Treating dysmenorrhea with anti-inflammatory agents: a double-blind trial with naproxen sodium. An attempt at real prophylaxis of primary dysmenorrhea: comparison between meclofenamate sodium and naproxen sodium. The efficacy and safety of aceclofenac versus placebo and naproxen in women with primary dysmenorrhoea. 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. Ibuprofen and naproxen-sodium in the treatment of primary dysmenorrhea: a double-blind cross-over study. Dysmenorrhea in women with intrauterine contraceptive device. Treatment with a prostaglandin synthetase inhibitor, naproxen. Treatment of primary dysmenorrhea with diclofenac sodium. Transcutaneous electrical nerve stimulation (TENS) for the treatment of primary dysmenorrhea: a randomized crossover comparison with placebo TENS and ibuprofen. Diflunisal compared with naproxen in the treatment of dysmenorrhea. [Magnesium--a new therapeutic alternative in primary dysmenorrhea]. Analgesic efficacy of ibuprofen for treatment of primary dysmenorrhea. Clinical experience of naproxen in the treatment of primary dysmenorrhea. Comparison of ketoprofen and naproxen in the treatment of dysmenorrhoea, with special regard to the time of onset of pain relief. Randomized controlled trial assessing a traditional Chinese medicine remedy in the treatment of primary dysmenorrhea. A clinical trial of hydroxyethylrutosides in the treatment of haemorrhoids of pregnancy. Surgical treatment of primary dysmenorrhea with laparoscopic uterine nerve ablation. Naproxen sodium in dysmenorrhea. Its influence in allowing continuation of work/school activities. The treatment of dysmenorrhea with naproxen sodium: a report on two independent double-blind trials. Psychological treatments of dysmenorrhea: differential effectiveness for spasmodics and congestives. Efficacy and tolerability of lumiracoxib 200 mg once daily for treatment of primary dysmenorrhea: results from two randomized controlled trials. Efficacy and tolerability of lumiracoxib in the treatment of primary dysmenorrhoea. Valdecoxib, a cyclooxygenase-2-specific inhibitor, is effective in treating primary dysmenorrhea. Flufenamic acid in treatment of primary spasmodic dysmenorrhoea. A double-blind crossover study. Analgesic effect of a herbal medicine for treatment of primary dysmenorrhea--a double-blind study. Acupuncture for the management of primary dysmenorrhea. Piroxicam in primary dysmenorrhea. Indomethacin in the treatment of primary dysmenorrhoea. Dynamics and significance of placebo response in primary dysmenorrhea. Curative treatment of primary (spasmodic) dysmenorrhoea. Efficacy of ketoprofen in treating primary dysmenorrhea. Indomethacin in the treatment of primary dysmenorrhoea. Efficacy of a paracetamol and caffeine combination in the treatment of the key symptoms of primary dysmenorrhoea. Dysmenorrhoea unrelieved by an oral contraceptive. Alterations in intrauterine pressure, menstrual fluid prostaglandin F levels, and pain in dysmenorrheic women treated with nimesulide. A crossover comparison of bromfenac sodium, naproxen sodium, and placebo for relief of pain from primary dysmenorrhea. Transcutaneous electrical nerve stimulation in the relief of primary dysmenorrhea. Severe, primary dysmenorrhea treated with naproxen. A prospective, double-blind, crossover investigation. Analgesic efficacy of etoricoxib in primary dysmenorrhea: results of a randomized, controlled trial. Feldene in the symptomatic treatment of primary dysmenorrhoea. Pain of endometriosis: effects of nafarelin and danazol therapy. [Randomized controlled study on superficial needling for treatment of primary dysmenorrhea]. [Treatment of primary dysmenorrhea. Comparative study of ibuprofen and mefenamic acid]. Updating the clinical experience in endometriosis--the European perspective. [Piroxicam versus naproxen in primary dysmenorrhea]. A study of co-treatment of nonsteroidal anti-inflammatory drugs (NSAIDs) with misoprostol for cervical priming before suction termination of first trimester pregnancy. [Menstrual prostaglandin and dysmenorrhea: modulation by non-steroidal antiinflammatory drugs].
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. 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. 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. 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. 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. Twenty-one women with intrauterine contraceptive devices (IUCD) and severe dysmenorrhea were studied. All the women who participated in the study had primary dysmenorrhea of varying intensities. The insertion of IUCD increased the intensity of dysmenorrheic pain. The effect of naproxen (Naprosyn) on pain alleviation was studied in a double-blind cross-over trial using naproxen and placebo. The effect of naproxen was significantly better than that of placebo (P less than 0.01). No severe side effects occurred during the treatment. There was no difference in the duration and amount of the menstrual blood flow during naproxen treatment compared to placebo according to the women's own judgement. 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. In a randomized four-way crossover study, 32 women with primary dysmenorrhea were treated with transcutaneous electrical nerve stimulation (TENS) for two cycles, placebo (sham) TENS for one cycle, or ibuprofen 400 mg four times a day for one cycle. The TENS setting used was 100 pulses per second with 100-microsecond pulse widths. The subjects were allowed to adjust the amplitude to a comfortable level. The pain rescue medication was ibuprofen 400 mg as needed, up to 1600 mg/day. Significantly more subjects who had TENS treatment did not require rescue medication or required less backup ibuprofen at 0-4, 4-8, and 8-12 hours after the onset of dysmenorrhea and starting treatment, as well as during the first 24 hours and for the duration of the menstrual flow, when compared with placebo TENS or ibuprofen-treated cycles (Tukey multiple comparison, P less than .01). Transcutaneous electrical nerve stimulation significantly delayed the need for ibuprofen by an average of 5.9 hours, compared with 0.7 hours when using ibuprofen alone (P less than .05, paired t test). Transcutaneous electrical nerve stimulation alone provided good to excellent subjective pain relief in 42.4% of subjects, compared with 3.2% with placebo TENS, and significantly reduced diarrhea, menstrual flow, clot formation, and fatigue compared with placebo TENS. Transcutaneous electrical nerve stimulation plus less ibuprofen provided pain relief equivalent to that obtained with ibuprofen alone (71 and 75% of the subjects, respectively). We conclude that TENS is a safe, effective, non-medication method for managing primary dysmenorrhea and that TENS plus ibuprofen was the best overall treatment, as indicated by pain relief. 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. 50 patients suffering from primary dysmenorrhoea were treated with Magnesium (Mg 5-longoral, Artesan GmbH) in a double-blind study. After a six-month period 21 out of 25 women showed a decline of symptoms, only 4 ones reported no therapeutical effect. For monitoring treatment results prostaglandin F2 alpha (PGF2 alpha) was measured every second month. On Mg-therapy conditions we achieved a reduction of PGF2 alpha in menstrual blood to 45% of value before treatment started. As against that 90% of basic concentration were estimated from women who received a placebo. Probably, the specific therapeutical effect of Mg based on inhibition of biosynthesis of PGF2 alpha but also on its direct muscle relaxant and vasodilatory effect. Beside the PG-synthesis and ovulation inhibitors the use of Magnesium is a potential, natural opportunity to treat primary dysmenorrhoea, which is widely free of side effects. 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 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. 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. A proof-of-concept study to assess the safety and efficacy of a traditional Chinese medicine formula as treatment for primary dysmenorrhea showed no statistically significant benefit over placebo. However, some efficacy parameters suggested possible superiority of the active treatment and so a larger study needs to be performed to determine whether this remedy has a role in the treatment of dysmenorrhea. The safety and efficacy of 500 mg O-(beta-hydroxyethyl)rutosides given orally twice daily in the treatment of 97 patients with first-, second-, or third-degree haemorrhoids were investigated in a double-blind, randomized placebo-controlled trial. The rutosides produced a significant (P less than 0.001) improvement in patient-assessed subjective symptoms (pain, bleeding, exudation and pruritus) compared with placebo. There was also a significant (P less than 0.001) improvement in clinician-assessed subjective and objective signs (bleeding, inflammation and dilatation of the haemorrhoidal plexus) after 2 and 4 weeks' treatment compared with placebo. There were three mild, transient side-effects reported in the active treatment group and no drug-related problems in the pregnancy or delivery were observed. The results suggest that O-(beta-hydroxyethyl)rutosides provide a safe and effective treatment for women with haemorrhoids of pregnancy. With approximately 25% of dysmenorrheic patients reporting no improvement with nonsteroidal anti-inflammatory drugs, a study was devised to evaluate the effectiveness of a laparoscopic technique for the interruption of the uterosacral nerves. In a double-blind study of 21 patients with primary dysmenorrhea, 81% (9 of 11) reported significant relief from menstrual pain after the surgery. Performed as an outpatient procedure, laparoscopic uterine nerve ablation may alleviate dysmenorrheic complaints when other modalities have failed. Half the treated women reported continued relief of menstrual pain at 12 months. These results suggest that uterosacral nerve interruption may prove an effective alternative treatment for this menstrual disorder. 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. 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. Two studies are reported, examining the effectiveness of psychological treatments for dysmenorrhea. In Experiment 1, 33 women with spasmodic dysmenorrhea were treated with relaxation alone, or relaxation plus imagery, or assigned to a waiting-list control condition; and 29 women with congestive dysmenorrhea were treated with relaxation alone, or assigned to a waiting-list control condition. In Experiment 2, 18 additional congestives were treated with a coping skills package, or this package plus relaxation; these two groups were compared with the two congestive groups from Experiment 1. The dependent measures were reports of symptom severity, general discomfort, resting time, and medication use. Consistent with the literature, the main findings of the present studies are: (a) relaxation training (alone or with imagery) effectively reduces resting time for spasmodics; and (b) none of the treatments was shown to be effective for congestive sufferers. 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. 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. 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. 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. We evaluated the analgesic effect of Toki-shakuyaku-san (TSS) in women who had a combination of "deficiency," of "Yin," "cold," and "stagnated blood" syndromes, and were suffering from dysmenorrhea. A diagnostic scoring system was used for determination of these conditions. We treated patients with either TSS or placebo during 2 menstrual cycles with a double-blind technique, and we followed them for 2 additional cycles. A significant alleviation of dysmenorrhea was observed in patients treated with TSS as compared to those treated with placebo. Our results suggest that TSS is effective for treatment of dysmenorrhea in patients with the above-mentioned conditions. The effectiveness of acupuncture in managing the pain of primary dysmenorrhea was investigated in a randomized and controlled prospective clinical study. Forty-three women were followed for one year in one of four groups: the Real Acupuncture group was given appropriate acupuncture and the Placebo Acupuncture group was given random point acupuncture on a weekly basis for three menstrual cycles; the Standard Control group was followed without medical or acupuncture intervention; the Visitation Control group had monthly nonacupuncture visits with the project physician for three cycles. In the Real Acupuncture group, 10 of 11 (90.9%) women showed improvement; in the Placebo Acupuncture group, 4 of 11 (36.4%); in the Standard Control group, 2 of 11 (18.2%); and in the Visitation Control group 1 of 10 (10%). There was a 41% reduction of analgesic medication used by the women in the Real Acupuncture group after their treatment series, and no change or increased use of medication seen in the other groups. 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. 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. 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. To prove the efficacy of oral vitamin B1 administration for the treatment of primary dysmenorrhoea, a randomised, double-blind, placebo-controlled study was carried out on 556 girls aged 12-21 yr, having moderate to very severe spasmodic dysmenorrhoea. Thiamine hydrochloride (vitamin B1) was given in a dose of 100 mg orally, daily for 90 days. The combined final results of both the 'active treatment first' group and the 'placebo first' group, after 90 days of vitamin B1 administration, were 87 per cent completely cured, 8 per cent relieved (pain almost nil to reduced) and 5 per cent showed no effect whatsoever. The results remained the same two months later as well when no drug was administered. Unlike all the current treatments which are suppression-oriented, this curative treatment directly treats the cause, is free from side effects, is inexpensive and easy to administer. 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. 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. Primary dysmenorrhoea is characterised by pain, cramping and backache at the time of menses. Despite the high prevalence of dysmenorrhoea, few sufficiently powered, placebo-controlled studies have examined the efficacy of over the counter analgesics in this condition. Furthermore, even fewer studies have directly examined the efficacy of analgesics on specific dysmenorrhoea symptoms. Research design and main outcome measures: This was a single-dose, placebo-controlled, double blind, crossover study carried out in 320 women with moderate-to-severe dysmenorrhoea pain. At 2 h following dosing, 1 g paracetamol plus 130 mg caffeine led to significantly greater pain relief compared to 1 g paracetamol alone (p < 0.05), 130 mg caffeine alone (p < 0.01) or placebo (p < 0.01). The combination was also significantly more effective in relieving abdominal cramping and backache compared to the other treatment arms. No major treatment related adverse events were reported during this study.
                When taken at recommended doses, both paracetamol and the combination of paracetamol and caffeine are safe and effective treatments for primary dysmenorrhoea. Consistent with results from other acute pain states, caffeine acts as an analgesic adjuvant and enhances the efficacy of paracetamol. nan 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. 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. The purpose of this study was to replicate a previous study to determine the effectiveness of acupuncture-like transcutaneous electrical nerve stimulation in treating primary dysmenorrhea. Twenty-one women with dysmenorrhea received a placebo pill or 30 minutes of acupuncture-like TENS. All subjects completed two pain questionnaires before treatment; immediately posttreatment; 30, 60, 120, and 180 minutes posttreatment; and the next morning upon awakening. Each woman also participated in a separate study measuring electrical resistance at four auricular acupuncture points before and immediately after treatment. The data were analyzed with a two-factor repeated-measures analysis of variance, which revealed statistical significance over time but not for group or interaction between group and time. Results revealed an average pain relief of at least 50% immediately posttreatment, indicating that acupuncture-like TENS may be useful for dysmenorrheic pain. This study also suggests that auriculotherapy via acupressure may relieve the pain of primary dysmenorrhea. 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. 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 nan To compare the efficacy of nafarelin acetate with danazol in the treatment of dysmenorrhea, dyspareunia, and pelvic pain associated with endometriosis.
                Prospective, randomized double-blind controlled study. PATIENTS, SETTING, TREATMENTS: Two hundred thirteen patients aged 18 to 48 with laparoscopically confirmed pelvic endometriosis and dysmenorrhea, dyspareunia or pelvic pain were randomly assigned to 6 months of treatment with either nafarelin acetate 800 micrograms per day or 400 micrograms per day, or danazol 800 micrograms per day.
                The percentage of patients with dysmenorrhea, dyspareunia or pelvic pain before treatment who still had these symptoms after 6 months of treatment and 6 months following completion of treatment. RESULTS [table: see text]
                Nafarelin acetate and danazol both provided significant relief of dysmenorrhea, dyspareunia, and pelvic pain during treatment and for 6 months following treatment in women with endometriosis. To observe clinical therapeutic effect of superficial needling at distal and proximal acupoints on primary dysmenorrhea (PD).
                One hundred and twenty cases of PD were randomly divided into a treatment group (n =60) and a control group (n = 60). The treatment group were treated with superficial needling at Sanyinjiao (SP 6) and the control group with oral administration of indometacin entric-coater tablets.
                Of the 120 cases, 116 cases completed the investigation. The total effective rate was 93. 3% in the treatment group and 75. 0% in the control group. The comprehensive therapeutic effect and the cured rate in the treatment group were significantly better than that in the control group (P<0. 001), with a more rapid effect and lasting a longer time than the control group.
                Clinical therapeutic effect of superficial needling at Sanyinjiao (SP 6) on primary dysmenorrhea is better than that of oral administration of indometacin entric-coater tablets. 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. In a large, double-blind, multicentre study, 269 patients with confirmed endometriosis were randomly allocated to receive either danazol (200 mg twice daily; n = 137) or gestrinone (2.5 mg twice weekly; n = 132) for 6 months. The two groups were comparable in terms of the staging of endometriosis by the American Fertility Society (1979) score. After the sixth month of treatment, repeat laparoscopy was performed. Clinical assessment, haematological and biochemical investigations were carried out during the 6 months of treatment and for a further 12 months' follow-up and are compared between the two groups. A total of 15 patients from the gestrinone group, including four patients with hirsutism, and 17 patients from the danazol group, including six patients with headache, withdrew because of adverse symptoms. An additional 22 patients, including 10 from the gestrinone group and 12 from the danazol group withdrew because of lack of efficacy, pregnancy, elevated hepatic function tests or for reasons unrelated to the trial. Total American Fertility Society scoring showed an improvement of 73.3% in 101 patients receiving gestrinone and 72.7% in 99 patients receiving danazol. The results showed a significant reduction in the severity of dysmenorrhoea by the third month in the danazol group and at 6 months in both groups. There was a significant (P < 0.001) increase in weight observed in both groups during treatment. Overall, the tolerability of danazol and gestrinone was good; however, significantly more patients with gestrinone complained of hirsutism while significantly more with danazol complained of leg cramps. During the 12 months of follow-up, mild, moderate or severe degrees of lower abdominal pain, dysmenorrhoea and deep dyspareunia all fluctuated, with no statistically significant increase in frequency in either group. 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. This double-blind randomized control study was conducted to evaluate whether a nonsteroidal anti-inflammatory drug (NSAID) could act as an effective pain control method during first trimester suction abortion, and whether co-treatment of NSAID with misoprostol will decrease the efficacy of the cervical ripening effect of misoprostol. Subjects were randomized to receive misoprostol alone or misoprostol together with diclofenac sodium. Both groups of subjects suffered from similar incidence of preoperative side effects. Co-treatment of NSAID with misoprostol did not attenuate the cervical ripening efficacy of misoprostol. There was no significant pain reduction in the group treated with NSAID, except that a marginal benefit was found in the subgroup of multiparous women. About two thirds of the subjects in both treatment groups found that this was a satisfactory pain relief method during the procedure. 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).
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.