Dynamics and significance of placebo response in primary dysmenorrhea. Effects of naproxen sodium on menstrual prostaglandins and primary dysmenorrhea. Piroxicam in primary dysmenorrhea. Comparison of ketoprofen and naproxen in the treatment of dysmenorrhoea, with special regard to the time of onset of pain relief. The treatment of dysmenorrhea with naproxen sodium: a report on two independent double-blind trials. Feldene in the symptomatic treatment of primary dysmenorrhoea. Primary dysmenorrhea treated with indomethacin. Double-blind crossover comparison of ketoprofen, naproxen, and placebo in patients with primary dysmenorrhea. Comparison of fenoprofen calcium, ibuprofen and placebo in primary dysmenorrhea. Alterations in intrauterine pressure, menstrual fluid prostaglandin F levels, and pain in dysmenorrheic women treated with nimesulide. Efficacy of indomethacin suppository in primary dysmenorrhoea. Indomethacin in the treatment of primary dysmenorrhoea. An attempt at real prophylaxis of primary dysmenorrhea: comparison between meclofenamate sodium and naproxen sodium. [Piroxicam versus naproxen in primary dysmenorrhea]. Diflunisal compared with naproxen in the treatment of dysmenorrhea. Treatment of primary dysmenorrhea with diclofenac sodium. Comparative efficacy of diclofenac dispersible 50 mg and ibuprofen 400 mg in patients with primary dysmenorrhea. A randomized, double-blind, within-patient, placebo-controlled study. Efficacy of ketoprofen in treating primary dysmenorrhea. Efficacy and tolerability of lumiracoxib in the treatment of primary dysmenorrhoea. Ibuprofen and naproxen-sodium in the treatment of primary dysmenorrhea: a double-blind cross-over study. A double-blind, placebo-controlled study comparing three single-dose regimens of piroxicam with ibuprofen in patients with primary dysmenorrhea. A crossover comparison of bromfenac sodium, naproxen sodium, and placebo for relief of pain from primary dysmenorrhea. Piroxicam in the treatment of primary dysmenorrhea. Analgesic efficacy of ibuprofen for treatment of primary dysmenorrhea. Indomethacin in the treatment of primary dysmenorrhoea. Comparison of the efficacy and tolerability of dexketoprofen and ketoprofen in the treatment of primary dysmenorrhea. Efficacy and tolerability of lumiracoxib 200 mg once daily for treatment of primary dysmenorrhea: results from two randomized controlled trials. Mefenamic acid therapy in dysmenorrhea. [Menstrual prostaglandin and dysmenorrhea: modulation by non-steroidal antiinflammatory drugs]. [Nimesulide in the treatment of primary dysmenorrhea. Comparative clinical evaluation with mefenamic acid and fentiazac]. Diclofenac potassium attenuates dysmenorrhea and restores exercise performance in women with primary dysmenorrhea. Analgesic efficacy of etoricoxib in primary dysmenorrhea: results of a randomized, controlled trial. The effect of three cyclo-oxygenase inhibitors on intensity of primary dysmenorrheic pain. [A new pharmacologic treatment of primary dysmenorrhea]. Clinical experience of naproxen in the treatment of primary dysmenorrhea. Flufenamic acid in treatment of primary spasmodic dysmenorrhoea. A double-blind crossover study. Naproxen in dysmenorrhoea. Severe, primary dysmenorrhea treated with naproxen. A prospective, double-blind, crossover investigation. An objective evaluation of flurbiprofen and tranexamic acid in the treatment of idiopathic menorrhagia. [Treatment of primary dysmenorrhea. Comparative study of ibuprofen and mefenamic acid]. The efficacy and safety of aceclofenac versus placebo and naproxen in women with primary dysmenorrhoea. Valdecoxib, a cyclooxygenase-2-specific inhibitor, is effective in treating primary dysmenorrhea. Comparison of the efficacy and safety of nonprescription doses of naproxen and naproxen sodium with ibuprofen, acetaminophen, and placebo in the treatment of primary dysmenorrhea: a pooled analysis of five studies. Efficacy of fenoprofen in the treatment of primary dysmenorrhea. Treating dysmenorrhea with anti-inflammatory agents: a double-blind trial with naproxen sodium. Naproxen sodium in dysmenorrhea. Its influence in allowing continuation of work/school activities. Rofecoxib, a specific cyclooxygenase-2 inhibitor, in primary dysmenorrhea: a randomized controlled trial.
A total of 55 patients with primary dysmenorrhea who had shown a favorable response to a preliminary treatment cycle with placebo were admitted to a double-blind study on placebo versus antiprostaglandin agents (naproxen and pirprofen). To evaluate the placebo effect and its duration, the treatment was given for 4 successive cycles. Whereas the antiprostaglandin agents were effective in most of the patients (in 80% of the pirprofen group and 85.7% of the naproxen group) and this efficacy was maintained throughout the study, a favorable response to placebo was observed in 84% in the first cycle, 29% in the second, 16% in the third and 10% in the fourth. The incidence of side effects was similar in the placebo and the active treatment groups (35.4% vs. 37.5%). It is postulated that a placebo effect in dysmenorrhea is due to a central analgesic mechanism mediated by endorphin release or possibly to psychological dynamics (mental or conditioning theories). However, this effect loses efficacy with time possibly due to a decreased susceptibility to the opioid action of the central nervous circuits responsible for menstrual pain perception or to deconditioning mechanisms. Prostaglandins E2 and F2 alpha in the menstrual fluid from 12 patients with primary dysmenorrhea were measured by radioimmunoassay (RIA). Each patient was studied for 3 cycles, using vaginal tampons issued for this study. All tampons were collected individually for prostaglandin extraction and RIA. Severity of dysmenorrhea and clinical response to treatment were evaluated by a scoring method and by the patients' self-assessment. Each patient in this double-blind cross-over study had a control cycle and 2 treatment cycles with naproxen sodium tablets (275 mg) or placebo in random order. The treatment regimen was 2 tablets at the first sign of menses followed by one tablet 4 times daily for 3 days. Nine patients obtained good to excellent relief from naproxen sodium, but no relief from the placebo. Two patients had moderate to good response to both naproxen and placebo, and one patient showed no response. Naproxen therapy but not placebo therapy sharply reduced menstrual prostaglandin F2 alpha and prostaglandin E2 release. There was a positive correlation between menstrual prostaglandin levels and the severity of dysmenorrhea. Symptomatically, naproxen sodium was most effective in alleviating severe menstrual cramps but had little effect on mild cramps. It was also effective in ameliorating many but not all of the subjective symptoms such as dizziness, nausea, and vomiting. Relief of dysmenorrhea was apparent within one hour after the initial dose, attained maximum level in 2 hours, and was maintained throughout therapy. Ninety-two patients with primary dysmenorrhea were included in a double-blind randomized crossover trial to study the efficacy of piroxicam on menstrual pain and associated symptoms, with placebo as control. Ninety patients completed the 4-month study period. Piroxicam afforded a highly significant relief from menstrual pain and reduced the need for the supplementary analgesic paracetamol. Piroxicam also had a significant effect on associated symptoms. The drug was well tolerated, with only a few side effects of a mild nature reported and with no difference between the piroxicam and placebo groups in this respect. In a double-blind, crossover study in 39 women with dysmenorrhoea, the effects of oral treatment with single doses of 100 mg ketoprofen and 500 mg naproxen were compared with regard to time for onset of pain relief and overall effect on symptoms. Assessments of pain severity using a visual analogue scale and an activity-related scale were made at 15-minute intervals for 2.5 hours. The results showed that ketoprofen was significantly more effective at 60 and 45 minutes, respectively, after intake of medicine and the differences remained significant until 120 and 105 minutes, respectively. Reduction in original pain by 50%, the patient's view on the overall effect after each treatment as well as a comparison of effects at the end of the study all differed significantly in favour of ketoprofen. No significant differences were found between treatments in the need for additional analgesic therapy after the 2-hour observation period or in the incidence of side-effects, which was low with both medications. It is suggested that ketoprofen could have a therapeutic advantage over naproxen, particularly in patients in whom menstrual pain develops rapidly. The efficacy of naproxen sodium (naproxen-Na) in dysmenorrhea has been established in two independent double-blind (placebo-controlled) studies. An initial dose of 550 mg. of naproxen-Na was followed by 275 mg. every six hours for a maximum of five days. Twenty patients were included in Study I (10 treated with naproxen-Na) and 23 patients in Study II (12 treated with naproxen-Na). Each patient received the medication during four dysmenorrheic episodes. Thus, a total of 172 treatment courses could be evaluated. A variety of efficacy criteria were measured: frequency of pill intake, changes in pain intensity, the degree of relief achieved by the medication, and need for additional analgesics. In both studies naproxen-Na was demonstrated to be superior to the placebo treatment with high statistical significance in each of these parameters. nan Primary dysmenorrhea is a difficult entity to treat, and therapy is usually directed at relieving symptoms. There is some indication that this disorder is caused by an increase in prostaglandin F2alpha. Therefore, logically the treatment may include antiprostaglandin agents. We have studied 32 women with the diagnosis of primary dysmenorrhea in a randomized double-blind fashion using a placebo and indomethacin. Both agents were taken three times a day over four cycles, and therapy was begun two days before the usual onset of pelvic pain. Only two of 16 patients in the placebo group were significantly improved in the four-month treatment cycles while all 16 in the treatment group showed some improvement, 11 having cessation of pain. In the six months following the study period, all patients were given indomethacin. The original treatment group did not change significantly. However, all in the placebo group when switched to indomethacin had some relief, 12 of the 16 showing complete cessation of pain. Gastric irritation was the main side effect and was present in 18% of the treatment group and 12% in the placebo group. Indomethacin appears to effectively relieve primary dysmenorrhea and does not appear to be associated with a high incidence of side effects. Sixty-three women, aged 18 to 39 years, with primary dysmenorrhea received 25 mg, 50 mg, or 75 mg of ketoprofen, 500 mg of naproxen, or placebo as a first dose at the onset of moderate or severe pain. Each patient received three treatments and each treatment was tested in 36 patients. Mean pain relief scores (on a five-point scale) indicated a significant analgesic response for all active treatments; superiority over placebo was shown by ketoprofen 50 mg for six hours, by ketoprofen 75 mg for five hours, by ketoprofen 25 mg for four hours, and by naproxen for four hours. The onset of pain relief and peak relief were reached faster and pain relief lasted longer after 75 mg and 50 mg of ketoprofen than after 25 mg of ketoprofen or 500 mg of naproxen, which in turn were superior to placebo. Treatment was rated good to excellent by 20 patients after 25 mg of ketoprofen, by 26 after 50 mg, and by 28 after 75 mg, and by 22 after naproxen and 11 after placebo. The incidence of side effects was similar in the ketoprofen-treated and naproxen-treated patients. This prospective, double-blind, parallel, two clinic study compared fenoprofen calcium, 200 mg; ibuprofen, 400 mg; and placebo in the treatment of pain due to primary dysmenorrhea. By various criteria, the treatment groups, prior to treatment, were not significantly different (P greater than 0.05) in paired comparisons. However, after oral administration of the study medications, the pain scores were significantly greater (P less than 0.05) for the placebo group than for either other group. The posttreatment pain scores for the fenoprofen and ibuprofen treated groups were not significantly different (P greater than 0.05). A double-blind crossover study was carried out to evaluate the therapeutic efficacy of nimesulide and its effects on uterine activity, menstrual fluid prostaglandin F, and pain in women suffering from primary dysmenorrhea. Twenty-three women entered the clinical pharmacologic study. Intrauterine pressure was monitored with a microballoon-tipped catheter on the first day of menstruation. During the maximal pain period (based on monitoring in six patients), nimesulide significantly decreased intrauterine pressure; the measure of pain relief was consistent with decrease of uterine activity. In another six patients, the registration of intrauterine pressure during the submaximal pain period demonstrated that both in the nimesulide- and placebo-treated cycles, the uterine activity was at a lower mean level than that registered during maximal pain. Furthermore, when two 100-mg oral doses of nimesulide were administered to 11 dysmenorrheic women, in double-blind, crossover conditions with placebo as a blank reference, it brought about a reduction of menstrual fluid prostaglandin F2 levels from 382 to 94 ng/mL, (P less than .001). Fourteen women entered a four-cycle, double-blind, crossover therapeutic trial. Each patient was randomly assigned to one of two treatment sequences with nimesulide 200 mg/d PO or placebo. The therapy was judged very effective or good in 22 of 28 cycles treated with nimesulide compared with nine of 27 cycles treated with placebo (P less than .01). The amount of bleeding during the treated cycles did not change, and there were no complaints of untoward signs or symptoms related to the therapies. The efficacy of indomethacin suppositories (100 mg 1-3 times a day) in the treatment of primary dysmenorrhoea was investigated in a double-blind, crossover study involving 40 patients, in comparison to placebo. The patients were treated for four menstrual periods-two periods with placebo and two periods with indomethacin suppositories. A dysmenorrhoeic score based on subjective estimations of nine symptoms was used, the symptoms including pelvic pain, backache, headache, dizziness, nausea, vomiting, diarrhoea, nervousness and incapacitation. As compared to placebo, indomethacin suppositories led to a insignificant decrease in the frequency and severity of the associated symptoms, as evaluated by subjective rating (P less than 0.05). Indomethacin suppositories were well tolerated and there was no drop-out. No side effects were reported except for a mild burning sensation in the rectal region experienced by 3 patients on indomethacin suppositories. Thirty-two patients were treated with placebo tablets or indomethacin (25 mg three times daily) in a six-month, double-blind, cross-over trial. During indomethacin therapy, 75 per cent of patients experienced significant pain relief while associated vomiting and diarrhoea were relieved in 44 per cent and 64 per cent of patients respectively. The efficacy of indomethacin was comparable to that of other prostaglandin synthetase inhibitors. Dysmenorrhea is a widespread phenomenon, affecting mainly young nulliparous women, often inducing difficulties in study or in work. Its pathogenesis involves a release of local vasoconstrictors like Prostaglandins and Leukotrienes. Modern therapy is based firstly on the administration of prostaglandin-Synthetase Inhibitors or Contraceptive Pills, with the aim of reducing the menstrual excess of pain inducing substances. In order to achieve more efficacy, on the basis of the already proven effectiveness of the Non Steroid Anti-Inflammatory Drugs (NSAID)s in this field, we recently set out to prevent dysmenorrhea in a double-blind randomized study with Meclofenamate Sorium and Naproxen Sodium. Through the observation of the drop in Basal Body Temperature which usually precedes menstrual flow, we were able to instruct our patients in the earlier recognition of impending menstrual onset, leading to earlier prevention of Prostaglandin and Leukotriene release. Meclofenamate Sodium in particular led to considerable pain reduction, with very good patient compliance and without significant complications, probably of its additional receptor effect. In this study 198 patients with primary dysmenorrhea were entered into a double-blind, randomized crossover trial to study the efficiency of piroxicam compared to naproxen on menstrual pain and associated symptoms. The dosage for piroxicam was 40 mg on the first and second day of the menstrual cycle, and if necessary an additional 20 mg on the third day. The dosage for naproxen was 1,000 mg on the first and second day, and if necessary an additional 500 mg on the third day. Piroxicam and naproxen afforded high relief from menstrual pain and associated symptoms. The drugs were well tolerated with only a few side effects of a mild nature. There were no statistically significant differences between piroxicam and naproxen. A randomized double-blind cross-over study was carried out in 19 young female undergraduates with severe primary dysmenorrhea to compare the efficacy and tolerance of treatment with diflunisal and naproxen. All patients received both substances twice during four consecutive cycles. The first tablet was taken at the onset of dysmenorrheic symptoms and continued according to the individual need, maximally four tablets daily. The overall relieving effect was good or moderate in 73.7% of the diflunisal cycles and in 92.1% of the naproxen cycles. The difference was not statistically significant. One third of the women estimated decreased menstrual blood loss during treatment with both the drugs. Side effects were mild and did not cause discontinuation of the therapy. Diflunisal seems to be as equally effective in the treatment of primary dysmenorrhea as naproxen, which is a well-documented and widely used prostaglandin synthetase inhibitor. The efficacy of diclofenac sodium was investigated in the painful symptoms of primary dysmenorrhea and in reducing menstrual bleeding. Thirty-five nulliparous women (17-28 yr of age) were included in a double-blind cross-over study for four menstrual periods, two periods with diclofenac sodium and two periods with placebo. The diclofenac sodium treatment (total of 58 periods) reduced the pain significantly in comparison with placebo (57 periods), as evaluated by subjective rating (P less than 0.001) and by a 6-point scale of pain intensity (P less than 0.05). Also the amount of menstrual bleeding was significantly reduced as measured by subjective rating (P less than 0.001) and by counting the number of sanitary pads used (P less than 0.05). The results indicate that diclofenac sodium in low dose (about 75 mg daily) is effective not only in reducing the pain at menstruation, but also the bleeding. Sixty female out-patients suffering from moderate to severe primary dysmenorrhea, aged 14-40 years (mean 27 years), entered this randomized, double-blind, 3-period, within-patient study, evaluating the efficacy and tolerability of diclofenac dispersible 46.5 mg (equivalent to 50 mg of diclofenac sodium), ibuprofen 400 mg and placebo taken up to 4 times daily for a maximum of 3 days. Pain relief was evaluated on a verbal rating scale (0 = none, 1 = slight, 2 = moderate, 3 = considerable, 4 = complete) at 0.5, 1,2,3,4,5 and 6 hours after the first dose; the weighted sum of pain relief scores over the 6-hour observation period was also investigated (TOTPAR-6). Pain intensity was assessed on a verbal rating scale (0 = nil, 1 = mild, 2 = moderate, 3 = severe) at baseline and at the above mentioned time points; the weighted sum of pain intensity differences at each time point was also analyzed (SPID-6). A rescue medication was permitted 1 hour or more after the intake of the test drug: in such cases the last value of pain intensity/relief scores was carried forward and used for the analysis. A global evaluation of efficacy and of trial medication as compared to her usual medication was performed by the patient at the end of each treatment period. Finally, adverse experiences were recorded throughout the study period. Analysis of covariance and Koch's adaptation of the Wilcoxon-Mann-Whitney rank sum test were used, where appropriate, for statistical analysis. Mean TOTPAR-6 values for diclofenac dispersible, ibuprofen and placebo were 16.5, 17.8 and 14.7, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) A 6-month double-blind crossover trial compared ketoprofen with placebo in the treatment of primary dysmenorrhea in 27 women who satisfied explicit inclusion and exclusion criteria. The response to treatment was assessed with a pain scale and a disability scale and by noting amelioration of associated symptoms, such as nausea, vomiting, diarrhea, fatigue, dizziness and headache. Ketoprofen was significantly superior to placebo in relieving the pain (p less than 0.001), disability (p less than 0.001) and headache (p less than 0.01) associated with menstruation. No order effect of treatment was observed. Adverse effects were few and minimal. Two randomised, multicentre, double-blind, placebo- and active-controlled, 3-way crossover studies were performed to evaluate the efficacy and tolerability of the novel COX-2 selective inhibitor lumiracoxib in the treatment of primary dysmenorrhoea. Subjects with moderate-to-severe dysmenorrhoea received lumiracoxib 400 mg once daily (od), rofecoxib 50 mg od and placebo (Study 1; n = 84) or lumiracoxib 400 mg od, naproxen 500 mg twice daily and placebo (Study 2; n = 99). For the primary variable, summed pain intensity difference from 0 to 8 h on day 1 (SPID-8), all active treatments were superior to placebo in each study (p < 0.001); lumiracoxib was comparable to rofecoxib and naproxen. For PID (categorical scale), all active treatments were significantly better than placebo from 2 to 12 h; lumiracoxib was generally comparable to rofecoxib and naproxen. All treatments were well tolerated. Lumiracoxib 400 mg is effective and well tolerated in the treatment of primary dysmenorrhoea, with efficacy comparable to rofecoxib and naproxen. The efficacy of ibuprofen and naproxen-sodium for the treatment of primary dysmenorrhea was evaluated in a double-blind cross-over study in 57 otherwise healthy women. The severity of pain reported by the patients was significantly (P less than 0.01) reduced during treatment with both ibuprofen and naproxen-sodium compared to the severity of pain before the first dose. The mean pain relief during treatment with ibuprofen was significantly (P less than 0.05) greater than during treatment with naproxen-sodium in the dosages indicated. Sixty-eight women with primary dysmenorrhea were randomly assigned to one of five four-times-daily treatment groups for a minimum of three days and a maximum of five days. Three of the groups received different initial single-daily doses of piroxicam, which were followed on each treatment day with placebo for the second through fourth doses, namely, piroxicam 20 mg daily for five days (piroxicam 20 mg for five days); piroxicam 40 mg on Day 1, followed by piroxicam 20 mg on Days 2 through 5 (piroxicam 40 mg for one day); and piroxicam 40 mg on Days 1 and 2, followed by piroxicam 20 mg on Days 3 through 5 (piroxicam 40 mg for two days). The fourth group received ibuprofen 400 mg four times per day, and the fifth group received placebo four times per day. Patients determined the severity of overall discomfort and pelvic-abdominal pain at baseline and prior to each dose using a four-point numerical scale. Supplemental ibuprofen, 400 mg four times per day, was provided for those patients requiring additional pain relief. Patients also made a global determination of overall relief at the end of the study. At 24 hours, the results revealed that piroxicam 40 mg for two days, piroxicam 20 mg for five days, and ibuprofen provided significantly more relief of overall discomfort compared with placebo (p = 0.003, p = 0.018, and p = 0.026, respectively). All four active treatment groups also experienced significantly more relief of pelvic-abdominal pain compared with placebo: piroxicam 40 mg for two days followed by three days of 20 mg (p = 0.002), piroxicam 40 mg for one day followed by four days of 20 mg (p = 0.023), piroxicam 20 mg for five days (p = 0.012), and ibuprofen (p = 0.011). A significantly smaller percentage of patients treated with piroxicam 40 mg for two days required supplemental medication as compared with those treated with piroxicam 20 mg for five days (p = 0.035) and patients treated with placebo (p = 0.010). A greater amount of overall relief was obtained by patients treated with piroxicam 40 mg for two days compared with patients treated with piroxicam 40 mg for one day (p = 0.041) and placebo-treated patients (p = 0.001). It was concluded that single daily doses of piroxicam 20 mg and 40 mg were as effective as ibuprofen, 400 mg four times per day, for the relief of primary dysmenorrhea. Single and multiple oral doses of bromfenac sodium (10 or 50 mg) were compared with naproxen sodium (550 mg loading/275 mg repeat doses) for the relief of pain from primary dysmenorrhea in 54 women using a crossover design. Pain intensity and pain relief were assessed over 6 h after the first dose, and global ratings were made at the end of day 1 and on day 2. A single dose of bromfenac 10 or 50 mg was as effective as the loading dose of naproxen sodium (550 mg) in relieving the pain from dysmenorrhea through a 6-h period. All three active treatments were statistically superior (p < 0.001) to placebo for the primary efficacy variables, 3-h and 6-h total pain relief and 3-h and 6-h summed pain intensity difference. All active treatments were statistically superior (p < 0.05) to placebo for the first dose and day 1 global assessments. One or more adverse study events were reported by 13 patients (25%) who received bromfenac 50 mg, 15 (29%) who received bromfenac 10 mg, 20 (38%) who received naproxen sodium, and 19 (37%) who received placebo. There were no clinically significant differences among the treatments in the types of adverse study events. No serious or unexpected adverse study events were reported, and no women withdrew from the study because of an adverse event. Bromfenac sodium (10 mg or 50 mg) is as effective as naproxen sodium (550 mg loading dose/275 mg repeat doses) for relief of pain from dysmenorrhea. In double-blind, crossover studies, piroxicam was compared with naproxen sodium and with placebo. The different parameters studied were pain intensity, patient's opinion of the drugs tested, complementary pharmacological treatment, ability to work, overall effect, treatment preference, and side effects. It was concluded that piroxicam was comparable to naproxen sodium and that piroxicam was significantly better than placebo, as regards these parameters. It was also concluded that piroxicam has an effect equivalent to that of naproxen sodium, an accepted treatment for dysmenorrhea. Fifty-five women with primary dysmenorrhea were enrolled in a study which each took ibuprofen (400 mg), propoxyphene hydrochloride (64 mg), or a placebo alternately in consecutive menstrual cycles for relief of pain. Fifty-one completed the study during three successive cycles in this triple-blind, crossover, randomized investigation. Ibuprofen was clearly superior to propoxyphene and the placebo in patient preference, degree of relief, and need for supplementary analgesics. In addition, a significantly greater number of patients were able to pursue their normal daily functions during the ibuprofen cycle. Propoxyphene was superior to the placebo but not to the same extent as ibuprofen. Only three side effects were reported during the study, two relative to propoxyphene and one recorded during a placebo cycle. These data show that ibuprofen is an effective agent when used for treatment of dysmenorrhea without organic etiology. The efficacy of indomethacin, a prostaglandin synthetase inhibitor, in severe dysmenorrhoea was established in a double-blind crossover study using aspirin and placebo as the control drugs. Forty-seven female undergraduates were treated twice with each of the three substances during six consecutive menstrual cycles. Good or moderate relief was achieved in 71% of the cycles treated with indomethacin, in 40% of those treated with aspirin and in 21% of those treated with the placebo. Dizziness and drowsiness were cited by 14 patients (30%) as side-effects of indomethacin, none of these patients discontinued the therapy because all obtained good or moderate relief from dysmenorrhoea. Indomethacin proved to be a valuable agent, and significantly better than aspirin in the treatment of dysmenorrhoea. It allowed many dysmenorrhoeic women to carry out their normal activities and work during the menstrual period. Dexketoprofen, the pure S(+)-enantiomer of ketoprofen, is a promising new analgesic, but few clinical trials have yet examined its efficacy and tolerability. In this study, patients with a history of primary dysmenorrhea were treated with dexketoprofen doses of 12.5 and 25 mg, ketoprofen 50 mg, and placebo using a randomized, four-way crossover design. Efficacy analyses showed that dexketoprofen 12.5 and 25 mg and racemic ketoprofen 50 mg significantly reduced pain intensity compared with placebo from 1 h after dose to 4-6 h after dose. Interestingly, dexketoprofen at 12.5 mg was significantly superior to placebo at 30 min after dose. Mean pain relief scores also demonstrated that both doses of dexketoprofen and racemic ketoprofen were significantly superior to placebo at 1-6 h after the first dose. No indices of analgesic efficacy showed any significant differences between the two doses of dexketoprofen or between dexketoprofen and ketoprofen. After repeated dose administration, similar results were obtained. There were no significant effects of any treatment on activities of daily living, menstrual flow, or associated symptoms. Dexketoprofen was effective, well tolerated, and had no difference in the incidence of adverse events compared to ketoprofen or placebo. Nonsteroidal anti-inflammatory drugs (NSAIDs) are established as treatment for managing pain associated with primary dysmenorrhea. However, the efficacy and tolerability of lumiracoxib 200 mg once daily (q.d.) has not previously been examined in primary dysmenorrhea.
                Two randomized, multicenter, double-blind, placebo-controlled, crossover studies of similar design have assessed the efficacy and tolerability of two regimens of lumiracoxib compared with placebo (Study 1) or naproxen and placebo (Study 2) in women (aged 18-45 years) with moderate to severe primary dysmenorrhea. In Study 1 (n = 132), patients received lumiracoxib 200 mg q.d., lumiracoxib 200 mg with a 200 mg redose (p.r.n.) on day 1, or placebo. In Study 2 (n = 144), patients received lumiracoxib 200 mg q.d., lumiracoxib 200 mg with a 200 mg redose p.r.n. on day 1, naproxen 500 mg twice daily (b.i.d.), or placebo. Patients recorded study medication use, efficacy assessments, and rescue medication use.
                The primary efficacy variable, summed (time-weighted) pain intensity difference (categorical scale) over the first 8 hours (SPID-8), was similar between all active treatments (e.g., p = 0.939 for naproxen 500 mg b.i.d. vs. lumiracoxib 200 mg q.d. in Study 2), and all active treatments were superior to placebo (p < 0.001). Median time-to-onset of analgesia was similar between lumiracoxib 200 mg q.d. and naproxen 500 mg b.i.d. Similar trends were observed for all other secondary efficacy variables. All treatments were well tolerated.
                Short-term administration of lumiracoxib 200 mg q.d. is effective and well tolerated and provides an alternative treatment option for the management of moderate to severe pain associated with primary dysmenorrhea. nan The analgesic efficacy and tolerance of lysine clonixinate (LC) as well as LC-induced changes in menstrual prostaglandin levels were studied according to a prospective double-blind randomized crossover design, controlled with ibuprofen (I) and placebo (P). Treatment consisted in 4 consecutive phases: in the first phase, patients refrained from taking medication and during the remaining three phases, they received double-blind fixed doses of 1 tablet of lysine clonixinate 125 mg, I 400 mg or P, q.6 h. at random, three days before onset of menses and during 8 days thereafter. Controls were carried out at each menstrual cycle, assessing pain according to a scale from 0 to 4, onset of premenstrual and intramenstrual symptoms, relief of pain and occurrence of side-effects. During menstruation, patients recorded their assessments of pain in a diary and collected the whole menstrual bleeding during the first three days. The intensity of menstrual pain remained unchanged in controls upon admission (3.16) and during the phase with no treatment (3.04), but was significantly reduced with P (2.4), LC (1.79) and I (1.54). Significantly lower pain intensities compared with placebo were seen with active treatment phases. Forty-two percent of patients treated with P reported premenstrual pain which was significantly reduced to 17% with LC and to 12.5% with I. Active treatment phases revealed 21% of asymptomatic patients during premenstrual and menstrual periods and 71% (LC) and 75% (I) of cases with partial relief of pain. Patients' diaries showed significant pain reductions with LC and I, during the 1st and 2nd days compared with P; such differences were gradually reduced to nil by the 4th day. Levels of menstrual PGs changed according to pain intensity reductions from baseline (P: 29%, (NS); LC: 58% and I: 61%; both were statistically significant, p < 0.01). Sixty patients with primary dismenorrhea were treated: 20 with nimesulide, 20 with fentiazac and 20 with mefenamic acid during three consecutive cycles under double blind design. The doses used in each group were: nimesulide or fentiazac 100 mg, every 12 hrs., mefenamic acid 500 mg. every 8 hrs. in all cases during 5 days, beginning a day before the beginning, of the menstruation. The pain evolution and the symptoms were evaluated three times a day using a scale from 0 to 10, so measure its intensity. Concluding, the nimesulide is useful in the treatment of pain associated with primary dismenorrhea, answering with little statistical advantage over the fentiazac and with bigger statistical advantage over the mefenamic acid. The tolerance was excellent with the three drugs studied. We assessed the efficacy of diclofenac potassium, a nonsteroidal anti-inflammatory drug, in alleviating menstrual pain and restoring exercise performance to that measured in the late-follicular phase of the menstrual cycle. Twelve healthy young women with a history of primary dysmenorrhea completed, in a random order, laboratory exercise-testing sessions when they were in the late-follicular (no menstruation, no pain) phase of the menstrual cycle and when they were experiencing dysmenorrhea and receiving, in a double-blinded fashion, either 100 mg of diclofenac potassium or placebo. We assessed the women's leg strength (1-repetition maximum test), aerobic capacity (treadmill walking test), and ability to perform a functional test (task-specific test). Compared with placebo, diclofenac potassium significantly decreased dysmenorrhea on the day of administration (Visual Analog Scale, P < .001 at all times). When receiving placebo for menstrual pain, the women's performance in the tests was decreased significantly, compared with when they were receiving diclofenac potassium for menstrual pain (P < .05) and compared with when they were in the late-follicular phase of the menstrual cycle (P < .05 for treadmill test, P < .01 for task-specific test and 1-repetition maximum test). Administration of diclofenac potassium for menstrual pain restored exercise performance to a level not different from that achieved in the late-follicular phase of the cycle.
                In women with primary dysmenorrhea, menstrual pain, if untreated, decreases laboratory-assessed exercise performance. A recommended daily dose of a readily available nonsteroidal anti-inflammatory drug, diclofenac potassium, is effective in relieving menstrual pain and restoring physical performance to levels achieved when the women were in the late-follicular (no menstruation, no pain) phase of the menstrual cycle. To determine the efficacy of etoricoxib in the treatment of primary dysmenorrhea.
                Seventy-three women were randomly assigned to receive single oral doses of etoricoxib 120 mg, placebo, or naproxen sodium 550 mg at the onset of moderate to severe pain associated with menses. During 3 consecutive menstrual cycles in this double-blind, 3-period, crossover study, pain intensity and pain relief were assessed over the 24-hour period following dosing, and global ratings of therapy were made at 8 and 24 h after dosing. Tolerability was assessed by spontaneous reports of adverse experiences.
                Etoricoxib 120 mg provided analgesic efficacy superior to placebo for the primary endpoint, total pain relief over 8 h (TOPAR8, p<0.001), and for all secondary endpoints (p<0.050). The analgesic effect of etoricoxib 120 mg over the first 8 h was similar to that of naproxen sodium 550 mg. All treatments were well tolerated.
                Etoricoxib 120 mg provided rapid and sustained analgesia that was superior to placebo and similar to that of naproxen sodium 550 mg.
                Copyright 2003 S. Karger AG, Basel To determine the effect of 3 different cyclo-oxygenase (COX) inhibitors on primary dysmenorrheic pain.
                Eleven female patients self-medicated with either placebo (sugar), 25 mg of the COX-2 specific inhibitor rofecoxib, 50 mg of the nonselective COX inhibitor diclofenac potassium, or 7.5 mg of the COX-2 selective inhibitor meloxicam, over 4 menstrual cycles. Pain was assessed using the McGill Pain Questionnaire and a visual analog scale.
                The pain response index, present pain index, and visual analog scale were highly correlated as measures of intensity of pain (r=0.81 to 0.96, P<0.0001). Rofecoxib and diclofenac potassium both decreased the duration of dysmenorrheic pain compared with placebo (P<0.001) and with meloxicam (P<0.01), and were equally effective in improving pain, compared with placebo, after each capsule (P<0.001). When compared with placebo, both drugs also provided 50% or more pain relief, after each capsule (P<0.0048). Meloxicam, although superior to placebo, was not as effective as rofecoxib and diclofenac potassium in reducing pain, and when compared with placebo, was associated with providing 50% or more of pain relief only after the third and fourth capsules (P=0.016).
                Rofecoxib and diclofenac potassium, when taken in recommended doses, were equally effective in alleviating pain associated with primary dysmenorrhea. nan The effect of naproxen, Naprosyn, Syntex, in treatment of primary dysmenorrhea was studied in a double-blind, randomized, placebo controlled multicenter study. Nintyseven women, aged between 18--40 years, with severe dysmenorrhea, were treated with either naproxen, 48 women, or placebo, 49 women, for two consecutive menstrual cycles. No oral contraceptive was used. The patients were allowed to take supplementary analgesics 4--6 hours after the study drug was taken if adequate relief was not achieved. The recommended dose of naproxen was 1--2 tablets, 250 mg, as needed, with a maximum of 5 tablets daily. Medication was started at first sign of menstrual distress. Improvement was achieved in 70 per cent of the women in the naproxen group (good to excellent relief) but only in 30 per cent in the placebo group. This difference is statistically significant (p less than 0.001). There was much more supplementary medication used in the placebo group compared to the naproxen treated patients (p less than 0.001). Fewer patients had to stay in bed, or stay at home from work or school, in the naproxen group compared to the placebo group. Few side-effects were reported and most of them belonged to the dysmenorrhea symptomatology. No side-effects could be rement according to the patients' own judgement. A double-blind cross-over trial of flufenamic acid three times a day (200 mg) was carried out in forty-four patients with primary dysmenorrhoea. While on flufenamic for 3 months 82% of patients experienced significant pain relief. Associated gastrointestinal symptoms, i.e--vomiting and diarrhoea--were relieved in 66% and 52% patients respectively while on flufenamic acid. It is concluded that the fenamates are useful and safe drugs in the treatment of primary dysmenorrhoea. nan 26 women aged 15-45 with severe, primary dysmenorrhea were treated with naproxen (NAPROSYN, SYNTEX) and placebo during 2 x 2 consecutive menstrual cycles in a randomized, double-blind crossover study. The dosage of naproxen was 500 mg (2 tablets) initially, followed by 250 mg as needed, with a maximum of 1250 mg daily. In most cases medication started at the first sign of menstrual distress. 80 per cent of the women preferred naproxen to placebo. The number of tablets taken during each menstruation fell from a mean of 17.8 in the placebo period to 5.1 in the naproxen period. Likewise, additional analgesics fell from 7.1 to 1.6 and hours of bed rest from 16.4 to 1.2. Total number of days of sick leave per two menstruations decreased from 40 to 7. These differences are statistically significant (P < 0.001). The side effects were mild. CNS or gastrointestinal side effects were not seen. Naproxen changed the amount of bleeding in 12 and delayed bleeding in three. Two developed acne, which however gradually diminished during the next five bleeding periods treated with naproxen. The influence of prostaglandin synthetase inhibitors on the ovarian production of steroids is discussed. The effect of flurbiprofen (100 mg x 2 for 5 days) was compared with tranexamic acid (1.5 g x 3 for 3 days, 1 g x 2 days 4 and 5) in the treatment of 15 women with idiopathic menorrhagia. The mean blood loss during two medication-free periods was 295 +/- 52 ml. A significant (p less than 0.01) reduction in menstrual blood loss was recorded during treatment with both flurbiprofen and tranexamic acid. The menstrual blood loss was significantly (p less than 0.01) lower during treatment with tranexamic acid (155 +/- 33 ml) than with flurbiprofen (223 +/- 44 ml). Various side effects were recorded by 7 of 15 women during treatment with tranexamic acid and by 4 women of 15 during treatment with flurbiprofen. Many women with menorrhagia suffer simultaneously from dysmenorrhea. Thus although tranexamic acid was generally more effective in reducing menstrual blood loss, flurbiprofen provides an important therapeutic alternative to antifibrinolytic agents, especially in patients with concomitant dysmenorrhea. In double-blind studies, mefenamic acid (group A) was compared with ibuprofen (group B) in the treatment of primary dysmenorrhea in 60 patients, during two cycles. The initial pain intensity was 8.9 for group A and 8.5 for B. The medication were administered at cero time (when the colic begin) and each 8 hours during the menstrual period. The decrease of pain intensity was presented after the second pill administration in group A for 8.6 + 1.8 at 6.0 + 2.4 in the first cycle and 8.5 +/- 1.8 at 5.9 +/- 2.6 in the second cycle. The group B the decrease of pain was similar of 8.2 +/- 1.7 at 5.1 +/- 2.6 for the first cycle and the 8.2 +/- 1.7 at 4.7 +/- 2.6 in the second cycle of treatment. The number of tablets administered for both groups were for group A 5.5 and for B 4.4. The duration of pain were 22.1 hours for group A and 19.3 for B. To determine the analgesic efficacy and safety of a single oral dose of aceclofenac 100 mg and compare that with placebo and naproxen 500 mg in women with primary dysmenorrhoea.
                In this double-blind, prospective, multicentre, randomised, three-way, crossover study, women were randomly assigned to receive one of six treatment sequences, comprising single oral doses of aceclofenac 100 mg, naproxen 500 mg or placebo, when menstrual pain reached a predetermined level of severity. A single dose of the assigned study medication was taken on three menstrual periods; a different medication was taken on each treatment day. Analgesic efficacy was determined by self-reported analgesia scoring and participants' and investigators' global evaluation of treatment effectiveness. Measurements also included physical examination and adverse events.
                Total pain relief scores were not statistically significantly different for aceclofenac and naproxen, and both were statistically significantly more effective than placebo (p = 0.019 and 0.002, respectively). This finding was supported by secondary endpoints including sum of pain intensity differences (SPID/8), peak analgesia (peak pain intensity and peak pain relief), and participants' and investigators' overall evaluation of effectiveness. Both aceclofenac and naproxen were well tolerated.
                Aceclofenac (100 mg) and naproxen (500 mg) effectively treated the pain associated with primary dysmenorrhoea, and both were more effective than placebo at easing menstrual pain assessed by various pain relief criteria. To compare the efficacy of the cyclooxygenase (COX)-2-specific inhibitor valdecoxib with naproxen sodium in treating menstrual pain associated with primary dysmenorrhea.
                This single-center, double-blind, placebo-controlled, randomized, crossover study compared the efficacy and safety of single oral doses of valdecoxib 20 mg and 40 mg with naproxen sodium 550 mg, or placebo, with an option of treatment for up to 3 days, twice daily. Efficacy was assessed by time-weighted sum of total pain relief, sum of pain intensity difference, time-specific pain relief, and pain intensity difference over 12 hours, time to rescue medication or first re-medication, the percentage of patients taking rescue medication, and patient's global evaluation of study medication.
                Mean time-weighted sum of total pain relief and sum of pain intensity difference were significantly superior to placebo for the first 8 and 12 hours after the initial dose of valdecoxib 20 mg (P <.01) and 40 mg (P <.001). Valdecoxib 20 mg and 40 mg were comparable to naproxen sodium 550 mg for all efficacy measures. Other differences in efficacy measures favoring the higher dose of valdecoxib did not achieve statistical significance, with the exception of sum of pain intensity difference-12. Both doses of valdecoxib were well tolerated.
                Both valdecoxib 20- and 40-mg doses were effective and well tolerated for the treatment of primary dysmenorrhea. Valdecoxib 20 mg and 40 mg demonstrate analgesic efficacy, based on onset, magnitude, and duration of analgesia that is similar to naproxen sodium, making it a potential choice for treating women with primary dysmenorrhea. Dysmenorrhea is the most common menstrual complaint in young women, with a prevalence as high as 90%. It is responsible for substantial repeated short-term absenteeism from school and work in young women. Effective treatments are available, including nonsteroidal anti-inflammatory drugs (NSAIDs). In many countries, a variety of NSAIDs have become available as over-the-counter (OTC) drugs.
                The goal of this study was to compare the efficacy and safety of OTC doses of naproxen (400 mg) and naproxen/naproxen sodium (200/220 mg) with acetaminophen (1000 mg), ibuprofen (200 mg), and placebo in the treatment of primary dysmenorrhea.
                A pooled analysis of 5 trials was performed. Efficacy was assessed by pain relief, relief of other dysmenorrheic symptoms, time to backup medication or remedication, and treatment preference. Tolerability was assessed by recording adverse events (AEs).
                A total of 443 women were enrolled in the combined studies. Naproxen 400 mg provided greater pain relief than acetaminophen and placebo within 30 minutes of administration (P < 0.01 and P < 0.05, respectively). Furthermore, naproxen 400 mg and 200 mg provided greater pain relief than both acetaminophen (P < 0.01 and P < 0.05, respectively) and ibuprofen (P < 0.001 and P < 0.01, respectively) at 6 hours after administration. Both doses of naproxen had higher scores than placebo for symptom relief and drug preference (all P < 0.001). The AEs and their frequency were similar among the treatment groups. No serious AEs were reported.
                When administered at OTC doses, naproxen was effective in the relief of pain and other symptoms of primary dysmenorrhea and had a good safety profile in the population studied. We compared fenoprofen calcium, 200 mg; fenoprofen calcium, 400 mg; aspirin, 650 mg; and a placebo in 85 women for the relief of primary dysmenorrhea in a double-blind, clinical trial. The usefulness of these drugs was judged from data obtained over four consecutive menstrual periods on: restriction of daily activity, pain intensity scores, need for rescue analgesics, withdrawal due to lack of efficacy, and adverse events. Both fenoprofen, 200 mg, and fenoprofen, 400 mg, offered significant (P less than .01) pain relief when compared to placebo and aspirin. Analyses of data on 1, 2 and 3 indicated that aspirin was not significantly different from placebo. The aspirin-treated group reported the greatest number of adverse reactions, but the differences between the four groups were not statistically significant. Our study lends support to the concept of a "plateau analgesic effect" of nonsteroidal antiinflammatory drugs (NSAIDs): fenoprofen, 200 mg, appears to be as effective as fenoprofen, 400 mg. When this type of drug fails to provide relief for a woman suffering from primary dysmenorrhea, switching to another NSAID may be more appropriate than increasing the dosage and the probability of dosage-related side effects. Thirty-two dysmenorrheic patients participated in a double-blind trial of naproxen sodium for three consecutive menstrual cycles. The women were divided into two groups: 15 women were given naproxen sodium (the sodium salt of d-2-(6-methoxy-2-naphthyl) propionic acid) and 17 women received placebo tablets. The women were prescribed two tablets (550 mg) at the first sign of menstrual pain and one tablet (275 mg) thereafter every six hours, as required. There were no significant differences between the two groups in physical characteristics, obstetric and gynecologic histories, including the character of dysmenorrhea and pretreatment pain intensity scores (p = 0.7). Following intake of the drug or placebo, the participants rated the relief provided by the medication with a six-point scoring system. When the scores for pain relief were tallied for the three treatment cycles, the naproxen sodium group averaged 13.7 +/- 0.65 standard error, while the placebo group averaged 8.8 +/- 0.95 standard error out of a possible maximum relief score of 18. The difference between the two groups was statistically significant at p = 0.0004. Few patients reported side effects. Sixty-four women with primary dysmenorrhea participated in a double-blind, parallel trial of maproxen sodium versus placebo during three menstrual cycles. Comparative measures employed to assess the efficacy of the medications included changes in pain intensity during each dysmenorrheic episode, the degree of pain relief afforded, the necessity of using a supplementary analgesic, and the extent to which medication enabled the patients to continue their daily activities unimpeded. By these measures, naproxen sodium was significantly superior as compared to the placebo. Particularly striking was the fact that of 22 naproxen sodium treated women who historically had to stay at home from work and/or in bed, only 5 remained incapacitated compared with 21 of 26 patients of the placebo group. Only 1 patient experienced side effects (nausea and hypomenorrhea) from naproxen sodium. To determine whether rofecoxib is effective for treating primary dysmenorrhea and whether cyclooxygenase-2 is involved in the pathophysiology of primary dysmenorrhea.
                A double-masked, randomized, placebo and active-comparator-controlled clinical trial including 127 subjects with histories of primary dysmenorrhea was conducted in an outpatient clinical research center. Subjects were randomly assigned to placebo, rofecoxib 25 or 50 mg followed by 25 mg every 24 hours as needed, or naproxen sodium 550 mg every 12 hours as needed for up to 3 days. Subjects took all four treatments in a balanced, complete-block, crossover design. Measurements included self-administered questionnaires of analgesic efficacy, spontaneous reports of adverse experiences, physical examinations, and laboratory safety tests.
                Rofecoxib 25 and 50 mg provided analgesic efficacy greater than placebo (P < or = .006) for the primary endpoint of total pain relief over the first 8 hours. For other efficacy endpoints (sum of the pain intensity difference over the first 8 hours, subject's global evaluation, peak pain relief, peak pain intensity difference, and time to remedication) both doses of rofecoxib were better than placebo (P < or = .006) and were not distinguishable from naproxen sodium for all efficacy endpoints. All treatments were well tolerated.
                Rofecoxib effectively treated primary dysmenorrhea, and cyclooxygenase-2-derived prostanoids play a role in the pathophysiology of primary dysmenorrhea.
NSAIDs are an effective treatment for dysmenorrhoea, though women using them need to be aware of the significant risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea.