***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: A double-blind r and omised crossover trial of oral micronised progesterone and placebo had demonstrated that progesterone had beneficial effects over placebo for some mood and physical premenstrual symptoms . A further trial using identical methodology was carried out to assess whether dydrogesterone would have the same beneficial effects . Prospect i ve assessment confirmed the presence of a premenstrual syndrome in 30 women . Of these , six withdrew during the 4 months of the study . Twenty-four women completed the double-blind crossover protocol . All women were interviewed premenstrually before treatment and in each month of treatment . They completed the Moos Menstrual Distress Question naire , Beck Depression Inventory , Spielberger State Anxiety Inventory , Mood Adjective Checklist and a Daily Symptom Record . Analysis of data found an overall beneficial effect of being treated for most variables . Further analysis showed that the most major effects occurred in the first 2 treatment months . This study could find no evidence that  dydrogesterone  was more effective than placebo in treating premenstrual complaints Objective To determine the pharmacokinetics of a progesterone cream  following short and long term dermal administration 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 Approximately 10 % of women are severely affected by premenstrual syndrome ( PMS ) during their reproductive years . Several biological theories of causation have been proposed and each has provoked treatment attempts through medication to little sustained effect . As many of the reported complaints are psychological , a new treatment approach was considered using cognitive-behavioral therapy . A preliminary study which combined cognitive-behavioral therapy with drug treatment produced considerable symptom reduction . The present study examined the efficacy of cognitive-behavioral therapy  alone in direct comparison with hormone treatment . Relaxation instructions were provided to a control group . Initial rapid responses to drug treatment and relaxation diminishes after 2 months , together with marked attrition in the control group . Significant positive benefits from  cognitive-behavioral therapy  were achieved after the first treatment month that continued throughout and were maintained at follow-up 3 months later . Implication s for future management are discussed 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 Fifteen women with moderate to severe premenstrual symptoms , defined and grade d according to a recently developed scoring system , took part in a double blind study of the effect of progesterone on premenstrual symptoms . The dosage was 100 mg progesterone twice daily delivered in vaginal pessaries . The women were improved with a statistically significant decrease in their scores by progesterone as well as by placebo treatment . There was no statistically significant difference between the two regimes OBJECTIVE To determine the effectiveness of oral micronized progesterone , alprazolam , and placebo in premenstrual syndrome ( PMS ) treatment and the effect of clinical contact on treatment responses . DESIGN R and omized , double-blind , placebo-controlled 3-month parallel treatment arms with flexible dosage and with the length of clinical contact r and omized within each treatment group . SETTING University hospital PMS medical treatment outpatient program in obstetrics/gynecology department . SUBJECTS Among volunteers for PMS treatment , 444 were evaluated and 185 meeting defined PMS criteria were r and omized to treatment ; treatment data are available for 170 . There were no medical withdrawals for adverse events . INTERVENTION A double-blinded protocol in which 300 mg of oral micronized progesterone , 0.25 mg of alprazolam , or placebo was administered four times a day from day 18 of the menstrual cycle through day 2 of the next cycle , including taper . The mean daily dose at the third treatment was 1760 mg of progesterone or 1.5 mg of alprazolam . Subjects were r and omized to brief ( < 20 minutes ) or extended ( 50 minutes ) visits . MAIN OUTCOME MEASURES Daily symptom report ( DSR ) scored for total DSR symptoms , four DSR factors . RESULTS Alprazolam was significantly better than placebo or progesterone for total premenstrual symptoms and DSR factors of mental function , pain , and mood . Thirty-seven percent of the alprazolam group experienced a 50 % reduction in total DSR scores . There were no clinical ly significant withdrawal symptoms when alprazolam administration was restricted to the luteal phase . Oral micronized progesterone therapy was no better than placebo . Brief vs extended visits had no effect on treatment outcome . Treatment response was associated with severity of premenstrual symptoms at baseline but with no other diagnostic variables . CONCLUSIONS Alprazolam has a role in PMS treatment and offers a therapy limited to the luteal phase . Oral micronized progesterone is ineffective for PMS A double-blind , cross-over , placebo-controlled study of dydrogesterone ( 10 mg b.d . ) in the treatment of premenstrual syndrome is described . Two groups of women were studied : secondarily referred hospital clinic patients , and self-referred patients . Only one-third of patients screened completed the study . All patients showed significant improvements in symptom scores during the course of the study , the only significant difference between placebo- and dydrogesterone-treated patients being an increase in frequency of breast tenderness and a decrease in pain with menstrual bleeding in the latter Patients with premenstrual syndrome recorded their symptoms daily using menstrual distress question naires . These were analysed by a least mean square method of fitting sine waves . After recording an untreated cycle , patients were given progesterone 200 mg b.d . and placebo in a double-blind crossover manner ; 75 per cent of patients were then given progesterone 400 mg b.d . and placebo in a similar manner . Treated cycles were rated by both daily menstrual distress question naires and retrospective self- assessment . Both rating methods showed there was no significant difference between progesterone and placebo in reducing symptoms of premenstrual syndrome , and in the majority of cases placebo was more effective , although never significantly so Progesterone is the most widely used treatment for  premenstrual syndrome .  To answer definitely the question of whether progesterone suppositories are effective for the treatment of premenstrual syndrome  , a r and omized , placebo-controlled , double-blind crossover study of 168 women , receiving progesterone in doses of 400 and 800 mg or placebo , was carried out . Premenstrual symptoms were not significantly improved by progesterone compared with placebo in any measure used in the study , including daily symptom reports maintained throughout treatment , clinician evaluation of improvement , and patient global reports of symptoms severity , relief , and disruption of daily activity . No symptom cluster or individual symptom differed significantly between progesterone and placebo treatment . These treatment results were not significantly affected by fluctuations in response during the placebo washout period , pretreatment levels of depression or anxiety at either postmenstrual or premenstrual times , or any of 19 other background , medical history , or symptom variables examined individually as covariates with treatment Forty-eight women with premenstrual problems were recruited for therapy with either medroxyprogesterone ( MPA ) or norethisterone ( NET ) , both compared with placebo , in a double-blind cross-over study . Thirty-five ( 73 % ) completed the study . At an oral dose of 15 mg daily for 21 days each cycle , both MPA and NET suppressed ovulation , although reduction of urinary total oestrogen excretion was significantly greater with NET . Breakthrough bleeding occurred in 74 % of the cycles treated with MPA but only in 22 % of those with NET . Symptoms were monitored daily by visual analogue scales . Both progestins significantly reduced breast discomfort , compared with placebo . While MPA significantly improved individual psychological symptom scores by the second active treatment cycle and pooled psychological symptom scores in both active cycles , NET was no more effective than the placebo . Similar numbers from both groups withdrew because of adverse effects . Among the women treated with MPA , the response to active and placebo therapy was related to the pretreatment psychological symptom profile . The results suggest that the beneficial effect of therapy with MPA in women with premenstrual problems was a consequence of disruption of menstrual cyclicity rather than a result of ovulation suppression Forty-three healthy women with a characteristic history of premenstrual tension participated in a placebo controlled , crossover study . The effects of spironolactone ( Aldactone ) and medroxyprogesterone acetate ( Gestapuran ) on ten symptoms of premenstrual tension were evaluated . Placebo tablets as well as spironolactone and medroxyprogesterone acetate significantly improved a mood index score ( which is a generally accepted method to measure premenstrual symptoms ) . Spironolactone and medroxyprogesterone acetate were however both significantly ( P less than 0.05 ) better than placebo in relieving the symptoms The effect of dydrogesterone on premenstrual symptoms was investigated in a double-blind , r and omized , placebo-controlled study comprising 161 patients from unselected practice material .  Dydrogesterone 10 mg twice daily from the 12th day until onset of the following menstrual period was compared with placebo throughout 3 cycles . No clinical ly relevant effect of dydrogesterone was found . There was an overall therapeutic effect in 52 % of the patients on dydrogesterone , and in 44 % of the placebo-treated patients . Therapeutic gain ranged between -7 and + 23 % ( 95 % confidence limits ) . Type II error risk of failure to detect a therapeutic gain of 20 % was 6 % . A significant effect of dydrogesterone was found on decreased libido , and statistical significance was nearly achieved for the symptoms irritability and headache . The significant effect on libido can be attributed to mass significance Two series of clinical trials in the treatment of  premenstrual tension  are reported . In the first series , 35 patients whose ages ranged from 21 to 40 participated , representing a total number of 140 menstrual cycles . The effect of a progestogen‐diuretic preparation was compared with the effect of progestogen only . A good or very good effect was found in 26 and 17 % of the cycles respectively . The difference was not statistically significant . In the second series 21 student nurses participated representing a total number of 84 menstrual cycles . In this group the effect of the combined preparation was compared with the effect of a placebo in a double blind series . The result was surprising , revealing no difference in effect in the two groups . Neither of the trials gave encouraging results . Other investigators have obtained far better results especially with preparations containing a tranquillizer  in addition to 
    Output:
    
CONCLUSION The evidence from these meta-analyses does not support the use of progesterone or progestogens in the management of premenstrual syndrome