly and statistically significant . Adverse events were reported by 51 % of patients in the progesterone treatment group and by 43 % in the placebo group . Irregularity of menstruation , vaginal pruritus and headache were reported more frequently by patients taking active therapy . CONCLUSION In this study , progesterone , given as pessaries by vaginal or rectal administration , was more effective than placebo in the relief of symptoms of premenstrual syndrome in a population of patients selected by strict entry criteria Plasma levels of prolactin , FSH , LH , progesterone and 17–β‐oestradiol in twenty women with premenstrual tension were compared with those in twenty controls . The former group was studied also during treatment with bromocriptine .  The mean prolactin level in the PMT group was lower in the follicular phase than in the luteal phase ( P < 0.±01 ) , but there was no difference between the PMT and control group in the luteal phase . No differences were found between the controls and the PMT group in FSH , LH , 17–β‐oestradiol and progesterone levels in the luteal phase . Bromocriptine  suppressed 
    Output:
    
The trials did not show that progesterone is an effective treatment for PMS nor that it is not .
Neither trial distinguished a subgroup of women who benefited , nor examined cl aim ed success with high doses